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India had just under 150,000 reported coronavirus disease (COVID-19) deaths in 2020, fewer per 1 million persons than many other countries, such as Spain, France, the United Kingdom, and the [...]

Enterovirus A71 (EV-A71) and coxsackievirus A6 (CVA6) primarily cause hand, foot and mouth disease and have emerged to cause potential fatal neurological and systemic manifestations. However, limited surveillance data collected through passive surveillance systems hampers characterization of their epidemiological dynamics. We fit a series of catalytic models to age-stratified seroprevalence data for EV-A71 and CVA6 collected in England at three time points (2006, 2011 and 2017) to estimate the force of infection (FOI) over time and assess possible changes in transmission. For both serotypes, model comparison does not support the occurrence of important changes in transmission over the study period, and we find that a declining risk of infection with age and / or seroreversion are needed to explain the seroprevalence data. Furthermore, we provide evidence that the increased number of reports of CVA6 during 2006–2017 is unlikely to be explained by changes in surveillance. Therefore, we hypothesize that the increased number of CVA6 cases observed since 2011 must be explained by increased virus pathogenicity. Further studies of seroprevalence data from other countries would allow to confirm this. Our results underscore the value of seroprevalence data to unravel changes in the circulation dynamics of pathogens with weak surveillance systems and large number of asymptomatic infections. Author summary: Enteroviruses commonly cause infections in people of all ages with symptoms ranging from mild to severe. Enterovirus infections create a significant healthcare burden during outbreaks and large epidemics. However, the absence of consistent and systematic surveillance greatly impedes documentation of their true prevalence and collective impact on human health. In the UK, reporting from clinical settings is voluntary and passive, which limits accurate estimation of the overall infection incidence in the population. Here, we use data from seroprevalence surveys, which can detect past infections, to estimate the force of infection (rate at which susceptible individuals acquire infection) of enterovirus A71 and coxsackievirus A6 in England, UK, between 2006 and 2017. We found that transmission intensity for both enterovirus serotypes has remained relatively unchanged in this 12-year period. Furthermore, we analyze changes in serotype-specific enterovirus detections in England over the same period and found evidence that the increased number of reported CVA6 detections cannot only be related to changes in testing intensity. We therefore conclude that the increase in CVA6-related disease cases across England during this period could be attributed to the acquisition of increased pathogenicity (probability of disease after infection) of this serotype. Our approach may be useful to study the population-wide infection burden of other enterovirus serotypes for which clinical surveillance is limited. [ABSTRACT FROM AUTHOR]

The factors leading to the global emergence of Enterovirus D68 (EV-D68) in 2014 as a cause of acute flaccid myelitis (AFM) in children are unknown. To investigate potential changes in virus transmissibility or population susceptibility, we measured the seroprevalence of EV-D68-specific neutralising antibodies in serum samples collected in England in 2006, 2011, and 2017. Using catalytic mathematical models, we estimate an approximately 50% increase in the annual probability of infection over the 10-year study period, coinciding with the emergence of clade B around 2009. Despite such increase in transmission, seroprevalence data suggest that the virus was already widely circulating before the AFM outbreaks and the increase of infections by age cannot explain the observed number of AFM cases. Therefore, the acquisition of or an increase in neuropathogenicity would be additionally required to explain the emergence of outbreaks of AFM. Our results provide evidence that changes in enterovirus phenotypes cause major changes in disease epidemiology. [ABSTRACT FROM AUTHOR]

Background Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s). Methods and Findings In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children 70% population immunity among children Conclusions Immunity against serotype-2 poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization., Author(s): Margarita Pons-Salort 1, Natalie A. Molodecky 1, Kathleen M. O'Reilly 1, Mufti Zubair Wadood 2, Rana M. Safdar 3, Andrew Etsano 4, Rui Gama Vaz 5, Hamid Jafari 6, [...]

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections. [ABSTRACT FROM AUTHOR]

Vaccination timeliness is often not considered among standard performance indicators of routine vaccination programmes, such as vaccination coverage, yet quantifying vaccination delay could inform policies to promote in-time vaccination and help design vaccination schedules. Here, we analysed vaccination timeliness for 24 routine childhood immunisations for 54 countries. We extracted individual vaccination status and timing from Demographic and Health Surveys data from 54 countries with surveys from 2010 onwards. Individual data was used to estimate age at vaccination for <5 year-old children. Recommended age of vaccination for each country and vaccine was compared to the age at vaccination to determine vaccination delay. The evolution of vaccination delay over time was described using estimates from different birth cohorts. To identify socio-demographic indicators associated with delayed vaccination, we used multivariable Cox regression models with country as random effect and estimated the Hazard Ratio for vaccination with each vaccine-dose for each week post recommended vaccination age. Vaccine coverage at the recommended age was highest for birth and first doses (e.g. 50.5% BCG, 18.5% DTP-D1) and lowest for later doses (e.g. 5.5% DTP-D3, 16.3% MCV-D1, 8.2% MCV-D2). Median delay was lowest for birth doses, e.g. BCG (1 week (IQR: 0 to 4)), and it increased with later doses in vaccination courses: 1 (0, 4) week for DTP-D1 versus 4 (2, 9) weeks for DTP-D3. Although the median delay for each vaccine-dose remained largely constant over time, the range of delay estimates moderately decreased. Children living in rural areas, their countries' poorer wealth quintiles and whose mothers had no formal education were more likely to received delayed vaccinations. Although we report most children are vaccinated within the recommended age window, we found little reduction on routine immunisation delays over the last decade and that children from deprived socioeconomic backgrounds are more likely to receive delayed vaccinations., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KAMG reports speaker fees from Sanofi Pasteur outside the submitted work. All other authors declare no competing interests., (Copyright: © 2024 Derqui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Enterovirus D68 (EV-D68), first isolated in 1962, emerged in 2014, causing outbreaks of severe respiratory infections and acute flaccid myelitis. In this systematic review, we have compiled all available literature on age-stratified seroprevalence estimates of EV-D68. Ten studies from six countries were retained, all conducted using microneutralisation assays, despite wide variations in protocols and challenge viruses. The age profiles of seroprevalence were similar across time and regions; seroprevalence increased quickly with age, reaching roughly 100% by the age of 20 years and with no sign of decline throughout adulthood. This suggests continuous or frequent exposure of the populations to the virus, or possible cross-reactivity with other viruses. Studies with two or more cross-sectional surveys reported consistently higher seroprevalence at later timepoints, suggesting a global increase in transmission over time. This systematic review concludes that standardising serological protocols, understanding the contribution of cross-reactivity with other pathogens to the high reported seroprevalence, and quantifying individual exposure to EV-D68 over time are the main research priorities for the future., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)