Abstract The Urgepi project is a measles emergency initiative implemented by Médecins Sans Frontières Operational Centre Paris (MSF-OCP) in the Katanga region of the Democratic Republic of Congo, a setting characterized by recurrent measles epidemics with substantial public health impact. To maximize impact, the project employs a risk-targeted approach directing resources to selected health zones to strengthen surveillance, implement preventive vaccination, and ensure timely epidemic response. This study presents the Urgepi approach, and, based on surveillance data from 2021-2023, evaluates the effectiveness of targeted preventive activities, explores strategies for prioritizing interventions amid multiple alerts, and assesses the overall impact of interventions on measles epidemics. Preventive vaccination successfully averted epidemics in six of the nine vaccinated high-risk health zones, while nine of ten non-vaccinated priority health zones experienced large epidemics. In the three vaccinated health zones that experienced epidemics, more locally adapted vaccination strategies would have been required to achieve higher coverage. Regarding the project’s approach to prioritize alerts for investigations and interventions, we found that the Urgepi alert prioritization score was positively associated with subsequent epidemic size, suggesting that this approach allowed effective and timely targeting of larger local measles epidemics. Although no clear impact of epidemic response vaccination on case numbers was observed, likely due to biases introduced in case reporting through provision of free case management, a 50% reduction in the median epidemic duration was recorded. In conclusion, the findings demonstrate the effectiveness of the Urgepi project’s risk-targeted approach for measles prevention and control and highlight the importance of timely and context-specific interventions. Key questions What is already known on this topic – Measles can, in theory, be effectively controlled through preventive vaccination or rapid immunization responses during outbreaks. However, many countries continue to face significant operational challenges. What this study adds – We demonstrate how a risk-targeted approach, with prioritization of both preventive and response actions, can optimize resources in the fight against measles. How this study might affect research, practice or policy – Similar risk-targeted approaches can help national programs prioritize geographic areas for measles prevention and outbreak response when it is not feasible to cover all regions due to operational constraints.

Household transmission studies provided key insights on SARS-CoV-2 transmission in high-income countries but were rarely implemented in Africa. To help fill this gap, we analyzed SARS-CoV-2 seroprevalence studies with a household-based recruitment, focusing on households with ≤7 members, in four Sub-Saharan African cities: Kinshasa (82 households, 370 individuals), Lubumbashi (225 households, 970 individuals), Conakry (149 households, 649 individuals), and Yaoundé (311 households, 1183 individuals), between late 2020 and mid-2021. Using an extended chain-binomial model accounting for missing serology, we estimated both the probability of community-acquired infection and within-household transmission. The proportion infected in the community rose sharply over time, reaching up to 73% by June 2021. Household transmission varied by location, with secondary attack rates ranging from 8.9% to 26.7%, and households accounting for 9% to 28% of infections. Simulations showed that including households with missing serology improved the precision of estimates without introducing bias. Secondary attack rate estimates were consistent with findings from South Africa and slightly lower than global pooled estimates, mostly from high-income settings, suggesting different transmission dynamics in African contexts. Our approach for handling missing serology can improve transmission estimates accuracy.

Nipah virus (NiV), a highly lethal virus in humans, circulates silently in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining genomes from bats means we have a poor understanding of NiV diversity, including how many lineages circulate within a roost and the spread of NiV over increasing spatial scales. Here we develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N=257, 175 from bats, 73 from humans) from six countries over 22 years (1999-2020). In Bangladesh, where most human infections occur, we find evidence of increased spillover risk from one of the two co-circulating sublineages. We divide the four major NiV sublineages into 15 genetic clusters (emerged 20-44 years ago). Within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1,500-2,000 km2. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate that each genetic cluster occupies an average area of 1.3 million km2 (95%CI: 0.6-2.3 million), with 14 clusters in an area of 100,000 km2 (95%CI: 6-24). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most of the genetic clusters have been identified, but only ~15% of overall NiV diversity has been uncovered. Our findings are consistent with entrenched co-circulation of distinct lineages, even within individual roosts, coupled with slow migration over larger spatial scales.

Although 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. The 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). In 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 <5 years old. In Abidjan, no overall increase was observed during the pandemic period (pre-pandemic: 0.05 deaths per 10 000 persons per day; pandemic: 0.07 deaths per 10 000 persons per day). However, an increase was observed during the third wave (0.11 deaths per 10 000 persons per day). The estimated seroprevalence in Lubumbashi was 15.7% (RDT) and 43.2% (laboratory-based). In Abidjan, the estimated seroprevalence was 17.4% (RDT) and 72.9% (laboratory-based) during the first phase of the survey and 38.8% (RDT) and 82.2% (laboratory-based) during the second phase of the survey. Although 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.

Enterovirus A71 (EV-A71)-related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.

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 3 diagnostic tests (based on up to 7 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 these outbreaks has however remained unclear due to nonoptimal assays. Using latent class methods, we estimate that 7% to 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 Y. 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 Y. 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.

Abstract 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.

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.

Global urbanization is leading to an inexorable spread of several major diseases that need to be stemmed. Dengue is one of these major diseases spreading in cities today, with its principal mosquito vector superbly adapted to the urban environment. Current mosquito control strategies are proving inadequate, especially in the face of such urbanisation and novel, evidence-based targeted approaches are needed. Through combined epidemiological and entomological approaches, we aimed to identify a novel sanitation strategy to alleviate the burden of dengue through how the dengue virus spreads through the community. We combined surveillance case mapping, prospective serological studies, year-round mosquito surveys, socio-economic and Knowledge Attitudes and Practices surveys across Delhi. We identified lack of access to tap water (≤98%) as an important risk factor for dengue virus IgG sero-positivity (adjusted Odds Ratio 4.69, 95% C.I. 2.06–10.67) and not poverty per se . Wealthier districts had a higher dengue burden despite lower mosquito densities than the Intermediary income communities (adjusted Odds Ratio 2.92, 95% C.I. 1.26–6.72). This probably reflects dengue being introduced by people travelling from poorer areas to work in wealthier houses. These poorer, high density areas, where temperatures are also warmer, also had dengue cases during the winter. Control strategies based on improved access to a reliable supply of tap water plus focal intervention in intra-urban heat islands prior to the dengue season could not only lead to a reduction in mosquito abundance but also eliminate the reservoir of dengue virus clearly circulating at low levels in winter in socio-economically disadvantaged areas.

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.

Background: Nipah 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. Methods: We 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. Results: The 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. Discussion: Without 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.

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 Medecins Sans Frontieres 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 (chi(2) p<0.0001), being highest among those living in workers' residences (88.7%, 95% CI 81.8-93.2), followed by emergency shelters (50.5%, 46.3-54.7), and food distribution sites (27.8%, 20.8-35.7). More than two thirds of COVID-19 seropositive individuals (68%, 95% CI 64.2-72.2; 291 of 426) did not report any symptoms during the recall period. COVID-19 seropositivity was strongly associated with overcrowding (medium density: adjusted odds ratio [aOR] 2.7, 95% CI 1.5-5.1, p=0.0020; high density: aOR 3.4, 1.7-6.9, p<0.0001). Interpretation These results show high exposure to SARS-CoV-2 with important variations between those at different study sites. Living in crowded conditions was the strongest factor associated with exposure level. This study underscores the importance of providing safe, uncrowded accommodation, alongside adequate testing and public health information. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

BackgroundReal-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.MethodsIn 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.Findings1195 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).InterpretationRapid 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.FundingMédecins Sans Frontières WACA and Médecins Sans Frontières OCG.TranslationsFor the French and Spanish translations of the abstract see Supplementary Materials section.

1. Epicentre, Paris, France 2. Médecins Sans Frontières, Paris, France 3. Environment and Infectious Risks Research and Expertise Unit, Global Health Department, Institut Pasteur, Paris, France 4. Unit of Lymphocyte Cell Biology, Immunology Department, Institut Pasteur, INSERM 1221, Paris, France 5. Unit of Molecular Virology and Vaccinology, Virology Department, Institut Pasteur, Paris, France 6. Theravectys, Paris, France 7. Unit of Chemistry and Biocatalysis, Institut Pasteur, UMR 3523 CNRS, Paris, France.

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%–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 (1.42–2.57)), and was negatively associated with population density (OR = 0.76 (0.69–0.84)). In contrast, in gold mining sites where population density was >400 people per km2, seroprevalence peaked significantly among adults (46% (27%–67%)) compared to all other individuals (20% (12%–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.

AbstractBackgroundA 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 p<0.001). It was highest at 88.7% (95%CI 81.8-93.2) among individuals living in workers’ residences, followed by 50.5% (95%CI 46.3-54.7) in emergency shelters and 27.8 % (95%CI 20.8-35.7) among individuals recruited from the food distribution sites. Seroprevalence also varied significantly between sites of the same type. Among other risk factors, the odds for seropositivity were higher among individuals living in crowded sites (medium: adj. OR 2.7, 95%CI 1.5-5.1, p=0.001; high: adj. OR 3.4, 95%CI 1.7-6.9, p<0.001) compared with individuals from low crowding sites and among those who reported transit accommodation in a gymnasium before the lockdown (adj. OR 3.1, 95%CI 1.2-8.1, p=0.023). More than two-thirds of the seropositive individuals (68.3%; 95%CI 64.2-72.2) did not report any symptoms during the recall period.InterpretationThe 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.

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.

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.

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.