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Summary: Objectives: Recent large cholera outbreaks highlight the need for improved understanding of the pathogenesis and epidemiology of cholera. The incubation period of cholera has important implications for clinical and public health decision-making, yet statements of the incubation period of cholera are often imprecise. Here we characterize the distribution of cholera''s incubation period. Methods: We conducted a systematic review of the literature for statements of the incubation period of cholera and data that might aid in its estimation. We extracted individual-level data, parametrically estimated the distribution of toxigenic cholera''s incubation period, and evaluated evidence for differences between strains. Results: The incubation period did not differ by a clinically significant margin between strains (except O1 El Tor Ogawa). We estimate the median incubation period of toxigenic cholera to be 1.4 days (95% CI, 1.3–1.6). Five percent of cholera cases will develop symptoms by 0.5 days (95% CI 0.4–0.5), and 95% by 4.4 days (95% CI 3.9–5.0) after infection. Conclusions: We recommend that cholera investigations use a recall period of at least five days to capture relevant exposures; significantly longer than recent risk factor studies from the Haitian epidemic. This characterization of cholera''s incubation period can help improve clinical and public health practice and advance epidemiologic research. [Copyright &y& Elsevier]

Globally, cholera epidemics continue to challenge disease control. Although mass campaigns covering large populations are commonly used to control cholera, spatial targeting of case households and their radius is emerging as a potentially efficient strategy. We did a Scoping Review to investigate the effectiveness of interventions delivered through case-area targeted intervention, its optimal spatiotemporal scale, and its effectiveness in reducing transmission. 53 articles were retrieved. We found that antibiotic chemoprophylaxis, point-of-use water treatment, and hygiene promotion can rapidly reduce household transmission, and single-dose vaccination can extend the duration of protection within the radius of households. Evidence supports a high-risk spatiotemporal zone of 100 m around case households, for 7 days. Two evaluations separately showed reductions in household transmission when targeting case households, and in size and duration of case clusters when targeting radii. Although case-area targeted intervention shows promise for outbreak control, it is critically dependent on early detection capacity and requires prospective evaluation of intervention packages. [ABSTRACT FROM AUTHOR]

• Cholera outbreaks affected 2% of the sub-Saharan Africa populations in the 2010 decade. • 692 outbreaks were identified in 492 districts with a systematic definition. • Larger outbreaks were associated with longer durations and lower reported mortality. • Population density was not always associated with severe cholera outbreak outcomes. • Surveillance needs to be enhanced to improve cholera outbreak monitoring. Cholera remains a public health threat but is inequitably distributed across sub-Saharan Africa. Lack of standardized reporting and inconsistent outbreak definitions limit our understanding of cholera outbreak epidemiology. From a database of cholera incidence and mortality, we extracted data from sub-Saharan Africa and reconstructed outbreaks of suspected cholera starting in January 2010 to December 2019 based on location-specific average weekly incidence rate thresholds. We then described the distribution of key outbreak metrics. We identified 999 suspected cholera outbreaks in 744 regions across 25 sub-Saharan African countries. The outbreak periods accounted for 1.8 billion person-months (2% of the total during this period) from January 2010 to January 2020. Among 692 outbreaks reported from second-level administrative units (e.g., districts), the median attack rate was 0.8 per 1000 people (interquartile range (IQR), 0.3-2.4 per 1000), the median epidemic duration was 13 weeks (IQR, 8-19), and the median early outbreak reproductive number was 1.8 (range, 1.1-3.5). Larger attack rates were associated with longer times to outbreak peak, longer epidemic durations, and lower case fatality risks. This study provides a baseline from which the progress toward cholera control and essential statistics to inform outbreak management in sub-Saharan Africa can be monitored. [ABSTRACT FROM AUTHOR]

Summary Background Pregnancy increases the risk of harmful effects from cholera for both mothers and their fetuses. A killed oral cholera vaccine, Shanchol (Shantha Biotechnics, Hydrabad, India), can protect against the disease for up to 5 years. However, cholera vaccination campaigns have often excluded pregnant women because of insufficient safety data for use during pregnancy. We did an observational cohort study to assess the safety of Shanchol during pregnancy. Methods This observational cohort study was done in two adjacent districts (Nsanje and Chikwawa) in Malawi. Individuals older than 1 year in Nsanje were offered oral cholera vaccine during a mass vaccination campaign between March 30 and April 30, 2015, but no vaccines were administered in Chikwawa. We enrolled women who were exposed to oral cholera vaccine during pregnancy in Nsanje district, and women who were pregnant in Chikwawa district (and thus not exposed to oral cholera vaccine) during the same period. The primary endpoint of our analysis was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were neonatal deaths and malformations. We evaluated these endpoints using log-binomial regression, adjusting for the imbalanced baseline characteristics between the groups. This study is registered with ClinicalTrials.gov , number NCT02499172 . Findings We recruited 900 women exposed to oral cholera vaccine and 899 women not exposed to the vaccine between June 16 and Oct 10, 2015, and analysed 835 in each group. 361 women exposed to the vaccine and 327 not exposed to the vaccine were recruited after their pregnancies had ended. The incidence of pregnancy loss was 27·54 (95% CI 18·41–41·23) per 1000 pregnancies among those exposed to the vaccine and 21·56 (13·65–34·04) per 1000 among those not exposed. The adjusted relative risk for pregnancy loss among those exposed to oral cholera vaccine was 1·24 (95% CI 0·64–2·43; p=0·52) compared with those not exposed to the vaccine. The neonatal mortality rate was 11·78 (95% CI 5·92–23·46) per 1000 livebirths for infants whose mothers were exposed to oral cholera vaccine versus 8·91 (4·02–19·77) per 1000 livebirths for infants whose mothers were not exposed to the vaccine (crude relative risk 1·32, 95% CI 0·46–3·84; p=0·60). Only three newborn babies had malformations, two in the vaccine exposure group and one in the no-exposure group, yielding a relative risk of 2·00 (95% CI 0·18–22·04; p=0·57), although this estimate is unreliable because of the small number of outcomes. Interpretation Our study provides evidence that fetal exposure to oral cholera vaccine confers no significantly increased risk of pregnancy loss, neonatal mortality, or malformation. These data, along with findings from two retrospective studies, support use of oral cholera vaccine in pregnant women in cholera-affected regions. Funding Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Serological studies have been critical in tracking the evolution of the COVID-19 pandemic. Data on anti-SARS-CoV-2 antibodies persistence remain sparse, especially from infected individuals with few to no symptoms. The objective of the study was to quantify the sensitivity for detecting historic SARS-CoV-2 infections as a function of time since infection for three commercially available SARS-CoV-2 immunoassays and to explore the implications of decaying immunoassay sensitivity in estimating seroprevalence. We followed a cohort of mostly mild/asymptomatic SARS-CoV-2-infected individuals (n = 354) at least 8 months after their presumed infection date and tested their serum for anti-SARS-CoV-2 antibodies with three commercially available assays: Roche-N, Roche-RBD and EuroImmun-S1. We developed a latent class statistical model to infer the specificity and time-varying sensitivity of each assay and show through simulations how inappropriately accounting for test performance can lead to biased serosurvey estimates. Antibodies were detected at follow-up in 74–100% of participants, depending on immunoassays. Both Roche assays maintain high sensitivity, with the EuroImmun assay missing 40% of infections after 9 months. Simulations reveal that without appropriate adjustment for time-varying assay sensitivity, seroprevalence surveys may underestimate infection rates. Antibodies persist for at least 8 months after infection in a cohort of mildly infected individuals with detection depending on assay choice. Appropriate assay performance adjustment is important for the interpretation of serological studies in the case of diminishing sensitivity after infection. [ABSTRACT FROM AUTHOR]

Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population-approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies. [ABSTRACT FROM AUTHOR]