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The use of biomarkers to measure immune responses in serum is crucial for understanding population-level exposure and susceptibility to human pathogens. Advances in sample collection, multiplex testing, and computational modeling are transforming serosurveillance into a powerful tool for public health program design and response to infectious threats. In July 2018, 70 scientists from 16 countries met to perform a landscape analysis of approaches that support an integrated serosurveillance platform, including the consideration of issues for successful implementation. Here, we summarize the group's insights and proposed roadmap for implementation, including objectives, technical requirements, ethical issues, logistical considerations, and monitoring and evaluation.

Background: Hepatitis E virus (HEV) causes acute jaundice and poses an important public health problem in low- and middle-income countries. Limited surveillance capacity and suboptimal access to diagnostics leads to under-reporting of HEV infections in affected countries, including Nepal. Serum antibodies against HEV are indicative of past infection. We analyzed existing samples from a nationally representative serosurvey to describe the geospatial distribution and factors associated with HEV seroprevalence in Nepal, as a proxy for infection. Methodology/Principle findings: A nationally representative cross-sectional serosurvey of 3,922 individuals ≥2 years old from 975 households spread across 65 wards throughout Nepal was conducted between November 2021 and January 2022. Bio-banked samples were tested for anti-HEV IgG. Seroprevalence and its 95% confidence interval were estimated by age, sex, ecological region, municipality type, and other waterborne-disease related risk factors. Bayesian geostatistical models were fitted to observed seroprevalence data and used to generate high-resolution maps of seroprevalence across Nepal. Available samples from 3,707 participants were tested for anti-HEV IgG, and 3,703 were used for final analysis. We found 20.8% (95% CI: 19.5–22.2) of participants had evidence of prior HEV infection. HEV seroprevalence increased with age, and was higher in males (23.5%, 95% CI: 21.5–25.5) than in females (18.6%, 95% CI: 16.9–20.3). Seroprevalence in hilly (28.9%, 95% CI: 26.6–31.2) and mountain (24.6%, 95% CI: 18.8–30.5) regions were significantly higher than in terai (14.2%, 95% CI: 12.7–15.8). While there was no significant difference between urban and rural populations, the predicted seroprevalence was highest in Kathmandu, the capital of Nepal, reaching seroprevalence of 50% in some selected area. No statistically significant differences were found for wealth quintile, water source, and toilet facility. Conclusions: This study provides population-based serologic evidence that HEV is endemic in Nepal, with the greatest risk of infection in Kathmandu. Author summary: Hepatitis E virus spreads through fecal to oral transmission, primarily via contaminated water. The virus can impair liver function and causes frequent outbreaks of acute jaundice in Nepal. Diagnostic tests are often not accessible, meaning many cases of hepatitis E go undetected and it is difficult to know how many people are affected or where to target interventions to protect those most at risk. However, infections can be detected retrospectively by looking for long-lasting antibodies produced by the body in response to the virus. We looked for these antibodies in blood specimens collected from a population representative sample of individuals across Nepal and found that, overall, around 1 in 5 people had likely been infected previously. Risk of past infection varied across the three ecological regions of Nepal and was higher in Hilly and Mountain regions than in the southern Terai. We fitted a geospatial model to our data to map the predicted risk across the country and found it to be highest in Kathmandu, with up to half the population previously infected. This research demonstrates the scale of hepatitis E virus infections in Nepal and identified parts of the Hilly region–particularly Kathmandu–as areas where people are most at risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Planning interventions to respond to cholera epidemics requires an understanding of the major transmission routes. Interrupting short-cycle (household, foodborne) transmission may require different approaches as compared long-cycle (environmentally-mediated/waterborne) transmission. However, differentiating the relative contribution of short- and long-cycle routes has remained difficult, and most cholera outbreak control efforts focus on interrupting long-cycle transmission. Here we use high-resolution epidemiological and municipal infrastructure data from a cholera outbreak in 1853 Copenhagen to explore the relative contribution of short- and long-cycle transmission routes during a major urban epidemic. METHODOLOGY/PRINCIPAL FINDINGS: We fit a spatially explicit time-series meta-population model to 6,552 physician-reported cholera cases from Copenhagen in 1853. We estimated the contribution of long-cycle waterborne transmission between neighborhoods using historical municipal water infrastructure data, fitting the force of infection from hydraulic flow, then comparing model performance. We found the epidemic was characterized by considerable transmission heterogeneity. Some neighborhoods acted as localized transmission hotspots, while other neighborhoods were less affected or important in driving the epidemic. We found little evidence to support long-cycle transmission between hydrologically-connected neighborhoods. Collectively, these findings suggest short-cycle transmission was significant. CONCLUSIONS/SIGNIFICANCE: Spatially targeted cholera interventions, such as reactive vaccination or sanitation/hygiene campaigns in hotspot neighborhoods, would likely have been more effective in this epidemic than control measures aimed at interrupting long-cycle transmission, such as improving municipal water quality. We recommend public health planners consider programs aimed at interrupting short-cycle transmission as essential tools in the cholera control arsenal.

Background: Indian subcontinent being an important region in the fight to eliminate cholera needs better cholera surveillance. Current methods miss most infections, skewing disease burden estimates. Triangulating serosurvey data, clinical cases, and risk factors could reveal India's true cholera risk. Methods: We synthesized data from a nationally representative serosurvey, outbreak reports and risk factors like water, sanitation and the Multidimensional Poverty Index, to create a composite vulnerability index for assessing state-wise cholera risk in India. We tested 7,882 stored sera samples collected during 2017–18 from individuals aged 9–45 years, for vibriocidal antibodies to Vibrio cholerae O1 using a cut-off titre ≥320 defining as elevated titre. We also extracted data from the 2015–19 Integrated Disease Surveillance Programme and published cholera reports. Results: Overall, 11.7% (CI: 10.4–13.3%) of the sampled population had an elevated titre of cholera vibriocidal antibodies (≥320). The Southern region experienced the highest incidence (16.8%, CI: 12.1–22.8), followed by the West (13.2%, CI: 10.0–17.3) and North (10.7%, CI: 9.3–12.3). Proportion of samples with an elevated vibriocidal titre (≥320) was significantly higher among individuals aged 18–45 years (13.0% CI: 11.2–15.1) compared to children 9–17 years (8.6%, CI 7.3–10.0, p<0.05); we found no differences between sex or urbanicity. Between 2015–2019, the Integrated Disease Surveillance Program (IDSP) reported 29,400 cases of cholera across the country. Using the composite vulnerability index, we found Karnataka, Madhya Pradesh, and West Bengal were the most vulnerable states in India in terms of risk of cholera. Conclusion: The present study showed that cholera infection is present in all five regions across India. The states with high cholera vulnerability could be prioritized for targeted prevention interventions. Author summary: Cholera remains a significant public health threat in areas with inadequate water, sanitation, and hygiene (WASH). The World Health Organization's Global Task Force on Cholera Control (GTFCC) launched "Ending Cholera: A Global Roadmap to 2030" to reduce cholera deaths and eliminate the disease in 20 countries by 2030 through targeted interventions, including improved WASH practices and disease surveillance. cholera surveillance, especially in developing countries seldom poses difficulty in terms of the need for laboratory infrastructure, and other resource constraints. Thereby, in this study, we utilized a viable approach with serosurvey data from 2017, cholera outbreak data, WASH indicators, and the Multidimensional Poverty Index (MPI) to create a composite vulnerability index for cholera risk in India. Overall, 11.7% of the sampled population had detectable levels of cholera antibodies reflecting previous infection. The Southern region of India experienced the highest incidence, followed by the West and North. the study showed that cholera infection is present in all five regions across India. Further, the vulnerability index which we built could be utilized in other settings so that effective tailored interventions could be applied in identified priority areas. [ABSTRACT FROM AUTHOR]

Background: Safely managed drinking water is critical to prevent diarrhoeal diseases, including cholera, but evidence on the effectiveness of piped water supply in reducing these diseases in low-income and complex emergency settings remains scarce. Methods: We conducted a trial of water supply infrastructure improvements in Uvira (DRC). Our primary objective was to estimate the relationship between a composite index of water service quality and the monthly number of suspected cholera cases admitted to treatment facilities and, as a secondary analysis, the number of cases confirmed by rapid diagnostic tests. Other exposures included the quantity of supplied water and service continuity. We used Poisson generalised linear models with generalised estimating equations to estimate incidence rate ratios. Findings: Associations between suspected cholera incidence and water service quality (RR 0·86, 95% CI 0·73–1·01), quantity (RR 0·80, 95% CI 0·62–1·02) and continuity (RR 0·81, 95% CI 0·77–0·86) were estimated. The magnitudes of the associations were similar between confirmed cholera incidence and water service quality (RR 0·84, 95% CI 0·73–0·97), quantity (RR 0·76, 95% CI 0·61–0·94) and continuity (RR 0·75, 95% CI 0·69–0·81). These results suggest that an additional 5 L/user/day or 1.2 hour per day of water production could reduce confirmed cholera by 24% (95% CI 6–39%) and 25% (95% CI 19–31%), respectively. Interpretation: Ensuring a sufficient and continuous piped water supply may substantially reduce the burden of endemic cholera and diarrhoeal diseases but evaluating this rigorously is challenging. Pragmatic strategies are needed for public health research on complex interventions in protracted emergency settings. Trial registration: The trial is registered in ClinicalTrials.gov ID NCT02928341. https://classic.clinicaltrials.gov/ct2/show/NCT02928341. Author summary: Diarrhoeal diseases including cholera remain a leading cause of mortality and morbidity, especially in areas with limited access to safe water, sanitation and hygiene (WASH). However, evidence for the effect of piped water supply in reducing diarrhoeal diseases and cholera in complex emergency settings remains scarce. We evaluated a large-scale infrastructure programme to improve and expand the piped drinking water supply service in the town of Uvira (South Kivu, Democratic Republic of the Congo), an area with a high burden of cholera and diarrhoeal diseases. We used five years of data from clinical surveillance and systematic cholera confirmation by rapid diagnostic tests in order to estimate associations between water supply infrastructure interventions and the incidence of diarrhoeal diseases and cholera. Our findings are consistent with existing evidence that a high-quality (or "safely managed") water service can be effective in reducing the burden of diarrhoeal diseases and cholera in low-income urban settings. Beyond overall service quality, the quantity of water supplied to the household and the continuity of the drinking water supply were both associated with a reduced risk of cholera. [ABSTRACT FROM AUTHOR]