The increasing complexity of arbovirus serology:An in-depth systematic review on cross-reactivity

Diagnosis of arbovirus infection or exposure by antibody testing is becoming increasingly difficult due to global expansion of arboviruses, which induce antibodies that may (cross-)react in serological assays. We provide a systematic review of the current knowledge and knowledge gaps in differential arbovirus serology. The search included Medline, Embase and Web of Science databases and identified 911 publications which were reduced to 102 after exclusion of studies not providing data on possible cross-reactivity or studies that did not meet the inclusion criteria regarding confirmation of virus exposure of reference population sets. Using a scoring system to further assess quality of studies, we show that the majority of the selected papers (N = 102) provides insufficient detail to support conclusions on specificity of serological outcomes with regards to elucidating antibody cross-reactivity. Along with the lack of standardization of assays, metadata such as time of illness onset, vaccination, infection and travel history, age and specificity of serological methods were most frequently missing. Given the critical role of serology for diagnosis and surveillance of arbovirus infections, better standards for reporting, as well as the development of more (standardized) specific serological assays that allow discrimination between exposures to multiple different arboviruses, are a large global unmet need

Spot the Difference-Development of a Syndrome Based Protein Microarray for Specific Serological Detection of Multiple Flavivirus Infections in Travelers

Background The family Flaviviridae, genus Flavivirus, holds many of the world’s most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods. Goal We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray. Results Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses. Conclusion Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.

Spot the Difference—Development of a Syndrome Based Protein Microarray for Specific Serological Detection of Multiple Flavivirus Infections in Travelers

The family Flaviviridae, genus Flavivirus, holds many of the world’s most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods. We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray. Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses

Het Rijksvaccinatieprogramma in Nederland. Ontwikkelingen in 2006

In 2006 several changes were made in the Dutch National Immunisation Programme (NIP): Hepatitis B vaccination at birth was added for children born to mothers positive for hepatitis B surface antigen; a new vaccine for diphtheria, tetanus, pertussis (a-cellular), poliomyelitis and Haemophilus influenzae (DTaP-IPV/Hib) was introduced; vaccination against pneumococcal disease was added at two, three, four and eleven months; risk groups for hepatitis B receive a combined vaccine for DTaP-IPV/Hib and HBV at the same ages; DT-IPV and aP at the age of four years were combined in one vaccine; and new MMR vaccines were introduced. As new information became available in 2006, the desirability to introduce vaccinations in the NIP for the following diseases could be (re)considered: hepatitis B (universal vaccination), rotavirus, varicella and human papillomavirus. For respiratory syncytial virus and meningococcal serogroup B disease no candidate vaccines are available yet. Extension of the programme with available vaccines for hepatitis A, influenza and tuberculosis is not (yet) recommended. The NIP in the Netherlands is effective and safe. However, continued monitoring of the effectiveness and safety of the NIP is important as changes are made regularly. Maintaining high vaccine uptake is vital to prevent (re)emergence of diseases. Furthermore, the programme should be regularly reviewed as new vaccines become available.In 2006 traden verschillende veranderingen op in het Rijksvaccinatieprogramma (RVP) in Nederland: kinderen die geboren worden uit moeders die chronisch geinfecteerd zijn met hepatitis B krijgen vlak na de geboorte een hepatitis B vaccinatie; er is een ander vaccin geintroduceerd voor difterie, kinkhoest (a-cellulair), tetanus, poliomyelitis en Haemophilus influenzae (DaKTP/Hib); vaccinatie tegen pneumokokken is toegevoegd op de leeftijd van 2, drie, vier en elf maanden; risicogroepen voor hepatitis B krijgen op diezelfde leeftijden een combinatievaccin voor DaKTP/Hib en hepatitis B; DTP en aK zijn gecombineerd in een vaccin op vierjarige leeftijd; en er zijn nieuwe BMR vaccins geintroduceerd. Op basis van informatie die in 2006 beschikbaar is gekomen wordt geadviseerd de introductie van vaccinaties voor de volgende ziekten te overwegen: hepatitis B (universele vaccinatie), rotavirus, waterpokken en humaan papillomavirus. Voor respiratoir syncytieel virus en meningokokken B zijn nog geen kandidaatvaccins beschikbaar en uitbreiding van het RVP met beschikbare vaccins voor hepatitis A, influenza en tuberculose wordt nog niet aanbevolen. Het RVP is effectief en veilig, maar voortdurende bewaking hiervan is groot belang, omdat er regelmatig veranderingen optreden. Handhaven van de hoge vaccinatiegraad is essentieel om terugkeer van ziekten te voorkomen. Verder moet regelmatig bekeken worden of het RVP aangepast moet worden aangezien er steeds nieuwe vaccins beschikbaar komen

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health—Climate Risk framework

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Nieuw van de markt? Coronavirusuitbraak in Wuhan.

China kampt met de uitbraak van een nieuw coronavirus die vooralsnog niet onder controle is. Wat is er precies aan de hand, wat weten we wel en wat niet, en hoe moet het verder? In dit artikel zetten we de huidige stand van zaken op een rij en bespreken we de internationale aanpak