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BackgroundAlthough seroprevalence studies have demonstrated the wide circulation of SARS-COV-2 in African countries, the impact on population health in these settings is still poorly understood. Using representative samples of the general population, we evaluated retrospective mortality and seroprevalence of anti-SARS-CoV-2 antibodies in Lubumbashi and Abidjan.MethodsThe studies included retrospective mortality surveys and nested anti-SARS-CoV-2 antibody prevalence surveys. In Lubumbashi the study took place during April-May 2021 and in Abidjan the survey was implemented in two phases: July-August 2021 and October-November 2021. Crude mortality rates were stratified between pre-pandemic and pandemic periods and further investigated by age group and COVID waves. Anti-SARS-CoV-2 seroprevalence was quantified by rapid diagnostic testing (RDT) and laboratory-based testing (ELISA in Lubumbashi and ECLIA in Abidjan).ResultsIn Lubumbashi, the crude mortality rate (CMR) increased from 0.08 deaths per 10 000 persons per day (pre-pandemic) to 0.20 deaths per 10 000 persons per day (pandemic period). Increases were particularly pronounced among ConclusionAlthough circulation of SARS-CoV-2 seems to have been extensive in both settings, the public health impact varied. The increases, particularly among the youngest age group, suggest indirect impacts of COVID and the pandemic on population health. The seroprevalence results confirmed substantial underdetection of cases through the national surveillance systems.

Background Pneumonic plague (PP), caused by Yersinia pestis, is the most feared clinical form of plague due to its rapid lethality and potential to cause outbreaks. PP outbreaks are now rare due to antimicrobial therapy. Methods A PP outbreak in Madagascar involving transmission of a Y. pestis strain resistant to streptomycin, the current recommended first-line treatment in Madagascar, was retrospectively characterized using epidemiology, clinical diagnostics, molecular characterization, and animal studies. Results The outbreak occurred in February 2013 in the Faratsiho district of Madagascar and involved 22 cases, including 3 untreated fatalities. The 19 other cases participated in funeral practices for the fatal cases and fully recovered after combination antimicrobial therapy: intramuscular streptomycin followed by oral co-trimoxazole. The Y. pestis strain that circulated during this outbreak is resistant to streptomycin resulting from a spontaneous point mutation in the 30S ribosomal protein S12 (rpsL) gene. This same mutation causes streptomycin resistance in 2 unrelated Y. pestis strains, one isolated from a fatal PP case in a different region of Madagascar in 1987 and another isolated from a fatal PP case in China in 1996, documenting this mutation has occurred independently at least 3 times in Y. pestis. Laboratory experiments revealed this mutation has no detectable impact on fitness or virulence, and revertants to wild-type are rare in other species containing it, suggesting Y. pestis strains containing it could persist in the environment. Conclusions Unique antimicrobial resistant (AMR) strains of Y. pestis continue to arise in Madagascar and can be transmitted during PP outbreaks.

Highlights • A(H7N9) patients mounted strong serum HAI antibody responses against A(H7N9) virus. • Mean A(H7N9) virus-specific HAI antibody titers remained above 80 for 11 months. • Severely ill patients mounted higher HAI antibody responses against A(H7N9) virus., Objectives The long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood. Methods We conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013–2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity. Results Of 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness. Conclusions Patients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1 and 11 months after illness onset.

During outbreaks, the lack of diagnostic “gold standard” can mask the true burden of infection in the population and hamper the allocation of resources required for control. Here, we present an analytical framework to evaluate and optimize the use of diagnostics when multiple yet imperfect diagnostic tests are available. We apply it to laboratory results of 2,136 samples, analyzed with three diagnostic tests (based on up to seven diagnostic outcomes), collected during the 2017 pneumonic (PP) and bubonic plague (BP) outbreak in Madagascar, which was unprecedented both in the number of notified cases, clinical presentation, and spatial distribution. The extent of this outbreaks has however remained unclear due to non-optimal assays. Using latent class methods, we estimate that 7%-15% of notified cases were Yersinia pestis-infected. Overreporting was highest during the peak of the outbreak and lowest in the rural settings endemic to Yersinia pestis. Molecular biology methods offered the best compromise between sensitivity and specificity. The specificity of the rapid diagnostic test was relatively low (PP: 82%, BP: 85%), particularly for use in contexts with large quantities of misclassified cases. Comparison with data from a subsequent seasonal Yersinia pestis outbreak in 2018 reveal better test performance (BP: specificity 99%, sensitivity: 91%), indicating that factors related to the response to a large, explosive outbreak may well have affected test performance. We used our framework to optimize the case classification and derive consolidated epidemic trends. Our approach may help reduce uncertainties in other outbreaks where diagnostics are imperfect.

BackgroundNipah virus (NiV) is an emerging, bat-borne pathogen that can be transmitted from person-to-person. Vaccines are currently being developed for NiV, and studies funded to evaluate their safety and immunogenicity, so that they could possibly be used to contain outbreaks. An important unanswered question is whether it will be possible to evaluate the efficacy of vaccine candidates in phase III clinical trials in a context where spillovers from the zoonotic reservoir are infrequent and associated with small outbreaks. The objective of this study was to investigate the feasibility of conducting a phase III vaccine trial in Bangladesh, the only country reporting regularly NiV cases.MethodsWe used simulations based on previously observed NiV cases from Bangladesh, an assumed vaccine efficacy of 90% and other NiV vaccine target characteristics, to compare three vaccination study designs: (i) cluster randomized ring vaccination, (ii) cluster randomized mass vaccination, and (iii) an observational case-control study design.ResultsThe simulations showed that, assuming a ramp-up period of 10 days and a mean hospitalization delay of 4 days, it would take 516 years and over 163,000 vaccine doses to run a ring vaccination trial under current epidemic conditions. A cluster-randomized trial in the two most affected districts would take 81 years and 2.3 million vaccine doses. An observational case-control design in these two districts would require seven years and 2.5 million vaccine doses.DiscussionWithout a change in the epidemiology of NiV, ring vaccination or cluster-randomized trials are unlikely to be completed within a reasonable time window. In this light, the remaining options are: (i) not conducting a phase III trial until the epidemiology of NiV changes, (ii) identifying alternative ways to licensure such as observational studies or controlled studies in animals such as in the US Food and Drug Administration’s (FDA) Animal Rule.

Summary: Background: During the COVID-19 lockdown period from March 17 to May 11, 2020, French authorities in Paris and its suburbs relocated people experiencing recurrent homelessness to emergency shelters, hotels, and large venues. A serological survey was done at some of these locations to assess the COVID-19 exposure prevalence in this group. Methods: We did a cross-sectional seroprevalence study at food distribution sites, emergency shelters, and workers' residences that were provided medical services by Médecins Sans Frontières in Paris and Seine-Saint-Denis in the Ile-de-France region. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seropositivity was detected by Luciferase-Linked Immunosorbent Assay and Pseudo Neutralization Test. Sociodemographic and exposure related information was collected via a verbal questionnaire to analyse risk factors and associations with various COVID-19 symptoms. Findings: Between June 23 and July 2, 2020, 426 (52%) of 818 individuals recruited tested positive in 14 sites. Seroprevalence varied significantly by type of recruitment site (χ2 p

Summary Background Real-time PCR is recommended to detect SARS-CoV-2 infection. However, PCR availability is restricted in most countries. Rapid diagnostic tests are considered acceptable alternatives, but data are lacking on their performance. We assessed the performance of four antibody-based rapid diagnostic tests and one antigen-based rapid diagnostic test for detecting SARS-CoV-2 infection in the community in Cameroon. Methods In this clinical, prospective, diagnostic accuracy study, we enrolled individuals aged at least 21 years who were either symptomatic and suspected of having COVID-19 or asymptomatic and presented for screening. We tested peripheral blood for SARS-CoV-2 antibodies using the Innovita (Biological Technology; Beijing, China), Wondfo (Guangzhou Wondfo Biotech; Guangzhou, China), SD Biosensor (SD Biosensor; Gyeonggi-do, South Korea), and Runkun tests (Runkun Pharmaceutical; Hunan, China), and nasopharyngeal swabs for SARS-CoV-2 antigen using the SD Biosensor test. Antigen rapid diagnostic tests were compared with Abbott PCR testing (Abbott; Abbott Park, IL, USA), and antibody rapid diagnostic tests were compared with Biomerieux immunoassays (Biomerieux; Marcy l'Etoile, France). We retrospectively tested two diagnostic algorithms that incorporated rapid diagnostic tests for symptomatic and asymptomatic patients using simulation modelling. Findings 1195 participants were enrolled in the study. 347 (29%) tested SARS-CoV-2 PCR-positive, 223 (19%) rapid diagnostic test antigen-positive, and 478 (40%) rapid diagnostic test antibody-positive. Antigen-based rapid diagnostic test sensitivity was 80·0% (95% CI 71·0–88·0) in the first 7 days after symptom onset, but antibody-based rapid diagnostic tests had only 26·8% sensitivity (18·3–36·8). Antibody rapid diagnostic test sensitivity increased to 76·4% (70·1–82·0) 14 days after symptom onset. Among asymptomatic participants, the sensitivity of antigen-based and antibody-based rapid diagnostic tests were 37·0% (27·0–48·0) and 50·7% (42·2–59·1), respectively. Cohen's κ showed substantial agreement between Wondfo antibody rapid diagnostic test and gold-standard ELISA (κ=0·76; sensitivity 0·98) and between Biosensor and ELISA (κ=0·60; sensitivity 0·94). Innovita (κ=0·47; sensitivity 0·93) and Runkun (κ=0·43; sensitivity 0·76) showed moderate agreement. An antigen-based retrospective algorithm applied to symptomatic patients showed 94·0% sensitivity and 91·0% specificity in the first 7 days after symptom onset. For asymptomatic participants, the algorithm showed a sensitivity of 34% (95% CI 23·0–44·0) and a specificity of 92·0% (88·0–96·0). Interpretation Rapid diagnostic tests had good overall sensitivity for diagnosing SARS-CoV-2 infection. Rapid diagnostic tests could be incorporated into efficient testing algorithms as an alternative to PCR to decrease diagnostic delays and onward viral transmission. Funding Medecins Sans Frontieres WACA and Medecins Sans Frontieres OCG. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

BackgroundA nationwide lockdown was implemented in France on 17 March 2020 to control the COVID-19 pandemic. People living in precarious conditions were relocated by the authorities to emergency shelters, hotels and large venues. Médecins sans Frontières (MSF) then intervened to provide medical care in several of these locations in Paris and in Seine-Saint-Denis, one of its suburbs, between March and June 2020. A seroprevalence survey was conducted to assess the level of exposure to COVID-19 among the population living in the sites. To our knowledge, this is the first assessment of the impact of the pandemic on populations living in insecure conditions in Europe.MethodsWe conducted a cross-sectional seroprevalence study in the food distribution sites, emergency shelters and workers residences supported by MSF in Paris and Seine-Saint-Denis, to determine the extent of COVID-19 exposure as determined by SARS-CoV2 antibody seropositivity. The detection of SARS-COV2 antibodies in serum was performed at the Institut Pasteur of Paris using two LuLISA (Luciferase-Linked Immunosorbent Assay) assays and a Pseudo Neutralization Test. A questionnaire covering sociodemographic characteristics, living conditions, adherence to sanitary recommendations and symptom manifestations was also completed. We describe here the seroprevalence site by site and identify the risk factors for seropositivity using a multivariable logistic regression model with site random effects. We also investigated associations between seropositivity and symptoms eventually reported.FindingsOverall, 426/818 individuals tested positive in the 14 sites investigated. Seroprevalence varied significantly with the type of site (chi2 pInterpretationThe results demonstrate rather high exposure to SARS-COV-2 with important variations between study sites. Living in crowded conditions was identified as the most important explanatory factor for differences in levels of exposure. This study describes the key factors which determine the risk of exposure and illustrates the importance of identifying populations at high risk of exposure in order to orient and adapt prevention and control strategies to their specific needs.

Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1642 contacts of 94 Nipah virus case patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case patients who died, peaked on the day of death. Given transmission has only been observed among fatal cases of Nipah virus infection, our findings suggest that changes in contact patterns during illness contribute to risk of infection.

It is of uttermost importance that the global health community develops the surveillance capability to effectively monitor emerging zoonotic pathogens that constitute a major and evolving threat for human health. In this study, we propose a comprehensive framework to measure changes in (1) spillover risk, (2) interhuman transmission, and (3) morbidity/mortality associated with infections based on 6 epidemiological key indicators derived from routine surveillance. We demonstrate the indicators’ value for the retrospective or real-time assessment of changes in transmission and epidemiological characteristics using data collected through a long-standing, systematic, hospital-based surveillance system for Nipah virus in Bangladesh. We show that although interhuman transmission and morbidity/mortality indicators were stable, the number and geographic extent of spillovers varied significantly over time. This combination of systematic surveillance and active tracking of transmission and epidemiological indicators should be applied to other high-risk emerging pathogens to prevent public health emergencies.

Background West Nile virus (WNV) transmission was much greater in 2018 than in previous seasons in Europe. Focusing on Emilia-Romagna region (northern Italy), we analyzed detailed entomological and epidemiological data collected in 2013–2018 to quantitatively assess environmental drivers of transmission and explore hypotheses to better understand why the 2018 epidemiological season was substantially different than the previous seasons. In particular, in 2018 WNV was detected at least two weeks before the observed circulation in 2013–2017 and in a larger number of mosquito pools. Transmission resulted in 100 neuroinvasive human cases in the region, more than the total number of cases recorded between 2013 and 2017. Methodology We used temperature-driven mathematical models calibrated through a Bayesian approach to simulate mosquito population dynamics and WNV infection rates in the avian population. We then estimated the human transmission risk as the probability, for a person living in the study area, of being bitten by an infectious mosquito in a given week. Finally, we translated such risk into reported WNV human infections. Principal findings The estimated prevalence of WNV in the mosquito and avian populations were significantly higher in 2018 with respect to 2013–2017 seasons, especially in the eastern part of the region. Furthermore, peak avian prevalence was estimated to have occurred earlier, corresponding to a steeper decline towards the end of summer. The high mosquito prevalence resulted in a much greater predicted risk for human transmission in 2018, which was estimated to be up to eight times higher than previous seasons. We hypothesized, on the basis of our modelling results, that such greater WNV circulation might be partially explained by exceptionally high spring temperatures, which have likely helped to amplify WNV transmission at the beginning of the 2018 season., Author summary West Nile virus (WNV) is one of the most recent emerging mosquito-borne diseases in Europe and North America. While most human infections are asymptomatic, about 1% of them can result in severe neurological diseases which might be fatal. WNV transmission was unusually greater in 2018 than in previous years in many European countries, resulting in a large number of human infections. Focusing on Emilia-Romagna region (Italy), we developed an epidemiological model informed by entomological data; through that we found that exceptionally high spring temperatures might have contributed at amplifying WNV transmission at the beginning of the season, causing greater WNV prevalence in mosquito and avian populations during the summer, which resulted in a higher estimated risk for human transmission. Thus, weather anomalies at the beginning of the mosquito breeding season, which are likely to become more common under the projected scenarios of climate change, might act as an early warning signal for public health authorities, enabling them to design efficient surveillance and prevention strategies.

Official case counts suggest Africa has not seen the expected burden of COVID-19 as predicted by international health agencies, and the proportion of asymptomatic patients, disease severity, and mortality burden differ significantly in Africa from what has been observed elsewhere. Testing for SARS-CoV-2 was extremely limited early in the pandemic and likely led to under-reporting of cases leaving important gaps in our understanding of transmission and disease characteristics in the African context. SARS-CoV-2 antibody prevalence and serologic response data could help quantify the burden of COVID-19 disease in Africa to address this knowledge gap and guide future outbreak response, adapted to the local context. However, such data are widely lacking in Africa. We conducted a cross-sectional seroprevalence survey among 1,192 individuals seeking COVID-19 screening and testing in central Cameroon using the Innovita antibody-based rapid diagnostic. Overall immunoglobulin prevalence was 32%, IgM prevalence was 20%, and IgG prevalence was 24%. IgM positivity gradually increased, peaking around symptom day 20. IgG positivity was similar, gradually increasing over the first 10 days of symptoms, then increasing rapidly to 30 days and beyond. These findings highlight the importance of diagnostic testing and asymptomatic SARS-CoV-2 transmission in Cameroon, which likely resulted in artificially low case counts. Rapid antibody tests are a useful diagnostic modality for seroprevalence surveys and infection diagnosis starting 5-7 days after symptom onset. These results represent the first step towards better understanding the SARS-CoV-2 immunological response in African populations.

Since its emergence in 2012, 2,260 cases and 803 deaths due to Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization. Most cases were due to transmission in healthcare settings, sometimes causing large outbreaks. We analyzed epidemiologic and clinical data of laboratory-confirmed MERS-CoV cases from eleven healthcare-associated outbreaks in the Kingdom of Saudi Arabia and the Republic of Korea between 2015–2017. We quantified key epidemiological differences between outbreaks. Twenty-five percent (n = 105/422) of MERS cases who acquired infection in a hospital setting were healthcare personnel. In multivariate analyses, age ≥65 (OR 4.8, 95%CI: 2.6–8.7) and the presence of underlying comorbidities (OR: 2.7, 95% CI: 1.3–5.7) were associated with increased mortality whereas working as healthcare personnel was protective (OR 0.07, 95% CI: 0.01–0.34). At the start of these outbreaks, the reproduction number ranged from 1.0 to 5.7; it dropped below 1 within 2 to 6 weeks. This study provides a comprehensive characterization of MERS HCA-outbreaks. Our results highlight heterogeneities in the epidemiological profile of healthcare-associated outbreaks. The limitations of our study stress the urgent need for standardized data collection for high-threat respiratory pathogens, such as MERS-CoV.

International audience; BackgroundNipah virus is a highly virulent zoonotic pathogen that can be transmitted between humans. Understanding the dynamics of person-to-person transmission is key to designing effective interventions.MethodsWe used data from all Nipah virus cases identified during outbreak investigations in Bangladesh from April 2001 through April 2014 to investigate case-patient characteristics associated with onward transmission and factors associated with the risk of infection among patient contacts.ResultsOf 248 Nipah virus cases identified, 82 were caused by person-to-person transmission, corresponding to a reproduction number (i.e., the average number of secondary cases per case patient) of 0.33 (95% confidence interval [CI], 0.19 to 0.59). The predicted reproduction number increased with the case patient’s age and was highest among patients 45 years of age or older who had difficulty breathing (1.1; 95% CI, 0.4 to 3.2). Case patients who did not have difficulty breathing infected 0.05 times as many contacts (95% CI, 0.01 to 0.3) as other case patients did. Serologic testing of 1863 asymptomatic contacts revealed no infections. Spouses of case patients were more often infected (8 of 56 [14%]) than other close family members (7 of 547 [1.3%]) or other contacts (18 of 1996 [0.9%]). The risk of infection increased with increased duration of exposure of the contacts (adjusted odds ratio for exposure of >48 hours vs. ≤1 hour, 13; 95% CI, 2.6 to 62) and with exposure to body fluids (adjusted odds ratio, 4.3; 95% CI, 1.6 to 11).ConclusionsIncreasing age and respiratory symptoms were indicators of infectivity of Nipah virus. Interventions to control person-to-person transmission should aim to reduce exposure to body fluids. (Funded by the National Institutes of Health and others.)

Background: Madagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200–700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings. Methods: Clinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations. Findings: 2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (

Mathematical models play an increasingly important role in our understanding of the transmission and control of infectious diseases. Here, we present concrete examples illustrating how mathematical models, paired with rigorous statistical methods, are used to parse data of different levels of detail and breadth and estimate key epidemiological parameters (e.g., transmission and its determinants, severity, impact of interventions, drivers of epidemic dynamics) even when these parameters are not directly measurable, when data are limited, and when the epidemic process is only partially observed. Finally, we assess the hurdles to be taken to increase availability and applicability of these approaches in an effort to ultimately enhance their public health impact., Highlights Many data can be used to estimate the transmission potential of a pathogen, including descriptions of the transmission chains, human cluster sizes, sources of infection, and epidemic curves. An important agenda in public health is understanding the impact of control methods. However, the dynamic nature of epidemics makes this task challenging. Models can disentangle the natural course of outbreaks from the effect of external factors. In the absence of reliable surveillance data, models can reconstruct epidemic history by combining age-specific seroprevalence data with an understanding of the natural history of infection. Mechanisms of immunity are hard to observe at an individual level, yet they affect population-level dynamics. Models can tease out such signatures. Morbidity and mortality can be difficult to estimate when many infections are unobserved and severe infections are reported more often. Models can be used to correct for under-reporting and selection bias.

Water, sanitation, and hygiene (WaSH) technologies and behaviors can prevent infection by soil-transmitted helminth species independently, but may also interact in complex ways. However, these interactions are poorly understood. The purpose of this study was to characterize how school and home WaSH exposures were associated with Ascaris lumbricoides infection and to identify relevant interactions between separate WaSH technologies and behaviors. A study was conducted among 4,404 children attending 51 primary schools in western Kenya. We used multivariable mixed effects logistic regression to characterize how various WaSH exposures were associated with A. lumbricoides infection after annual school-based deworming. Few WaSH behaviors and technologies were independently associated with A. lumbricoides infection. However, by considering relevant interdependencies between variables, important associations were elucidated. The association between handwashing and A. lumbricoides depended largely upon the pupils' access to an improved water source. Among pupils who had access to improved water sources, A. lumbricoides prevalence was lower for those who handwashed both at school and home compared with neither place (odds ratio: 0.38, 95% confidence interval: 0.18–0.83; P = 0.01). This study contributes to a further understanding of the impact of WaSH on A. lumbricoides infection and shows the importance of accounting for interactions between WaSH technologies and behaviors.

In Senegal, chikungunya virus (CHIKV) is maintained in a sylvatic cycle and causes sporadic cases or small outbreaks in rural areas. However, little is known about the influence of the environment on its transmission. To address the question, 120 villages were randomly selected in the Kedougou region of southeastern Senegal. In each selected village, 10 persons by randomly selected household were sampled and tested for specific anti-CHIKV IgG antibodies by ELISA. We investigated the association of CHIKV seroprevalence with environmental variables using logistic regression analysis and the spatial correlation of village seroprevalence based on semivariogram analysis. Fifty-four percent (51%&ndash, 57%) of individuals sampled during the survey tested positive for CHIKV-specific IgG. CHIKV seroprevalence was significantly higher in populations living close to forested areas (Normalized Difference Vegetation Index (NDVI), Odds Ratio (OR) = 1.90 (1.42&ndash, 2.57)), and was negatively associated with population density (OR = 0.76 (0.69&ndash, 0.84)). In contrast, in gold mining sites where population density was &gt, 400 people per km2, seroprevalence peaked significantly among adults (46% (27%&ndash, 67%)) compared to all other individuals (20% (12%&ndash, 31%)). However, traditional gold mining activities significantly modify the transmission dynamic of CHIKV, leading to a potential increase of the risk of human exposition in the region.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics., info:eu-repo/semantics/published

Dengue is the most common vector-borne viral disease worldwide, affecting 390 million people in tropical and sub-tropical areas each year [1]. The clinical spectrum of dengue ranges from a mild, non-specific febrile syndrome (classic dengue fever) to severe dengue with plasma leakage, haemorrhage or organ impairment [2]. In 20–97% of cases, dengue is clinically inapparent; this proportion varies considerably, across countries and years [3]. Asymptomatic infections may contribute significantly to virus transmission [4]. Aedes aegypti is the main vector of dengue virus in tropical areas [5]. Of more direct concern to continental Europe is a secondary vector, Ae. albopictus. Originally a tree-breeding mosquito of the forests of south-east Asia, Ae. albopictus has dramatically expanded its geographic distribution throughout the world in the past 40 years. Taking advantage of increasing global trade, Ae. albopictus spread to temperate regions in the late 1970s [6]. It was first reported in Europe in 1979 and has since been observed in France and 14 other countries along the Mediterranean. Given the recent establishment and rapid spread of Ae. albopictus in southern France, there is high potential for the emergence of arboviruses such as dengue virus (DENV), chikungunya and Zika viruses [7-10]. Limited local transmission of DENV was reported in southern France in 2010, 2013 and 2014, each cluster involving ≤ 2 cases [11-13]. Recently, from July to September 2015, a dengue outbreak occurred in the neighbourhood of Nimes, Occitanie region [14]. Epidemiological investigations including door-to-door case finding conducted in August 2015 revealed seven autochthonous cases of dengue serotype 1 (DENV-1) that arose from a likely primary case over a 2-month period [14]. In France, a national surveillance and response plan aims to prevent and control local dissemination of dengue and other Ae. albopictus-transmitted viruses. However, little is known about the drivers and determinants of local transmission of dengue in the European setting, and the national response plan may not be fully effective. In November 2015 we carried out a seroprevalence survey in order to determine the true extent of the dengue outbreak in Nimes and the proportion of asymptomatic infections. We also reconstructed the transmission chain to characterise the spatial pattern of dengue transmission and to contribute to improving the performance of the French surveillance and response plan.

Due to the increasing global spread of arboviruses, the geographic extent of virus co-circulation is expanding. This complicates the diagnosis of febrile conditions and can have direct effects on the epidemiology. As previously demonstrated, subsequent infections by two closely related viruses, such as those belonging to the Japanese encephalitis virus (JEV) serocomplex, can lead to partial or complete cross-immunity, altering the risk of infections or the outcome of disease. Two flaviviruses that may interact at population level are West Nile virus (WNV) and Usutu virus (USUV). These pathogens have antigenic cross-reactivity and affect human and animal populations throughout Europe. This systematic review investigates the overlap of WNV and USUV transmission cycles, not only geographically but also in terms of host and vector ranges. Co-circulation of WNV and USUV was reported in 10 countries and the viruses were found to infect 34 common bird species belonging to 11 orders. Moreover, four mosquito species are potential vectors for both viruses. Taken together, these data suggest that WNV and USUV transmission overlaps substantially in Europe and highlight the importance of further studies investigating the interactions between the two viruses within host and vector populations.

Background. School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. Methods. We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. Results. During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, −.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. Conclusions. Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01658774","term_id":"NCT01658774"}}NCT01658774.

Background School-based deworming is widely implemented in various countries to reduce the burden of soil-transmitted helminths (STHs), however, the frequency of drug administration varies in different settings. In this study, we compared the impact of a single annual treatment and 4-monthly treatment over a follow-up among Kenyan school children, and investigated the factors associated with residual infection. Methods We performed a secondary analysis of data from a randomized trial investigating whether deworming for STHs alters risk of acquiring malaria. Children received either a single treatment or 4-monthly albendazole treatments were followed longitudinally from February 2014 to October 2014. The relative impact of treatment and factors associated with residual infections were investigated using mixed-effects regression models. Predisposition to infection was assessed based on Spearman’s rank and Kendall’s Tau correlation coefficients. Results In the 4-monthly treatment group, the proportion of children infected with hookworm decreased from 59.9 to 5.7%, while Ascaris lumbricoides infections dropped from 55.7 to 6.2%. In the single treatment group, hookworm infections decreased over the same time period from 58.7 to 18.3% (12.6% absolute difference in reduction, 95% CI: 8.9–16.3%), and A. lumbricoides from 56.7 to 23.3% (17.1% absolute difference in reduction, 95% CI: 13.1–21.1%). There was strong evidence for predisposition to both STH types. Residual hookworm infection among children on 4-monthly treatment were associated with male sex and baseline nutritional status, whereas A. lumbricoides infection was associated with individual and school-level infection at baseline, latrine cleanliness at schools. Conclusions This study found that 4-monthly treatment w more effective than single annual treatment. Repeated treatments led to dramatic reductions in the intensities of STHs, but did not completely clear infections among school children in Kenya, a presumed reflection of reinfection in a setting where there is ongoing transmission. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0244-z) contains supplementary material, which is available to authorized users.

Background The International Health Regulations outline core requirements to ensure the detection of public health threats of international concern. Assessing the capacity of surveillance systems to detect these threats is crucial for evaluating a country’s ability to meet these requirements. Methods and Findings We propose a framework to evaluate the sensitivity and representativeness of hospital-based surveillance and apply it to severe neurological infectious diseases and fatal respiratory infectious diseases in Bangladesh. We identified cases in selected communities within surveillance hospital catchment areas using key informant and house-to-house surveys and ascertained where cases had sought care. We estimated the probability of surveillance detecting different sized outbreaks by distance from the surveillance hospital and compared characteristics of cases identified in the community and cases attending surveillance hospitals. We estimated that surveillance detected 26% (95% CI 18%–33%) of severe neurological disease cases and 18% (95% CI 16%–21%) of fatal respiratory disease cases residing at 10 km distance from a surveillance hospital. Detection probabilities decreased markedly with distance. The probability of detecting small outbreaks (three cases) dropped below 50% at distances greater than 26 km for severe neurological disease and at distances greater than 7 km for fatal respiratory disease. Characteristics of cases attending surveillance hospitals were largely representative of all cases; however, neurological disease cases aged, Henrik Salje and colleagues propose a framework to examine the capacity of hospital-based surveillance data to detect public health threats in Bangladesh., Author Summary Why Was This Study Done? Many countries rely on hospital-based surveillance for the detection of infectious diseases of national and global public health relevance. It is often difficult to access suitable external reference data to assess the capacity of a surveillance system to detect cases and outbreaks or to characterize cases. What Did the Researchers Do and Find? We demonstrate a novel approach using healthcare utilization data to evaluate the sensitivity and representativeness of severe infectious disease surveillance in Bangladesh. The capacity to detect cases and outbreaks decreased with distance from surveillance hospitals. Cases captured by surveillance differed from cases in communities by age and socioeconomic status. Geographic coverage of surveillance could be improved by including other hospitals in the surveillance system. What Do These Findings Mean? The presented approach is applicable for a wide range of infectious diseases in different settings, taking some practical considerations into account. Hospital-based surveillance may have low sensitivity in rural areas at greater distances from surveillance hospitals, suggesting a risk of unrecognized transmission of emerging infectious diseases. Alternative surveillance strategies, such as including additional hospitals in the surveillance system or considering alternative data streams, may help to increase surveillance performance in such remote regions.

Background Dengue is a mosquito-borne virus that causes extensive morbidity and economic loss in many tropical and subtropical regions of the world. Often present in cities, dengue virus is rapidly spreading due to urbanization, climate change and increased human movements. Dengue cases are often heterogeneously distributed throughout cities, suggesting that small-scale determinants influence dengue urban transmission. A better understanding of these determinants is crucial to efficiently target prevention measures such as vector control and education. The aim of this study was to determine which socioeconomic and environmental determinants were associated with dengue incidence in an urban setting in the Pacific. Methodology An ecological study was performed using data summarized by neighborhood (i.e. the neighborhood is the unit of analysis) from two dengue epidemics (2008–2009 and 2012–2013) in the city of Nouméa, the capital of New Caledonia. Spatial patterns and hotspots of dengue transmission were assessed using global and local Moran’s I statistics. Multivariable negative binomial regression models were used to investigate the association between dengue incidence and various socioeconomic and environmental factors throughout the city. Principal findings The 2008–2009 epidemic was spatially structured, with clusters of high and low incidence neighborhoods. In 2012–2013, dengue incidence rates were more homogeneous throughout the city. In all models tested, higher dengue incidence rates were consistently associated with lower socioeconomic status (higher unemployment, lower revenue or higher percentage of population born in the Pacific, which are interrelated). A higher percentage of apartments was associated with lower dengue incidence rates during both epidemics in all models but one. A link between vegetation coverage and dengue incidence rates was also detected, but the link varied depending on the model used. Conclusions This study demonstrates a robust spatial association between dengue incidence rates and socioeconomic status across the different neighborhoods of the city of Nouméa. Our findings provide useful information to guide policy and help target dengue prevention efforts where they are needed most., Author summary Dengue virus is rapidly spreading throughout tropical and subtropical regions worldwide, possibly aided by environmental change, urbanization and/or increase in human mobility. Already present in 120 countries, dengue virus causes extensive disease burden and generates large economic costs. As dengue is mosquito-borne, its transmission pattern is strongly influenced by climate. However, dengue cases are not always distributed evenly throughout cities, where climate can be assumed to be homogenous. This suggests that other factors which are heterogeneously distributed in cities could play a role in dengue transmission, such as socioeconomic status and environmental factors (both natural and built). Identifying those factors is crucial to develop and target dengue prevention interventions, such as mosquito control and education. Our study uses dengue incidence statistics from two large epidemics in Nouméa, the capital of New Caledonia, to investigate which socioeconomic or environmental factors correlate with dengue incidence in an urban setting. Dengue incidence was consistently higher in neighborhoods where socioeconomic status was lower (i.e. lower revenue or higher unemployment) and often higher where the proportion of single-family houses in all buildings was higher. Our data suggest that, if resources are limited, prevention measures should be targeted in priority towards neighborhoods of lower socioeconomic status.

Usutu virus (USUV) has been isolated in several African and European countries mainly from mosquitoes and birds. However, previous benign and two recent severe cases of human infections point out the need of a tool for the identification of USUV in human samples. A published real-time reverse transcription (RT) PCR assay for the detection of USUV in human blood or cerebrospinal fluid does not take into account the genetic variability of USUV in different geographic regions. Therefore, this article presents a quantitative real-time RT-PCR assay based on sequences from Europe and Africa. Primers and probe were designed in conserved regions among USUV strains that differed from closely related flaviviruses. The specificity of the assay was investigated by testing 16 other flaviviruses circulating in Africa. The sensitivity was determined by testing serial dilutions of virus and RNA standard. Intra- and inter-assay coefficients of variation were evaluated by 10 reactions in a same and in different assays, respectively. The assay provides high analytical specificity for USUV and detection limits of 1.2pfu/reaction for virus dilutions in L-15 medium or human serum and 60 copies/reaction for the RNA standard. The assay needs to be evaluated in a clinical context and integrated in standard diagnosis of flaviviral diseases. peerReviewed

Human enteroviruses are a major cause of neurological and other diseases. Over 100 serotypes are known that exhibit unexplained complex patterns of incidence, from regular cycles to more irregular patterns, and new emergences. Using 15 years of surveillance data from Japan (2000-2014) and a stochastic transmission model with accurate demography, we show that acquired serotype-specific immunity can explain the diverse patterns of 18 of the 20 most common serotypes (including Coxsackieviruses, Echoviruses and Enterovirus-A71). The remaining two serotypes required a change in viral characteristics, including an increase in pathogenicity for Coxsackievirus-A6, consistent with its recent global rise in incidence. Based on our findings, we are able to predict outbreaks two years ahead of time (2015-2016). These results have implications for the impact of vaccines under development.

Background Malaria among school children is increasingly receiving attention, yet the burden of malaria in this age group is poorly defined. This study presents data on malaria morbidity among school children in Bungoma county, western Kenya. Method This study investigated the burden and risk factors of Plasmodium falciparum infection, clinical malaria, and anaemia among 2346 school children aged 5–15 years, who were enrolled in an individually randomized trial evaluating the effect of anthelmintic treatment on the risks of malaria. At baseline, children were assessed for anaemia and nutritional status and information on household characteristics was collected. Children were followed-up for 13 months to assess the incidence of clinical malaria by active detection, and P. falciparum infection and density evaluated using repeated cross-sectional surveys over 15 months. Results On average prevalence of P. falciparum infection was 42 % and ranged between 32 and 48 % during the five cross-sectional surveys. Plasmodium falciparum prevalence was significantly higher among boys than girls. The overall incidence of clinical malaria was 0.26 episodes per person year (95 % confidence interval, 0.24–0.29) and was significantly higher among girls (0.23 versus 0.31, episodes per person years). Both infection prevalence and clinical disease varied by season. In multivariable analysis, P. falciparum infection was associated with being male, lower socioeconomic status and stunting. The risk of clinical malaria was associated with being female. Conclusion These findings show that the burden of P. falciparum parasitaemia, clinical malaria and anaemia among school children is not insignificant, and suggest that malaria control programmes should be expanded to include this age group. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1176-y) contains supplementary material, which is available to authorized users.

Introduction: \ud In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most costeffective treatment strategy and delivery system to achieve this goal?\ud \ud Methods and analysis: \ud Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.\ud \ud Ethics and dissemination: \ud Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site.\ud \ud Trial registration number: NCT02397772

Background The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya. Materials and Methods Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels. Principal Findings The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores. Conclusions The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes., Author Summary Most countries with endemic soil-transmitted helminth (STH) infections have started implementing deworming programmes in recent years. However, the achievable impact on the prevalence and intensity of infections will depend on the socioeconomic and environmental context in which the programme is implemented. We use a previously developed framework that considers the epidemiology of STH transmission, capacity to deliver treatment, operational and financial feasibility, to investigate reasons for the observed within-country variation of deworming programme impact based on data from the national school based deworming programme in Kenya. The study demonstrates that programme impact varied markedly within the country and that reductions in STH infection were associated with levels of access to water, sanitation and hygiene (at schools or within communities). The described framework can help to identify areas where lower programme impact can be expected, and also to determine which additional interventions should be implemented in support of the deworming efforts.

Background Soil-transmitted helminths, a class of parasitic intestinal worms, are pervasive in many low-income settings. Infection among children can lead to poor nutritional outcomes, anaemia, and reduced cognition. Mass treatment, typically administered through schools, with yearly or biannual drugs is inexpensive and can reduce worm burden, but reinfection can occur rapidly. Access to and use of sanitation facilities and proper hygiene can reduce infection, but rigorous data are scarce. Among school-age children, infection can occur at home or at school, but little is known about the relative importance of WASH in transmission in these two settings. Methods We explored the relationships between school and household water, sanitation, and hygiene conditions and behaviours during the baseline of a large-scale mass drug administration programme in Kenya. We assessed several WASH measures to quantify the exposure of school children, and developed theory and empirically-based parsimonious models. Results Results suggest mixed impacts of household and school WASH on prevalence and intensity of infection. WASH risk factors differed across individual worm species, which is expected given the different mechanisms of infection. Conclusions No trend of the relative importance of school versus household-level WASH emerged, though some factors, like water supply were more strongly related to lower infection, which suggests it is important in supporting other school practices, such as hand-washing and keeping school toilets clean. Electronic supplementary material The online version of this article (doi:10.1186/s13071-015-1024-x) contains supplementary material, which is available to authorized users.

Background Many school children living in Africa are infected with plasmodia and helminth species and are consequently at risk of coinfection. However, the epidemiology of such coinfection and the implications of coinfection for children’s health remain poorly understood. This study describes the epidemiology of Ascaris lumbricoides-Plasmodium and hookworm-Plasmodium coinfection among school children living in western Kenya and investigates the associated risk factors. Methods As part of a randomized trial, a baseline cross-sectional survey was conducted among school children aged 5–18 years in 23 schools in Bumula District. Single stool samples were collected to screen for helminth infections using the Kato-Katz technique and malaria parasitaemia was determined from a finger prick blood sample. Demographic and anthropometric data were also collected. Results Overall, 46.4 % of the children were infected with Plasmodium falciparum while 27.6 % of the children were infected with at least one soil transmitted helminth (STH) species, with hookworm being the most common (16.8 %) followed by A. lumbricoides (15.3 %). Overall 14.3 % of the children had STH-Plasmodium coinfection, with hookworm-Plasmodium (9.0 %) coinfection being the most common. Geographical variation in the prevalence of coinfection occurred between schools. In multivariable logistic regression analysis, hookworm was positively associated with P. falciparum infection. In stratified analysis, hookworm infection was associated with increased odds of P. falciparum infection among both boys (P

Background The diagnosis of lymphatic filariasis (LF) is based typically on either microfilaraemia as assessed by microscopy or filarial antigenaemia using an immuno-chromatographic test. While it is known that estimates of antigenaemia are generally higher than estimates of microfilaraemia, the extent of the difference is not known. Methods This paper presents the results of an extensive literature search for surveys that estimated both microfilaraemia and antigenaemia in order to better understand the disparity between the two measures. Results and Conclusions In some settings there was a very large disparity, up to 40–70%, between estimates of microfilaraemia and antigenaemia. Regression analysis was unable to identify any predictable relationship between the two measures. The implications of findings for risk mapping and surveillance of LF are discussed.

Neglected tropical diseases (NTDs) affect more than 1,000,000,000 poor and marginalized people worldwide [1]. NTDs are caused by diverse pathogens with differing modes of transmission and a range of vectors and intermediate hosts, which have their own ecological peculiarities. While there is considerable overlap in the geographical distribution of different NTDs at a national level [1], epidemiological differences of individual NTDs give rise to marked geographical variation at local levels. Since cost-effectiveness of intervention is greatest when targeted to areas having a high burden of multiple diseases, maps of the distribution of the different NTDs are essential for planning and implementing NTD interventions, as well as for providing visualization of program progress, so important for advocacy. In recent years there have been concerted, and very successful, efforts to develop detailed information resources on the geographical distribution of different NTDs (Table 1). Table 1 Currently available resources on the geographical distribution of NTDs. An important element of targeted NTD intervention is the delivery of mass drug administration (MDA) for treating the five major “preventive chemotherapy” NTDs, including lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), and trachoma [2]. MDAs targeting these NTDs are implemented alongside improvements in water and sanitation and hygienic behavior, as well as vector control. To help galvanize such global health efforts, the World Health Organization (WHO) and the NTD community defined targets to be achieved by 2020 and strategies to reach these targets (Table 2). As countries make progress towards the 2020 goals with an ever-increasing amount of data being collected, it is important to develop readily accessible tools that policymakers and program staff and partners can use to access, visualize, and compare data. Table 2 The five main NTDs and the drugs and strategies used to target them programmatically. In this Innovation to Application article, we describe the creation of an innovative NTD mapping tool (www.ntdmap.org) developed by a consortium of research and program partners for use particularly by program implementers. Its functionality and accessibility have been designed specifically to meet the needs of national programs and international partners. This tool provides an online resource allowing users to visualize and manipulate geographical data on a range of variables for the planning and managing of integrated NTD programs.