TY - JOUR T1 - Assessment of the clinical and analytical performance of three Seegene Allplex SARS-CoV-2 assays within the VALCOR framework. JF - Microbiol Spectr Y1 - 2024 A1 - Pui Yan Jenny Chung A1 - Sharon Dhillon A1 - Cindy Simoens A1 - Lize Cuypers A1 - Lies Laenen A1 - Bonde, Jesper A1 - Philippe Corbisier A1 - Gerhard Buttinger A1 - Clementina E Cocuzza A1 - Steven Van Gucht A1 - Marc Van Ranst A1 - M. Arbyn KW - Allplex KW - COVID-19 KW - diagnostics test accuracy KW - Quality Control KW - reference materials KW - RT-PCR KW - SARS-CoV-2 KW - Seegene KW - STANDARD KW - Test validation KW - VALCOR AB -

The coronavirus disease 2019 pandemic has a significant impact on global public health, economies, and societies. As shown through the first phases of the pandemic, accurate and timely diagnosis is crucial for disease control, prevention, and monitoring. Though the pandemic phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has concluded, diagnostic assays remain in demand to monitor SARS-CoV-2 at the individual patient level, regionally, and nationally, as well as to remain an infectious disease preparedness instrument to monitor any new SARS-CoV-2 dissemination across borders using population and wastewater surveillance. The anticipation by WHO and central health care policy entities such as the Center for Disease Control, EMA, and multiple national health authorities is that SARS-CoV-2 will reside as an endemic respiratory disease for years to come. The key strategic consideration is hence shifting from combating a pandemic situation with a high number of patients to instead allowing precise diagnostics of suspected patients with the intention of correct management in a low-prevalence setting.

M3 - 10.1128/spectrum.02397-23 ER - TY - JOUR T1 - Human papillomavirus negative high grade cervical lesions and cancers: Suggested guidance for HPV testing quality assurance JF - Journal of Clinical Virology Y1 - 2024 A1 - Jean Luc Prétet A1 - Laila Sara Arroyo Mühr A1 - Cuschieri, Kate A1 - Fellner, María Dolores A1 - Rita Mariel Correa A1 - Picconi, María Alejandra A1 - Suzanne M. Garland A1 - Gerald L. Murray A1 - Monica Molano A1 - Michael Peeters A1 - Steven Van Gucht A1 - Charlotte Lambrecht A1 - Broeck, Davy Vanden A1 - Padalko, Elizaveta A1 - M. Arbyn A1 - Quentin Lepiller A1 - Brunier, Alice A1 - Steffi Silling A1 - Kristiane Søreng A1 - Irene Kraus Christiansen A1 - Poljak, Mario A1 - Camilla Lagheden A1 - Emel Yilmaz A1 - Eklund, Carina A1 - Hem R. Thapa A1 - Troy D. Querec A1 - Elizabeth R. Unger A1 - Dillner, Joakim VL - 171 M3 - 10.1016/j.jcv.2024.105657 ER - TY - RPRT T1 - Wastewater-based epidemiological surveillance - Methodological appendix Y1 - 2024 A1 - Raphael Janssens A1 - Hadrien Maloux A1 - Sven Hanoteaux A1 - Laura Van Poelvoorde A1 - Nancy Roosens A1 - Bavo Verhaegen A1 - Julie Linussio A1 - Koenraad Van Hoorde A1 - Steven Van Gucht A1 - Karin De Ridder A1 - Koen Blot A1 - Veronik Hutse A1 - Marie Lesenfants KW - applied genomics KW - environment KW - epidemiology KW - Surveillance KW - wastewater KW - wastewater surveillance KW - wastewater-based epidemiology PB - Sciensano CY - Brussels, Belgium UR - https://www.sciensano.be/en/biblio/wastewater-based-epidemiological-surveillance-methodological-appendix ER - TY - RPRT T1 - Wastewater-based epidemiological surveillance - Weekly report Y1 - 2024 A1 - Raphael Janssens A1 - Hadrien Maloux A1 - Sven Hanoteaux A1 - Laura Van Poelvoorde A1 - Nancy Roosens A1 - Bavo Verhaegen A1 - Julie Linussio A1 - Koenraad Van Hoorde A1 - Steven Van Gucht A1 - Karin De Ridder A1 - Koen Blot A1 - Veronik Hutse A1 - Marie Lesenfants KW - applied genomics KW - environment KW - epidemiology KW - Surveillance KW - wastewater KW - wastewater surveillance KW - wastewater-based epidemiology PB - Sciensano CY - Brussels, Belgium UR - https://www.sciensano.be/en/biblio/wastewater-based-epidemiological-surveillance-weekly-report ER - TY - JOUR T1 - Development of Digital Droplet PCR Targeting the Influenza H3N2 Oseltamivir-Resistant E119V Mutation and Its Performance through the Use of Reverse Genetics Mutants. JF - Curr Issues Mol Biol Y1 - 2023 A1 - Laura Van Poelvoorde A1 - François Dufrasne A1 - Steven Van Gucht A1 - Saelens, Xavier A1 - Nancy Roosens KW - INFLUENZA KW - Oseltamivir KW - PCR KW - resistance AB -

The monitoring of antiviral-resistant influenza virus strains is important for public health given the availability and use of neuraminidase inhibitors and other antivirals to treat infected patients. Naturally occurring oseltamivir-resistant seasonal H3N2 influenza virus strains often carry a glutamate-to-valine substitution at position 119 in the neuraminidase (E119V-NA). Early detection of resistant influenza viruses is important for patient management and for the rapid containment of antiviral resistance. The neuraminidase inhibition assay allows the phenotypical identification of resistant strains; however, this test often has limited sensitivity with high variability depending on the virus strain, drugs and assays. Once a mutation such as E119V-NA is known, highly sensitive PCR-based genotypic assays can be used to identify the prevalence of such mutant influenza viruses in clinical samples. In this study, based on an existing reverse transcriptase real-time PCR (RT-qPCR) assay, we developed a reverse transcriptase droplet digital PCR assay (RT-ddPCR) to detect and quantify the frequency of the E119V-NA mutation. Furthermore, reverse genetics viruses carrying this mutation were created to test the performance of the RT-ddPCR assay and compare it to the standard phenotypic NA assay. We also discuss the advantage of using an RT-ddPCR instead of qPCR method in the context of viral diagnostics and surveillance.

VL - 45 CP - 3 M3 - 10.3390/cimb45030165 ER - TY - JOUR T1 - Development of Digital Droplet PCR Targeting the Influenza H3N2 Oseltamivir-Resistant E119V Mutation and Its Performance through the Use of Reverse Genetics Mutants JF - Current Issues in Molecular Biology Y1 - 2023 A1 - Laura Van Poelvoorde A1 - François Dufrasne A1 - Steven Van Gucht A1 - Xavier Saelens A1 - Nancy Roosens VL - 45 CP - 3 M3 - 10.3390/cimb45030165 ER - TY - JOUR T1 - Genomic monitoring of SARS-CoV-2 variants using sentinel SARI hospital surveillance. JF - Influenza Other Respir Viruses Y1 - 2023 A1 - Sarah Denayer A1 - François Dufrasne A1 - Bert Monsieurs A1 - Reinout van Eycken A1 - Sarah Houben A1 - Lucie Seyler A1 - Thomas Demuyser A1 - Els van Nedervelde A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Koen Magerman A1 - Jouck, Door A1 - Bénédicte Lissoir A1 - Catherine Sion A1 - Marijke Reynders A1 - Evelyn Petit A1 - Nicolas Dauby A1 - Marc Hainaut A1 - Lies Laenen A1 - Piet Maes A1 - Guy Baele A1 - Simon Dellicour A1 - Lize Cuypers A1 - Emmanuel André A1 - Simon Couvreur A1 - Ruben Brondeel A1 - Cyril Barbezange A1 - Nathalie Bossuyt A1 - Steven Van Gucht KW - COVID-19 KW - Genomics KW - hospitals KW - Humans KW - Pandemics KW - Pneumonia KW - SARS-CoV-2 KW - Sentinel Surveillance AB -

BACKGROUND: To support the COVID-19 pandemic response, many countries, including Belgium, implemented baseline genomic surveillance (BGS) programs aiming to early detect and characterize new SARS-CoV-2 variants. In parallel, Belgium maintained a sentinel network of six hospitals that samples patients with severe acute respiratory infections (SARI) and integrated SARS-CoV-2 detection within a broader range of respiratory pathogens. We evaluate the ability of the SARI surveillance to monitor general trends and early signals of viral genetic evolution of SARS-CoV-2 and compare it with the BGS as a reference model.

METHODS: Nine-hundred twenty-five SARS-CoV-2 positive samples from patients fulfilling the Belgian SARI definition between January 2020 and December 2022 were sequenced using the ARTIC Network amplicon tiling approach on a MinION platform. Weekly variant of concern (VOC) proportions and types were compared to those that were circulating between 2021 and 2022, using 96,251 sequences of the BGS.

RESULTS: SARI surveillance allowed timely detection of the Omicron (BA.1, BA.2, BA.4, and BA.5) and Delta (B.1.617.2) VOCs, with no to 2 weeks delay according to the start of their epidemic growth in the Belgian population. First detection of VOCs B.1.351 and P.1 took longer, but these remained minor in Belgium. Omicron BA.3 was never detected in SARI surveillance. Timeliness could not be evaluated for B.1.1.7, being already major at the start of the study period.

CONCLUSIONS: Genomic surveillance of SARS-CoV-2 using SARI sentinel surveillance has proven to accurately reflect VOCs detected in the population and provides a cost-effective solution for long-term genomic monitoring of circulating respiratory viruses.

VL - 17 CP - 10 M3 - 10.1111/irv.13202 ER - TY - JOUR T1 - Genomic monitoring of SARS‐CoV‐2 variants using sentinel SARI hospital surveillance JF - Influenza and Other Respiratory Viruses Y1 - 2023 A1 - Sarah Denayer A1 - François Dufrasne A1 - Bert Monsieurs A1 - Reinout Van Eycken A1 - Sarah, Houben A1 - Lucie Seyler A1 - Thomas Demuyser A1 - Els Van Nedervelde A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Koen Magerman A1 - Jouck, Door A1 - Bénédicte Lissoir A1 - Catherine Sion A1 - Marijke Reynders A1 - Evelyn Petit A1 - Nicolas Dauby A1 - Marc Hainaut A1 - Lies Laenen A1 - Piet Maes A1 - Guy Baele A1 - Simon Dellicour A1 - Lize Cuypers A1 - Emmanuel André A1 - Simon Couvreur A1 - Ruben Brondeel A1 - Cyril Barbezange A1 - Nathalie Bossuyt A1 - Steven Van Gucht VL - 17 CP - 10 M3 - 10.1111/irv.13202 ER - TY - JOUR T1 - Hepatitis E virus in pork meat products and exposure assessment in Belgium. JF - Int J Food Microbiol Y1 - 2023 A1 - Tatjana Locus A1 - Lambrecht, Ellen A1 - Michael Peeters A1 - Vanessa Suin A1 - Bavo Verhaegen A1 - Koenraad Van Hoorde A1 - Lamoral, Sophie A1 - Thomas Vanwolleghem A1 - Steven Van Gucht AB -

Zoonotic hepatitis E virus (HEV) genotype 3 infections are the predominant cause of acute viral hepatitis in Europe, mostly associated with the consumption of HEV contaminated pork meat. In this study we looked at the HEV RNA positivity rate of pork meat products readily available from Belgian supermarkets and evaluated the overall HEV consumer exposure in a Belgian context. Two basic assessments were performed in a 'worst-case' scenario setting: one solely focusing on the contamination level of the product itself (ingredients and processing parameters) and another estimating the overall consumer exposure, taking into account consumption habits in Belgium. Non-thermal-processed ready-to-eat (i.e. ready for consumption without additional cooking step by consumer) pork meat products (e.g. raw dried sausages), had a high estimated HEV contamination level, while thermal-processed ready-to-eat pork meat products (e.g. pork liver pâté) had the highest overall consumer exposure estimates. Following these assessments, pork liver pâtés, raw dried hams and raw dried sausages (n = 54) were purchased from Belgian supermarkets (n = 3) and analyzed for HEV RNA by RT-PCR. In total, 31 % (n = 17) products tested positive. HEV RNA was found in 65 % of the pork liver pâtés, 15 % of raw dried hams and 0 % of raw dried sausages. Phylogenetic analysis of four isolates (all gt3c) from pork liver pâté samples showed similarities with human clinical cases from Germany and Belgium.

VL - 397 M3 - 10.1016/j.ijfoodmicro.2023.110198 ER - TY - JOUR T1 - Hepatitis E virus in pork meat products and exposure assessment in Belgium JF - International Journal of Food Microbiology Y1 - 2023 A1 - Tatjana Locus A1 - Lambrecht, Ellen A1 - Michael Peeters A1 - Vanessa Suin A1 - Bavo Verhaegen A1 - Koenraad Van Hoorde A1 - Lamoral, Sophie A1 - Thomas Vanwolleghem A1 - Steven Van Gucht VL - 397 M3 - 10.1016/j.ijfoodmicro.2023.110198 ER - TY - JOUR T1 - Influenza versus other respiratory viruses – assessing severity among hospitalised children, Belgium, 2011 to 2020. JF - Eurosurveillance Y1 - 2023 A1 - Natalie Fischer A1 - S Moreels A1 - Nicolas Dauby A1 - Marijke Reynders A1 - Evelyn Petit A1 - Gerard, Michèle A1 - Lacor, Patrick A1 - Siel Daelemans A1 - Bénédicte Lissoir A1 - Xavier Holemans A1 - Koen Magerman A1 - Jouck, Door A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Sophie Quoilin A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Nathalie Bossuyt A1 - Cyril Barbezange VL - 28 CP - 29 M3 - 10.2807/1560-7917.ES.2023.28.29.2300056 ER - TY - JOUR T1 - A Multifaceted Approach for Evaluating Hepatitis E Virus Infectivity In Vitro: Cell Culture and Innovative Molecular Methods for Integrity Assessment JF - Veterinary Sciences Y1 - 2023 A1 - Tatjana Locus A1 - Lambrecht, Ellen A1 - Sophie Lamoral A1 - Sjarlotte Willems A1 - Steven Van Gucht A1 - Thomas Vanwolleghem A1 - Michael Peeters VL - 10 CP - 12 M3 - 10.3390/vetsci10120676 ER - TY - JOUR T1 - Scientific advisory councils in the COVID-19 response JF - The Lancet Y1 - 2023 A1 - Jean-François Delfraissy A1 - Mary Horgan A1 - Simón, Fernando Soria A1 - Patrick Vallance A1 - Laetitia Atlani-Duault A1 - Daniel Benamouzig A1 - Lila Bouadma A1 - Simon Cauchemez A1 - Catherine Chirouze A1 - Angèle Consoli A1 - Pierre-Louis Druais A1 - Arnaud Fontanet A1 - Marie-Aleth Grard A1 - Olivier Guérin A1 - Laetitia Huiart A1 - Hoang, Aymeril A1 - Thierry Lefrançois A1 - Bruno Lina A1 - Denis Malvy A1 - Yazdanpanah, Yazdan A1 - Chris Whitty A1 - Simon Whitfield A1 - Wendy Barclay A1 - Charlotte Caplan A1 - James Lobo A1 - Andrew Buckley A1 - Lothar Wieler A1 - Johanna Hanefeld A1 - Steffen Semmler A1 - Tim Eckmanns A1 - Fernando Simon Soria A1 - Walter Ricciardi A1 - Anna-Teresa Palamara A1 - Silvio Brusaferro A1 - Tanja Stadler A1 - Martin Ackermann A1 - Sarah Tschudin-Sutter A1 - Roman Stocker A1 - Steven Van Gucht A1 - Mathias Dewatripont A1 - Tinne Lernout A1 - Van Damme, Pierre A1 - Céline Nieuwenhuys A1 - Vlieghe, Erika A1 - Jaap van Dissel A1 - Lisa Schipper A1 - Susan van den Hof A1 - Corien Swaan A1 - Mary M. Horgan A1 - Paddy Mallon A1 - Mølbak, Kåre A1 - Didier Pittet M3 - 10.1016/S0140-6736(23)01846-9 ER - TY - RPRT T1 - Virological surveillance of influenza in Belgium, season 2019-2020 Y1 - 2023 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Steven Van Gucht A1 - Jeannine Weyckmans A1 - Ilham Fdillate A1 - Reinout van Eycken A1 - Assia Hamouda A1 - Nathalie Bossuyt A1 - Sophie Quoilin A1 - Dieter Van Cauteren KW - INFLUENZA KW - respiratory virus KW - Surveillance KW - virology AB -

The 2019-2020 winter season was characterized by the occurrence after the flu epidemic of the COVID-19 pandemic.  The Influenza epidemic in Belgium lasted 6 weeks and was a flu season of moderate intensity characterized by the co-circulation of A(H1N1)pdm09 and A(H3N2), with the predominance of A(H1N1). The epidemic threshold was crossed at  week 4-2020 (January 13 to January 19, 2020 with an incidence of 245 consultations /100.000 inhabitants and the peak was reached in week 5 with 550 consultations/100.000 inhabitants. After week 5- 2020, the incidence of ILI consultations decreased but remained above the threshold for several weeks likely due to the COVID-19 epidemic with a new ILI peak  at week 13 exceeding the influenza peak seen in  week 5  (Fig. 1). The emergence of COVID-19, spreading through respiratory transmission, required the implementation of physical distancing measures likely contributed to an abrupt decline of the influenza season.

The majority of the H1N1 viruses fell in the 6B.1A5A subgroup represented by the reference strain A/Norway/3433/2018.

About half of the sequenced A(H3N2) viruses belonged to the clade 3C.2a1 and the remaining belonged to the  clade 3C.3a close the vaccine strain for the northern hemisphere A/Kansas/14/2017.

Most of  the seqenced influenza B-Victoria viruses were triple-deletion variants similar to B/Washington/02/2019.  

Respiratory  samples were also analysed for other respiratory viruses. In the ILI population,  70 % of the patients were positive for at least one respiratory virus (including Influenza and co-infections). In the  SARI population, 52% of the patients were positive for at least one respiratory viruses (including influenza, SARS-COV-2, other respiratory viruses  or different combination of co-infection). From week 10 , the first SARS-CoV-2 patient were diagnosed.

These patients were mostly adults and children above 14 years old.

Severity was moderate in comparison to the previous season and comparable to previous seasons.

None of the analyzed strains presented mutations known to be associated to resistance to antivirals neuraminidase inhibitors (Oseltamivir et Zanamivir).

PB - Sciensano CY - Brussels, Belgium M3 - https://doi.org/10.25608/43gy-qs94 ER - TY - RPRT T1 - Virological surveillance report of the NRC influenza for season 2022-2023 Y1 - 2023 A1 - Cyril Barbezange A1 - Sarah Denayer A1 - François Dufrasne A1 - S. Leen A1 - Assia Hamouda A1 - Reinout van Eycken A1 - Ilham Fdillate A1 - Saira Yaqoob A1 - Steven Van Gucht KW - INFLUENZA KW - respiratory virus KW - Surveillance KW - virology AB -

Based on the sentinel surveillance networks for influenza-like illness (ILI) and severe acute respiratory infections (SARI), the 2022-2023 season was characterized by the circulation of several respiratory viruses with epidemic waves overlapping each others. Respiratory syncytial virus was responsible for an epidemic wave in November-December 2022, coinciding with a small wave of human metapneumovirus, but it continued to circulate in January 2023. Influenza viruses were responsible for a first epidemic wave at the end of December 2022 - so slightly earlier than during the seasons preceding the COVID-19 pandemic - which was followed by a second small wave in January-February 2023. Seasonal influenza A viruses of the H1N1pdm09 and H3N2 subtypes, and influenza B virus of the Victoria lineage co-circulated without clear dominance. SARS-CoV-2 virus continued to circulate during the whole period but a higher intensity of circulation was detected in March 2023, as well as in August 2023. Parainfluenza viruses were responsible for a small epidemic wave in May 2023. Other respiratory viruses such as seasonal coronaviruses, rhino- and enteroviruses, and adenoviruses were also regularly detected.

Epidemic waves of respiratory syncytial virus and influenza viruses occurred at periods that were close to historical data, indicating that the seasonality of these viruses might be returning to normal following the disruptions due to the COVID-19 pandemic. SARS-CoV-2 coronavirus still circulate without a clear seasonal pattern, but seems to cause smaller epidemic waves than during the pandemic phase. Surveillance all year round with multi-virus testing proves useful to better understand seasonality and interference of the different respiratory viruses.

PB - Sciensano CY - Brussels, Belgium M3 - https://doi.org/10.25608/dkjg-bj14 ER - TY - RPRT T1 - Virological surveillance report of the NRC influenza for season 2021-2022 Y1 - 2023 A1 - Cyril Barbezange A1 - Sarah Denayer A1 - François Dufrasne A1 - Assia Hamouda A1 - Reinout van Eycken A1 - Ilham Fdillate A1 - Bert Monsieurs A1 - Steven Van Gucht KW - INFLUENZA KW - respiratory virus KW - Surveillance KW - virology AB -

Based on the sentinel surveillance networks for influenza-like illness (ILI) and severe acute respiratory infections (SARI), the 2021-2022 season was characterized by the return of seasonal influenza viruses, cause an epidemic wave in Spring, so later than pre-COVID season. Seasonal influenza A viruses of the H3N2 subtype clearly dominated over the H1N1 subtype and the influenza B viruses. SARS-CoV-2 virus continued to intensively circulate during the whole period with several epidemic waves occurring throughout the season. Respiratory syncytial virus was not responsible for a true epidemic wave this season. Other respiratory viruses such as metapneumoviruses, parainfluenza viruses, seasonal coronaviruses, rhino- and enteroviruses, and adenoviruses were also regularly detected, without clear epidemic wave.

PB - Sciensano CY - Brussels, Belgium M3 - https://doi.org/10.25608/wkxe-vx35 ER - TY - RPRT T1 - Virological surveillance report of the NRC influenza for season 2020-2021 Y1 - 2023 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Sarah Denayer A1 - Jeannine Weyckmans A1 - Assia Hamouda A1 - Reinout van Eycken A1 - Ilham Fdillate A1 - Steven Van Gucht KW - INFLUENZA KW - respiratory virus KW - Surveillance KW - virology AB -

Amidst the COVID-19 pandemic, the sentinel surveillance resumed slowly in the season 2020-2021. Only the severe acute respiratory infections (SARI) allowed to properly evaluate the circulation of respiratory viruses during the 2020-2021 season. The season was characterized by the absence of an influenza virus epidemic, and the return of parainfluenza viruses and respiratory syncytial viruses detected mainly in children. SARS-CoV-2 continued to intensively circulate and was mainly detected in adults and older adults. Other respiratory viruses such as metapneumoviruses, seasonal coronaviruses, rhino- and enteroviruses, and adenoviruses were also detected, without clear epidemic wave.

PB - Sciensano CY - Brussels, Belgium M3 - https://doi.org/10.25608/y0b7-s054 ER - TY - JOUR T1 - Evaluation of dog vaccination schemes against rabies in Kinshasa, Democratic Republic of the Congo. JF - Prev Vet Med Y1 - 2022 A1 - Eric Kazadi Kawaya A1 - Tanguy Marcotty A1 - Leopold Kazadi Mulumba Mfumu A1 - Damien Marcotty A1 - Steven Van Gucht A1 - Kirschvink, Nathalie KW - Animals KW - Democratic Republic of the Congo KW - Dog Diseases KW - Dogs KW - Rabies KW - Rabies Vaccines KW - Vaccination KW - Vaccine Efficacy AB -

The traditional rabies control strategy based on annual mass vaccination of dogs appears to be costly and cumbersome. Given the existence of different risk zones for rabies transmission, the present study aimed at proposing risk-based vaccination schemes by considering canine population dynamics as well as vaccine efficacy and duration of immunity (DOI). The capital of the Democratic Republic of the Congo (RDC), Kinshasa, was chosen as study site. The turnover rate of dogs was used to assess their population dynamics in two low-roaming (<25 % of dogs are roaming) and in two high-roaming zones (>75 % of dogs are roaming). The sero-conversion rate was assessed in response to primo-vaccination in three age groups: 24 puppies (≤3months), 37 juveniles (4-12 months) and 22 adult dogs. The DOI was evaluated serologically by revaccinating dogs previously vaccinated since 1-2 years (n = 31), 2-3 years (n = 12) or 3-7.5 years (n = 4). Rapid Fluorescent Focus Inhibition Test was used to quantify antibodies. These data were used to implement vaccination outcome models.The turnover rate was twice as high in high-roaming zones (36 %) as that in lowroaming zones (17 %). Irrespective of roaming level, 75 % of dogs were less than 3 years old. The vaccine was equally effective in puppies (96 %), juvenile (97 %) and adult dogs (100 %, p = 0.24). The vaccine was effective in 93 % (11/12) of puppies without pre-vaccinal protective titers (≥0.5 IU/mL). The anamnestic response was strong within 5-8 days upon the booster vaccination, in 96 % (45/47) of dogs reported vaccinated 1-7.5 years before. This suggests that the vaccine provided a long-term protection (≥3 years) which is likely to occur in 75 % of dogs in Kinshasa.Hypothesizing a vaccination stop, the vaccination outcome model allowed to estimate the time point after which vaccination coverage would drop below 40 % in function of dog population turnover rate. The systematic vaccination of puppies as well as annual vaccination of dogs aged between 3 and 15 months or annual vaccination of all unvaccinated dogs aged more than 3 months of age appeared as valuable alternative to systematic annual mass vaccination.In conclusion, this study developed a vaccination outcome model pointing out the impact of dog population dynamics and of effective duration of immunity. It appears as a promising tool for designing cost-effective rabies vaccination campaigns.

VL - 198 M3 - 10.1016/j.prevetmed.2021.105531 ER - TY - JOUR T1 - A general approach to identify low-frequency variants within influenza samples collected during routine surveillance. JF - Microb Genom Y1 - 2022 A1 - Laura Van Poelvoorde A1 - Thomas Delcourt A1 - Marnik Vuylsteke A1 - Sigrid C.J. De Keersmaecker A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Saelens, Xavier A1 - Nancy Roosens A1 - Kevin Vanneste KW - COVID-19 KW - Genome, Viral KW - Humans KW - Influenza A Virus, H3N2 Subtype KW - Influenza, Human KW - SARS-CoV-2 AB -

Influenza viruses exhibit considerable diversity between hosts. Additionally, different quasispecies can be found within the same host. High-throughput sequencing technologies can be used to sequence a patient-derived virus population at sufficient depths to identify low-frequency variants (LFV) present in a quasispecies, but many challenges remain for reliable LFV detection because of experimental errors introduced during sample preparation and sequencing. High genomic copy numbers and extensive sequencing depths are required to differentiate false positive from real LFV, especially at low allelic frequencies (AFs). This study proposes a general approach for identifying LFV in patient-derived samples obtained during routine surveillance. Firstly, validated thresholds were determined for LFV detection, whilst balancing both the cost and feasibility of reliable LFV detection in clinical samples. Using a genetically well-defined population of influenza A viruses, thresholds of at least 10 genomes per microlitre and AF of ≥5 % were established as detection limits. Secondly, a subset of 59 retained influenza A (H3N2) samples from the 2016-2017 Belgian influenza season was composed. Thirdly, as a proof of concept for the added value of LFV for routine influenza monitoring, potential associations between patient data and whole genome sequencing data were investigated. A significant association was found between a high prevalence of LFV and disease severity. This study provides a general methodology for influenza LFV detection, which can also be adopted by other national influenza reference centres and for other viruses such as SARS-CoV-2. Additionally, this study suggests that the current relevance of LFV for routine influenza surveillance programmes might be undervalued.

VL - 8 CP - 9 M3 - 10.1099/mgen.0.000867 ER - TY - JOUR T1 - A High-Throughput Yellow Fever Neutralization Assay. JF - Microbiol Spectr Y1 - 2022 A1 - Madina Rasulova A1 - Thomas Vercruysse A1 - Jasmine Paulissen A1 - Catherina Coun A1 - Vanessa Suin A1 - Heyndrickx, Leo A1 - Ji Ma A1 - Katrien Geerts A1 - Jolien Timmermans A1 - Niraj Mishra A1 - Li, Li-Hsin A1 - Dieudonné Buh Kum A1 - Lotte Coelmont A1 - Steven Van Gucht A1 - Hadi Karimzadeh A1 - Julia Thorn-Seshold A1 - Simon Rothenfußer A1 - Ariën, Kevin K A1 - Neyts, Johan A1 - Kai Dallmeier A1 - Hendrik Jan Thibaut KW - Antibodies, Neutralizing KW - Antibodies, Viral KW - Encephalitis, Japanese KW - Humans KW - Neutralization Tests KW - Yellow Fever KW - Yellow fever virus KW - Zika virus KW - Zika Virus Infection AB -

Quick and accurate detection of neutralizing antibodies (nAbs) against yellow fever is essential in serodiagnosis during outbreaks for surveillance and to evaluate vaccine efficacy in population-wide studies. All of this requires serological assays that can process a large number of samples in a highly standardized format. Albeit being laborious, time-consuming, and limited in throughput, the classical plaque reduction neutralization test (PRNT) is still considered the gold standard for the detection and quantification of nAbs due to its sensitivity and specificity. Here, we report the development of an alternative fluorescence-based serological assay (SNT) with an equally high sensitivity and specificity that is fit for high-throughput testing with the potential for automation. Finally, our novel SNT was cross-validated in several reference laboratories and against international WHO standards, showing its potential to be implemented in clinical use. SNT assays with similar performance are available for the Japanese encephalitis, Zika, and dengue viruses amenable to differential diagnostics. Fast and accurate detection of neutralizing antibodies (nAbs) against yellow fever virus (YFV) is key in yellow fever serodiagnosis, outbreak surveillance, and monitoring of vaccine efficacy. Although classical PRNT remains the gold standard for measuring YFV nAbs, this methodology suffers from inherent limitations such as low throughput and overall high labor intensity. We present a novel fluorescence-based serum neutralization test (SNT) with equally high sensitivity and specificity that is fit for processing a large number of samples in a highly standardized manner and has the potential to be implemented for clinical use. In addition, we present SNT assays with similar performance for Japanese encephalitis, Zika, and dengue viruses, opening new avenues for differential diagnostics.

VL - 10 CP - 3 M3 - 10.1128/spectrum.02548-21 ER - TY - JOUR T1 - Immunogenicity and one-year boostability of a 3-dose intramuscular rabies pre-exposure prophylaxis schedule in adults receiving immunosuppressive monotherapy: a prospective single-Centre clinical trial. JF - J Travel Med Y1 - 2022 A1 - Hannah M Garcia Garrido A1 - Bridget van Put A1 - Cornelis A de Pijper A1 - Cornelis Stijnis A1 - Martin P Grobusch A1 - Abraham Goorhuis ED - Sanne Terryn ED - Steven Van Gucht AB -

BACKGROUND: For immunocompromised patients (ICPs), administration of rabies immunoglobulins (RIG) after exposure is still recommended regardless of prior vaccination, due to a lack of data. We aimed to assess the one-year boostability of a 3-dose rabies pre-exposure prophylaxis (PrEP) schedule in individuals using immunosuppressive monotherapy.

METHODS: In this prospective study, individuals on immunosuppressive monotherapy with a conventional immunomodulator (cIM) or a TNF-alpha inhibitor (TNFi) for a chronic inflammatory disease received a 3-dose intramuscular PrEP schedule (days 0,7,21-28) with 1 mL Rabipur®, followed by a 2-dose simulated post-exposure prophylaxis (PEP) schedule (days 0,3) after 12 months. Rabies neutralizing antibodies were assessed at baseline, on Day 21-28 (before 3rd PrEP dose), Day 60, Month 12 and Month 12 + 7 days. The primary outcome was one-year boostability, defined as the proportion of patients with a neutralizing antibody titre of ≥ 0.5 IU/mL at Month 12 + 7 days. Secondary outcomes were geometric mean titres and factors associated with the primary endpoint.

RESULTS: We included 56 individuals, of whom 52 completed the study. The one-year boostability was 90% (47/52) with a GMT of 6.16 (95% CI 3.83-9.91). All participants seroconverted at some point in the study. Early response to PrEP (at day 21-28) was significantly associated with 100% boostability (Odds ratio 51; 95% confidence interval [5.0-6956], p < 0.01). The vaccination schedule was safe and well tolerated. No vaccine-related serious adverse events occurred.

CONCLUSION: In patients using immunosuppressive monotherapy, a 3-dose rabies PrEP schedule followed by a 2-dose PEP schedule is immunogenic, with all patients seroconverting at some point in the study. Although boostability 7 days after PEP was not 100%, nobody would wrongly be denied RIG when only administered to those who responded early to PrEP, while reducing administration of RIG by 73%.

M3 - 10.1093/jtm/taac148 ER - TY - JOUR T1 - No molecular detection of tick-borne pathogens in the blood of patients with erythema migrans in Belgium JF - Parasites & Vectors Y1 - 2022 A1 - Geebelen, Laurence A1 - Tinne Lernout A1 - Katrien Tersago A1 - Sanne Terryn A1 - Joppe W. Hovius A1 - Arieke Docters van Leeuwen A1 - Steven Van Gucht A1 - Speybroeck, Niko A1 - Sprong, Hein KW - Erythema migrans KW - Ixodes ricinus KW - Lyme borreliosis KW - Neoehrlichosis KW - Neoerhlichia mikurensis KW - Tick-borne pathogens AB -

Background

A number of tick-borne pathogens circulate in the Belgian tick population in addition to the causative agent of Lyme borreliosis. However, so far, only a few patients with tick-borne diseases other than Lyme borreliosis have been reported in Belgium. The aim of this study was to investigate the occurrence of other human tick-borne infections in Belgium and their possible clinical manifestation.

Methods

Patients with fever (> 37.5 °C) after a tick bite or those with erythema migrans (EM) were included in the study. EDTA-blood samples were screened for the presence of DNA from Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, Neoehrlichia mikurensis, spotted fever group rickettsiae (genus Rickettsia), Babesia spp., Bartonella spp., Spiroplasma ixodetis and tick-borne encephalitis virus, using multiplex PCR methods. A questionnaire on, among others, demographics and clinical symptoms, was also filled in.

Results

Over a period of 3 years, 119 patients with EM and 14 patients with fever after a recent tick bite were enrolled in the study. Three samples initially tested positive for N. mikurensis by quantitative PCR (qPCR), but the results could not be confirmed by other PCR methods, and repetition of the DNA extraction procedure and qPCR test was not successful. The qPCR test results for the other tick-borne pathogens were negative.

Conclusions

In general, only a few patients with fever after a tick bite could be identified. Although no tick-borne pathogens were detected, their occurrence cannot be excluded based on the limited number of patients and the limitations inherent to current methodologies. This study underscores the possibility of false-positive PCR results and the necessity for the development of multiple independent tools for the sensitive and specific detection of emerging tick-borne pathogens.

VL - 15 CP - 1 M3 - 10.1186/s13071-021-05139-w ER - TY - JOUR T1 - Risks related to a possible reduction of the waiting period for dogs after rabies antibody titration to 30 days compared with 90 days of the current EU legislative regime. JF - EFSA J Y1 - 2022 A1 - Julio Alvarez A1 - Søren Saxmose Nielsen A1 - Emmanuelle Robardet A1 - Arjan Stegeman A1 - Steven Van Gucht A1 - Vlad Vuta A1 - Sotiria-Eleni Antoniou A1 - Inma Aznar A1 - Alexandra Papanikolaou A1 - Helen Clare Roberts KW - Antibody KW - Dogs KW - EU KW - Pets KW - Rabies KW - serology KW - Travel AB -

EFSA received a mandate from the European Commission to assess the risks related to a possible reduction of the waiting period after rabies antibody titration test to 30 days compared with 90 days of the current EU legislation, for dogs moving from certain non-EU countries to the EU. This Scientific Report assessed the probability of introduction of rabies into the EU through commercial and non-commercial movements of vaccinated dogs with a positive titration test (≥ 0.5 IU/mL) if the waiting period decreases from 90 to 30 days. Assuming that all the legal requirements are complied with, the risk of transmission of rabies through the movement of a vaccinated dog is related to the risk of introducing an animal incubating rabies that was infected before the day of vaccination or shortly after vaccination but before the development of immunity (21 days post-vaccination). Using published data on the incubation period for experimental and field cases in dogs and considering the rabies incidence data in certain countries, the aggregated probability for the annual introduction of rabies through dogs was assessed. Considering the uncertainty related to the duration of the incubation period, the number of imported dogs, and the disease incidence in some countries it was concluded with a 95% certainty that the maximum number of rabies-infected imported dogs complying with the regulations in a 20-year period could increase from 5 to 20 when decreasing the waiting period from 90 to 30 days. Nevertheless, the potential impact of even a small increase in probability means the risk is increased for a region like the EU where rabies has long been a focus for eradication, to protect human and animal health.

VL - 20 CP - 6 M3 - 10.2903/j.efsa.2022.7350 ER - TY - JOUR T1 - Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): A single blind, randomized, non-inferiority trial JF - PLOS Global Public Health Y1 - 2022 A1 - Pieter Pannus A1 - Stéphanie Depickère A1 - Delphine Kemlin A1 - Sarah Houben A1 - Kristof Y. Neven A1 - Heyndrickx, Leo A1 - Johan Michiels A1 - Willems, Elisabeth A1 - Stéphane De Craeye A1 - Antoine Francotte A1 - Félicie Chaumont A1 - Véronique Olislagers A1 - Alexandra Waegemans A1 - Mathieu Verbrugghe A1 - Marie-Noëlle Schmickler A1 - Steven Van Gucht A1 - Katelijne Dierick A1 - Arnaud Marchant A1 - I Desombere A1 - Kevin K. Ariën A1 - Maria Goossens KW - COVID-19; fractional dose; reduced dose; mRNA vaccination; non-inferiority; SARS-CoV-2 AB -

Fractional dosing of COVID-19 vaccines could accelerate vaccination rates in low-income countries. Dose-finding studies of the mRNA vaccine BNT162b2 (Pfizer-BioNTech) suggest that a fractional dose induces comparable antibody responses to the full dose in people <55 years. Here, we report the safety and immunogenicity of a fractional dose regimen of the BNT162b2 vaccine. REDU-VAC is a participant-blinded, randomised, phase 4, non-inferiority study. Adults 18–55 years old, either previously infected or infection naïve, were randomly assigned to receive 20μg/20μg (fractional dose) or 30μg/30μg (full dose) of BNT162b2. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-RBD IgG titres at 28 days post second dose between the reduced and full dose regimens. The reduced dose was considered non-inferior to the full dose if the lower limit of the two-sided 95% CI of the GMR was >0.67. Primary analysis was done on the per-protocol population, including infection naïve participants only. 145 participants were enrolled and randomized, were mostly female (69.5%), of European origin (95%), with a mean age of 40.4 years (SD 7.9). At 28 days post second dose, the geometric mean titre (GMT) of anti-RBD IgG of the reduced dose regimen (1,705 BAU/mL) was not non-inferior to the full dose regimen (2,387 BAU/mL), with a GMR of 0.714 (two-sided 95% CI 0.540–0.944). No serious adverse events occurred. While non-inferiority of the reduced dose regimen was not demonstrated, the anti-RBD IgG titre was only moderately lower than that of the full dose regimen and, importantly, still markedly higher than the reported antibody response to the licensed adenoviral vector vaccines. These data suggest that reduced doses of the BNT162b2 mRNA vaccine may offer additional benefit as compared to the vaccines currently in use in most low and middle-income countries, warranting larger immunogenicity and effectiveness trials.

VL - 2 CP - 12 M3 - 10.1371/journal.pgph.0001308 ER - TY - Generic T1 - Sentinel SARI surveillance in Belgium in times of COVID-19 pandemic Y1 - 2022 A1 - Nathalie Bossuyt A1 - Sarah Denayer A1 - Marijke Reynders A1 - Evelyne Petit A1 - Koen Magerman A1 - Door Jouck A1 - Marieke Bleyen A1 - Nicolas Dauby A1 - Marc Hainaut A1 - Lucie Seyler A1 - Thomas Demuyser A1 - Els Van Nedervelde A1 - Bénédicte Lissoir A1 - Xavier Holemans A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Steven Van Gucht A1 - François Dufrasne A1 - Melissa Vermeulen A1 - Cyril Barbezange JF - OPTIONS XI for the Control of Influenza PB - ISIRV CY - Belfast, United-Kingdom ER - TY - JOUR T1 - Viral clade is associated with severity of symptomatic genotype 3 Hepatitis E virus infections in Belgium, 2010-2018. JF - Journal of Hepatology Y1 - 2022 A1 - Michael Peeters A1 - Julie Schenk A1 - Thomas De Somer A1 - Tania Roskams A1 - Tatjana Locus A1 - Sofieke Klamer A1 - Lorenzo Subissi A1 - Vanessa Suin A1 - Jean Delwaide A1 - Peter Stärkel A1 - Stéphane De Maeght A1 - Philippe Willems A1 - Colle, Isabelle A1 - Marc Van Hoof A1 - Van Acker, Jos A1 - Christophe Van Steenkiste A1 - Christophe Moreno A1 - Filip Janssens A1 - Marijke Reynders A1 - Matthias Steverlynck A1 - Wim Verlinden A1 - Luc Lasser A1 - Chantal de Galocsy A1 - Geerts, Anja A1 - Jeroen Maus A1 - Marie Gallant A1 - Steven Van Outryve A1 - Astrid Marot A1 - Hendrik Reynaert A1 - Jochen Decaestecker A1 - Bottieau, Emmanuel A1 - Jonas Schreiber A1 - Jean-Pierre Mulkay A1 - Sébastien de Goeij A1 - Mikhaël Salame A1 - Diederik Dooremont A1 - Sergio Negrín Dastis A1 - Juul Boes A1 - Jochen Nijs A1 - Jan Beyls A1 - Hens, Niel A1 - Frederik Nevens A1 - Steven Van Gucht A1 - Thomas Vanwolleghem VL - 78 CP - 1 M3 - 10.1016/j.jhep.2022.08.033 ER - TY - Generic T1 - Was SARI surveillance successful at monitoring SARS-CoV-2 circulation and its genomic evolution in Belgium throughout the pandemic? Y1 - 2022 A1 - Sarah Denayer A1 - Bert Monsieurs A1 - Reinout Van Eycken A1 - Marijke Reynders A1 - Evelyn Petit A1 - Koen Magerman A1 - Door Jouck A1 - Marieke Bleyen A1 - Nicolas Dauby A1 - Marc Hainaut A1 - Lucie Seyler A1 - Thomas Demuyser A1 - Els Van Nedervelde A1 - Bénédicte Lissoir A1 - Xavier Holemans A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Steven Van Gucht A1 - Michael Peeters A1 - Melissa Vermeulen A1 - Nathalie Bossuyt A1 - François Dufrasne A1 - Cyril Barbezange KW - SARI surveillance JF - OPTIONS XI for the Control of Influenza PB - ISIRV CY - Belfast, United-Kingdom ER - TY - JOUR T1 - Whole-Genome Sequence Approach and Phylogenomic Stratification Improve the Association Analysis of Mutations With Patient Data in Influenza Surveillance. JF - Front Microbiol Y1 - 2022 A1 - Laura Van Poelvoorde A1 - Kevin Vanneste A1 - Sigrid C.J. De Keersmaecker A1 - Nancy Roosens ED - Isabelle Thomas ED - Steven Van Gucht AB -

Each year, seasonal influenza results in high mortality and morbidity. The current classification of circulating influenza viruses is mainly focused on the hemagglutinin gene. Whole-genome sequencing (WGS) enables tracking mutations across all influenza segments allowing a better understanding of the epidemiological effects of intra- and inter-seasonal evolutionary dynamics, and exploring potential associations between mutations across the viral genome and patient's clinical data. In this study, mutations were identified in 253 Influenza A (H3N2) clinical isolates from the 2016-2017 influenza season in Belgium. As a proof of concept, available patient data were integrated with this genomic data, resulting in statistically significant associations that could be relevant to improve the vaccine and clinical management of infected patients. Several mutations were significantly associated with the sampling period. A new approach was proposed for exploring mutational effects in highly diverse Influenza A (H3N2) strains through considering the viral genetic background by using phylogenetic classification to stratify the samples. This resulted in several mutations that were significantly associated with patients suffering from renal insufficiency. This study demonstrates the usefulness of using WGS data for tracking mutations across the complete genome and linking these to patient data, and illustrates the importance of accounting for the viral genetic background in association studies. A limitation of this association study, especially when analyzing stratified groups, relates to the number of samples, especially in the context of national surveillance of small countries. Therefore, we investigated if international databases like GISAID may help to verify whether observed associations in the Belgium A (H3N2) samples, could be extrapolated to a global level. This work highlights the need to construct international databases with both information of viral genome sequences and patient data.

VL - 13 M3 - 10.3389/fmicb.2022.809887 ER - TY - JOUR T1 - Whole-Genome Sequence Approach and Phylogenomic Stratification Improve the Association Analysis of Mutations With Patient Data in Influenza Surveillance JF - Frontiers in Microbiology Y1 - 2022 A1 - Laura Van Poelvoorde A1 - Kevin Vanneste A1 - Sigrid C.J. De Keersmaecker A1 - Isabelle Thomas A1 - Nina Van Goethem A1 - Steven Van Gucht A1 - Xavier Saelens A1 - Nancy Roosens VL - 13 M3 - 10.3389/fmicb.2022.809887 ER - TY - JOUR T1 - Deepening of In Silico Evaluation of SARS-CoV-2 Detection RT-qPCR Assays in the Context of New Variants JF - Genes Y1 - 2021 A1 - Mathieu Gand A1 - Kevin Vanneste A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Arnaud Capron A1 - Philippe Herman A1 - Nancy Roosens A1 - Sigrid C.J. De Keersmaecker KW - SARS-CoV-2; COVID-19; variants; detection; RT-qPCR; in silico specificity evaluation; bioinformatics tool; WGS data; mismatches; primers and probes AB -

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set of primers and probe. It is important to frequently evaluate the performance of these tests and this can be done first by an in silico approach. Previously, we reported some mismatches between the oligonucleotides of publicly available RT-qPCR assays and SARS-CoV-2 genomes collected from GISAID and NCBI, potentially impacting proper detection of the virus. In the present study, 11 primers and probe sets investigated during the first study were evaluated again with 84,305 new SARS-CoV-2 unique genomes collected between June 2020 and January 2021. The lower inclusivity of the China CDC assay targeting the gene N has continued to decrease with new mismatches detected, whereas the other evaluated assays kept their inclusivity above 99%. Additionally, some mutations specific to new SARS-CoV-2 variants of concern were found to be located in oligonucleotide annealing sites. This might impact the strategy to be considered for future SARS-CoV-2 testing. Given the potential threat of the new variants, it is crucial to assess if they can still be correctly targeted by the primers and probes of the RT-qPCR assays. Our study highlights that considering the evolution of the virus and the emergence of new variants, an in silico (re-)evaluation should be performed on a regular basis. Ideally, this should be done for all the RT-qPCR assays employed for SARS-CoV-2 detection, including also commercial tests, although the primer and probe sequences used in these kits are rarely disclosed, which impedes independent performance evaluation.

VL - 12 CP - 4 M3 - 10.3390/genes12040565 ER - TY - RPRT T1 - Key considerations for the implementation of high throughput sequencing based metagenomics (mNGS) in diagnostic clinical, food and veterinary labs : a no-nonsense pointer. the Metastava consortium Y1 - 2021 A1 - Steven Van Borm A1 - Frank Vandenbussche A1 - Kris De Clercq A1 - Andy Haegeman A1 - Sigrid C.J. De Keersmaecker A1 - Kevin Vanneste A1 - Michael Peeters A1 - Steven Van Gucht A1 - Yannick Blanchard A1 - Nicole Pavio A1 - Sandra Martin-Latil A1 - Fabrice Touzain A1 - Isabelle Kempf A1 - Liu, Lihong A1 - Mickhayil Hakhverdyan A1 - Mikael Leijon A1 - Alex Bossers A1 - van der Poel, Wim A1 - Marcel Hulst A1 - Bas Oude Munnink A1 - Miranda De Graaf A1 - Sander van Boheemen A1 - Marion Koopmans A1 - Beer, Martin A1 - Anne Pohlmann A1 - Höper, Dirk ER - TY - JOUR T1 - Long-term memory response after a single intramuscular rabies booster vaccination, 10-24 years after primary immunization. JF - J Infect Dis Y1 - 2021 A1 - Cornelis A De Pijper A1 - Annefleur C Langedijk A1 - Sanne Terryn A1 - Steven Van Gucht A1 - Martin P Grobusch A1 - Abraham Goorhuis A1 - Cornelis Stijnis KW - Rabies KW - Vaccination AB -

BACKGROUND: To date, published data regarding long-lasting immunological rabies memory after a pre-exposure prophylaxis (PrEP)-schedule are scarce. We tested the hypothesis that rabies booster immunization elicits rapid anamnestic responses.

METHODS: For this observational study, we included participants who had received PrEP 10-24 years before inclusion. We measured rabies antibody titers before, and on days 3, 7 and 14 after one single intramuscular booster.

RESULTS: All 28 participants responded adequately regardless route of administration or (2-dose vs. 3-dose) PrEP-regimen.

CONCLUSION: Rabies immunological memory is reactivated within 7 days after a single intramuscular booster immunization, even when administered 10-24 years after PrEP.

M3 - 10.1093/infdis/jiab034 ER - TY - JOUR T1 - A look into the future of the COVID-19 pandemic in Europe: an expert consultation JF - The Lancet Regional Health - Europe Y1 - 2021 A1 - Emil Nafis Iftekhar A1 - Viola Priesemann A1 - Rudi Balling A1 - Simon Bauer A1 - Beutels, Philippe A1 - André Calero Valdez A1 - Sarah Cuschieri A1 - Thomas Czypionka A1 - Uga Dumpis A1 - Enrico Glaab A1 - Eva Grill A1 - Claudia Hanson A1 - Pirta Hotulainen A1 - Peter Klimek A1 - Mirjam Kretzschmar A1 - Krüger, Tyll A1 - Jenny Krutzinna A1 - Nicola Low A1 - Helena Machado A1 - Carlos Martins A1 - McKee, Martin A1 - Sebastian Bernd Mohr A1 - Armin Nassehi A1 - Matjaž Perc A1 - Elena Petelos A1 - Martyn Pickersgill A1 - Barbara Prainsack A1 - Joacim Rocklöv A1 - Eva Schernhammer A1 - Anthony Staines A1 - Ewa Szczurek A1 - Tsiodras, Sotirios A1 - Steven Van Gucht A1 - Peter Willeit KW - COVID-19 KW - pandemic VL - 8 M3 - 10.1016/j.lanepe.2021.100185 ER - TY - JOUR T1 - Monitoring of human coronaviruses in Belgian primary care and hospitals, 2015-20: a surveillance study. JF - Lancet Microbe Y1 - 2021 A1 - Nathalie Fischer A1 - Nicolas Dauby A1 - Nathalie Bossuyt A1 - Marijke Reynders A1 - Gerard, Michèle A1 - Lacor, Patrick A1 - Siel Daelemans A1 - Bénédicte Lissoir A1 - Xavier Holemans A1 - Koen Magerman A1 - Door Jouck A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Sophie Quoilin A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Lorenzo Subissi AB -

Background: Seasonal human coronaviruses (hCoVs) broadly circulate in humans. Their epidemiology and effect on the spread of emerging coronaviruses has been neglected thus far. We aimed to elucidate the epidemiology and burden of disease of seasonal hCoVs OC43, NL63, and 229E in patients in primary care and hospitals in Belgium between 2015 and 2020.

Methods: We retrospectively analysed data from the national influenza surveillance networks in Belgium during the winter seasons of 2015-20. Respiratory specimens were collected through the severe acute respiratory infection (SARI) and the influenza-like illness networks from patients with acute respiratory illness with onset within the previous 10 days, with measured or reported fever of 38°C or greater, cough, or dyspnoea; and for patients admitted to hospital for at least one night. Potential risk factors were recorded and patients who were admitted to hospital were followed up for the occurrence of complications or death for the length of their hospital stay. All samples were analysed by multiplex quantitative RT-PCRs for respiratory viruses, including seasonal hCoVs OC43, NL63, and 229E. We estimated the prevalence and incidence of seasonal hCoV infection, with or without co-infection with other respiratory viruses. We evaluated the association between co-infections and potential risk factors with complications or death in patients admitted to hospital with seasonal hCoV infections by age group. Samples received from week 8, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Findings: 2573 primary care and 6494 hospital samples were included in the study. 161 (6·3%) of 2573 patients in primary care and 371 (5·7%) of 6494 patients admitted to hospital were infected with a seasonal hCoV. OC43 was the seasonal hCoV with the highest prevalence across age groups and highest incidence in children admitted to hospital who were younger than 5 years (incidence 9·0 [95% CI 7·2-11·2] per 100 000 person-months) and adults older than 65 years (2·6 [2·1-3·2] per 100 000 person-months). Among 262 patients admitted to hospital with seasonal hCoV infection and with complete information on potential risk factors, 66 (73·3%) of 90 patients who had complications or died also had at least one potential risk factor (p=0·0064). Complications in children younger than 5 years were associated with co-infection (24 [36·4%] of 66; p=0·017), and in teenagers and adults (≥15 years), more complications arose in patients with a single hCoV infection (49 [45·0%] of 109; p=0·0097). In early 2020, the Belgian SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case with no travel history to China.

Interpretation: The main burden of severe seasonal hCoV infection lies with children younger than 5 years with co-infections and adults aged 65 years and older with pre-existing comorbidities. These age and patient groups should be targeted for enhanced observation when in medical care and in possible future vaccination strategies, and co-infections in children younger than 5 years should be considered during diagnosis and treatment. Our findings support the use of national influenza surveillance systems for seasonal hCoV monitoring and early detection, and monitoring of emerging coronaviruses such as SARS-CoV-2.

Funding: Belgian Federal Public Service Health, Food Chain Safety, and Environment; Belgian National Insurance Health Care (Institut national d'assurance maladie-invalidité/Rijksinstituut voor ziekte-en invaliditeitsverzekering); and Regional Health Authorities (Flanders Agentschap zorg en gezondheid, Brussels Commission communautaire commune, Wallonia Agence pour une vie de qualité).

VL - 2 CP - 3 M3 - 10.1016/S2666-5247(20)30221-4 ER - TY - JOUR T1 - Performance of five rapid serological tests in mild-diseased subjects using finger prick blood for exposure assessment to SARS-CoV-2. JF - J Clin Virol Y1 - 2021 A1 - David Triest A1 - Geebelen, Laurence A1 - Robby De Pauw A1 - Stéphane De Craeye A1 - Alexandra Vodolazkaia A1 - Mathieu Verbrugghe A1 - Koen Magerman A1 - Lara-Lauren Robben A1 - Pieter Pannus A1 - Kristof Neven A1 - Dirk Ramaekers A1 - Steven Van Gucht A1 - Katelijne Dierick A1 - Nele Van Loon A1 - Maria Goossens A1 - I Desombere KW - Antibodies, Viral KW - COVID-19 KW - Humans KW - SARS-CoV-2 KW - Sensitivity and Specificity KW - Seroepidemiologic Studies KW - Serologic Tests AB -

OBJECTIVES: Assess the performance of five SARS-CoV-2 rapid serological tests (RST) using finger prick (FP) blood on-site to evaluate their usability for exposure assessment in population-based seroprevalence studies.

STUDY DESIGN: Since cross-reactivity with common cold human coronaviruses occurs, serological testing includes a risk of false-positive results. Therefore, the selected cohort for RST-validation was based on combined immunoassay (presence of specific antibodies) and RT-qPCR (presence of SARS-CoV-2) data. RST-performance for FP blood and serum was assessed by performing each RST in two groups, namely SARSCoV- 2 positive (n=108) and negative healthcare workers (n=89). Differences in accuracy and positive and negative predictive values (PPV, NPV) were calculated for a range (1-50%) of SARS-CoV-2 prevalence estimates.

RESULTS: The OrientGene showed overall acceptable performance, with sensitivities of 94.4% and 100%, and specificities of 96.6% and 94.4%, using FP blood and serum, respectively. Although three RST reach optimal specificities (100%), the OrientGene clearly outperforms in sensitivity. At a SARS-CoV-2 prevalence rate of 40%, this RST outperforms the other tests in NPV (96.3%) and reaches comparable PPV (94.9%). Although the specificity of the Covid-Presto is excellent when using FP blood or serum (100% and 97.8%, respectively), its sensitivity decreases when using FP blood (76.9%) compared to serum (98.1%).

CONCLUSIONS: Performances of the evaluated RST differ largely. Only one out of five RST (OrientGene) had acceptable sensitivity and specificity using FP blood. Therefore, the latter could be used for seroprevalence studies in a high-prevalence situation. The OrientGene, which measures anti-RBD antibodies, can be valuable after vaccination as well.

VL - 142 M3 - 10.1016/j.jcv.2021.104897 ER - TY - JOUR T1 - Persistence of IgG response to SARS-CoV-2. JF - Lancet Infect Dis Y1 - 2021 A1 - Els Duysburgh A1 - Laure Mortgat A1 - Cyril Barbezange A1 - Katelijne Dierick A1 - Nathalie Fischer A1 - Heyndrickx, Leo A1 - Veronik Hutse A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Vuylsteke, Bea A1 - Ariën, Kevin K A1 - I Desombere KW - Antibodies, Neutralizing KW - Antibodies, Viral KW - COVID-19 KW - Health Personnel KW - Host-Pathogen Interactions KW - Humans KW - Immunoglobulin G KW - SARS-CoV-2 KW - Seroepidemiologic Studies VL - 21 CP - 2 M3 - 10.1016/S1473-3099(20)30943-9 ER - TY - JOUR T1 - Persistence of IgG response to SARS-CoV-2 JF - The Lancet Infectious Diseases Y1 - 2021 A1 - Els Duysburgh A1 - Laure Mortgat A1 - Cyril Barbezange A1 - Katelijne Dierick A1 - Nathalie Fischer A1 - Heyndrickx, Leo A1 - Veronik Hutse A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Vuylsteke, Bea A1 - Ariën, Kevin K A1 - I Desombere VL - 21 CP - 2 M3 - 10.1016/S1473-3099(20)30943-9 ER - TY - JOUR T1 - Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes. JF - Clin Infect Dis Y1 - 2021 A1 - Pieter Pannus A1 - Kristof Y Neven A1 - Stéphane De Craeye A1 - Heyndrickx, Leo A1 - Sara Vande Kerckhove A1 - Daphnée Georges A1 - Johan Michiels A1 - Antoine Francotte A1 - Marc Van den Bulcke A1 - Maan Zrein A1 - Steven Van Gucht A1 - Marie-Noëlle Schmickler A1 - Mathieu Verbrugghe A1 - André Matagne A1 - Isabelle Thomas A1 - Katelijne Dierick A1 - Joshua A Weiner A1 - Margaret E Ackerman A1 - Stanislas Goriely A1 - Maria Goossens A1 - Ariën, Kevin K A1 - I Desombere A1 - Arnaud Marchant AB -

BACKGROUND: Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities.

METHODS: Seventy-eight residents and 106 staff members, naïve or previously infected with SARS-CoV-2, were recruited in NH in Belgium before immunization with two doses of 30µg BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49.

RESULTS: SARS-CoV-2 naïve residents had lower Ab responses to BNT162b2 mRNA vaccination than naïve staff. These poor responses involved lower levels of IgG to all spike domains, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naïve resident had detectable neutralizing Ab to the B.1.351 variant. In contrast, SARS-CoV-2 infected residents had high responses to mRNA vaccination, with Ab levels comparable to infected staff. Cluster analysis revealed that poor vaccine responders not only included naïve residents but also naïve staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population.

CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection naïve residents and in some naïve staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

M3 - 10.1093/cid/ciab998 ER - TY - JOUR T1 - The prior infection with SARS-CoV-2 study (PICOV) in nursing home residents and staff - study protocol description and presentation of preliminary findings on symptoms. JF - Arch Public Health Y1 - 2021 A1 - Maria Goossens A1 - Kristof Y Neven A1 - Pieter Pannus A1 - Cyril Barbezange A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Katelijne Dierick A1 - Marie-Noëlle Schmickler A1 - Mathieu Verbrugghe A1 - Nele Van Loon A1 - Ariën, Kevin K A1 - Arnaud Marchant A1 - Stanislas Goriely A1 - I Desombere AB -

BACKGROUND: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented itself as one of the most important health concerns of the 2020's, and hit the geriatric population the hardest. The presence of co-morbidities and immune ageing in the elderly lead to an increased susceptibility to COVID-19, as is the case for other influenza-like illnesses (ILI) or acute respiratory tract infections (ARI). However, little is known, about the impact of a previous or current infection on the other in terms of susceptibility, immune response, and clinical course. The aim of the "Prior Infection with SARS-COV-2" (PICOV) study is to compare the time to occurrence of an ILI or ARI between participants with a confirmed past SARS-CoV-2 infection (previously infected) and those without a confirmed past infection (naïve) in residents and staff members of nursing homes. This paper describes the study design and population characteristics at baseline.

METHODS: In 26 Belgian nursing homes, all eligible residents and staff members were invited to participate, resulting in 1,226 participants. They were classified as naïve or previously infected based on the presence of detectable SARS-CoV-2 antibodies and/or a positive RT-qPCR result before participation in the study. Symptoms from a prior SARS-CoV-2 infection between March and August 2020 were compared between previously infected residents and staff members.

RESULTS: Infection naïve nursing home residents reported fewer symptoms than previously infected residents: on average 1.9 and 3.1 symptoms, respectively (p = 0.016). The same effect was observed for infection naïve staff members and previously infected staff members (3.1 and 6.1 symptoms, respectively; p <0.0001). Moreover, the antibody development after a SARS-CoV-2 infection differs between residents and staff members, as previously infected residents tend to have a higher rate of asymptomatic cases compared to previously infected staff members (20.5% compared to 12.4%; p <0.0001).

CONCLUSIONS: We can postulate that COVID-19 disease development and symptomatology are different between a geriatric and younger population. Therefore, the occurrence and severity of a future ILI and/or ARI might vary from resident to staff.

VL - 79 CP - 1 M3 - 10.1186/s13690-021-00715-z ER - TY - JOUR T1 - Spotlight influenza: Extending influenza surveillance to detect non-influenza respiratory viruses of public health relevance: analysis of surveillance data, Belgium, 2015 to 2019. JF - Euro Surveill Y1 - 2021 A1 - Lorenzo Subissi A1 - Nathalie Bossuyt A1 - Marijke Reynders A1 - Gerard, Michèle A1 - Nicolas Dauby A1 - Lacor, Patrick A1 - Siel Daelemans A1 - Bénédicte Lissoir A1 - Xavier Holemans A1 - Koen Magerman A1 - Door Jouck A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Sophie Quoilin A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Cyril Barbezange KW - Belgium KW - Child KW - Humans KW - Infant KW - Influenza, Human KW - Orthomyxoviridae KW - public health KW - Respiratory Tract Infections KW - Sentinel Surveillance KW - Viruses AB -

BackgroundSeasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRV) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals has been ongoing since 2011.AimWe report the results of using in-house multiplex qPCR for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated with each virus.MethodsWe defined ILI as an illness with onset of fever and cough or dyspnoea. SARI was defined as an illness requiring hospitalisation with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected in four winter seasons and tested by multiplex qPCR for influenza virus and NIRV. Using catchment population estimates, we calculated incidence rates of SARI associated with each virus.ResultsOne third of the SARI cases were positive for NIRV, reaching 49.4% among children younger than 15 years. In children younger than 5 years, incidence rates of NIRV-associated SARI were twice that of influenza (103.5 vs 57.6/100,000 person-months); co-infections with several NIRV, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributed most (33.1, 13.6, 15.8 and 18.2/100,000 person-months, respectively).ConclusionEarly testing for NIRV could be beneficial to clinical management of SARI patients, especially in children younger than 5 years, for whom the burden of NIRV-associated disease exceeds that of influenza.

VL - 26 CP - 38 M3 - 10.2807/1560-7917.ES.2021.26.38.2001104 ER - TY - JOUR T1 - Towards a European strategy to address the COVID-19 pandemic. JF - Lancet Y1 - 2021 A1 - Viola Priesemann A1 - Rudi Balling A1 - Simon Bauer A1 - Beutels, Philippe A1 - André Calero Valdez A1 - Sarah Cuschieri A1 - Thomas Czypionka A1 - Uga Dumpis A1 - Enrico Glaab A1 - Eva Grill A1 - Pirta Hotulainen A1 - Emil N Iftekhar A1 - Jenny Krutzinna A1 - Christos Lionis A1 - Helena Machado A1 - Carlos Martins A1 - McKee, Martin A1 - George N Pavlakis A1 - Matjaž Perc A1 - Elena Petelos A1 - Martyn Pickersgill A1 - Barbara Prainsack A1 - Joacim Rocklöv A1 - Eva Schernhammer A1 - Ewa Szczurek A1 - Tsiodras, Sotirios A1 - Steven Van Gucht A1 - Peter Willeit KW - COVID-19 KW - COVID-19 Vaccines KW - Europe KW - HEALTH POLICY KW - Humans KW - incidence KW - Mass Vaccination KW - Pandemics KW - Physical Distancing KW - SARS-CoV-2 VL - 398 CP - 10303 M3 - 10.1016/S0140-6736(21)01808-0 ER - TY - JOUR T1 - Whole-genome-based phylogenomic analysis of the Belgian 2016-2017 influenza A(H3N2) outbreak season allows improved surveillance. JF - Microb Genom Y1 - 2021 A1 - Laura Van Poelvoorde A1 - Bert Bogaerts A1 - Fu, Qiang A1 - Sigrid C.J. De Keersmaecker A1 - Isabelle Thomas A1 - Nina Van Goethem A1 - Steven Van Gucht A1 - Raf Winand A1 - Saelens, Xavier A1 - Nancy Roosens A1 - Kevin Vanneste KW - Belgium KW - Hemagglutinin Glycoproteins, Influenza Virus KW - Humans KW - Influenza A Virus, H3N2 Subtype KW - Influenza, Human KW - Phylogeny KW - Public Health Surveillance KW - whole genome sequencing AB -

Seasonal influenza epidemics are associated with high mortality and morbidity in the human population. Influenza surveillance is critical for providing information to national influenza programmes and for making vaccine composition predictions. Vaccination prevents viral infections, but rapid influenza evolution results in emerging mutants that differ antigenically from vaccine strains. Current influenza surveillance relies on Sanger sequencing of the haemagglutinin (HA) gene. Its classification according to World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) guidelines is based on combining certain genotypic amino acid mutations and phylogenetic analysis. Next-generation sequencing technologies enable a shift to whole-genome sequencing (WGS) for influenza surveillance, but this requires laboratory workflow adaptations and advanced bioinformatics workflows. In this study, 253 influenza A(H3N2) positive clinical specimens from the 2016-2017 Belgian season underwent WGS using the Illumina MiSeq system. HA-based classification according to WHO/ECDC guidelines did not allow classification of all samples. A new approach, considering the whole genome, was investigated based on using powerful phylogenomic tools including beast and Nextstrain, which substantially improved phylogenetic classification. Moreover, Bayesian inference via beast facilitated reassortment detection by both manual inspection and computational methods, detecting intra-subtype reassortants at an estimated rate of 15 %. Real-time analysis (i.e. as an outbreak is ongoing) via Nextstrain allowed positioning of the Belgian isolates into the globally circulating context. Finally, integration of patient data with phylogenetic groups and reassortment status allowed detection of several associations that would have been missed when solely considering HA, such as hospitalized patients being more likely to be infected with A(H3N2) reassortants, and the possibility to link several phylogenetic groups to disease severity indicators could be relevant for epidemiological monitoring. Our study demonstrates that WGS offers multiple advantages for influenza monitoring in (inter)national influenza surveillance, and proposes an improved methodology. This allows leveraging all information contained in influenza genomes, and allows for more accurate genetic characterization and reassortment detection.

VL - 7 CP - 9 M3 - 10.1099/mgen.0.000643 ER - TY - JOUR T1 - Antibody response in Dutch marines to a single intramuscular rabies booster immunization 1-2.5 years after an intradermal pre-exposure schedule: An observational study. JF - Travel Med Infect Dis Y1 - 2020 A1 - Cornelis Adrianus De Pijper A1 - Sanne Terryn A1 - Steven Van Gucht A1 - Martin Peter Grobusch A1 - Abraham Goorhuis A1 - Cornelis Stijnis KW - Antibodies, Viral KW - Antibody Formation KW - Follow-Up Studies KW - Humans KW - Immunization Schedule KW - Immunization, Secondary KW - Immunogenicity, Vaccine KW - Injections, Intradermal KW - Injections, Intramuscular KW - Military Personnel KW - Netherlands KW - Pre-Exposure Prophylaxis KW - Rabies KW - Rabies Vaccines KW - Rabies virus VL - 38 M3 - 10.1016/j.tmaid.2020.101907 ER - TY - JOUR T1 - Capturing respiratory syncytial virus season in Belgium using the influenza severe acute respiratory infection surveillance network, season 2018/19. JF - Euro Surveill Y1 - 2020 A1 - Lorenzo Subissi A1 - Nathalie Bossuyt A1 - Marijke Reynders A1 - Gerard, Michèle A1 - Nicolas Dauby A1 - Marc Bourgeois A1 - Bénédicte Delaere A1 - Sophie Quoilin A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Cyril Barbezange KW - ADOLESCENT KW - Adult KW - Aged KW - Belgium KW - Child KW - Child, Preschool KW - Female KW - Fever KW - Hospitalization KW - Humans KW - incidence KW - Infant KW - Influenza, Human KW - Male KW - middle aged KW - Pilot Projects KW - Respiratory Syncytial Virus Infections KW - Respiratory Syncytial Virus, Human KW - Respiratory Tract Infections KW - Risk Factors KW - Seasons KW - Sentinel Surveillance KW - Young adult AB -

BackgroundRespiratory syncytial virus (RSV) is a common cause of severe respiratory illness in young children (< 5 years old) and older adults (≥ 65 years old) leading the World Health Organization (WHO) to recommend the implementation of a dedicated surveillance in countries.AimWe tested the capacity of the severe acute respiratory infection (SARI) hospital network to contribute to RSV surveillance in Belgium.MethodsDuring the 2018/19 influenza season, we started the SARI surveillance for influenza in Belgium in week 40, earlier than in the past, to follow RSV activity, which usually precedes influenza virus circulation. While the WHO SARI case definition for influenza normally used by the SARI hospital network was employed, flexibility over the fever criterion was allowed, so patients without fever but meeting the other case definition criteria could be included in the surveillance.ResultsBetween weeks 40 2018 and 2 2019, we received 508 samples from SARI patients. We found an overall RSV detection rate of 62.4% (317/508), with rates varying depending on the age group: 77.6% in children aged < 5 years (253/326) and 34.4% in adults aged ≥ 65 years (44/128). Over 90% of the RSV-positive samples also positive for another tested respiratory virus (80/85) were from children aged < 5 years. Differences were also noted between age groups for symptoms, comorbidities and complications.ConclusionWith only marginal modifications in the case definition and the period of surveillance, the Belgian SARI network would be able to substantially contribute to RSV surveillance and burden evaluation in children and older adults, the two groups of particular interest for WHO.

VL - 25 CP - 39 M3 - 10.2807/1560-7917.ES.2020.25.39.1900627 ER - TY - JOUR T1 - Challenges to Differentiate Hepatitis C Genotype 1 and 6: Results from A Field-Study in Cambodia. JF - Infect Dis Ther Y1 - 2020 A1 - Anja De Weggheleire A1 - Irith De Baetselier A1 - An, Sokkab A1 - Sylvie Goletti A1 - Vanessa Suin A1 - Thai, Sopheak A1 - Sven Francque A1 - Tania Crucitti A1 - Lutgarde Lynen A1 - Steven Van Gucht A1 - Benoît Kabamba Mukadi KW - Genotype KW - Hepatitis C AB -

INTRODUCTION: We aim to report on results and challenges of different methods used for hepatitis C (HCV) genotyping in a Cambodian HCV/HIV coinfection project.

METHODS: Samples of 106 patients were available. HCV genotyping was initially (63 samples) done by the LightPower Taqman real-time PCR method (Viet A Corp.) and quality controlled using the Versant 2.0 line probe assay (Siemens Healthcare). Next, following interim quality control results, all 106 samples were (re)genotyped with Versant 2.0, complemented with 5'UTR/core sequencing for uninterpretable/incomplete Versant results.

RESULTS: Using Versant, 103 (97.2%) of the 106 HCV-coinfected patients had an interpretable genotype result: 1b (50.5%), 6 non-a/non-b (30.1%), 1a (6.8%), 6a or b (4.9%), 2 (3.9%), 1 (2.9%) and 3 (1.0%). For 16 samples that were interpreted as genotype 1 or 1b per Versant's current instructions, it could not be excluded that it concerned a genotype 6 infection as the core region line patterns on the Versant test strip were unavailable, inconclusive or atypical. Upon sequencing, seven of these were genotyped as 1b and nine as genotype 6. Combining Versant and sequencing results, a definitive genotype was assigned in 104 patients: 1b (44.2%), 6 non-a/non-b (39.4%), 1a (6.7%), 6a or b (4.8%), 2 (3.8%) and 3 (1.0%). Genotyping by LightPower and Versant was discordant for 23 (of 63) samples. The LightPower assay misclassified all genotype 6 non-a/non-b samples as genotype 1, which indicates that this assay is only using 5'UTR information.

CONCLUSIONS: HCV genotype 1b and genotype 6 non-a/non-b were most common. With Versant 2.0 (using 5'UTR and core information), genotype classification (1 or 6) remained inconclusive in 15% of samples. The locally available method (LightPower assay) failed to identify genotype 6 non-a/non-b, which highlights that methods using 5'UTR information only should not be used in Cambodia. Regional/national guidelines should be explicit about this.

TRIAL REGISTRATION: This study was performed as part of a larger cross-sectional study on the burden of hepatitis C coinfection in HIV patients in Cambodia (Clinical.trials.gov: HCV-Epi NCT02361541).

VL - 9 CP - 3 M3 - 10.1007/s40121-020-00304-7 ER - TY - JOUR T1 - Factors of maintenance of rabies transmission in dogs in Kinshasa, Democratic Republic of the Congo. JF - Prev Vet Med Y1 - 2020 A1 - Eric Kazadi Kawaya A1 - Tanguy Marcotty A1 - Leopold Kazadi Mulumba Mfumu A1 - Steven Van Gucht A1 - Kirschvink, Nathalie KW - Animals KW - Democratic Republic of the Congo KW - Dog Diseases KW - Dogs KW - Female KW - Geography KW - Male KW - Maps as Topic KW - Rabies KW - Rabies Vaccines KW - Risk Factors KW - Vaccination VL - 176 M3 - 10.1016/j.prevetmed.2020.104928 ER - TY - JOUR T1 - A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses JF - International Journal of Infectious Diseases Y1 - 2020 A1 - Sylvia Broeders A1 - Linda Garlant A1 - Marie-Alice Fraiture A1 - Els Vandermassen A1 - Vanessa Suin A1 - Jessica Vanhomwegen A1 - Myrielle Dupont-Rouzeyrol A1 - Dominique Rousset A1 - Steven Van Gucht A1 - Nancy Roosens KW - Chikungunya virus KW - discrimination KW - identification KW - multiplex KW - RT-qPCR KW - Zika virus AB -

Objective

The re-emergence and spread of tropical viruses to new areas has raised a wave of concern worldwide. In order to treat patients at an early stage and prevent the diffusion of an outbreak, early diagnosis, and therefore fast and adequate detection, is needed. To this end, a multiplex reverse transcription real-time polymerase chain reaction TaqMan method was designed to detect Zika (ZIKV) and chikungunya (CHIKV) viruses simultaneously.

Methods

Two methods targeting different genome segments were selected from the literature for each virus. These were adapted for high genome coverage and combined in a four-plex assay that was thoroughly validated in-house. The SCREENED tool was used to evaluate the sequence coverage of the method.

Results

The full validation approach showed that the new four-plex method allows the specific and sensitive identification and discrimination of ZIKV and CHIKV in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes is shown for the first time.

Conclusions

PCR is a reliable user-friendly technique that can be applied in remote areas. Such multiplex methods enable early and efficient diagnosis, leading to rapid treatment and effective confinement in outbreak cases. They may also serve as an aid for surveillance, and the full validation permits easy method-transfer allowing worldwide harmonization.

VL - 92 M3 - 10.1016/j.ijid.2019.12.028 ER - TY - JOUR T1 - Stable HEV IgG seroprevalence in Belgium between 2006 and 2014. JF - J Viral Hepat Y1 - 2020 A1 - Erwin Ho A1 - Julie Schenk A1 - Veronik Hutse A1 - Vanessa Suin A1 - Amber Litzroth A1 - Stéphanie Blaizot A1 - Sereina A Herzog A1 - Vera Verburgh A1 - Marjorie Jacques A1 - Rahman, Abbas A1 - Michielsen, Peter A1 - Van Damme, Pierre A1 - Steven Van Gucht A1 - Heidi Theeten A1 - Hens, Niel A1 - Thomas Vanwolleghem KW - Belgium KW - Hepatitis Antibodies KW - Hepatitis E KW - Hepatitis E virus KW - Humans KW - Immunoglobulin G KW - Immunoglobulin M KW - Seroepidemiologic Studies AB -

Recent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort-specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log-log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero-)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1-5.1) and 5.8% (121/2087, CI 4.8-6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.

VL - 27 CP - 11 M3 - 10.1111/jvh.13347 ER - TY - JOUR T1 - Use of Whole Genome Sequencing Data for a First in Silico Specificity Evaluation of the RT-qPCR Assays Used for SARS-CoV-2 Detection. JF - Int J Mol Sci Y1 - 2020 A1 - Mathieu Gand A1 - Kevin Vanneste A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Arnaud Capron A1 - Philippe Herman A1 - Nancy Roosens A1 - Sigrid C.J. De Keersmaecker KW - Betacoronavirus KW - Coronavirus Infections KW - Databases, Genetic KW - Genome, Viral KW - Humans KW - Open Reading Frames KW - Pandemics KW - Pneumonia, Viral KW - Polymorphism, Single Nucleotide KW - Real-Time Polymerase Chain Reaction KW - RNA Replicase KW - RNA, Viral KW - Sensitivity and Specificity KW - whole genome sequencing AB -

The current COronaVIrus Disease 2019 (COVID-19) pandemic started in December 2019. COVID-19 cases are confirmed by the detection of SARS-CoV-2 RNA in biological samples by RT-qPCR. However, limited numbers of SARS-CoV-2 genomes were available when the first RT-qPCR methods were developed in January 2020 for initial in silico specificity evaluation and to verify whether the targeted loci are highly conserved. Now that more whole genome data have become available, we used the bioinformatics tool SCREENED and a total of 4755 publicly available SARS-CoV-2 genomes, downloaded at two different time points, to evaluate the specificity of 12 RT-qPCR tests (consisting of a total of 30 primers and probe sets) used for SARS-CoV-2 detection and the impact of the virus' genetic evolution on four of them. The exclusivity of these methods was also assessed using the human reference genome and 2624 closely related other respiratory viral genomes. The specificity of the assays was generally good and stable over time. An exception is the first method developed by the China Center for Disease Control and prevention (CDC), which exhibits three primer mismatches present in 358 SARS-CoV-2 genomes sequenced mainly in Europe from February 2020 onwards. The best results were obtained for the assay of Chan et al. (2020) targeting the gene coding for the spiking protein (S). This demonstrates that our user-friendly strategy can be used for a first in silico specificity evaluation of future RT-qPCR tests, as well as verifying that the former methods are still capable of detecting circulating SARS-CoV-2 variants.

VL - 21 CP - 15 M3 - 10.3390/ijms21155585 ER - TY - JOUR T1 - Epidemiology and genotype 3 subtype dynamics of hepatitis E virus in Belgium, 2010 to 2017. JF - Euro Surveill Y1 - 2019 A1 - Vanessa Suin A1 - Sofieke Klamer A1 - Veronik Hutse A1 - Wautier, Magali A1 - Marjorie Meurisse A1 - Mona Abady A1 - Lamoral, Sophie A1 - Vera Verburgh A1 - Isabelle Thomas A1 - Bernard Brochier A1 - Lorenzo Subissi A1 - Steven Van Gucht KW - hepatitis E; HEV; surveillance; epidemiology; genotype; Belgium AB -

BackgroundHepatitis E virus (HEV) is an emerging public health concern in high-income countries and can cause acute and chronic hepatitis. Reported numbers of indigenously acquired HEV infection have increased in the past decade in many European countries. Since 2010, the National Reference Centre (NRC) for Hepatitis Viruses has been testing samples of suspected hepatitis E cases in Belgium.AimIn this surveillance report, we present the epidemiological trends of symptomatic HEV infections in Belgium, from the distribution by age, sex and geography to the molecular characterisation of the viral strains.MethodSerum samples of suspected cases sent to the NRC between 2010 and 2017 were analysed for the presence of HEV-specific IgM and RNA. Virus was sequenced for genotyping and phylogenetic analysis in all samples containing sufficient viral RNA.ResultsThe NRC reported an increase in the number of samples from suspected cases (from 309 to 2,663 per year) and in the number of laboratory-confirmed hepatitis E cases (from 25 to 117 per year). Among 217 sequenced samples, 92.6% were genotype 3 (HEV-3), followed by 6.5% of genotype 1 and 0.9% of genotype 4. HEV-3 subtype viruses were mainly 3f, 3c and 3e. HEV-3f was the most common subtype until 2015, while HEV-3c became the most common subtype in 2016 and 2017.ConclusionThe increasing trend of HEV diagnoses in Belgium may be largely explained by increased awareness and testing.

VL - 24 CP - 10 M3 - 10.2807/1560-7917.ES.2019.24.10.1800141 ER - TY - JOUR T1 - Factors of rabies maintenance in dog population in Kinshasa, Democratic Republic of Congo (DRC) JF - International Journal of Infectious Diseases Y1 - 2019 A1 - E.K. Kazadi A1 - T. Marcotty A1 - B. Muylkens A1 - N. Antoine-Moussiaux A1 - Steven Van Gucht A1 - L. Mulumba A1 - N. Kirschvink KW - Rabies VL - 79 M3 - 10.1016/j.ijid.2018.11.147 ER - TY - JOUR T1 - Isolation and Characterization of Clinical RSV Isolates in Belgium during the Winters of 2016–2018 JF - Viruses Y1 - 2019 A1 - Winke Van der Gucht A1 - Kim Stobbelaar A1 - Matthias Govaerts A1 - Thomas Mangodt A1 - Cyril Barbezange A1 - Annelies Leemans A1 - Benedicte De Winter A1 - Steven Van Gucht A1 - Guy Caljon A1 - Louis Maes A1 - Jozef De Dooy A1 - Philippe Jorens A1 - Smet, Annemieke A1 - Paul Cos A1 - Stijn Verhulst A1 - Peter L. Delputte KW - RSV VL - 11 CP - 11 M3 - 10.3390/v11111031 ER - TY - JOUR T1 - Low hepatitis C prevalence in Belgium: implications for treatment reimbursement and scale up. JF - BMC Public Health Y1 - 2019 A1 - Amber Litzroth A1 - Vanessa Suin A1 - Chloé Wyndham-Thomas A1 - Sophie Quoilin A1 - Gaetan Muyldermans A1 - Thomas Vanwolleghem A1 - Kabamba-Mukadi, Benoît A1 - Vera Verburgh A1 - Marjorie Meurisse A1 - Steven Van Gucht A1 - Veronik Hutse AB -

BACKGROUND: Prevalence data of chronic hepatitis C virus (HCV) infection are needed to estimate the budgetary impact of reimbursement of direct-acting antivirals (DAAs). In Belgium, the restricted reimbursement criteria are mainly guided by regional seroprevalence estimates of 0.87% from 1993 to 1994. In this first Belgian nationwide HCV prevalence study, we set out to update the seroprevalence and prevalence of chronic HCV infection estimates in the Belgian general population in order to guide decisions on DAA reimbursement.

METHODS: Residual sera were collected through clinical laboratories. We collected data on age, sex and district. HCV antibody status was determined with ELISA and confirmed with a line-immunoassay (LIA). In specimens with undetermined or positive LIA result, HCV viral load was measured. Specimens were classified seronegative, seropositive with resolved infection, indicative of chronic infection and with undetermined HCV status according to the test outcomes. Results were standardized for age, sex and population per district, and adjusted for clustered sampling.

RESULTS: In total 3209 specimens, collected by 28 laboratories, were tested. HCV seropositivity in the Belgian general population was estimated to be 0.22% (95% CI: 0.09-0.54%), and prevalence of chronic HCV infection 0.12% (95% CI: 0.03-0.41). In individuals of 20 years and older, these estimates were 0.26% (95% CI: 0.10-0.64%) and 0.13% (95% CI: 0.04-0.43), respectively. Of the total estimated number of HCV seropositive individuals in Belgium, 66% were between 50 and 69 years old.

CONCLUSIONS: Prevalence of HCV seropositivity and chronic infection in the Belgian general population were low and comparable to many surrounding countries. These adjusted prevalences can help estimate the cost of reimbursement of DAAs and invite Belgian policy makers to accelerate the scaling up of reimbursement, giving all chronically infected HCV patients a more timely access to treatment.

VL - 19 CP - 1 M3 - 10.1186/s12889-018-6347-z ER - TY - JOUR T1 - A new multiplex RT-qPCR method for the simultaneous detection and discrimination of Zika and chikungunya viruses. JF - Int J Infect Dis Y1 - 2019 A1 - Sylvia Broeders A1 - Linda Garlant A1 - Marie-Alice Fraiture A1 - Els Vandermassen A1 - Vanessa Suin A1 - Jessica Vanhomwegen A1 - Myrielle Dupont-Rouzeyrol A1 - Dominique Rousset A1 - Steven Van Gucht A1 - Nancy Roosens KW - chikungunya KW - VIRUS KW - Zika AB -

OBJECTIVE: The re-emergence and spreading of tropical viruses to new areas raised worldwide a wave of concern. To treat patients in an early stage and prevent diffusion of the outbreak, an early diagnosis, and thus fast and adequate detection, is needed. To this aim, a multiplex reverse transcription real-time polymerase chain reaction TaqMan® method was designed to detect universally Zika and chikungunya viruses.

DESIGN: Two methods, targeting different genome segments, were selected from literature for each virus, adapted for high genome coverage and joined into a four-plex assay which was thoroughly in-house validated. The SCREENED tool was used to evaluate the sequence coverage of the method.

RESULTS: The full validation approach showed that the new four-plex method allows specific and sensitive identification and discrimination of Zika and chikungunya in routine samples. The combination of two targets per virus allowing almost 100% coverage of about 500 genomes was shown for the first time.

CONCLUSION: PCR being a reliable user-friendly technique, applicable in remote areas, such multiplex methods enable early and efficient diagnosis leading to rapid treatment and effective confinement in outbreak cases as well as being an aid for surveillance and the full validation permits easy method-transfer allowing worldwide harmonization.

M3 - 10.1016/j.ijid.2019.12.028 ER - TY - JOUR T1 - Subsequent mortality in survivors of Ebola virus disease in Guinea: a nationwide retrospective cohort study JF - The Lancet Infectious Diseases Y1 - 2019 A1 - Keita Mory A1 - Boubacar Diallo A1 - Samuel Mesfin A1 - Marega, Abdourahmane A1 - Yacouba Koumpingni Nebie A1 - Magassouba, N'Faly A1 - Barry, Ahmadou A1 - Seydou Coulibaly A1 - Barry, Boubacar A1 - Mamadou Oury A1 - Raymond Pallawo A1 - Sadou Sow A1 - Alpha Oumar Bah A1 - Mamadou Saliou Balde A1 - Steven Van Gucht A1 - Mandy Kader Kondé A1 - Amadou Bailo Diallo A1 - Mamoudou Harouna Djingarey A1 - é Fall A1 - Pierre Formenty A1 - Judith R Glynn A1 - Lorenzo Subissi KW - ebola M3 - 10.1016/S1473-3099(19)30313-5 ER - TY - JOUR T1 - Subsequent mortality in survivors of Ebola virus disease in Guinea: a nationwide retrospective cohort study JF - The Lancet Infectious Diseases Y1 - 2019 A1 - Keita Mory A1 - Boubacar Diallo A1 - Samuel Mesfin A1 - Marega, Abdourahmane A1 - Yacouba Koumpingni Nebie A1 - Magassouba, N'Faly A1 - Barry, Ahmadou A1 - Seydou Coulibaly A1 - Barry, Boubacar A1 - Mamadou Oury A1 - Raymond Pallawo A1 - Sadou Sow A1 - Alpha Oumar Bah A1 - Mamadou Saliou Balde A1 - Steven Van Gucht A1 - Mandy Kader Kondé A1 - Amadou Bailo Diallo A1 - Mamoudou Harouna Djingarey A1 - é Fall A1 - Pierre Formenty A1 - Judith R Glynn A1 - Lorenzo Subissi KW - ebola M3 - 10.1016/S1473-3099(19)30313-5 ER - TY - JOUR T1 - Subtype-specific differences in the risk of hospitalisation among patients infected with hepatitis E virus genotype 3 in Belgium, 2010-2018. JF - Epidemiol Infect Y1 - 2019 A1 - Lorenzo Subissi A1 - Michael Peeters A1 - Lamoral, Sophie A1 - Sofieke Klamer A1 - Vanessa Suin A1 - Steven Van Gucht KW - hepatitits E AB -

Some European countries recently reported an increase in hepatitis E virus genotype 3 (HEV-3) of the subtype 3c. No link between HEV-3 subtypes and severity is established to date. Here, we report that patients infected with HEV-3c were at lower risk of hospitalisation, compared to those infected with HEV-3f, the other main subtype circulating in Belgium.

VL - 147 M3 - 10.1017/S0950268819001122 ER - TY - JOUR T1 - Tick-Borne Encephalitis Virus Antibodies in Roe Deer, the Netherlands. JF - Emerg Infect Dis Y1 - 2019 A1 - Rijks, Jolianne M A1 - Margriet GE Montizaan A1 - Nine Bakker A1 - de Vries, Ankje A1 - Steven Van Gucht A1 - Corien Swaan A1 - Jan van den Broek A1 - Andrea Gröne A1 - Sprong, Hein AB -

To increase knowledge of tick-borne encephalitis virus (TBEV) circulation in the Netherlands, we conducted serosurveillance in roe deer (Capreolus capreolus) during 2017 and compared results with those obtained during 2010. Results corroborate a more widespread occurrence of the virus in 2017. Additional precautionary public health measures have been taken.

VL - 25 CP - 2 M3 - 10.3201/eid2502.181386 ER - TY - JOUR T1 - Time of administration of rabies immunoglobulins and adequacy of antibody response upon post-exposure prophylaxis: a descriptive retrospective study in Belgium. JF - Acta Clin Belg Y1 - 2019 A1 - Patrick Soentjens A1 - Mieke Croughs A1 - Christophe Burm A1 - Steven Declerq A1 - Jan Clerinx A1 - Ula Maniewski A1 - Steven Van Den Brouck A1 - Caroline Theunissen A1 - Ralph Huits A1 - Isabel Brosius A1 - Florence, Eric A1 - Chris Kenyon A1 - Johan Van Griensven A1 - Sabrina Van Ierssel A1 - Lut Lynen A1 - Katleen Balliauw A1 - Steven Van Gucht A1 - Van Esbroeck, Marjan A1 - Vlieghe, Erika A1 - Bottieau, Emmanuel A1 - Yven Van Herrewege KW - rabies; prophylaxis; AB -

: Data on rabies post-exposure prophylaxis (PEP) and the use of human rabies immunoglobulins (HRIG) in Belgium are scarce. The main objective of this study was to evaluate the timely administration of HRIG after rabies exposure. The secondary objective was to evaluate the adequate antibody response following PEP. : We reviewed all medical records from July 2017 to June 2018 of patients seeking care at, or referred to, the Institute of Tropical Medicine and the University Hospital, Antwerp for the administration of human rabies immunoglobulins following potential rabies exposure abroad or in Belgium. A timely response was defined as starting HRIG with a delay of ≤48 h and rabies vaccination in the first 7 days after exposure. Adequate antibody response was defined as a titer of >5.0 IU/mL in case of bat-related exposure and >3.0 IU/mL in case of exposure to other animals. Titers were measured 10 days after the last PEP vaccine dose, using the rapid fluorescent focus inhibition test (RFFIT). : Of the 92 cases treated with HRIG, 75 were evaluated. The majority of injuries were acquired in Asia (n = 26,34%) and in Western Europe (n = 18, 24%), of which 17 in Belgium. The five most frequently recorded countries overseas were Indonesia (n = 13), Thailand (n = 7), Morocco (n = 4), Peru (n = 3) and Costa Rica (n = 3). Administration of immunoglobulins was related to injuries by dogs (36%), monkeys (25%) or bats (22%). A timely response was observed in 16 (21,33%) and in 55 (73,33%) of subjects receiving HRIG (≤48 h) or rabies vaccine (<7days) respectively. The mean time between exposure and the first administered dose of rabies vaccine and HRIG was 7.7 and 8.7 days, respectively. The mean delay for HRIG administration was 9.6 days and 6 days for abroad and inland risks, respectively. In 15 of 16 (94%) bat-related cases the antibody titer after full PEP was >5.0 IU/ml. In 38 of 47 (81%) cases related to other animals the RFFIT titer was >3.0 IU/ml. All low-responders received additional rabies injections. : This study showed a substantial time delay between the animal-related risk and the administration of HRIG, in particular when the injury occurred abroad. More targeted communication about the risks of rabies and preventable measures may reduce this delay. Furthermore, the antibody response was inadequate in some cases following full PEP administration according to the Belgian recommendation.

M3 - 10.1080/17843286.2019.1662993 ER - TY - JOUR T1 - Application of whole genome data for in silico evaluation of primers and probes routinely employed for the detection of viral species by RT-qPCR using dengue virus as a case study. JF - BMC Bioinformatics Y1 - 2018 A1 - Kevin Vanneste A1 - Linda Garlant A1 - Sylvia Broeders A1 - Steven Van Gucht A1 - Nancy Roosens AB -

BACKGROUND: Viral infection by dengue virus is a major public health problem in tropical countries. Early diagnosis and detection are increasingly based on quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) directed against genomic regions conserved between different isolates. Genetic variation can however result in mismatches of primers and probes with their targeted nucleic acid regions. Whole genome sequencing allows to characterize and track such changes, which in turn enables to evaluate, optimize, and (re-)design novel and existing RT-qPCR methods. The immense amount of available sequence data renders this however a labour-intensive and complex task.

RESULTS: We present a bioinformatics approach that enables in silico evaluation of primers and probes intended for routinely employed RT-qPCR methods. This approach is based on analysing large amounts of publically available whole genome data, by first employing BLASTN to mine the genomic regions targeted by the RT-qPCR method(s), and afterwards using BLASTN-SHORT to evaluate whether primers and probes will anneal based on a set of simple in silico criteria. Using dengue virus as a case study, we evaluated 18 published RT-qPCR methods using more than 3000 publically available genomes in the NCBI Virus Variation Resource, and provide a systematic overview of method performance based on in silico sensitivity and specificity.

CONCLUSIONS: We provide a comprehensive overview of dengue virus RT-qPCR method performance that will aid appropriate method selection allowing to take specific measures that aim to contain and prevent viral spread in afflicted regions. Notably, we find that primer-template mismatches at their 3' end may represent a general issue for dengue virus RT-qPCR detection methods that merits more attention in their development process. Our approach is also available as a public tool, and demonstrates how utilizing genomic data can provide meaningful insights in an applied public health setting such as the detection of viral species in human diagnostics.

VL - 19 CP - 1 M3 - 10.1186/s12859-018-2313-0 ER - TY - JOUR T1 - Clinical burden of hepatitis E virus infection in a tertiary care center in Flanders, Belgium. JF - J Clin Virol Y1 - 2018 A1 - Cattoir, Lien A1 - Van Hoecke, Frederik A1 - Van Maerken, Tom A1 - Nys, Eveline A1 - Ryckaert, Inge A1 - De Boulle, Matthias A1 - Geerts, Anja A1 - Verhelst, Xavier A1 - Colle, Isabelle A1 - Veronik Hutse A1 - Vanessa Suin A1 - Wautier, Magali A1 - Steven Van Gucht A1 - Van Vlierberghe, Hans A1 - Padalko, Elizaveta AB -

BACKGROUND: Hepatitis E virus (HEV) infection is increasingly recognized as a cause of hepatitis in developed countries. A high HEV IgG seroprevalence in humans and pigs is reported as well as sporadic clinical cases of autochtonous HEV but there are currently no data available on the clinical burden of HEV in Belgium.

OBJECTIVES: The objective of the current study was to evaluate the actual clinical burden of HEV infections in our tertiary care center in Flanders, Belgium.

STUDY DESIGN: In the setting of Ghent University Hospital, patients were assessed for the presence of HEV IgG and IgM as well as HEV RNA if no other cause was found for one of the following clinical presentations: a) elevation of liver enzymes in post-liver transplant; b) suspicion of acute or toxic hepatitis; c) unexplainable elevation of liver enzymes; d) cirrhosis with acute-on-chronic exacerbation.

RESULTS: In a period of 39 months (January 2011-April 2014) 71 patients were enrolled. HEV IgG was found positive in 13 (18,3%) patients; HEV IgM in 6 patients (8,5%) and HEV RNA in 4 (5,6%) patients. All HEV IgM/RNA positive patients were male, aged 41-63, and classified in the clinical groups a), b) or d). HEV IgG seroprevalence was slightly higher but not significantly different from the seroprevalence in the general population in this region in Belgium previously reported to be 14% (p-value 0.41) by our group.

CONCLUSIONS: HEV should be considered as a cause of liver pathology especially in middle-aged men with elevation of liver enzymes.

VL - 103 M3 - 10.1016/j.jcv.2018.03.004 ER - TY - JOUR T1 - A Comparative Immunogenicity and Safety Trial of Two Different Schedules of Single-visit Intradermal Rabies Post-exposure Vaccination Following a Single-visit Pre-exposure Vaccination. JF - Clin Infect Dis Y1 - 2018 A1 - P Soentjens A1 - K De Koninck A1 - A Tsoumanis A1 - N Herssens A1 - D Van Den Bossche A1 - Sanne Terryn A1 - Steven Van Gucht A1 - Van Damme, P A1 - Y Van Herrewege A1 - E Bottieau AB -

BACKGROUND: Effective and safe single-visit rabies vaccination for pre- and post-exposure prophylaxis (PrEP and PEP) could substantially simplify rabies prevention and therefore increase compliance.

METHODS: In a comparative trial, 303 healthy adults received a primary vaccination consisting of two intradermal (ID) doses of 0.1mL of the purified chicken embryo cell vaccine (PCEV) during a single visit. One year later, subjects were randomly assigned to receive either four or two ID PEP booster doses of 0.1mL of PCEV during a single visit. The primary endpoint for immunogenicity was the percentage of subjects with an adequate antibody level (>0.5 IU/mL) seven days after the booster doses. The safety endpoint was the proportion of participants developing adverse events (AE) following primary and/or booster vaccination.

RESULTS: ll subjects, except one (99.3%) in each study group, had a rabies antibody titer >0.5 IU/mL on day 7 following the booster schedules. Subjects exposed to the four-dose PEP schedule had a geometric mean titer of 20 IU/mL versus 14 IU/mL for the two-dose PEP schedule (p=0.0228). Local reactions at the injection site following PrEP and PEP were mild and transient and only seen in 14.9% and 49.6 to 53% of the participants respectively. No serious AE were reported.

CONCLUSION: In healthy adults, a two-dose (2x 0.1mL) single-visit intradermal post-exposure prophylaxis schedule was as immunologically adequate and safe as a four-dose (4x 0.1mL) single-visit PEP schedule, seven to twenty-eight months following a two-dose (2x 0.1mL) single-visit intradermal pre-exposure prophylaxis.

M3 - 10.1093/cid/ciy983 ER - TY - Generic T1 - Development of a bioinformatics pipeline for the routine analysis of Influenza whole genome sequencing data Y1 - 2018 A1 - Qiang Fu A1 - Raf Winand A1 - Julien Van Braekel A1 - Cyril Barbezange A1 - Veronik Hutse A1 - Isabelle Thomas A1 - Steven Van Gucht A1 - Sigrid C.J. De Keersmaecker A1 - Nancy Roosens A1 - Kevin Vanneste JF - European Conference on Computational Biology 2018 conference (http://eccb18.org/). 8 – 12 September, 2018, Athens, Greece ER - TY - JOUR T1 - Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins. JF - Sci Rep Y1 - 2018 A1 - Sigrid Gouma A1 - Tessa Vermeire A1 - Steven Van Gucht A1 - Lennart Martens A1 - Veronik Hutse A1 - Jeroen Cremer A1 - Paul A Rota A1 - Geert Leroux-Roels A1 - Marion Koopmans A1 - Rob van Binnendijk A1 - Elien Vandermarliere KW - Mumps; vaccine AB -

The surface proteins of the mumps virus, the fusion protein (F) and haemagglutinin-neuraminidase (HN), are key factors in mumps pathogenesis and are important targets for the immune response during mumps virus infection. We compared the predicted amino acid sequences of the F and HN genes from Dutch mumps virus samples from the pre-vaccine era (1957-1982) with mumps virus genotype G strains (from 2004 onwards). Genotype G is the most frequently detected mumps genotype in recent outbreaks in vaccinated communities, especially in Western Europe, the USA and Japan. Amino acid differences between the Jeryl Lynn vaccine strains (genotype A) and genotype G strains were predominantly located in known B-cell epitopes and in N-linked glycosylation sites on the HN protein. There were eight variable amino acid positions specific to genotype A or genotype G sequences in five known B-cell epitopes of the HN protein. These differences may account for the reported antigenic differences between Jeryl Lynn and genotype G strains. We also found amino acid differences in and near sites on the HN protein that have been reported to play a role in mumps virus pathogenesis. These differences may contribute to the occurrence of genotype G outbreaks in vaccinated communities.

VL - 8 CP - 1 M3 - 10.1038/s41598-018-31630-z ER - TY - JOUR T1 - Distribution of HCV genotypes in Belgium from 2008 to 2015. JF - PLoS One Y1 - 2018 A1 - Lobna Bouacida A1 - Vanessa Suin A1 - Veronik Hutse A1 - Michaël Boudewijns A1 - Reinoud Cartuyvels A1 - Laurent Debaisieux A1 - Emmanuel De Laere A1 - Hallin, Marie A1 - Nicolas Hougardy A1 - Lagrou, Katrien A1 - Els Oris A1 - Padalko, Elizaveta A1 - Marijke Reynders A1 - Gatien Roussel A1 - Jean-Marc Senterre A1 - Michel Stalpaert A1 - Dominique Ursi A1 - Carl Vael A1 - Vaira, Dolorès A1 - Van Acker, Jos A1 - Walter Verstrepen A1 - Steven Van Gucht A1 - Kabamba, Benoît A1 - Sophie Quoilin A1 - Gaetan Muyldermans KW - hepatitis C virus AB -

BACKGROUND: The knowledge of circulating HCV genotypes and subtypes in a country is crucial to guide antiviral therapy and to understand local epidemiology. Studies investigating circulating HCV genotypes and their trends have been conducted in Belgium. However they are outdated, lack nationwide representativeness or were not conducted in the general population.

METHODS: In order to determine the distribution of different circulating HCV genotypes in Belgium, we conducted a multicentre study with all the 19 Belgian laboratories performing reimbursed HCV genotyping assays. Available genotype and subtype data were collected for the period from 2008 till 2015. Furthermore, a limited number of other variables were collected: some demographic characteristics from the patients and the laboratory technique used for the determination of the HCV genotype.

RESULTS: For the study period, 11,033 unique records collected by the participating laboratories were used for further investigation. HCV genotype 1 was the most prevalent (53.6%) genotype in Belgium, with G1a and G1b representing 19.7% and 31.6%, respectively. Genotype 3 was the next most prevalent (22.0%). Further, genotype 4, 2, and 5 were responsible for respectively 16.1%, 6.2%, and 1.9% of HCV infections. Genotype 6 and 7 comprise the remaining <1%. Throughout the years, a stable distribution was observed for most genotypes. Only for genotype 5, a decrease as a function of the year of analysis was observed, with respectively 3.6% for 2008, 2.3% for 2009 and 1.6% for the remaining years. The overall M:F ratio was 1.59 and was mainly driven by the high M:F ratio of 3.03 for patients infected with genotype 3. Patients infected with genotype 3 are also younger (mean age 41.7 years) than patients infected with other genotypes (mean age above 50 years for all genotypes). The patients for whom a genotyping assay was performed in 2008 were younger than those from 2015. Geographical distribution demonstrates that an important number of genotyped HCV patients live outside the Belgian metropolitan cities.

CONCLUSION: This national monitoring study allowed a clear and objective view of the circulating HCV genotypes in Belgium and will help health authorities in the establishment of cost effectiveness determinations before implementation of new treatment strategies. This baseline characterization of the circulating genotypes is indispensable for a continuous surveillance, especially for the investigation of the possible impact of migration from endemic regions and prior to the increasing use of highly potent direct-acting antiviral (DAA) agents.

VL - 13 CP - 12 M3 - 10.1371/journal.pone.0207584 ER - TY - JOUR T1 - Ebola Virus Transmission Caused by Persistently Infected Survivors of the 2014-2016 Outbreak in West Africa. JF - J Infect Dis Y1 - 2018 A1 - Lorenzo Subissi A1 - Keita Mory A1 - Samuel Mesfin A1 - Giovanni Rezza A1 - Boubacar Diallo A1 - Steven Van Gucht A1 - Emmanuel Onuche Musa A1 - Yoti, Zabulon A1 - Keita, Sakoba A1 - Mamoudou Harouna Djingarey A1 - Amadou Bailo Diallo A1 - Ibrahima Socé Fall KW - Ebola virus; ebola; survivors; persistence AB -

The 2014-2016 Ebola virus (EBOV) disease outbreak affected over 29000 people and left behind the biggest cohort (over 17000 individuals) of Ebola survivors in history. Although the persistence of EBOV in body fluids of survivors was reported before the recent outbreak, new evidence revealed that the virus can be detected up to 18 months in the semen, which represents the biggest risk of Ebola resurgence in affected communities. In this study, we review the knowledge on the Ebola flare-ups that occurred after the peak of the 2014-2016 Ebola epidemic in West Africa.

M3 - 10.1093/infdis/jiy280 ER - TY - RPRT T1 - Epidemiologische surveillance van rabiës - 2017 Y1 - 2018 A1 - Javiera Rebolledo A1 - Bernard Brochier A1 - Sanne Terryn A1 - Steven Van Gucht PB - Sciensano CY - Brussel ER - TY - JOUR T1 - Inhibition of MALT1 decreases neuroinflammation and pathogenicity of virulent rabies virus in mice. JF - J Virol Y1 - 2018 A1 - E Kip A1 - J Staal A1 - Hermann Tima Giresse A1 - L Verstrepen A1 - Marta Romano A1 - K Lemeire A1 - Vanessa Suin A1 - Assia Hamouda A1 - M Baens A1 - C Libert A1 - Kalai, M A1 - Steven Van Gucht A1 - Beyaert, R AB -

Rabies virus is a neurovirulent RNA virus, which causes about 59000 human deaths each year. Treatment for rabies does not exist due to incomplete understanding of the pathogenesis. MALT1 mediates activation of several immune cell types and is involved in the proliferation and survival of cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, leading to the expression of immunoregulatory genes. Here, we examined the impact of genetic or pharmacological MALT1 inhibition in mice on disease development after infection with the virulent rabies virus strain CVS-11. Morbidity and mortality were significantly delayed in compared to mice, which was associated with a lower viral load, proinflammatory gene expression and infiltration and activation of immune cells in brain. Specific deletion of in T cells also delayed disease development while deletion in myeloid cells, neuronal cells or NK cells had no effect. Disease development was also delayed in mice treated with the MALT1 protease inhibitor mepazine, and in knock-in mice expressing a catalytically inactive MALT1 mutant protein, showing an important role of MALT1 proteolytic activity. The described protective effect of MALT1 inhibition against infection with a virulent rabies virus is the precise opposite of the sensitizing effect of MALT1 inhibition that we previously observed in case of infection with an attenuated rabies virus strain. Together, these data demonstrate that the role of immunoregulatory responses in rabies pathogenicity is dependent on virus virulence, and reveal the potential of MALT1 inhibition for therapeutic intervention. Rabies virus is a neurotropic RNA virus that causes encephalitis and still poses an enormous challenge to animal and public health. Efforts to establish reliable therapeutic strategies have been unsuccessful and are hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protease that mediates the activation of several innate and adaptive immune cells in response to multiple receptors, and therapeutic MALT1 targeting is believed to be a valid approach for autoimmunity and MALT1-addicted cancers. Here, we study the impact of MALT1 deficiency on brain inflammation and disease development in response to infection of mice with the highly virulent CVS-11 rabies virus. We demonstrate that pharmacological or genetic MALT1 inhibition decreases neuroinflammation and extends the survival of CVS-11 infected mice, providing new insights in the biology of MALT1 and rabies virus infection.

M3 - 10.1128/JVI.00720-18 ER - TY - JOUR T1 - MALT1 controls attenuated rabies virus by inducing early inflammation and T cell activation in the brain. JF - J Virol Y1 - 2018 A1 - E Kip A1 - J Staal A1 - L Verstrepen A1 - H Tima Giresse A1 - Sanne Terryn A1 - Marta Romano A1 - K Lemeire A1 - Vanessa Suin A1 - Assia Hamouda A1 - Kalai, M A1 - Beyaert, R A1 - Steven Van Gucht KW - MALT1 KW - Rabies AB -

MALT1 is involved in the activation of immune responses as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signalling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. While MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus (ERA) and observed increased susceptibility with ERA in MALT1-/- mice. Indeed, following intranasal infection with ERA, wild-type mice developed mild transient clinical signs with recovery at 35 DPI. Interestingly, MALT1-/- mice developed severe disease requiring euthanasia around 17 DPI. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1-/- mice at 10DPI as compared to MALT1+/+ infected mice. At 17 DPI, however, inflammatory cell activation was comparable to the one observed in MALT1+/+ mice. Moreover, MALT1-/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain.IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protein involved in innate and adaptive immunity, and an interesting therapeutic target because MALT1-deregulated activity has been associated with autoimmunity and cancers. The role of MALT1 in viral infection is however largely unknown. Here, we study the impact of MALT1 on virus infection in the brain, using the attenuated ERA rabies virus in different models of MALT1 deficient mice. We reveal the importance of MALT1-mediated inflammation and T cell activation to control ERA virus, providing new insights in the biology of MALT1 and rabies virus infection.

M3 - 10.1128/JVI.02029-17 ER - TY - Generic T1 - Monitoring of influenza: Whole-Genome Sequencing to provide insights in the disease severity Y1 - 2018 A1 - Laura Van Poelvoorde A1 - Sigrid C.J. De Keersmaecker A1 - Kevin Vanneste A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Xavier Saelens A1 - Cyril Barbezange A1 - Nancy Roosens JF - The 6th International Influenza Meeting, 2-4 September 2018 Münster, Germany ER - TY - JOUR T1 - Pre-exposure intradermal rabies vaccination: a non-inferiority trial in healthy adults on shortening the vaccination schedule from 28 to 7 days. JF - Clin Infect Dis Y1 - 2018 A1 - P Soentjens A1 - P Andries A1 - A Aerssens A1 - A Tsoumanis A1 - R Ravinetto A1 - W Heuninckx A1 - H van Loen A1 - B Brochier A1 - Steven Van Gucht A1 - Van Damme, P A1 - Y Van Herrewege A1 - E Bottieau AB -

Background: The existing four-week pre-exposure rabies vaccination schedule is costly and often not practicable. Shorter effective schedules would result in wider acceptance.

Methods: We conducted a non-inferiority trial in 500 healthy adults comparing the safety and immunogenicity of a two-visit (day 0 and day 7) intradermal (ID) primary vaccination (two doses of 0.1 ml ID of the human diploid cell culture rabies vaccine (HDCV) at day 0 and 7) versus a standard three-visit schedule (single dose of 0.1 mL ID at day 0, 7, and 28). One to three years after primary vaccination, a single booster dose of 0.1 mL ID of HDCV was given to evaluate the anamnestic rabies antibody response. The primary endpoint for immunogenicity was the percentage of subjects with an adequate antibody level >0.5 IU/mL seven days after the booster injection. The safety endpoint was the proportion of participants developing adverse reactions following the primary vaccination and/or booster dose.

Results: All subjects in both study groups possessed a rabies antibody titer >0.5 IU/mL on day 7 following the booster dose. Following the booster dose, subjects exposed to the double-dose two-visit ID schedule had a geometric mean titer of 37 IU/ml versus 25 IU/ml for the single-dose three-visit schedule (p<0.001). Local reactions at the injection site following primary vaccination were mild and transient.

Conclusion: In healthy adults, ID administration of a double dose of 0.1 ml of HDCV over two-visits (day 0 and day 7) was safe and not inferior to the single-dose three-visit schedule.

M3 - 10.1093/cid/ciy513 ER - TY - JOUR T1 - Rabies antibody response after two intradermal pre-exposure prophylaxis immunizations: An observational cohort study. JF - Travel Med Infect Dis Y1 - 2018 A1 - Cornelis Adrianus De Pijper A1 - Jimmy Boersma A1 - Sanne Terryn A1 - Steven Van Gucht A1 - Abraham Goorhuis A1 - Martin Peter Grobusch A1 - Cornelis Stijnis AB -

BACKGROUND: Rabies is a lethal, but vaccine preventable disease. Vaccination uptake is however hampered by the time-consuming three-dose, 21/28-day schedule. The aim of this study was to examine whether adequate rabies antibody titers are reached after two intradermal (ID) doses of rabies vaccine, with a seven-day window.

METHOD: We conducted an observational cohort study with military personnel. A titer was assessed by RFFIT, on the day of the third vaccination, to ensure an adequate rabies antibody response after ID immunization.

RESULTS: After this abbreviated two-dose, seven-day ID schedule, seroconversion was reached in 99.3% (427/430) with a geometric mean titer of 7.59 IU/mL (95% CI 7.04-8.17).

CONCLUSIONS: Implementation of this two-dose schedule will protect more people against Rabies. Travelers and military personnel under time constraints, who otherwise would remain unvaccinated, can be considered adequately protected after this two-dose schedule. For populations in endemic areas, local application of a two-dose schedule could provide an opportunity to vaccinate more people with less vaccine. Given the paucity of published data, this study adds relevant evidence in support of the new policy (2017) of WHO, concerning a two-dose, seven-day schedule is approved for all healthy individuals.

M3 - 10.1016/j.tmaid.2018.03.006 ER - TY - JOUR T1 - Sera from different age cohorts in Belgium show limited cross-neutralisation between the mumps vaccine and outbreak strains JF - Clinical Microbiology and Infection Y1 - 2018 A1 - Tessa Vermeire A1 - Cyril Barbezange A1 - Aurélie Francart A1 - Assia Hamouda A1 - Amber Litzroth A1 - Veronik Hutse A1 - Lennart Martens A1 - Elien Vandermarliere A1 - Steven Van Gucht AB -

OBJECTIVES:

Mumps used to affect children between two and 15 years old. The MMR (mumps-measles-rubella) vaccine is available with vaccine coverage rate of about 85% after two vaccine doses. Recently, new mumps outbreaks emerged in highly vaccinated populations and the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralising capacity against the vaccine and wild type viruses exists and if waning immunity could be detected.

METHODS:

In this study, 570 serum samples (age group 2-3y (N=96), 8-9y (N=95), 13-14y (N=94), 18-20y (N=96), 24-26y (N=92) and 50+ (N=97)) in Belgium were tested in the rapid fluorescent focus inhibition test (RFFIT) for their neutralizing capacity against the vaccine and wild type viruses.

RESULTS:

Neutralising antibodies against the vaccine strain were present in 81% (84/97) of the 2-3y, 70% (70/95) of the 8-9y, 76% (76/94) of the 13-14y, 73% (73/96) of the 18-20y, 62% (62/92) of the 24-26y and 75% (75/97) of the 50+ age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild type virus. The geometric mean titres for the vaccine and wild type virus for all younger age groups, except 24-26y, were significantly different, demonstrating poor in vitro cross-neutralisation.

CONCLUSIONS:

A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower than optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralisation and should be further studied.

M3 - 10.1016/j.cmi.2018.11.016 ER - TY - RPRT T1 - Surveillance épidémiologique de la rage - 2017 Y1 - 2018 A1 - Javiera Rebolledo A1 - Bernard Brochier A1 - Sanne Terryn A1 - Steven Van Gucht ER - TY - RPRT T1 - Virological Surveillance of Influenza in Belgium Season 2017-2018 Y1 - 2018 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Steven Van Gucht A1 - Jeannine Weyckmans A1 - Ilham Fdillate A1 - Reinout Van Eycken A1 - Assia Hamouda A1 - Nathalie Bossuyt A1 - Sophie Quoilin A1 - Viviane Van Casteren A1 - Yolande Pirson VL - ISSN number: D/2018/14.440/40 ER - TY - JOUR T1 - Comparative Tick-Borne Encephalitis (Virus) Surveillance in Belgium 2009-2015: Experiences with Diagnostic Tests, Sentinel Species and Surveillance Designs JF - Journal of Zoonotic Diseases and Public Health Y1 - 2017 A1 - Sophie Roelandt A1 - Vanessa Suin A1 - Steven Van Gucht A1 - Yves Van der Stede A1 - S. Roels KW - Tick-borne encephalitis (virus); Wild boar; Roe deer; Sentinel species; AB -

When it is not overtly affecting human beings, the Tick-Borne Encephalitis Flavivirus (TBEV) remains mostly unnoticed during its enzootic cycles within vectors and unaffected animal species. Until recently, Belgium was “presumed” free of this important neuro-pathogenic virus without any scientific substantiation. Nonetheless, Belgium is clearly at risk of Tick-Borne Encephalitis (TBE) emergence

and incursions from endemic zones in the neighboring countries. This comparative review paper describes 5 Belgian veterinary serological studies with enzyme-linked immunosorbent assays and seroneutralisation tests (ELISA/SNT), in which several surveillance schemes were used (active/passive, risk-/laboratory-/range-based) in classic TBE sentinel species (dogs, cattle, roe deer, wild boar). Additionally, passive syndromic surveillance in two medical laboratories resulted in inconclusive medical data. Details are given on the scientists’ experiences with available first/second line diagnostic tests and with the different surveillance methods/survey designs. Each of the veterinary studies clearly demonstrated the presence of TBEV-specific antibodies in Belgian sentinels, sometimes even at high seroneutralisation (SNT) titers, while the medical data remain so far inconclusive, despite positive

reactions of some patients in some TBEV-tests. These results have substantiated our suspicion of TBEV-presence in Belgium from 2010 onwards and have allowed sentinel comparisons based on “suitability criteria”. Furthermore, the studies have highlighted the need for further veterinary validation of commercial ELISA tests in comparison to the gold standard SNT.

VL - 1 CP - 4 M3 - http://www.imedpub.com/articles/comparative-tickborne-encephalitisvirus-surveillance-in-belgium-20092015experiences-with-diagnostic-tests-sentinelspecies-and-surv.php?aid=19858 ER - TY - RPRT T1 - European Centre for Disease Prevention and Control. EU Laboratory Capability Monitoring System (EULabCap) – Report on 2015 survey of EU/EEA country capabilities and capacities. Y1 - 2017 A1 - Katrin Leitmeye A1 - Joana Revez A1 - Marc Struelens A1 - Steven Van Gucht A1 - Katelijne Dierick KW - 2015 KW - EU Laboratory Capability Monitoring System KW - report KW - survey PB - European Centre for Disease Prevention and Control CY - Stockholm, Sweden SN - 978-92-9498-058-8 M3 - 10.2900/27007 ER - TY - RPRT T1 - European OneHealth/EcoHealth workshop report - Brussels, 6-7 October 2016. Y1 - 2017 A1 - Keune, Hans A1 - Flandroy, Lucette A1 - Thys, Séverine A1 - Nick De Regge A1 - Marcella Mori A1 - Thierry van den Berg A1 - Antoine-Moussiaux, Nicolas A1 - Vanhove, Maarten P M A1 - Javiera Rebolledo A1 - Steven Van Gucht A1 - Deblauwe, Isra A1 - Biot, Pierre A1 - Hiemstra, Wim A1 - Häsler, Barbara A1 - Binot, Aurélie KW - 2016 KW - European One Health / Eco Health Workshop PB - Biodiversity & Health Community of Practice and the Belgian Biodiversity Platform. CY - Brussels, Belgium ER - TY - RPRT T1 - Flu impact: European & Belgian insights. Meeting report: Grasp Flu prevention. Get ready to act through science and policy for flu prevention. Y1 - 2017 A1 - Steven Van Gucht (contributing scientist) KW - Flu KW - POLICY KW - prevention KW - Science PB - Ms. Françoise Grossetête, Member of the European Parliament (MEP) CY - Brussels, Belgium ER - TY - JOUR T1 - Hepatitis E virus serology and PCR: does the methodology matter? JF - Arch Virol Y1 - 2017 A1 - Cattoir, Lien A1 - Van Hoecke, Frederik A1 - Van Maerken, Tom A1 - Nys, Eveline A1 - Ryckaert, Inge A1 - De Boulle, Matthias A1 - Geerts, Anja A1 - Verhelst, Xavier A1 - Colle, Isabelle A1 - Veronik Hutse A1 - Vanessa Suin A1 - Wautier, Magali A1 - Steven Van Gucht A1 - Van Vlierberghe, Hans A1 - Padalko, Elizaveta KW - Antibodies, Viral KW - Hepatitis E KW - Hepatitis E virus KW - Humans KW - Immunoglobulin G KW - Immunoglobulin M KW - polymerase chain reaction KW - Sensitivity and Specificity KW - Serologic Tests AB -

Hepatitis E virus (HEV) genotype 3 is an emerging pathogen in the developed world. As the clinical manifestations and routine laboratory parameters are often nonspecific, accurate diagnostic tests are crucial. In the current study, the performance of six serological assays and three PCR assays for the detection of HEV was evaluated. In the setting of the Ghent University Hospital, patients with clinically suspected HEV infection were tested for the presence of HEV IgM and IgG as well as HEV RNA. Serology was performed using six commercial HEV ELISA assays: Biorex, Wantai and Mikrogen IgM and IgG. HEV RNA was detected using one commercial assay (Altona RealStar®), and two optimized in-house real-time RT-PCR assays (according to Jothikumar et al., 2006 and Gyarmati et al., 2007). In addition, all three PCR assays were performed on 16 external quality control (EQC) samples. In a period of 39 months (January 2011-April 2014), 70 patients were enrolled. Using different ELISA assays, the prevalence of antibodies varied from 5.7% to 14.3% for HEV IgM and from 15.7% to 20.0% for IgG. All but two of the results of the PCR assays performed on clinical samples agreed. However, 10 out of 16 EQC samples results showed major discrepancies. We observed important differences in the performance of various serological and PCR assays. For this reason, results of both serological and molecular tests for HEV should be interpreted with caution.

VL - 162 CP - 9 U1 - https://www.ncbi.nlm.nih.gov/pubmed/28523520?dopt=Abstract M3 - 10.1007/s00705-017-3395-0 ER - TY - JOUR T1 - The HUMTICK study: protocol for a prospective cohort study on post-treatment Lyme disease syndrome and the disease and cost burden of Lyme borreliosis in Belgium. JF - Arch Public Health Y1 - 2017 A1 - Geebelen, Laurence A1 - Tinne Lernout A1 - Kabamba-Mukadi, Benoît A1 - Saegeman, Veroniek A1 - Sprong, Hein A1 - Steven Van Gucht A1 - Beutels, Philippe A1 - Speybroeck, Niko A1 - Katrien Tersago AB -

BACKGROUND: In Belgium, different routine surveillance systems are in place to follow-up Lyme borreliosis trends. However, accurate data on the disease and monetary burden for the different clinical manifestations are lacking. Despite recommended antibiotic treatment, a proportion of Lyme patients report persisting aspecific symptoms for six months or more (e.g. fatigue, widespread musculoskeletal pain, cognitive difficulties), a syndrome now named "post-treatment Lyme disease syndrome" (PTLDS). Controversy exists on the cause, incidence and severity of PTLDS. This study aims to estimate the incidence of PTLDS in patients with Lyme borreliosis and to quantify the disease burden and economic costs associated with the different clinical manifestations of Lyme borreliosis in Belgium.

METHODS: The project is a prospective cohort study in which about 600 patients with an erythema migrans and 100 patients with disseminated Lyme borreliosis will be followed up. Questionnaires, including the SF-36 vitality and pain subscale, the Cognitive Failure Questionnaire and the EQ-5D-5L, will be used to collect information on acute and persisting symptoms and the impact on quality of life. Symptom frequency and severity will be compared with self-reported pre-Lyme health status, a control group and existing Belgian population norms. Additionally, information on the associated costs and possible risk factors for the development of PTLDS will be collected.

DISCUSSION: A study of the health burden will allow evaluation of the relative importance of Lyme borreliosis in Belgium and information on the economic cost will help to formulate cost-effective measures. There are only few prospective studies conducted estimating the incidence of PTLDS and even though discussion exists about the prevalence of subjective symptoms in the general population, a control group of non-Lyme borreliosis participants has often not been included.

VL - 75 U1 - https://www.ncbi.nlm.nih.gov/pubmed/28794875?dopt=Abstract M3 - 10.1186/s13690-017-0202-z ER - TY - JOUR T1 - Impact of caspase-1/11, -3, -7, or IL-1/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease. JF - Cell Death Discov Y1 - 2017 A1 - E Kip A1 - Nazé, F A1 - Suin, V A1 - Vanden Berghe, T A1 - Aurélie Francart A1 - Lamoral, S A1 - Vandenabeele, P A1 - Beyaert, R A1 - Steven Van Gucht A1 - Kalai, M AB -

Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals. Infection of Mf4/4 macrophages with both strains led to caspase-1 activation and IL-1 and IL-18 production, as well as activation of caspases-3, -7, -8, and -9. Moreover, absence of caspase-3, but not of caspase-1 and -11 or -7, partially inhibited virus-induced cell death of bone marrow-derived macrophages. Intranasal inoculation with CVS-11 of mice deficient for either caspase-1 and -11 or -7 or both IL-1 and IL-18 led to general brain infection and lethal disease similar to wild-type mice. Deficiency of caspase-3, on the other hand, significantly delayed the onset of disease, but did not prevent final lethal outcome. Interestingly, deficiency of caspase-1/11, the key executioner of pyroptosis, aggravated disease severity caused by ERA virus, whereas wild-type mice or mice deficient for either caspase-3, -7, or both IL-1 and IL-18 presented the typical mild symptoms associated with ERA virus. In conclusion, rabies virus infection of macrophages induces caspase-1- and caspase-3-dependent cell death. caspase-1/11 and caspase-3 differently affect disease development in response to infection with the attenuated ERA strain or the virulent CVS-11 strain, respectively. Inflammatory caspases seem to control attenuated rabies virus infection, while caspase-3 aggravates virulent rabies virus infection.

VL - 3 U1 - https://www.ncbi.nlm.nih.gov/pubmed/28280602?dopt=Abstract M3 - 10.1038/cddiscovery.2017.12 ER - TY - RPRT T1 - Jaarrapport 2016: Hepatitis C virus Y1 - 2017 A1 - Gaetan Muyldermans A1 - Steven Van Gucht A1 - L Van Baelen KW - Hepatitis C AB -

Het aantal serologische aanvragen voor hepatits C virus (HCV) diagnose stabiliseert zich sinds 2012 in België: 744.409 aanvragen in 2016 waarvan 42,0% voor patiënten waarvoor gedurende de vorige 9 jaar geen HCV serologische analyse uitgevoerd werd.

Het aantal nieuwe HCV gediagnosticeerde gevallen blijft sinds 2008 stabiel.

Op basis van het aantal gerapporteerde gevallen in het netwerk van peillaboratoria en het aantal uitgevoerde genotyperingen wordt de jaarlijkse HCV incidentie op 1500 geschat (13.6/100.000 inwoners).

De verdeling volgens de gewesten zijn als volgt: 41% in Vlaanderen, 35% in Wallonië en 23% in Brussel.

Ondanks de verhoogde screening bij vrouwen tussen 20-39 jaar is er een hogere prevalentie van HCV geïnfecteerden bij mannen met mediaan leeftijd 45-49 jaar. De mediaan leeftijd verhoogt met de tijd

Een seroprevalentiestudie en een register van hepatitis C (en B) infecties blijft evenwel aangewezen om het percentage behandelde patiënten en de impact van behandeling te kunnen opvolgen en om te voldoen aan de internationale vraag tot datacollectie.

Bij een groep van 3.352 patiënten die minstens één keer in hun leven hebben geïnjecteerd en die tussen 2011 en 2014 een beroep hebben gedaan op de drughulpverlening, werd tussen 2008 en 2015 85% gescreend op HCV. Bij 504 (15%) werd een genotypering uitgevoerd.

PB - WIV-ISP CY - Brussels, Belgium UR - https://nrchm.wiv-isp.be/nl/ref_centra_labo/hepatitis/Rapporten/Forms/AllItems.aspx ER - TY - JOUR T1 - The need for European OneHealth/EcoHealth networks. JF - Arch Public Health Y1 - 2017 A1 - Keune, Hans A1 - Flandroy, Lucette A1 - Thys, Séverine A1 - Nick De Regge A1 - Marcella Mori A1 - Antoine-Moussiaux, Nicolas A1 - Vanhove, Maarten P M A1 - Javiera Rebolledo A1 - Steven Van Gucht A1 - Deblauwe, Isra A1 - Hiemstra, Wim A1 - Häsler, Barbara A1 - Binot, Aurélie A1 - Savic, Sara A1 - Ruegg, Simon R A1 - De Vries, Sjerp A1 - Garnier, Julie A1 - Thierry van den Berg KW - Community of Practice KW - Crosssectorial KW - EcoHealth KW - Europe KW - Interdisciplinarity KW - One Health KW - Transdisciplinarity AB -

Elaborating from the European One Health/Ecohealth (OH/EH) workshop that took place in fall 2016 and aimed to bring together different communities and explore collaborative potential, the creation of European networks focusing on the development of important OH/EH perspectives was a direct output from discussions at the end of some sessions, in particular: - A network on transdisciplinary One Health education. - A network integrating inputs from social sciences in One Health/EcoHealth actions and networks. - A network aiming at translating research findings on the Environment-Microbiome-Health axis into policy making, with a view to make healthy ecosystems a cost-effective disease prevention healthcare strategy. It was also suggested that a European Community of Practice could be initiated in order to support these several concrete networking initiatives, and to help to promote the building of other emerging initiatives.

VL - 75 M3 - 10.1186/s13690-017-0232-6 ER - TY - RPRT T1 - Seasonal influenza surveillance (Belgique/België/Belgium) : Résumé saison 2016-2017 - Overzicht seizoen 2016-2017 - Overview season 2016-2017 Y1 - 2017 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Steven Van Gucht A1 - Nathalie Bossuyt A1 - Natalia Bustos Sierra A1 - Sophie Quoilin A1 - Viviane Van Casteren A1 - Y. Pirson KW - 2016 KW - 2017 KW - Belgium KW - overview season KW - Seasonal influenza surveillance PB - WIV-ISP CY - Brussels, Belgium ER - TY - JOUR T1 - Survey on the Use of Whole-Genome Sequencing for Infectious Diseases Surveillance: Rapid Expansion of European National Capacities, 2015-2016. JF - Front Public Health Y1 - 2017 A1 - Joana Revez A1 - Laura Espinosa A1 - Barbara Albiger A1 - Katrin Claire Leitmeyer A1 - Marc Jean Struelens KW - infectious disease KW - sequencing KW - Surveillance KW - whole genome AB -

Whole-genome sequencing (WGS) has become an essential tool for public health surveillance and molecular epidemiology of infectious diseases and antimicrobial drug resistance. It provides precise geographical delineation of spread and enables incidence monitoring of pathogens at genotype level. Coupled with epidemiological and environmental investigations, it delivers ultimate resolution for tracing sources of epidemic infections. To ascertain the level of implementation of WGS-based typing for national public health surveillance and investigation of prioritized diseases in the European Union (EU)/European Economic Area (EEA), two surveys were conducted in 2015 and 2016. The surveys were designed to determine the national public health reference laboratories' access to WGS and operational WGS-based typing capacity for national surveillance of selected foodborne pathogens, antimicrobial-resistant pathogens, and vaccine-preventable diseases identified as priorities for European genomic surveillance. Twenty-eight and twenty-nine out of the 30 EU/EEA countries participated in the survey in 2015 and 2016, respectively. National public health reference laboratories in 22 and 25 countries had access to WGS-based typing for public health applications in 2015 and 2016, respectively. Reported reasons for limited or no access were lack of funding, staff, and expertise. Illumina technology was the most frequently used followed by Ion Torrent technology. The access to bioinformatics expertise and competence for routine WGS data analysis was limited. By mid-2016, half of the EU/EEA countries were using WGS analysis either as first- or second-line typing method for surveillance of the pathogens and antibiotic resistance issues identified as EU priorities. The sampling frame as well as bioinformatics analysis varied by pathogen/resistance issue and country. Core genome multilocus allelic profiling, also called cgMLST, was the most frequently used annotation approach for typing bacterial genomes suggesting potential bioinformatics pipeline compatibility. Further capacity development for WGS-based typing is ongoing in many countries and upon consolidation and harmonization of methods should enable pan-EU data exchange for genomic surveillance in the medium-term subject to the development of suitable data management systems and appropriate agreements for data sharing.

VL - 5 M3 - 10.3389/fpubh.2017.00347 ER - TY - BOOK T1 - TBE in Belgium T2 - TBE in Belgium Y1 - 2017 A1 - Vanessa Suin A1 - Bernard Brochier A1 - Steven Van Gucht A1 - Sophie Roelandt KW - Belgium KW - TBE JF - TBE in Belgium PB - Global Health Press Pte Ltd CY - Singapore SN - 978-981-1903-3 M3 - https://id-ea.org/tbe ER - TY - JOUR T1 - Tick-Borne Encephalitis Virus in Ticks and Roe Deer, the Netherlands. JF - Emerg Infect Dis Y1 - 2017 A1 - Jahfari, Setareh A1 - de Vries, Ankje A1 - Rijks, Jolianne M A1 - Steven Van Gucht A1 - Vennema, Harry A1 - Sprong, Hein A1 - Rockx, Barry KW - Animals KW - Antibodies, Viral KW - Arachnid Vectors KW - Deer KW - Encephalitis Viruses, Tick-Borne KW - Encephalitis, Tick-Borne KW - Humans KW - Ixodes KW - Netherlands KW - Nymph KW - Phylogeny KW - RNA, Viral KW - Seroepidemiologic Studies AB -

We report the presence of tick-borne encephalitis virus (TBEV) in the Netherlands. Serologic screening of roe deer found TBEV-neutralizing antibodies with a seroprevalence of 2%, and TBEV RNA was detected in 2 ticks from the same location. Enhanced surveillance and awareness among medical professionals has led to the identification of autochthonous cases.

VL - 23 CP - 6 U1 - https://www.ncbi.nlm.nih.gov/pubmed/28518024?dopt=Abstract M3 - 10.3201/eid2306.161247 ER - TY - Generic T1 - Bats as reservoirs of emerging pathogens Y1 - 2016 A1 - Steven Van Gucht KW - AS KW - bat KW - bats KW - disease KW - Diseases KW - Infectious KW - Infectious diseases KW - pathogen JF - SSID Scientific Seminar Infectious Diseases PB - NA CY - NA CP - WIV-ISP U1 - 37207 U2 - 19/05/2016 ER - TY - JOUR T1 - De rol van koude bij verkoudheid JF - Tijdscrift voor Geneeskunde Y1 - 2016 A1 - Vankrunkelsven,P. A1 - Finoulst,M. A1 - Steven Van Gucht KW - de AB - . VL - 72 CP - 1 U1 - 39313 ER - TY - Generic T1 - Differences among mumps virus surface proteins between genotype G and other genotypes and their potential effect on mumps virus immunity and pathogenesis. Y1 - 2016 A1 - T. Vermeire A1 - Gouma,S. A1 - Steven Van Gucht A1 - Martens,L. A1 - Veronik Hutse A1 - Cremer,J. A1 - G. Leroux-Roels A1 - Koopmans,M. A1 - Van Binnendijk,R. A1 - Vandermarliere,E. KW - Clinical KW - differences KW - effect KW - European KW - Genotype KW - meeting KW - Mumps KW - ON KW - protein KW - Proteins KW - Societies KW - Society KW - virology KW - VIRUS JF - 19th Annual Meeting of the European Society for Clinical Virology (ESCV) PB - NA CY - NA CP - ESCV U1 - 37110 U2 - 09/2016 ER - TY - JOUR T1 - First TBEV serological screening in Flemish wild boar. JF - Infect Ecol Epidemiol Y1 - 2016 A1 - Sophie Roelandt A1 - Vanessa Suin A1 - Yves Van der Stede A1 - Lamoral, Sophie A1 - Sylvie Marché A1 - Marylène Tignon A1 - Saiz, Juan Carlos A1 - Escribano-Romero, Estela A1 - Casaer, Jim A1 - Bernard Brochier A1 - Steven Van Gucht A1 - S. Roels A1 - Vervaeke, Muriel AB -

In the frame of a Flemish wildlife surveillance in 2013, a serological screening was performed on sera from wild boar (Sus scrofa; n=238) in order to detect tick-borne encephalitis virus (TBEV)-specific antibodies. Neutralising antibodies were titrated with a seroneutralisation test (SNT), using two cut-off titres (1/10-1/15). Seven wild boars were found TBEV-seropositive and showed moderate (>1/15) to high (>1/125) SNT-titres; three individuals had borderline results (1/10-1/15). This study demonstrated the presence of TBEV-specific antibodies in wild boar and highlighted potential TBEV-foci in Flanders. Additional surveillance including direct virus testing is now recommended.

VL - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27087689?dopt=Abstract M3 - 10.3402/iee.v6.31099 ER - TY - RPRT T1 - Infectieziekten bij kinderen, die voorkomen kunnen worden door vaccinatie. Jaarrapport 2015 Y1 - 2016 A1 - Mendes da Costa,E. A1 - Tine Grammens A1 - Amber Litzroth A1 - Virginie Maes A1 - Gaetan Muyldermans A1 - Sophie Quoilin A1 - Martine Sabbe A1 - Sophie Bertrand A1 - Marie-Luce Delforge A1 - I Desombere A1 - Veronik Hutse A1 - Helena Martini A1 - Martiny, Delphine A1 - Wesley Mattheus A1 - S Moreels A1 - Denis Piérard A1 - Carole Schirvel A1 - Béatrice Swennen A1 - Heidi Theeten A1 - Geert Top A1 - Jean-Marie Tremerie A1 - Viviane Van Casteren A1 - Steven Van Gucht A1 - Van Ranst, M A1 - Jan Verhaegen KW - 2015 KW - Infectieziekten KW - kinderen KW - vaccinatie PB - WIV-ISP CY - Brussel, België SN - 2507-0274 ER - TY - RPRT T1 - Maladies infectieuses pédiatriques à prévention vaccinale. Rapport annuel 2015 Y1 - 2016 A1 - Mendes da Costa,E. A1 - Tine Grammens A1 - Amber Litzroth A1 - Virginie Maes A1 - Gaetan Muyldermans A1 - Sophie Quoilin A1 - Martine Sabbe A1 - Sophie Bertrand A1 - Marie-Luce Delforge A1 - I Desombere A1 - Veronik Hutse A1 - Helena Martini A1 - Martiny, Delphine A1 - Wesley Mattheus A1 - S Moreels A1 - Denis Piérard A1 - Carole Schirvel A1 - Béatrice Swennen A1 - Heidi Theeten A1 - Geert Top A1 - Jean-Marie Tremerie A1 - Viviane Van Casteren A1 - Steven Van Gucht A1 - Van Ranst, M A1 - Jan Verhaegen KW - 2015 KW - Maladies infectieuses pédiatriques KW - Vaccination PB - WIV-ISP CY - Bruxelles, Belgique SN - 2507-0266 ER - TY - JOUR T1 - Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves Protection of Mice from Lethal Rabies Infection. JF - PLoS Negl Trop Dis Y1 - 2016 A1 - Terryn, Sanne A1 - Francart, Aurélie A1 - Rommelaere, Heidi A1 - Stortelers, Catelijne A1 - Steven Van Gucht KW - Animals KW - Antibodies, Neutralizing KW - Antibodies, Viral KW - Cell Line KW - Disease Models, Animal KW - Female KW - Half-Life KW - Humans KW - mice KW - Neutralization Tests KW - Post-Exposure Prophylaxis KW - Rabies KW - Rabies Vaccines KW - Rabies virus KW - Single-Domain Antibodies KW - Vaccination KW - Viral Load AB -

Post-exposure prophylaxis (PEP) against rabies infection consists of a combination of passive immunisation with plasma-derived human or equine immune globulins and active immunisation with vaccine delivered shortly after exposure. Since anti-rabies immune globulins are expensive and scarce, there is a need for cheaper alternatives that can be produced more consistently. Previously, we generated potent virus-neutralising VHH, also called Nanobodies, against the rabies glycoprotein that are effectively preventing lethal disease in an in vivo mouse model. The VHH domain is the smallest antigen-binding functional fragment of camelid heavy chain-only antibodies that can be manufactured in microbial expression systems. In the current study we evaluated the efficacy of half-life extended anti-rabies VHH in combination with vaccine for PEP in an intranasal rabies infection model in mice. The PEP combination therapy of systemic anti-rabies VHH and intramuscular vaccine significantly delayed the onset of disease compared to treatment with anti-rabies VHH alone, prolonged median survival time (35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue mice from lethal disease. As reported also for immune globulins, some interference of anti-rabies VHH with the antigenicity of the vaccine was observed, but this did not impede the synergistic effect. Post exposure treatment with vaccine and human anti-rabies immune globulins was unable to protect mice from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect mice after rabies virus exposure, which further validates the possible use of anti-rabies VHH for rabies PEP.

VL - 10 CP - 8 U1 - https://www.ncbi.nlm.nih.gov/pubmed/27483431?dopt=Abstract M3 - 10.1371/journal.pntd.0004902 ER - TY - Generic T1 - Presentation of the National Reference Centre for Human Papillomavirus in Belgium Y1 - 2016 A1 - Steven Van Gucht KW - Belgium KW - HPV KW - Human KW - national KW - PRESENTATION KW - symposium JF - HPV Symposium and AML-Riatol chair inauguration PB - NA CY - NA CP - UA U1 - 37208 U2 - 28/05/2016 ER - TY - Generic T1 - Rabiës bij mens en dier: cave canem Y1 - 2016 A1 - Steven Van Gucht KW - de KW - EN KW - MEN KW - symposium JF - Voordracht voor het Symposium van de Wetenschappelijke Commissie van de Koninklijke Kynologische Unie Sint-Hubertus PB - NA CY - NA CP - WCKKUSH U1 - 37209 U2 - 20/05/2016 ER - TY - Generic T1 - Rabiës in bats and wolves Y1 - 2016 A1 - Steven Van Gucht ED - Institute of Tropical Medicine KW - bat KW - bats KW - Belgian KW - Crossing KW - disease KW - health KW - Societies KW - Society KW - symposium JF - Joint Symposium: Belgian Wildlife Disease Society & Dutch Society for Wildlife Health. Wildlife crossing borders. CP - Institute of Tropical Medicine U1 - 37210 U2 - 7/10/2016 ER - TY - Generic T1 - The Rabies ONEDAY Study: Results of an alternative single visit intradermal pre-exposure vaccination schedule in an open-label randomized clinical trial on rabies boostability Y1 - 2016 A1 - Soentjens,P. A1 - Andries,P. A1 - DeKoninck,K. A1 - C. Maussen A1 - Bernard Brochier A1 - Steven Van Gucht A1 - P. Van Damme A1 - E. Bottieau KW - alternative KW - an KW - Clinical KW - clinical trial KW - conference KW - European KW - intradermal KW - Medicine KW - ON KW - Rabies KW - result KW - results KW - study KW - Travel KW - Vaccination JF - Northern European Conference on Travel Medicine CP - . U1 - 37204 U2 - 06/2016 ER - TY - RPRT T1 - Virological surveillance of influenza in Belgium season 2015-2016 Y1 - 2016 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Hombrouck,A. A1 - Steven Van Gucht A1 - Weyckmans,J. A1 - Ullens,L. A1 - Abady,M. A1 - Fdillate,I. A1 - Nathalie Bossuyt A1 - Viviane Van Casteren A1 - Y. Pirson KW - Belgium KW - INFLUENZA KW - Surveillance PB - Johan Peeters/WIV-ISP CY - Bruxelles SN - D/2016/2505/40 U1 - 37183 ER - TY - RPRT T1 - Zoönosen en vectoroverdraagbare ziekten. Samenvattend jaaroverzicht 2015 Y1 - 2016 A1 - Javiera Rebolledo A1 - Tinne Lernout A1 - Amber Litzroth A1 - Dominique Van Beckhoven A1 - Bernard Brochier A1 - Delaere, B A1 - David Fretin A1 - Hing,M. A1 - Jacobs,J.A. A1 - B Kabamba Mukadi A1 - Marcella Mori A1 - Patteet,S. A1 - Saegeman,V. A1 - Vanessa Suin A1 - Truyens,C. A1 - Vanrompay, D A1 - Van Esbroeck, Marjan A1 - Steven Van Gucht A1 - P Wattiau KW - 2015 KW - Surveillance KW - vectoroverdraagbare ziekten KW - zoonosen PB - WIV-ISP CY - Brussel, België ER - TY - RPRT T1 - Zoonoses et maladies à transmission vectorielle. Surveillance épidémiologique en Belgique - Synthèse annuelle 2015 Y1 - 2016 A1 - Javiera Rebolledo A1 - Tinne Lernout A1 - Amber Litzroth A1 - Dominique Van Beckhoven A1 - Bernard Brochier A1 - Delaere,B. A1 - David Fretin A1 - Hing,M. A1 - B Kabamba Mukadi A1 - Marcella Mori A1 - Patteet,S. A1 - Saegeman,V. A1 - Vanessa Suin A1 - Truyens,C. A1 - Vanrompay, D A1 - Van Esbroeck, Marjan A1 - Steven Van Gucht A1 - P Wattiau KW - 2015 KW - Belgique KW - maladies à transmission vectorielle KW - Surveillance KW - Zoonoses PB - WIV-ISP CY - Bruxelles, Belgique ER - TY - Generic T1 - Arbo-VIRTUESS: Evaluation of the use of non-invasive tests for early screening and survey of arboviruses Y1 - 2015 A1 - Sylvia Broeders A1 - Sigrid C.J. De Keersmaecker A1 - Vanessa Suin A1 - Steven Van Gucht A1 - Pol,M. A1 - Gourinat,A.C. A1 - Biron,A. A1 - Dupont-Rouzeyrol,M. A1 - Vanhomwegen,J. A1 - Manuguerra,J.C. A1 - Berlioz-Arthaud,A. A1 - Enfissi,A. A1 - Matheus,S A1 - Rousset,D. A1 - Nancy Roosens KW - Arbo-virtuess KW - EVALUATION KW - International KW - non-invasive KW - SCREENING KW - survey KW - symposium KW - Test KW - tests KW - use JF - International Scientific Symposium PB - NA CY - NA CP - Institut Pasteur International Network U1 - 5224 U2 - 14-16/10/2015 ER - TY - Generic T1 - Berichten in Het Nieuwsblad in verband met het de uitbraak van MERS CoV in Zuid-Korea. Y1 - 2015 A1 - Steven Van Gucht KW - de U1 - 37061 ER - TY - BOOK T1 - Chapter Twenty Seven - Generation of immune globulin single variable domains by display technologies T2 - Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention Y1 - 2015 A1 - H.J. de Haard A1 - A. Hultberg A1 - Verrips,T. A1 - Vanlandschoot,P. A1 - Saunders,M. A1 - Stortelers,C. A1 - Steven Van Gucht ED - Rupprecht,C. ED - Nagarajan,T. KW - antibodies KW - Antibody KW - Diagnosis KW - Epitopes KW - Genetic KW - Glycoprotein KW - Heavy-Chain Antibody Fragments KW - Immune Globulin Single Variable Domains KW - Laboratories KW - llama KW - nanobody KW - ON KW - Phage Display KW - prevention KW - Rabies KW - Rabies virus KW - Research KW - Selection KW - strain KW - Target KW - Technique KW - technology KW - Variable domain on Heavy-Chain (VHH) KW - VHH KW - VIRUS AB - Rabies virus-specific, cross-neutralizing, llama-derived heavy-chain antibody fragments (VHH) can be generated rapidly from immune llamas using phage display technology. The selection procedure can be tailor-made depending on the epitope to be targeted, whereas the single-chain nature of the VHH allows for facile genetic fusion of different VHH to create multivalent VHH. These VHH can target one or several different epitopes, thereby increasing the chance of neutralization of different strains of virus JF - Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention PB - Academic Press CY - Amsterdam VL - 1 SN - 978-0-12-800014-4 U1 - 37450 M3 - http://dx.doi.org/10.1016/B978-0-12-800014-4.00027-5 ER - TY - Generic T1 - Computational analysis of mumps surface proteins reveals their interaction mechanism. Y1 - 2015 A1 - T. Vermeire A1 - Vermaere,S. A1 - Steven Van Gucht A1 - Veronik Hutse A1 - Martens,L. A1 - Vandermarliere,E. KW - analysi KW - analysis KW - Belgian KW - interaction KW - mechanism KW - meeting KW - Mumps KW - protein KW - Proteins KW - Societies KW - Society KW - virology JF - Third meeting of the Belgian Society for Virology CP - BELVIR U1 - 37055 U2 - 18/12/2015 ER - TY - RPRT T1 - Evaluatie van een ontwerp van ministerieel besluit over de bestrijding van hondsdolheid en over de noodzaak van verplichte vaccinatie tegen hondsdolheid in België. Advies 17-2015 (dossier 2015-09). Y1 - 2015 A1 - Steven Van Gucht KW - België KW - de KW - EN KW - vaccinatie PB - FAVV CY - Brussels U1 - 37046 ER - TY - JOUR T1 - Impact of a trace element supplementation programme on health and performance of cross-breed (Bos indicus x Bos taurus) dairy cattle under tropical farming conditions: a double-blinded randomized field trial36964 JF - J.Anim Physiol Anim Nutr.(Berl) Y1 - 2015 A1 - Dermauw,V. A1 - Dierenfeld,E. A1 - Du Laing,G. A1 - Buyse,J. A1 - Bernard Brochier A1 - Steven Van Gucht A1 - Luc Duchateau A1 - Janssens,G.P. KW - 0 KW - a KW - Animal KW - antibodies KW - Antibody KW - Antioxidant KW - article KW - AS KW - Belgium KW - Benefit KW - blood KW - Cattle KW - composition KW - conditions KW - d KW - Deficiency KW - effect KW - electronic KW - farms KW - Field KW - Group KW - health KW - i KW - immune response KW - Impact KW - Increase KW - intervention KW - IS KW - journal KW - Laboratories KW - milk KW - n KW - NUTRITION KW - observed KW - ON KW - parameters KW - performance KW - plasma KW - present KW - programme KW - protein KW - Proteins KW - Rabies KW - response KW - Score KW - serum KW - status KW - study KW - Supplementation KW - Thiobarbituric Acid Reactive Substances KW - time KW - treatment KW - Universities KW - university KW - urban KW - Vaccination KW - Yield AB - Small-scale urban dairy farms (n = 16) in and around Jimma, Ethiopia with cross-bred (Bos indicus x Bos taurus) cows were enrolled in a double-blinded intervention study to investigate the effect of a trace element supplementation programme on trace element status and milk concentrations as well as performance [body condition score (BCS), milk yield, leptin], milk composition, antioxidant status (ferric-reducing ability of plasma (FRAP), thiobarbituric acid-reactive substances (TBARS)], blood biochemistry, serum proteins and immune response (antibody titre upon rabies vaccination). The farms were allocated to a (1) placebo or (2) Cu, Zn, Se, Co and I supplementation treatment for 150 d. On days 0 and 120, four lactating cows per farm were sampled for milk and plasma, and on day 150 for serum, following primo-vaccination. Cu deficiency was present in 17% and marginal Se deficiency in 30% of initially sampled cows, while no Zn shortage was detected. Over 120 days, trace element supplementation caused a bigger increase in plasma Se and Cu concentrations, but also a larger decrease of plasma Fe concentrations. A larger increase in milk Se concentrations was observed in the supplemented group, whereas none of the other elements were affected. BCS decreased more over time in the supplemented group. None of the other parameters of performance and antioxidant status nor milk composition or blood biochemistry was affected by treatment. Antibody response to rabies vaccination did not differ between groups, whereas alpha1-globulins tended to be lower and beta-globulins tended to be higher in the supplemented group. In conclusion, despite improved Cu and Se status and Se concentrations in milk, cows on tropical urban dairy farms did not seem to benefit from trace element supplementation, with respect to the parameters investigated VL - 99 CP - 3 U1 - 39159 M3 - http://dx.doi.org/10.1111/jpn.12209 ER - TY - Generic T1 - Impact of MALT1, an upstream mediator of NF-kB and immune cell activation, on rabies virus disease. Y1 - 2015 A1 - E Kip A1 - Vanessa Suin A1 - J Staal A1 - Michael Kalai A1 - Beyaert,R. A1 - Steven Van Gucht KW - Activation KW - an KW - Cell KW - conference KW - disease KW - Impact KW - ON KW - Rabies KW - Rabies virus KW - VIRUS JF - RITA conference: Rabies in the Americas CP - XX U1 - 37052 U2 - 4/10/2015;8/10/2015 ER - TY - RPRT T1 - Infectieziekten bij kinderen die voorkomen kunnen worden door vaccinatie. Jaarrapport 2013 Y1 - 2015 A1 - Tine Grammens A1 - Toon Braeye A1 - Corinne Bleyenheuft A1 - Sophie Quoilin A1 - Sophie Bertrand A1 - Dediste,A. A1 - Detemmerman,L. A1 - K. De Schrijver A1 - Goubert,P. A1 - Heymans,C. A1 - K Huygen A1 - Veronik Hutse A1 - Stéphanie Jacquinet A1 - Mak,R. A1 - Wesley Mattheus A1 - S Moreels A1 - Gaetan Muyldermans A1 - Denis Piérard A1 - Carole Schirvel A1 - Béatrice Swennen A1 - Heidi Theeten A1 - Geert Top A1 - Jean-Marie Tremerie A1 - Viviane Van Casteren A1 - Steven Van Gucht A1 - Marc Van Ranst A1 - Jan Verhaegen A1 - Waegenaere,J. A1 - Zinnen,V. KW - Infectieziekten KW - kinderen PB - WIV-ISP CY - Brussel SN - D/2015/2505/05 U1 - 39200 ER - TY - RPRT T1 - Influenza virological surveillance in Belgium season 2014-2015. Y1 - 2015 A1 - Hombrouck,A. A1 - Nathalie Bossuyt A1 - Viviane Van Casteren A1 - Steven Van Gucht A1 - Isabelle Thomas KW - Belgium KW - INFLUENZA KW - Surveillance PB - WHO CY - . U1 - 39174 ER - TY - Generic T1 - Initial Neutralising Antibody Response on Day 14 after a ONE DAY Intradermal Rabies Pre-exposure Vaccination Schedule: Preliminary Data of 144 subjects. Y1 - 2015 A1 - Soentjens,P. A1 - Andries,P. A1 - Damanet,B. A1 - DeKoninck,K. A1 - C. Maussen A1 - Steven Van Gucht A1 - Van Gompel,A. A1 - E. Bottieau KW - a KW - antibodies KW - Antibody KW - conference KW - data KW - International KW - intradermal KW - Medicine KW - ON KW - Rabies KW - response KW - Societies KW - Society KW - Travel KW - Vaccination JF - Conference of the International Society for Travel Medicine (CISTM) PB - NA CY - NA CP - The International Society of Travel Medicine U1 - 37053 U2 - 05/2015 ER - TY - Generic T1 - Post-exposure treatment with anti-rabies VHH and to protect mice from rabies. Y1 - 2015 A1 - Sanne Terryn A1 - A. Francart A1 - H Rommelaere A1 - Stortelers,C. A1 - Steven Van Gucht KW - Belgian KW - meeting KW - mice KW - Rabies KW - Societies KW - Society KW - treatment KW - VHH KW - virology JF - Third meeting of the Belgian Society for Virology PB - NA CY - NA CP - The Belgian Society of Virology BELVIR U1 - 37054 U2 - 18/12/2015 ER - TY - Generic T1 - Rabies in humans and animals: cave canem. Y1 - 2015 A1 - Steven Van Gucht KW - Animal KW - Animals KW - Human KW - Humans KW - Rabies CY - Rega Instituut, KUL, Leuven U1 - 39221 ER - TY - RPRT T1 - Report on 2013 survey of EU/EEA country capabilities and capacities. Y1 - 2015 A1 - Steven Van Gucht A1 - Michael Kalai KW - Countries KW - ON KW - report KW - survey PB - ECDC CY - Stockholm U1 - 39164 ER - TY - RPRT T1 - Risk Assessment concerning a new lethal bornavirus on the 25th Y1 - 2015 A1 - Steven Van Gucht KW - a KW - assessment KW - Case KW - Laboratories KW - ON KW - risk KW - Risk Assessment PB - WIV-ISP CY - Brussels U1 - 38414 ER - TY - JOUR T1 - Scop3D: Three-dimensional visualization of sequence conservation36934 JF - Proteomics. Y1 - 2015 A1 - T. Vermeire A1 - Vermaere,S. A1 - Schepens,B. A1 - Saelens,X. A1 - Steven Van Gucht A1 - Martens,L. A1 - Vandermarliere,E. KW - a KW - Absolute KW - acid KW - an KW - analysi KW - analysis KW - article KW - AS KW - Back KW - Belgium KW - conservation KW - Development KW - electronic KW - function KW - Human KW - identify KW - im KW - INFORMATION KW - IS KW - IT KW - journal KW - mapping KW - medical KW - Multiple KW - Mumps KW - occurrence KW - ON KW - Output KW - protein KW - Proteins KW - relative KW - Research KW - Respiratory KW - SB - IM KW - Sequence Alignment KW - structure KW - Term KW - Universities KW - university KW - vaccine KW - variation KW - VIRUS AB -

The integration of a protein's structure with its known sequence variation provides insight on how that protein evolves, for instance in terms of (changing) function or immunogenicity. Yet, collating the corresponding sequence variants into a multiple sequence alignment, calculating each position's conservation, and mapping this information back onto a relevant structure is not straightforward. We therefore built the Sequence Conservation on Protein 3D structure (scop3D) tool to perform these tasks automatically. The output consists of two modified PDB files in which the B-values for each position are replaced by the percentage sequence conservation, or the information entropy for each position, respectively. Furthermore, text files with absolute and relative amino acid occurrences for each position are also provided, along with snapshots of the protein from six distinct directions in space. The visualization provided by scop3D can for instance be used as an aid in vaccine development or to identify antigenic hotspots, which we here demonstrate based on an analysis of the fusion proteins of human respiratory syncytial virus and mumps virus

VL - 15 CP - 8 U1 - 36934 M3 - http://dx.doi.org/10.1002/pmic.201400354 ER - TY - Generic T1 - Vaccine effectiveness estimates in preventing laboratory-confirmed mild and moderate-to-severe influenza in the Belgian population during the last 3 seasons. Y1 - 2015 A1 - Hombrouck,A. A1 - Viviane Van Casteren A1 - Steven Van Gucht A1 - Sophie Quoilin A1 - Françoise Wuillaume A1 - Isabelle Thomas A1 - Nathalie Bossuyt KW - Belgian KW - Belgian population KW - de KW - ET KW - INFLUENZA KW - Laboratory-confirmed KW - Maladies infectieuse KW - Mild KW - POPULATION KW - Seasons KW - Surveillance KW - vaccine JF - Séminaire Diagnostic et surveillance des maladies infectieuses. PB - NA CY - NA CP - WIV-ISP U1 - 38230 U2 - 21/05/2015 ER - TY - RPRT T1 - Virological Surveillance of Influenza in Belgium Season 2014-2015. Y1 - 2015 A1 - Isabelle Thomas A1 - Hombrouck,A. A1 - Steven Van Gucht A1 - Weyckmans,J. A1 - K. El Kadaani A1 - Abady,M. A1 - Fdillate,I. A1 - Nathalie Bossuyt A1 - Viviane Van Casteren A1 - Y. Pirson KW - Belgium KW - INFLUENZA KW - Surveillance PB - WIV-ISP CY - Brussels SN - D/2015/2505/60 U1 - 37049 ER - TY - Generic T1 - Wekelijkse nieuwsberichten en perscommuniqués in verband met de evolutie van de seizoensgriepepidemie in België. Y1 - 2015 A1 - Isabelle Thomas A1 - Hombrouck,A. A1 - Steven Van Gucht KW - België KW - de KW - EN U1 - 37058 ER - TY - RPRT T1 - Zoönosen en Vector-Overdraagbare Ziekten. Epidemiologische surveillance in België, 2013 en 2014 Y1 - 2015 A1 - Javiera Rebolledo A1 - Tinne Lernout A1 - Amber Litzroth A1 - Dominique Van Beckhoven A1 - Bernard Brochier A1 - Delaere,B. A1 - David Fretin A1 - Heuninckx,W. A1 - Hing,M. A1 - Jacobs, J. A1 - B Kabamba Mukadi A1 - Maes,P. A1 - Marcella Mori A1 - Patteet,S. A1 - Sophie Quoilin A1 - Saegeman,V. A1 - Vanessa Suin A1 - Truyens,C. A1 - Vanrompay, D A1 - M. Van Esbroeck A1 - Steven Van Gucht A1 - P Wattiau KW - 2013 KW - 2014 KW - jaarrapport KW - overdraagbare ziekten KW - Vector KW - zoonosen PB - WIV-ISP CY - Brussel, België ER - TY - RPRT T1 - Zoonoses et maladies à transmission vectorielle. Surveillance épidémiologique en Belgique, 2013 et 2014 Y1 - 2015 A1 - Javiera Rebolledo A1 - Tinne Lernout A1 - Amber Litzroth A1 - Dominique Van Beckhoven A1 - Bernard Brochier A1 - Delaere,B. A1 - David Fretin A1 - Heuninckx,W. A1 - Hing,M. A1 - Jacobs,J.A. A1 - B Kabamba Mukadi A1 - Maes,P. A1 - Marcella Mori A1 - Patteet,S. A1 - Sophie Quoilin A1 - Saegeman,V. A1 - Vanessa Suin A1 - Truyens,C. A1 - Vanrompay, D A1 - Van Esbroeck, Marjan A1 - Steven Van Gucht A1 - P Wattiau KW - 2013 KW - 2014 KW - maladies à transmission vectorielle KW - Surveillance KW - Zoonoses PB - WIV-ISP CY - Bruxelles, Belgique ER - TY - JOUR T1 - Autochthonous tick-borne encephalitis virus-seropositive cattle in Belgium: a risk-based targeted serological survey. JF - Vector Borne Zoonotic Dis Y1 - 2014 A1 - Sophie Roelandt A1 - Vanessa Suin A1 - Riocreux, Flavien A1 - Lamoral, Sophie A1 - Van der Heyden, Sara A1 - Yves Van der Stede A1 - Bénédicte Lambrecht A1 - Ann Brigitte Cay A1 - Bernard Brochier A1 - S. Roels A1 - Steven Van Gucht KW - Animals KW - Antibodies, Viral KW - Arachnid Vectors KW - Belgium KW - Cattle KW - Cattle Diseases KW - cross-sectional studies KW - Encephalitis Viruses, Tick-Borne KW - Encephalitis, Tick-Borne KW - Female KW - Humans KW - Ixodes KW - mice KW - risk KW - Sentinel Surveillance KW - Seroepidemiologic Studies KW - Zoonoses AB -

The risk of tick-borne encephalitis virus (TBEV) introduction into Belgium remains high, and the presence of infected wildlife in Belgium is suspected. Domestic animals can serve as excellent sentinels for TBEV surveillance to install an early warning surveillance component for this emerging zoonotic disease of public health importance. In a targeted, risk-based and cross-sectional sampling design, serological screening was performed on Belgian cattle (n=650), selected from the 2010 Belgian national cattle surveillance serum bank. All samples were subjected to a gold standard TBEV seroneutralization test (SNT), based on the rapid fluorescent focus inhibition test (RFFIT) protocol. Seventeen bovines were seropositive (titer >1/15) and six had borderline results (1/10 < titer < 1/15). The accuracy of the RFFIT-SNT was confirmed in a mouse inoculation test. The overall bovine TBEV seroprevalence in the targeted area was estimated between 2.61% and 4.29%. This confirms for the first time the presence of infected foci in Belgium. Further surveillance in cattle, other sentinels, ticks, and humans at risk is recommended to further determine the location and size of endemic foci and the risk for public health.

VL - 14 CP - 9 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25229702?dopt=Abstract M3 - 10.1089/vbz.2014.1576 ER - TY - BOOK T1 - Chapter Twenty Seven - Generation of immune globulin single variable domains by display technologies36931 T2 - Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention Y1 - 2014 A1 - H.J. de Haard A1 - A. Hultberg A1 - Verrips,T. A1 - Vanlandschoot,P. A1 - Saunders,M. A1 - Stortelers,C. A1 - Steven Van Gucht ED - Rupprecht,C. ED - Nagarajan,T. KW - antibodies KW - Antibody KW - Diagnosis KW - Epitopes KW - Genetic KW - Glycoprotein KW - Heavy-Chain Antibody Fragments KW - Immune Globulin Single Variable Domains KW - Laboratories KW - llama KW - nanobody KW - ON KW - Phage Display KW - prevention KW - Rabies KW - Rabies virus KW - Research KW - Selection KW - strain KW - Target KW - Technique KW - technology KW - Variable domain on Heavy-Chain (VHH) KW - VHH KW - VIRUS AB - Rabies virus-specific, cross-neutralizing, llama-derived heavy-chain antibody fragments (VHH) can be generated rapidly from immune llamas using phage display technology. The selection procedure can be tailor-made depending on the epitope to be targeted, whereas the single-chain nature of the VHH allows for facile genetic fusion of different VHH to create multivalent VHH. These VHH can target one or several different epitopes, thereby increasing the chance of neutralization of different strains of virus JF - Current Laboratory Techniques in Rabies Diagnosis, Research and Prevention PB - Academic Press CY - Amsterdam VL - 1 SN - 978-0-12-800014-4 U1 - 36931 M3 - http://dx.doi.org/10.1016/B978-0-12-800014-4.00027-5 ER - TY - JOUR T1 - Eradicating rabies at source. JF - Rev Sci Tech Y1 - 2014 A1 - Pastoret, P-P A1 - Steven Van Gucht A1 - B Brochier KW - Animal Husbandry KW - Animals KW - Animals, Wild KW - Chiroptera KW - Communicable Disease Control KW - Dog Diseases KW - Dogs KW - Humans KW - Ownership KW - Rabies KW - Rabies Vaccines KW - Rabies virus KW - Zoonoses AB -

Along with zoonotic influenza and antimicrobial resistance, rabies has been identified as a key One Health issue by the World Organisation for Animal Health (OIE), World Health Organization (WHO) and Food and Agriculture Organization of the United Nations (FAO). It provides an excellent example of a disease that has an impact on public, animal and environmental health, and therefore benefits from a One Health approach to management. Regrettably, this zoonotic disease is still neglected despite the fact that, annually, it kills as many as 70,000 people worldwide (chiefly children in Asia and Africa), millions of dogs suffer and die, and the disease threatens some populations of endangered wildlife. This is particularly unfortunate, given that effective means of prevention exist. As Her Royal Highness Princess Haya of Jordan pointed out in a video to mark World Rabies Day on 28 September 2013, rabies is a serious world public health problem that is all too often underestimated and even neglected. Yet we know it can be eliminated. By combatting rabies at its source in animals and vaccinating 70% of dogs, we can eradicate it.

VL - 33 CP - 2 U1 - https://www.ncbi.nlm.nih.gov/pubmed/25707180?dopt=Abstract M3 - http://boutique.oie.int/index.php?page=ficprod&id_prec=1308&id_produit=1432&fichrech=1&lang=en ER - TY - JOUR T1 - Impact of a trace element supplementation programme on health and performance of cross-breed (Bos indicus x Bos taurus) dairy cattle under tropical farming conditions: a double-blinded randomized field trial JF - J.Anim Physiol Anim Nutr.(Berl) Y1 - 2014 A1 - Dermauw,V. A1 - Dierenfeld,E. A1 - Du Laing,G. A1 - Buyse,J. A1 - Bernard Brochier A1 - Steven Van Gucht A1 - Luc Duchateau A1 - Janssens,G.P. KW - 0 KW - Animal KW - antibodies KW - Antibody KW - Antioxidant KW - article KW - AS KW - Belgium KW - Benefit KW - blood KW - Cattle KW - composition KW - conditions KW - d KW - Deficiency KW - effect KW - electronic KW - farms KW - Field KW - Group KW - health KW - i KW - immune response KW - Impact KW - Increase KW - intervention KW - IS KW - journal KW - Laboratories KW - milk KW - n KW - NUTRITION KW - observed KW - ON KW - parameters KW - performance KW - plasma KW - present KW - programme KW - protein KW - Proteins KW - Rabies KW - response KW - Score KW - serum KW - status KW - study KW - Supplementation KW - Thiobarbituric Acid Reactive Substances KW - time KW - treatment KW - Universities KW - university KW - urban KW - Vaccination KW - Yield AB - Small-scale urban dairy farms (n = 16) in and around Jimma, Ethiopia with cross-bred (Bos indicus x Bos taurus) cows were enrolled in a double-blinded intervention study to investigate the effect of a trace element supplementation programme on trace element status and milk concentrations as well as performance [body condition score (BCS), milk yield, leptin], milk composition, antioxidant status (ferric-reducing ability of plasma (FRAP), thiobarbituric acid-reactive substances (TBARS)], blood biochemistry, serum proteins and immune response (antibody titre upon rabies vaccination). The farms were allocated to a (1) placebo or (2) Cu, Zn, Se, Co and I supplementation treatment for 150 d. On days 0 and 120, four lactating cows per farm were sampled for milk and plasma, and on day 150 for serum, following primo-vaccination. Cu deficiency was present in 17% and marginal Se deficiency in 30% of initially sampled cows, while no Zn shortage was detected. Over 120 days, trace element supplementation caused a bigger increase in plasma Se and Cu concentrations, but also a larger decrease of plasma Fe concentrations. A larger increase in milk Se concentrations was observed in the supplemented group, whereas none of the other elements were affected. BCS decreased more over time in the supplemented group. None of the other parameters of performance and antioxidant status nor milk composition or blood biochemistry was affected by treatment. Antibody response to rabies vaccination did not differ between groups, whereas alpha1-globulins tended to be lower and beta-globulins tended to be higher in the supplemented group. In conclusion, despite improved Cu and Se status and Se concentrations in milk, cows on tropical urban dairy farms did not seem to benefit from trace element supplementation, with respect to the parameters investigated VL - 99 CP - 3 U1 - 37412 M3 - http://dx.doi.org/10.1111/jpn.12209 ER - TY - Generic T1 - NeXSplorer.iph: Development of next generation sequencing data analysis tools in support of a fast response for public health and food chain safety Y1 - 2014 A1 - Sigrid C.J. De Keersmaecker A1 - Sophie Bertrand A1 - Wesley Mattheus A1 - Philippe Herman A1 - Katelijne Dierick A1 - N Botteldoorn A1 - Sarah Denayer A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Deforce,D. A1 - Marchal,K. A1 - Nancy Roosens KW - a KW - analysi KW - analysis KW - application KW - applications KW - bioinformatics KW - data KW - Development KW - food KW - Food Chain KW - GMO KW - health KW - NGS KW - public KW - public health KW - Public-health JF - Applications of Next Generation Sequencing for public health PB - NA CY - NA CP - =WIV-ISP U1 - 38637 U2 - 10/10/2014 ER - TY - JOUR T1 - No evidence of coronavirus infection by reverse transcriptase-PCR in bats in Belgium. JF - J Wildl Dis Y1 - 2014 A1 - Steven Van Gucht A1 - Nazé, Florence A1 - El Kadaani, Karim A1 - Bauwens, Danielle A1 - Aurélie Francart A1 - Bernard Brochier A1 - Françoise Wuillaume A1 - Isabelle Thomas KW - Animals KW - Belgium KW - Chiroptera KW - Coronavirus KW - Coronavirus Infections KW - Feces KW - Reverse Transcriptase Polymerase Chain Reaction AB -

No coronavirus was detected by PCR in lung and intestine samples of 100 bats, mostly common pipistrelles (Pipistrellus pipistrellus), collected dead between 2008 and 2013 for rabies surveillance in Belgium. The negative results contrast with the high prevalence of coronaviruses detected in fecal pellets from live-captured bats in some European countries.

VL - 50 CP - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25098304?dopt=Abstract M3 - 10.7589/2013-10-269 ER - TY - Generic T1 - ORIENT-EXPRESS in times of crisis Y1 - 2014 A1 - Sylvia Broeders A1 - Sigrid C.J. De Keersmaecker A1 - Steven Van Gucht A1 - Isabelle Thomas A1 - Vanessa Suin A1 - Katelijne Dierick A1 - N Botteldoorn A1 - Steven Van Borm A1 - Nancy Roosens KW - application KW - applications KW - arbovirus KW - crisis KW - detection KW - gasto-intestinal parasites KW - GMO KW - health KW - Luminex KW - NGS KW - public KW - public health KW - Public-health KW - qPCR KW - time KW - Times JF - Applications of Next Generation Sequencing for public health PB - NA CY - NA CP - WIV-ISP U1 - 4873 U2 - 10/10/2014 ER - TY - JOUR T1 - Protective effect of different anti-rabies virus VHH constructs against rabies disease in mice. JF - PLoS One Y1 - 2014 A1 - Terryn, Sanne A1 - Francart, Aurélie A1 - Lamoral, Sophie A1 - Hultberg, Anna A1 - Rommelaere, Heidi A1 - Wittelsberger, Angela A1 - Callewaert, Filip A1 - Stohr, Thomas A1 - Meerschaert, Kris A1 - Ottevaere, Ingrid A1 - Stortelers, Catelijne A1 - Vanlandschoot, Peter A1 - Kalai, Michael A1 - Steven Van Gucht KW - Animals KW - Antibodies, Neutralizing KW - Antibodies, Viral KW - Cell Line KW - Disease Models, Animal KW - Female KW - Half-Life KW - Immunoglobulin Heavy Chains KW - mice KW - Rabies KW - Rabies Vaccines KW - Rabies virus KW - Single-Domain Antibodies KW - Tissue Distribution KW - Viral Load AB -

Rabies virus causes lethal brain infection in about 61000 people per year. Each year, tens of thousands of people receive anti-rabies prophylaxis with plasma-derived immunoglobulins and vaccine soon after exposure. Anti-rabies immunoglobulins are however expensive and have limited availability. VHH are the smallest antigen-binding functional fragments of camelid heavy chain antibodies, also called Nanobodies. The therapeutic potential of anti-rabies VHH was examined in a mouse model using intranasal challenge with a lethal dose of rabies virus. Anti-rabies VHH were administered directly into the brain or systemically, by intraperitoneal injection, 24 hours after virus challenge. Anti-rabies VHH were able to significantly prolong survival or even completely rescue mice from disease. The therapeutic effect depended on the dose, affinity and brain and plasma half-life of the VHH construct. Increasing the affinity by combining two VHH with a glycine-serine linker into bivalent or biparatopic constructs, increased the neutralizing potency to the picomolar range. Upon direct intracerebral administration, a dose as low as 33 µg of the biparatopic Rab-E8/H7 was still able to establish an anti-rabies effect. The effect of systemic treatment was significantly improved by increasing the half-life of Rab-E8/H7 through linkage with a third VHH targeted against albumin. Intraperitoneal treatment with 1.5 mg (2505 IU, 1 ml) of anti-albumin Rab-E8/H7 prolonged the median survival time from 9 to 15 days and completely rescued 43% of mice. For comparison, intraperitoneal treatment with the highest available dose of human anti-rabies immunoglobulins (65 mg, 111 IU, 1 ml) only prolonged survival by 2 days, without rescue. Overall, the therapeutic benefit seemed well correlated with the time of brain exposure and the plasma half-life of the used VHH construct. These results, together with the ease-of-production and superior thermal stability, render anti-rabies VHH into valuable candidates for development of alternative post exposure treatment drugs against rabies.

VL - 9 CP - 10 U1 - https://www.ncbi.nlm.nih.gov/pubmed/25347556?dopt=Abstract M3 - 10.1371/journal.pone.0109367 ER - TY - JOUR T1 - A two-step lyssavirus real-time polymerase chain reaction using degenerate primers with superior sensitivity to the fluorescent antigen test. JF - Biomed Res Int Y1 - 2014 A1 - Vanessa Suin A1 - Nazé, Florence A1 - Aurélie Francart A1 - Lamoral, Sophie A1 - Stéphane De Craeye A1 - Kalai, Michael A1 - Steven Van Gucht KW - Animals KW - Base Sequence KW - brain KW - Cats KW - Chiroptera KW - Computer Simulation KW - Dogs KW - Fluorescent Antibody Technique KW - Humans KW - Limit of Detection KW - Lyssavirus KW - mice KW - Molecular Sequence Data KW - Real-Time Polymerase Chain Reaction KW - Reproducibility of Results KW - Reverse Transcriptase Polymerase Chain Reaction KW - Rhabdoviridae Infections KW - RNA, Viral KW - Sequence Alignment AB -

A generic two-step lyssavirus real-time reverse transcriptase polymerase chain reaction (qRT-PCR), based on a nested PCR strategy, was validated for the detection of different lyssavirus species. Primers with 17 to 30% of degenerate bases were used in both consecutive steps. The assay could accurately detect RABV, LBV, MOKV, DUVV, EBLV-1, EBLV-2, and ABLV. In silico sequence alignment showed a functional match with the remaining lyssavirus species. The diagnostic specificity was 100% and the sensitivity proved to be superior to that of the fluorescent antigen test. The limit of detection was ≤ 1 50% tissue culture infectious dose. The related vesicular stomatitis virus was not recognized, confirming the selectivity for lyssaviruses. The assay was applied to follow the evolution of rabies virus infection in the brain of mice from 0 to 10 days after intranasal inoculation. The obtained RNA curve corresponded well with the curves obtained by a one-step monospecific RABV-qRT-PCR, the fluorescent antigen test, and virus titration. Despite the presence of degenerate bases, the assay proved to be highly sensitive, specific, and reproducible.

VL - 2014 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24822188?dopt=Abstract M3 - 10.1155/2014/256175 ER - TY - RPRT T1 - Virological Surveillance of Influenza in Belgium Season 2013-2014. National influenza Centre (WHO). Y1 - 2014 A1 - Isabelle Thomas A1 - Hombrouck,A. A1 - Steven Van Gucht A1 - Weyckmans,J. A1 - Bauwens,D. A1 - K. El Kadaani A1 - Abady,M. A1 - Fdillate,I. A1 - Nathalie Bossuyt A1 - Viviane Van Casteren A1 - Y. Pirson KW - Belgium KW - INFLUENZA KW - national KW - Surveillance KW - WHO AB - NA PB - WIV-ISP CY - Brussels SN - D/2014/2505/65 U1 - 39214 ER - TY - Generic T1 - Emergence of the deadly Middle East Respiratory Syndrome coronavirus: are bats to blame? Y1 - 2013 A1 - Steven Van Gucht A1 - Françoise Wuillaume A1 - K. El Kadaani A1 - A. Francart A1 - Bernard Brochier A1 - Naze,F. A1 - Isabelle Thomas KW - bat KW - bats KW - Belgian KW - Congresses KW - Coronavirus KW - disease KW - Middle East KW - Respiratory KW - Societies KW - Society JF - Fifth Belgian Wildlife Disease Society (BWDS) Congress PB - NA CY - NA CP - Belgian Wildlife Disease Society (BWDS) U1 - 38421 U2 - 18/10/2013 ER - TY - JOUR T1 - Favourable outcome in a patient bitten by a rabid bat infected with the European bat lyssavirus-1. JF - Acta Clin Belg Y1 - 2013 A1 - Steven Van Gucht A1 - Verlinde, R A1 - Colyn, J A1 - Jean Vanderpas A1 - Vanhoof, R A1 - S. Roels A1 - Francart, A A1 - Bernard Brochier A1 - Vanessa Suin KW - Animals KW - Belgium KW - Bites and Stings KW - Chiroptera KW - Cross Protection KW - Europe KW - Genotype KW - Humans KW - Lyssavirus KW - Male KW - Post-Exposure Prophylaxis KW - Rabies KW - Rabies Vaccines KW - Rhabdoviridae Infections KW - Treatment Outcome KW - Vaccination AB -

The classic rabies virus (genotype 1) has been eliminated in Western Europe, but related lyssaviruses still circulate in local bats. In August 2010, a Belgian photographer was bitten upon provocation of a disoriented Eptesicus serotinus bat in Spain. The bat was infected with European bat lyssavirus-1 (genotype 5). The isolate proved highly neurovirulent in mice. The patient had received preventive rabies immunisations years before the incident and received two boosters with the HDCV rabies vaccine afterwards. Available vaccines are based on the classic rabies virus, which is significantly divergent from the European bat lyssavirus-1. Fortunately, the patient's serological immune response demonstrated satisfactory neutralisation of the 2010 EBLV-1 isolate, using an intracerebral challenge model in mice. Most likely, the patient's life was saved thanks to vaccination with the classic rabies vaccine, which proved sufficiently protective against European bat lyssavirus-1. This case highlights the need for preventive rabies vaccination in people, who come in contact with bats and to seek medical council after a scratch or bite from a bat.

VL - 68 CP - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23627196?dopt=Abstract M3 - 10.2143/ACB.68.1.2062721 ER - TY - RPRT T1 - Favourable outcome of a bite incident by a rabid bat infected with the European bat lyssavirus-1 Y1 - 2013 A1 - Steven Van Gucht A1 - Colyn,J. A1 - Jean Vanderpas A1 - R. Vanhoof A1 - A. Francart A1 - Bernard Brochier A1 - Vanessa Suin KW - a KW - bat KW - bite KW - European KW - incident KW - Lyssavirus KW - outcome PB - WIV-ISP CY - Brussels U1 - 38420 ER - TY - Generic T1 - Hepatitis E in Belgium: an imported disease or a viral zoonosis? Y1 - 2013 A1 - Wautier,M. A1 - Veronik Hutse A1 - Steven Van Gucht ED - International Meeting on Emerging Diseases (Vienna) KW - a KW - an KW - at KW - Belgium KW - disease KW - Diseases KW - e KW - Hepatitis KW - Hepatitis E KW - International KW - meeting KW - ON JF - International Meeting on Emerging Diseases at Vienna T3 - International Meeting on Emerging Diseases at Vienna CP - International Meeting on Emerging Diseases at Vienna U1 - 38467 U2 - 15-18/02/2013 ER - TY - JOUR T1 - Infectivity of rabies virus-exposed macrophages. JF - Microbes Infect Y1 - 2013 A1 - Nazé, Florence A1 - Vanessa Suin A1 - Lamoral, Sophie A1 - Aurélie Francart A1 - Bernard Brochier A1 - S. Roels A1 - Jan Mast A1 - Kalai, Michael A1 - Steven Van Gucht KW - Animals KW - Antibodies, Neutralizing KW - Antibodies, Viral KW - Antibody Formation KW - Antigens, Viral KW - Bone Marrow KW - brain KW - Cell Death KW - Immunity, Humoral KW - Injections, Intramuscular KW - Macrophages KW - mice KW - Mice, Inbred C57BL KW - Microscopy, Electron KW - Nose KW - Rabies KW - Rabies virus KW - RNA, Viral KW - Spleen KW - Viral Load KW - Virus Cultivation AB -

Rabies virus distributes widely in infected mice, including lymphoid tissues and spleen macrophages. The infection characteristics in murine macrophages and the infectivity of virus-exposed macrophages were examined upon inoculation in mice. In vitro, Mf4/4 spleen macrophages supported mild virus production (10(4)-fold less than neuroblastoma), with formation of typical virions. Bone marrow-derived macrophages (BMM) were most efficient to capture virus, but new virus production was not detected. Virus-induced cell death was significantly stronger in BMM, which might have eliminated BMM with productive infection. Still, viral RNA remained detectable in the remaining BMM for at least 4 weeks. Injection of in vitro-infected Mf4/4 in the nose or brain proved efficient to propagate infection in mice, even when cells were pre-incubated with neutralizing antibodies. Surprisingly, injection of ex-vivo-infected BMM in the brain also led to lethal infection in 8 out of 12 mice. Injection of infected Mf4/4 in the muscle mostly favoured a protective antibody response. Despite that macrophages are less fit to support virus production, they can still act as a source of infectious virus upon transfer in mice. This may be relevant for screening donor organs/cells, for which RT-PCR should be preferred over the traditional antigen or virus isolation assays.

VL - 15 CP - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23159243?dopt=Abstract M3 - 10.1016/j.micinf.2012.10.018 ER - TY - Generic T1 - Initial neutralising antibody response on day 35 after two different intradermal rabies pre-exposure vaccination schedules: preliminary unpooled data of a large prospective clinical trial on rabies boostability Y1 - 2013 A1 - Soentjens,P. A1 - Andries,P. A1 - Damanet,B. A1 - Wauters,A. A1 - DeKoninck,K. A1 - Heuninckx,W. A1 - L. Remy A1 - Dooms,E. A1 - Steven Van Gucht A1 - De Crop,M. A1 - Ravinetto,R. A1 - Van Gompel,A. A1 - Aerssens,A. KW - a KW - antibodies KW - Antibody KW - Clinical KW - clinical trial KW - conference KW - data KW - International KW - intradermal KW - Medicine KW - ON KW - Rabies KW - response KW - Societies KW - Society KW - Travel KW - Vaccination JF - http://dx.doi.org/10.1093/cid/cit080 PB - NA CY - Maastricht CP - CISTM U1 - 38351 U2 - 05/2013 ER - TY - JOUR T1 - Low-cost intradermal rabies vaccination is indeed very promising33971 JF - Clin.Infect.Dis. Y1 - 2013 A1 - Soentjens,P. A1 - Aerssens,A. A1 - Steven Van Gucht A1 - Ravinetto,R. A1 - Van Gompel,A. KW - 0 KW - administration & dosage KW - Comment KW - electronic KW - Humans KW - im KW - immunology KW - intradermal KW - IS KW - prevention & control KW - Rabies KW - Rabies Vaccines KW - Rabies virus KW - SB - IM KW - Vaccination KW - vaccine KW - vaccines AB - na VL - 56 CP - 10 U1 - 38352 M3 - http://dx.doi.org/10.1093/cid/cit080 ER - TY - JOUR T1 - Serological evidence of Ostertagia ostertagi infection in dairy cows does not impact the efficacy of rabies vaccination during the housing period33969 JF - Res.Vet.Sci. Y1 - 2013 A1 - Charlier,J. A1 - Forbes,A. A1 - Steven Van Gucht A1 - Luc Duchateau A1 - B. Goddeeris A1 - Vercruysse,J. KW - 0 KW - a KW - Adult KW - ALL KW - an KW - Animal KW - Animals KW - antibodies KW - Antibody KW - Antigens KW - article KW - AS KW - association KW - Associations KW - at KW - Belgium KW - Cattle KW - challenge KW - Change KW - Changes KW - effect KW - electronic KW - evidence KW - exposure KW - Faculty KW - future KW - Housing KW - Human KW - Humans KW - im KW - immune response KW - immunology KW - Impact KW - Increase KW - INFECTION KW - infections KW - IS KW - journal KW - Kinetics KW - LEVEL KW - levels KW - Medicine KW - ON KW - parasitology KW - period KW - present KW - Rabies KW - region KW - Research KW - Research Support KW - response KW - Responses KW - SB - IM KW - scale KW - serum KW - Statistical KW - study KW - Universities KW - university KW - Vaccination KW - vaccine KW - vaccines KW - veterinary KW - Veterinary Medicine KW - virology AB - Nematode infections modulate the immune reaction of humans and livestock and may impair immune responses to non-parasitic antigens such as those present in vaccines. In this study, the relationship between antibodies directed against Ostertagia ostertagi, the economically most important nematode infection of cattle in temperate regions, and the magnitude and the kinetics of the antibody response to rabies vaccination was investigated in a commercial dairy herd of 46 cows. During the stabling period, all animals received a single intramuscular administration with a commercial inactivated rabies vaccine (Rabisin(R), Merial). The serum antibody levels against O. ostertagi on day 0 were compared with anti-rabies IgM, IgA, IgG1, IgG2 and virus-neutralizing antibodies on days 0, 7, 14 and 21 after vaccination. In addition, to explore the potential effect of newly acquired O. ostertagi infections, the kinetics of the O. ostertagi antibody levels during the first 2 months after turnout on pasture were compared with concurrent changes in the rabies antibodies. During the stabling period the O. ostertagi antibody level tended to be positively associated with the magnitude, rate of increase and rate of decrease of the rabies antibodies. However, none of these associations were significant (P>0.05). Over the first 2 months at pasture, an increase in O. ostertagi antibody level tended to be associated with a decrease in rabies IgG2 and IgM, but again these associations lacked statistical significance (P>0.20). We conclude that the O. ostertagi antibody level in adult cattle over the housing period has no significant association with the antibody response to rabies vaccination. We recommend that future studies aiming to assess the relationship of nematode infections with humoral immune responses to vaccines are conducted on a larger scale and focus on the summer period when cattle are exposed continuously to nematode challenge from the pasture and hence are actively responding immunologically to nematode antigen exposure VL - 95 CP - 3 U1 - 33969 M3 - http://dx.doi.org/10.1016/j.rvsc.2013.09.001 ER - TY - Generic T1 - Tick-borne encephalitis virus - seropositive cattle in Belgium: a risk-based screening for (TBEV) antibodies in bovine sera Y1 - 2013 A1 - Sophie Roelandt A1 - Vanessa Suin A1 - Riocreux,F. A1 - S. Lamoral A1 - Yves Van der Stede A1 - Steven Van Gucht A1 - Bernard Brochier A1 - S. Roels ED - Technical University of Denmark KW - a KW - antibodies KW - Antibody KW - association KW - Belgium KW - Cattle KW - conference KW - International KW - SCREENING KW - serum KW - TBEV KW - VIRUS JF - MedVetNet Association International Scientific Conference 2013 CP - Technical University of Denmark U1 - 38336 U2 - 24-25/06/2013 ER - TY - Generic T1 - Tick-borne encephalitis virus (TBEV) - Seroprevalence study for TBEV antibodies in bovine sera in Belgium: a risk-based screening Y1 - 2013 A1 - Vanessa Suin A1 - Sophie Roelandt A1 - S. Lamoral A1 - Riocreux,F. A1 - Yves Van der Stede A1 - Bernard Brochier A1 - S. Roels A1 - Steven Van Gucht KW - a KW - antibodies KW - Antibody KW - Belgium KW - SCREENING KW - serum KW - study KW - TBEV KW - VIRUS JF - Epizone PB - NA CY - NA CP - Epizone U1 - 38361 U2 - October 2013 ER - TY - Generic T1 - Treatment with anti-rabies VHH prevents or delays disease and mortality in mice depending on the timing of treatment Y1 - 2013 A1 - Sanne Terryn A1 - A. Francart A1 - S. Lamoral A1 - A. Hultberg A1 - Vanlandschoot,P. A1 - H Rommelaere A1 - A. Wittelsberger A1 - Michael Kalai A1 - Steven Van Gucht KW - Belgian KW - disease KW - Immunoglobulin KW - Imogam KW - meeting KW - mice KW - mortality KW - nanobody KW - ON KW - prevent KW - prophylaxis KW - Rabies KW - Societies KW - Society KW - treatment KW - VHH KW - virology JF - First meeting of the Belgian Society for Virology PB - NA CY - NA CP - Belgian Society for Virology U1 - 38384 U2 - 08/11/2013 ER - TY - Generic T1 - Treatment with anti-rabies VHH prevents or delays rabies virus disease in mice Y1 - 2013 A1 - Sanne Terryn A1 - Y. Fikri A1 - A. Francart A1 - S. Lamoral A1 - A. Hultberg A1 - Vanlandschoot,P. A1 - H Rommelaere A1 - A. Wittelsberger A1 - Michael Kalai A1 - Steven Van Gucht KW - disease KW - mice KW - prevent KW - Rabies KW - Rabies virus KW - treatment KW - VHH KW - VIRUS JF - Epizone PB - NA CY - NA CP - Epizone U1 - 38385 U2 - October 2013 ER - TY - RPRT T1 - Infectieziekten bij kinderen die voorkomen kunnen worden door vaccinatie. Trends en Ontwikkelingen in België en de Gemeenschappen, 2011. Y1 - 2012 A1 - Toon Braeye A1 - D Hue A1 - Tine Grammens A1 - Sophie Quoilin A1 - Sophie Bertrand A1 - Bots,J. A1 - Ducoffre,G. A1 - Goubau,P. A1 - Heymans,C. A1 - Denis Piérard A1 - Carole Schirvel A1 - Béatrice Swennen A1 - Geert Top A1 - Viviane Van Casteren A1 - Vandenberg,O. A1 - Steven Van Gucht A1 - Marc Van Ranst A1 - Vanthomme,K. A1 - Jan Verhaegen A1 - Françoise Wuillaume KW - België KW - de KW - EN KW - trend KW - trends PB - WIV-ISP CY - Brussel SN - D/2012/2050/80 U1 - 30418 ER - TY - RPRT T1 - An intranasal infection model of rabies to study disease mechanisms and therapies of viral encephalitis Y1 - 2012 A1 - Vanessa Suin A1 - Rosseels,V. A1 - Naze,F. A1 - A. Francart A1 - S. Lamoral A1 - Michael Kalai A1 - Steven Van Gucht KW - an KW - disease KW - INFECTION KW - mechanism KW - mechanisms KW - MODEL KW - Rabies KW - study KW - Therapy PB - WIV-ISP CY - Brussels U1 - 285 ER - TY - RPRT T1 - Maladies infectieuses pédiatriques à prévention vaccinale. Tendances et évolutions en Belgique et dans les Communautés, 2011. Y1 - 2012 A1 - Toon Braeye A1 - D Hue A1 - Tine Grammens A1 - Sophie Quoilin A1 - Sophie Bertrand A1 - Bots,J. A1 - Ducoffre,G. A1 - Goubau,P. A1 - Heymans,C. A1 - Denis Piérard A1 - Carole Schirvel A1 - Béatrice Swennen A1 - Geert Top A1 - Viviane Van Casteren A1 - Vandenberg,O. A1 - Steven Van Gucht A1 - Marc Van Ranst A1 - Vanthomme,K. A1 - Jan Verhaegen A1 - Françoise Wuillaume KW - Belgique KW - EN KW - ET KW - LE KW - Maladies infectieuse KW - pédiatrique KW - trends PB - WIV-ISP CY - Bruxelles VL - 2012-44 SN - D/2012/2050/81 U1 - 30419 ER - TY - JOUR T1 - Immunogenicity of an adjuvanted 2009 pandemic influenza A (H1N1) vaccine in haemodialysed patients JF - Nephrol.Dial.Transplant. Y1 - 2011 A1 - Labriola,L. A1 - Hombrouck,A. A1 - Marechal,C. A1 - Steven Van Gucht A1 - Bernard Brochier A1 - Isabelle Thomas A1 - Jadoul,M. A1 - Goubau,P. KW - 0 KW - 2009 KW - Adjuvants,Immunologic KW - administration & dosage KW - Adult KW - Aged KW - Aged,80 and over KW - an KW - antibodies KW - Antibody KW - article KW - AS KW - at KW - Belgium KW - Brussels KW - Case-Control Studies KW - Comparative Study KW - Control KW - de KW - electronic KW - Female KW - Follow-Up Studies KW - GM KW - Hemagglutination Inhibition Tests KW - High risk KW - HIGH-RISK KW - Humans KW - im KW - immunology KW - Increase KW - INFLUENZA KW - Influenza A Virus,H1N1 Subtype KW - Influenza Vaccines KW - Influenza,Human KW - IS KW - journal KW - Kidney Failure,Chronic KW - LEVEL KW - Male KW - males KW - method KW - methods KW - middle aged KW - observed KW - ON KW - p KW - pandemic KW - Pandemics KW - Patient KW - patients KW - prevention & control KW - Prognosis KW - Prospective Studies KW - Renal Dialysis KW - result KW - results KW - SB - IM KW - Still KW - study KW - Survival Rate KW - Therapy KW - Vaccination KW - vaccine KW - vaccines KW - Young adult AB - BACKGROUND: The 2009 pandemic of influenza A (H1N1) prompted an urgent worldwide vaccination campaign, especially of high-risk subjects, such as maintenance haemodialysis (HD) patients. Still the immunogenicity of the pandemic A (H1N1) vaccine in HD patients is unknown. METHODS: We prospectively studied the immunogenicity of a monovalent adjuvanted influenza A/California/2009 (H1N1) vaccine (Pandemrix, GSK Biologicals, Rixensart, Belgium) in HD patients and controls. Antibody level was measured using a seroneutralization assay before (D(0)) and 30 days after (D(30)) a single 3.75 mug vaccine dose. Specimens were tested in quadruplicates. Geometric mean (GM) antibody titers were determined in each subject at D(0) and D(30). Seroconversion was defined as an increase in GM titers by a factor 4 or more. RESULTS: Fifty-three adult HD patients [aged 71 +/- 10, 58.5% males, on HD for a median of 38 (3 - 146) months] and 32 control subjects (aged 47.3 +/- 14, 31.3% males) were analyzed. Baseline GM titers were similar in HD patients and controls [7.9 (6.6 - 9.6) vs 10 (6 - 17); p = 0.69]. Seroconversion was observed in 30 (93.8%) controls and 34 (64.2%) HD patients (p = 0.002). In addition, GM titers at D(30) were significantly higher in controls than in HD patients [373 ( VL - 26 CP - 4 U1 - 36552 M3 - http://dx.doi.org/10.1093/ndt/gfq782 ER - TY - JOUR T1 - Influenza A/H1N1 vaccine in patients treated by kidney transplant or dialysis: a cohort study36521 JF - Clin.J.Am.Soc.Nephrol. Y1 - 2011 A1 - Broeders,N.E. A1 - Hombrouck,A. A1 - Lemy,A. A1 - Wissing,K.M. A1 - Racape,J. A1 - Gastaldello,K. A1 - Massart,A. A1 - Steven Van Gucht A1 - Weichselbaum,L. A1 - De Mul,A. A1 - Bernard Brochier A1 - Isabelle Thomas A1 - Abramowicz,D. KW - 0 KW - 2009 KW - a KW - administration & dosage KW - Adult KW - adverse effects KW - Aged KW - Agent KW - Agents KW - alpha-Tocopherol KW - Analysis of Variance KW - antibodies KW - Antibodies,Neutralizing KW - Antibodies,Viral KW - Antibody KW - Antigens KW - article KW - Belgium KW - blood KW - Brussels KW - Case-Control Studies KW - Chi-Square Distribution KW - Class KW - clinic KW - Cohort Studies KW - Cohort study KW - Combination KW - Confidence Intervals KW - Control KW - data KW - Design KW - disease KW - DRUG KW - Drug Combinations KW - electronic KW - Female KW - GM KW - Histocompatibility Antigens Class I KW - Histocompatibility Antigens Class II KW - hospital KW - Humans KW - i KW - im KW - Immunization KW - immunology KW - Immunosuppressive Agents KW - improve KW - Increase KW - INFLUENZA KW - Influenza A Virus,H1N1 Subtype KW - Influenza Vaccines KW - Influenza,Human KW - interval KW - IS KW - journal KW - Kidney KW - Kidney Failure,Chronic KW - Kidney Transplantation KW - Luminex KW - Male KW - measurement KW - measurements KW - middle aged KW - objectives KW - ODDS RATIO KW - p KW - pandemic KW - PARTICIPANTS KW - Patient KW - patients KW - Polysorbates KW - POPULATION KW - Populations KW - prevalence KW - prevention & control KW - proportion KW - Ratio KW - Ratios KW - recommendation KW - Recommendations KW - regression analysis KW - RENAL KW - Renal Dialysis KW - Research KW - Research Support KW - response KW - result KW - results KW - SB - IM KW - serum KW - Squalene KW - study KW - surgery KW - technology KW - Therapy KW - Time Factors KW - Treatment Outcome KW - Vaccination KW - vaccine KW - vaccines KW - virology AB - BACKGROUND AND OBJECTIVES: In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix(R) vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: >/=4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. RESULTS: The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39). CONCLUSIONS: The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations VL - 6 CP - 11 U1 - 38093 M3 - http://dx.doi.org/10.2215/CJN.04670511 ER - TY - JOUR T1 - Lipoteichoic acid from Staphylococcus aureus exacerbates respiratory disease in porcine respiratory coronavirus-infected pigs34019 JF - Vet.J. Y1 - 2011 A1 - Atanasova,K. A1 - Steven Van Gucht A1 - Barbe,F. A1 - Luc Duchateau A1 - Van Reeth,K. KW - 0 KW - acid KW - Acids KW - Animal KW - Animals KW - article KW - AS KW - Belgium KW - biosynthesis KW - Bronchoalveolar Lavage Fluid KW - Cell KW - cells KW - Clinical KW - Coronavirus KW - Coronavirus Infections KW - Cytokines KW - disease KW - drug effects KW - electronic KW - Female KW - im KW - immunology KW - IS KW - journal KW - Lipopolysaccharides KW - Lung KW - Male KW - metabolism KW - Objective KW - pathology KW - pharmacology KW - Pig KW - Pigs KW - Porcine Respiratory Coronavirus KW - Random Allocation KW - Research KW - Research Support KW - Respiratory KW - Respiratory disease KW - Respiratory Tract Diseases KW - S KW - SB - IM KW - Severity of Illness Index KW - staphylococcus KW - Staphylococcus aureus KW - study KW - Swine KW - Swine Diseases KW - Teichoic Acids KW - Universities KW - university KW - veterinary KW - virology KW - VIRUS AB - The objective of this study was to assess if lipoteichoic acid (LTA), produced by Staphylococcus aureus, exacerbates respiratory disease in porcine respiratory coronavirus (PRCV)-infected pigs, as has previously been shown with lipopolysaccharide. Piglets were inoculated with PRCV and 24h later with S. aureus LTA. Clinical signs, lung virus titres, inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were compared with those of animals in VL - 188 CP - 2 U1 - 38029 M3 - http://dx.doi.org/10.1016/j.tvjl.2010.03.001 ER - TY - JOUR T1 - Llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules36549 JF - PLoS.One. Y1 - 2011 A1 - A. Hultberg A1 - Temperton,N.J. A1 - Rosseels,V. A1 - Koenders,M. A1 - Gonzalez-Pajuelo,M. A1 - Schepens,B. A1 - Ibanez,L.I. A1 - Vanlandschoot,P. A1 - Schillemans,J. A1 - Saunders,M. A1 - Weiss,R.A. A1 - Saelens,X. A1 - J. Melero A1 - Verrips,C.T. A1 - Steven Van Gucht A1 - H.J. de Haard KW - 0 KW - a KW - Agent KW - Agents KW - ALL KW - Animals KW - antibodies KW - Antibodies,Neutralizing KW - Antibody KW - Antibody Specificity KW - Antiviral Agents KW - article KW - Binding Sites KW - Biology KW - biosynthesis KW - Camelids,New World KW - Cross Reactions KW - Dose-Response Relationship,Immunologic KW - electronic KW - Epitopes KW - genetics KW - Genotype KW - Glycoprotein KW - H5N1 KW - im KW - Immunoglobulin KW - Immunoglobulin Heavy Chains KW - immunology KW - INFECTION KW - infections KW - INFLUENZA KW - Influenza A Virus,H5N1 Subtype KW - IS KW - isolation & purification KW - journal KW - llama KW - Lyssavirus KW - metabolism KW - Monoclonal antibodies KW - monoclonal-antibodies KW - Multiple KW - Netherlands KW - ON KW - Phage Display KW - prevention KW - protection KW - protein KW - Proteins KW - Rabies KW - Rabies virus KW - RANGE KW - Receptor KW - Research KW - Research Support KW - Respiratory KW - Respiratory Syncytial Viruses KW - result KW - results KW - SB - IM KW - SELECTED KW - Sites KW - strain KW - Strategies KW - Strategy KW - The Netherlands KW - Therapy KW - Universities KW - university KW - VHH KW - Viral Proteins KW - VIRUS KW - Viruses AB - For efficient prevention of viral infections and cross protection, simultaneous targeting of multiple viral epitopes is a powerful strategy. Llama heavy chain antibody fragments (VHH) against the trimeric envelope proteins of Respiratory Syncytial Virus (Fusion protein), Rabies virus (Glycoprotein) and H5N1 Influenza (Hemagglutinin 5) were selected from llama derived immune libraries by phage display. Neutralizing VHH recognizing different epitopes in the receptor binding sites on the spikes with affinities in the low nanomolar range were identified for all the three viruses by viral neutralization assays. By fusion of VHH with variable linker lengths, multimeric constructs were made that improved neutralization potencies up to 4,000-fold for RSV, 1,500-fold for Rabies virus and 75-fold for Influenza H5N1. The potencies of the VHH constructs were similar or better than best performing monoclonal antibodies. The cross protection capacity against different viral strains was also improved for all three viruses, both by multivalent (two or three identical VHH) and biparatopic (two different VHH) constructs. By combining a VHH neutralizing RSV subtype A, but not subtype B with a poorly neutralizing VHH with high affinity for subtype B, a biparatopic construct was made with low nanomolar neutralizing potency against both subtypes. Trivalent anti-H5N1 VHH neutralized both Influenza H5N1 clade1 and 2 in a pseudotype assay and was very potent in neutralizing the NIBRG-14 Influenza H5N1 strain with IC(50) of 9 picomolar. Bivalent and biparatopic constructs against Rabies virus cross neutralized both 10 different Genotype 1 strains and Genotype 5.The results show that multimerization of VHH fragments targeting multiple epitopes on a viral trimeric spike protein is a powerful tool for anti-viral therapy to achieve "best-in-class" and broader neutralization capacity VL - 6 CP - 4 U1 - 36549 M3 - http://dx.doi.org/10.1371/journal.pone.0017665 ER - TY - JOUR T1 - A non-invasive intranasal inoculation technique using isoflurane anesthesia to infect the brain of mice with rabies virus. JF - J Virol Methods Y1 - 2011 A1 - Rosseels, Valérie A1 - Nazé, Florence A1 - Stéphane De Craeye A1 - Aurélie Francart A1 - Kalai, Michael A1 - Steven Van Gucht KW - Anesthetics, Inhalation KW - Animals KW - brain KW - Disease Models, Animal KW - Isoflurane KW - mice KW - Rabies KW - Survival Analysis AB -

Methods for intranasal inoculation of viruses are often described poorly and the effects of variations in the technique on the outcome are unknown. Standardization of protocols is key to compare studies and minimize animal use. The clinical and virological outcome of infection with rabies virus (genotypes 1 and 5) upon administration of different inoculum volumes (25, 50 and 100μl) and different anesthetic regimens were examined. Administration of 25μl of virus as a drop on both nostrils under brief superficial isoflurane anesthesia (92μl/dm(3), recovery after 85 ± 1 0s) was the most effective to infect the brain and induced 100% lethal infection 9 days later. Increasing the inoculum volume reduced infectivity significantly, with decreased viral loads in the brain and only 40% mortality. Increasing the depth of isoflurane anesthesia (230μl/dm(3)) improved the infectivity of the large-volume inoculum (90% mortality), probably because of suppression of swallow and sneeze reflexes. Compared to isoflurane anesthesia, xylazine-ketamine anesthesia reduced the infectivity of the inoculum significantly. Thus, administration of a small volume of virus on the nostrils under brief gas anesthesia is a safe and reproducible technique to induce infection of the brain. Since needles are not required, this helps to preserve the integrity of the physical barriers, animal welfare and the manipulator's safety.

VL - 173 CP - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21295615?dopt=Abstract M3 - 10.1016/j.jviromet.2011.01.019 ER - TY - Generic T1 - Prevalence of Toxoplasma gondii in Belgian Wildlife. Y1 - 2011 A1 - Niko Speybroeck A1 - Baert,K. A1 - Ajzenberg,D. A1 - Darde,M.L. A1 - Collinet,F. A1 - P. Tavernier A1 - Steven Van Gucht A1 - Pierre Dorny A1 - Katelijne Dierick KW - a KW - an KW - Animal KW - Animals KW - antibodies KW - Antibody KW - Belgian KW - brain KW - Congresses KW - cysts KW - Deer KW - Dna KW - European KW - Foxes KW - gene KW - High prevalence KW - Human KW - Humans KW - International KW - occurrence KW - ON KW - PCR KW - prevalence KW - rats KW - real time PCR KW - RED KW - Sample KW - Samples KW - serum KW - study KW - Target KW - time KW - Toxoplasma KW - Toxoplasmosis KW - Type AB - Toxoplasma gondii, JF - 11th International Congress on Toxoplasmosis CP - ? U1 - 38133 U2 - 25/06/2011 ER - TY - JOUR T1 - Toxoplasma gondii and Neospora caninum in wildlife: common parasites in Belgian foxes and Cervidae? JF - Vet Parasitol Y1 - 2011 A1 - Stéphane De Craeye A1 - Speybroeck, N A1 - Ajzenberg, D A1 - Dardé, M L A1 - Collinet, F A1 - Tavernier, P A1 - Steven Van Gucht A1 - Dorny, P A1 - Katelijne Dierick KW - Animals KW - Belgium KW - brain KW - Coccidiosis KW - Deer KW - DNA, Protozoan KW - Foxes KW - Genotype KW - Neospora KW - Toxoplasma KW - Toxoplasmosis, Animal AB -

Sera from Cervidae were tested for the presence of antibodies against Neospora caninum using ELISA; and against Toxoplasma gondii using SAG1-ELISA and a commercially available agglutination test. The T. gondii seroprevalence was 52% (38/73) in roe deer (Capreolus capreolus), 0% in bred fallow deer (0/4) (Dama dama) and red deer (0/7) (Cervus elaphus). We found 2.7% of the roe deer samples and none of the bred deer samples positive for N. caninum. Brain samples from wild roe deer, red deer and red foxes (Vulpes vulpes) were tested for the presence of T. gondii and N. caninum DNA using multiplex real-time PCR. We detected T. gondii in 18.8% (57/304) of the red foxes and in 1 of the 33 deer samples. N. caninum was found in 6.6% of the red foxes and in 2 roe deer samples. Twenty-six of the T. gondii positive DNA extracts from the red fox samples were genotyped. Twenty-five were type II and only one was found to be type III.

VL - 178 CP - 1-2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21236577?dopt=Abstract M3 - 10.1016/j.vetpar.2010.12.016 ER - TY - JOUR T1 - Anti-TNF-alpha therapy does not ameliorate disease in a model of acute virus-endotoxin mediated respiratory disease in pigs36852 JF - Vet.Immunol.Immunopathol. Y1 - 2010 A1 - Atanasova,K. A1 - Steven Van Gucht A1 - Van Reeth,K. KW - 0 KW - a KW - Activity KW - acute KW - Acute Disease KW - ALL KW - analysis KW - Animal KW - Animals KW - antagonists & inhibitors KW - article KW - AS KW - at KW - Autoimmune Diseases KW - Belgium KW - Bronchoalveolar Lavage Fluid KW - Cell KW - Clinical KW - conditions KW - Control KW - Coronavirus KW - cytology KW - Development KW - differences KW - disease KW - Disease Models,Animal KW - Diseases KW - DRUG KW - drug therapy KW - drugs KW - effect KW - effects KW - electronic KW - Faculty KW - Female KW - Group KW - Human KW - Humans KW - im KW - Immunoglobulin KW - Immunoglobulin G KW - immunology KW - IS KW - IT KW - journal KW - Laboratories KW - LEVEL KW - levels KW - Lipopolysaccharides KW - Lung KW - Lung Diseases KW - Medicine KW - MODEL KW - Necrosis KW - observed KW - ON KW - parameters KW - pathology KW - Pig KW - Pigs KW - Porcine Reproductive and Respiratory Syndrome KW - Porcine Respiratory Coronavirus KW - protein KW - Receptor KW - receptors KW - Receptors,Tumor Necrosis Factor KW - Research KW - Research Support KW - Respiratory KW - Respiratory disease KW - Role KW - SB - IM KW - serum KW - severity KW - study KW - Swine KW - Symptom KW - Symptoms KW - therapeutic use KW - Therapy KW - time KW - Times KW - toxicity KW - treatment KW - tumor KW - Tumor Necrosis Factor-alpha KW - Universities KW - university KW - veterinary KW - Veterinary Medicine KW - virology KW - VIRUS KW - Virus Replication AB - Tumour necrosis factor-alpha (TNF-alpha) has been shown to play a role in many inflammatory conditions. Currently anti-TNF-alpha drugs (e.g. etanercept) are used in humans for treatment of autoimmune diseases. In this study we aimed to elucidate the role of TNF-alpha in the development of virus-endotoxin-induced respiratory disease. Twenty-two caesarean derived colostrum deprived pigs were used. Initially, the availability in the lungs and circulation, and possible clinical and inflammatory effects of etanercept alone were assessed in 4 pigs after intratracheal and intraperitoneal administration of 0.5mg/per route/per pig. High anti-TNF-alpha activity was detected in bronchoalveolar lavage (BAL) fluids, peritoneal lavage fluids and serum of all animals for at least 8h post-inoculation (HPI). No clinical symptoms, lung lesions, lung cell infiltration or induction of IFN-alpha, IL-1, IL-6, IL-12 and TNF-alpha in BAL were detected. Subsequently, the ability of etanercept to block porcine TNF-alpha and its effect on the above mentioned parameters and on lung virus titres were assessed in 8 pigs. They were inoculated intratracheally with porcine respiratory coronavirus (PRCV) followed by lipopolysaccharide (LPS) 24h later. Etanercept was administered at the time of LPS inoculation via the same routes and dose as in the initial experiment. The parameters were compared with a control group (n=8), receiving only PRCV-LPS. Half of the animals from each group were euthanized at 4 and the rest at 8h after LPS inoculation. TNF-alpha was completely neutralized in 3 of the 4 animals euthanized at 4 HPI and significantly lower than in the PRCV-LPS group at all times. No significant differences in disease severity, lung lesions, virus replication, lung cell infiltration or levels of IFN-alpha, IL-1, IL-6 and IL-12/IL-23 were observed between the two groups. Blocking of TNF-alpha alone was not sufficient to ameliorate disease in the PRCV-LPS model of respiratory disease, possibly due to the redundancy in the proinflammatory cytokine cascade, or the involvement of other unidentified disease mediators VL - 137 CP - 1-2 U1 - 38028 M3 - http://dx.doi.org/10.1016/j.vetimm.2010.04.003 ER - TY - JOUR T1 - Evaluation du risque vis-à-vis des parasites du genre Trichinella en Belgique: état des lieux et perspectives.36858 JF - Annales de Médecine Vétérinaire Y1 - 2010 A1 - S. Cardoen A1 - Dirk Berkvens A1 - Claes,L. A1 - Steven Van Gucht A1 - Dewulf,J. A1 - L. De Zutter A1 - Saegerman,C. KW - Belgique KW - de KW - EN KW - ET KW - EVALUATION KW - Parasites KW - richinella AB - Not available VL - 154 U1 - 38106 ER - TY - JOUR T1 - No emergence of Echinococcus multilocularis in foxes in Flanders and Brussels anno 2007-2008. JF - Zoonoses Public Health Y1 - 2010 A1 - Steven Van Gucht A1 - Van Den Berge, K A1 - Quataert, P A1 - Verschelde, P A1 - Le Roux, I KW - Animals KW - Belgium KW - Communicable Diseases, Emerging KW - Echinococcosis KW - Echinococcus multilocularis KW - Foxes KW - Humans KW - Parasitic Diseases, Animal KW - prevalence KW - public health AB -

Echinococcus multilocularis is highly endemic in red foxes in southern Belgium (region of Wallonia), especially in the higher located forested areas. The north of Belgium, including the regions of Flanders and Brussels, is more urbanized and has been colonized entirely by red foxes since the 1980s. A temperospatial analysis of compiled epidemiological data from 1996 to 2003 predicted a northwest spread of the cestode from Wallonia and the Netherlands towards Flanders and Brussels (Prev. Vet. Med. 2006, 76, 137-150). In 2007-2008, none of 187 examined foxes from the north tested positive (<2.8%, α = 0.01), compared to 1.7% in 1996-1999. This suggests that the parasite is not emerging in the examined area and the endemic region has not significantly extended northwest during the last decade. The possible reasons are discussed in the article, including the relatively low altitude, milder climate or low abundance of suitable intermediate hosts. The low prevalence in foxes and the generally low infection rate in humans imply that the risk for public health in Flanders and Brussels is limited anno 2007-2008.

VL - 57 CP - 7-8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20163572?dopt=Abstract M3 - 10.1111/j.1863-2378.2009.01322.x ER - TY - RPRT T1 - VHH-based nanobodies® selected against the viral spike protein can protect mice against lethal rabies virus challenge Y1 - 2010 A1 - Steven Van Gucht KW - challenge KW - mice KW - protein KW - Rabies KW - Rabies virus KW - SELECTED KW - VIRUS PB - WIV-ISP CY - Brussels U1 - 38419 ER - TY - PAT T1 - Amino acid sequences directed against envelope proteins of a virus and polypeptides comprising the same for the treatment of viral diseases Y1 - 2009 A1 - Steven Van Gucht A1 - A. Hultberg A1 - Maassen,B. A1 - Vanlandschoot,P. A1 - Depla,E. A1 - Stortelers,C. A1 - Verrips,C.T. A1 - J. Melero KW - a KW - acid KW - Amino Acid Sequence KW - disease KW - Diseases KW - llama KW - nanobody KW - protein KW - Proteins KW - Rabies KW - treatment KW - VHH KW - VIRUS ER - TY - JOUR T1 - Prevalence of Toxoplasma gondii infection in Belgian house cats. JF - Vet Parasitol Y1 - 2008 A1 - Stéphane De Craeye A1 - Aurélie Francart A1 - Chabauty, Julie A1 - De Vriendt, Veerle A1 - Steven Van Gucht A1 - Leroux, Ingrid A1 - Jongert, Erik KW - Animals KW - Antibodies, Protozoan KW - Belgium KW - Cat Diseases KW - Cats KW - Enzyme-Linked Immunosorbent Assay KW - Fluorescent Antibody Technique, Indirect KW - Immunoglobulin G KW - Immunoglobulin M KW - prevalence KW - Protozoan Proteins KW - Seroepidemiologic Studies KW - Toxoplasma KW - Toxoplasmosis, Animal AB -

Five hundred and sixty seven sera of healthy house cats aged 3 months to 7 years, were examined for the presence of anti-toxoplasma antibodies by indirect immunofluorescence assay and compared to SAG1 and TLA enzyme linked immunosorbent assays as alternative test. Twenty-five percent of cats tested positive for IgG and/or IgM. Seroprevalence increased with age from 2% below 12 months of age up to 44% at age 7. Sensitivities of SAG1 and TLA ELISA were 84.1% and 88.6%, respectively. Peak levels in seroprevalence were correlated to increased IgG titers in TLA ELISA. Our results suggest that T. gondii infections are common in house cats and that there is a high chance for a negative cat to seroconvert in its second life-year.

VL - 157 CP - 1-2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/18707811?dopt=Abstract M3 - 10.1016/j.vetpar.2008.07.001 ER - TY - Generic T1 - Speuren naar rabies in the skye Y1 - 2008 A1 - Steven Van Gucht A1 - Le Roux,I. KW - bats KW - Rabies KW - vleermuizen AB - Not available JF - Zoogdier VL - 19 CP - 4 U1 - 36811 ER - TY - JOUR T1 - Toxoplasmosis in Belgian pet cats: recommendations for owners.35180 JF - Flemish Veterinary Journal Y1 - 2008 A1 - A. Francart A1 - Chabauty,J. A1 - Steven Van Gucht A1 - G. Leroux-Roels A1 - Jongert,E. KW - a KW - age KW - AGE GROUP KW - Age-group KW - an KW - antibodies KW - Antibody KW - at KW - Belgian KW - Belgium KW - Brussels KW - Cats KW - Flanders KW - Group KW - Healthy KW - Human KW - Humans KW - Increase KW - INFECTION KW - IS KW - observed KW - recommendation KW - Recommendations KW - risk KW - serum KW - study KW - Toxoplasma KW - Toxoplasmosis KW - Transmission KW - Wallonia AB - Pet cats live in close proximity with their owners and are considered a potential source of VL - 77 CP - 5 U1 - 35180 ER - TY - Generic T1 - Two cases of imported canine rabies in the Brussels area within six months time36806 Y1 - 2008 A1 - Le Roux,I. A1 - Steven Van Gucht KW - Area KW - Brussels KW - Case KW - Rabies KW - time AB - na JF - WHO Rabies Bulletin VL - 32 CP - 1 U1 - 38260 ER - TY - Generic T1 - La rage des chiroptères Y1 - 2006 A1 - Le Roux,I. A1 - Steven Van Gucht A1 - Klein,F. KW - chiroptères KW - de KW - rage AB - na JF - La feuille de contact Plecotus VL - 39 U1 - 36764 ER - TY - Generic T1 - Positive rubella sample in Belgium after vaccination of 15-month-old child Y1 - 0 A1 - Inne Nauwelaers A1 - E. Cornelissen A1 - M. Lapaille A1 - M. Abady A1 - Hubschen,J.M. A1 - Alexandra Vodolazkaia A1 - Marina Mukovnikova A1 - Steven Van Gucht ER - TY - RPRT T1 - Virological Surveillance of Influenza in Belgium: season 2018-2019 Y1 - 0 A1 - Isabelle Thomas A1 - Cyril Barbezange A1 - Steven Van Gucht A1 - Weyckmans,J. A1 - Ilham Fdillate A1 - Reinout Van Eycken A1 - Assia Hamouda A1 - Nathalie Bossuyt A1 - Sophie Quoilin A1 - Dieter Van Cauteren A1 - Sarah Denayer A1 - François Dufrasne ER -