Search

Background: A global shortage of cholera vaccines has increased the use of single-dose regimens, rather than the standard two-dose regimen. There is sparse evidence on single-dose protection, particularly in children. In 2020, a mass vaccination campaign was conducted in Uvira, an endemic urban setting in eastern Democratic Republic of the Congo, resulting in largely single-dose coverage. We examined the effectiveness of a single-dose of the oral cholera vaccine Euvichol-Plus in this high-burden setting., Methods: In this matched case-control study, we recruited individuals with medically attended confirmed cholera in the two cholera treatment facilities in the city of Uvira. The control group consisted of age-matched, sex-matched, and neighbourhood-matched community individuals. We recruited across two distinct periods: Oct 14, 2021, to March 10, 2022 (12-17 months after vaccination), and Nov 21, 2022, to Oct 18, 2023 (24-36 months after vaccination). Study staff administered structured questionnaires to all participants to capture demographics, household conditions, potential confounding variables, and vaccination status. The odds of vaccination for the case and control groups were contrasted in conditional logistic regression models to estimate unadjusted and adjusted vaccine effectiveness., Findings: We enrolled 658 individuals with confirmed cholera and 2274 matched individuals for the control group. 99 (15·1%) individuals in the case group were younger than 5 years at the time of vaccination. The adjusted single-dose vaccine effectiveness was 52·7% (95% CI 31·4 to 67·4) 12-17 months after vaccination and 44·7% (24·8 to 59·4) 24-36 months after vaccination. Although protection in the first 12-17 months after vaccination was similar for children aged 1-4 years and older individuals, the estimate of protection in children aged 1-4 years appeared to wane during the third year after vaccination (adjusted vaccine effectiveness 32·9%, 95% CI -30·7 to 65·5), with CIs spanning the null., Interpretation: A single dose of Euvichol-Plus provided substantial protection against medically attended cholera for at least 36 months after vaccination in this cholera-endemic setting. Although the evidence provides support for similar levels of protection in young children and others in the short term, protection among children younger than 5 years might wane significantly during the third year after vaccination., Funding: Wellcome Trust and Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In 2017, the Global Task Force for Cholera Control (GTFCC) set a goal to eliminate cholera from ≥ 20 countries and to reduce cholera deaths by 90% by 2030. Many countries have included oral cholera vaccine (OCV) in their cholera control plans. We felt that a simple, user-friendly monitoring tool would be useful to guide national progress toward cholera elimination. We reviewed cholera surveillance data of Uganda from 2015 to 2021 by date and district. We defined a district as having eliminated cholera if cholera was not reported in that district for at least 4 years. We prepared maps to show districts with cholera, districts that had eliminated it, and districts that had eliminated it but then "relapsed." These maps were compared with districts where OCV was used and the hotspot map recommended by the GTFCC. Between 2018 and 2021, OCV was administered in 16 districts previously identified as hotspots. In 2018, cholera was reported during at least one of the four previous years from 36 of the 146 districts of Uganda. This number decreased to 18 districts by 2021. Cholera was deemed "eliminated" from four of these 18 districts but then "relapsed." The cholera elimination scorecard effectively demonstrated national progress toward cholera elimination and identified districts where additional resources are needed to achieve elimination by 2030. Identification of the districts that have eliminated cholera and those that have relapsed will assist the national programs to focus on addressing the factors that result in elimination or relapse of cholera.

The recommended schedule for killed oral cholera vaccine (OCV) is two doses, 2 weeks apart. However, during vaccine campaigns, the second round is often delayed by several months. Because more information is needed to document antibody responses when the second dose is delayed, we conducted an open-label, phase 2, noninferiority clinical trial of OCV. One hundred eighty-six participants were randomized into three dose-interval groups (DIGs) to receive the second dose 2 weeks, 6 months, or 11.5 months after the first dose. The DIGs were stratified into three age strata: 1 to 4, 5 to 14, and > 14 years. Inaba and Ogawa vibriocidal titers were assessed before and after vaccination. The primary analysis was geometric mean titer (GMT) 2 weeks after the second dose. Data for primary analysis was available from 147 participants (54, 44, and 49 participants from the three DIGs respectively). Relative to the 2-week interval, groups receiving a delayed second dose had significantly higher GMTs after the second dose. Two weeks after the second dose, Inaba GMTs were 55.1 190.3, and 289.8 and Ogawa GMTs were 70.4, 134.5, and 302.4 for the three DIGs respectively. The elevated titers were brief, returning to lower levels within 3 months. We conclude that when the second dose of killed oral cholera vaccine was given after 6 or 11.5 months, vibriocidal titers were higher than when given after the standard period of 2 weeks. This provides reassurance that a delayed second dose does not compromise, but rather enhances, the serological response to the vaccine.

Two-dose killed oral cholera vaccines (OCV) are currently being used widely to control cholera. The standard dose-interval for OCV is 2 weeks; however, during emergency use of the vaccine, it may be more appropriate to use the available doses to quickly give a single dose to more people and give a delayed second dose when more vaccine becomes available. This study is an open label, randomized, phase 2 clinical trial of the vibriocidal response induced by OCV, comparing the responses when the second dose was given either 2 weeks (standard dose interval) or 6 months (extended dose interval) after the first dose. Vaccine was administered to healthy participants > 1 year of age living in the Lukanga Swamps area of Zambia. Three age cohorts (<5 years, 5-14 years, and ≥ 15 years) were randomized to the either dose-interval. The primary outcome was the vibriocidal GMT 14 days after the second dose. 156 of 172 subjects enrolled in the study were included in this analysis. The Inaba vibriocidal titers were not significantly different 14 days post dose two for a standard dose-interval GMT: 45.6 (32-64.9), as compared to the GMT 47.6 (32.6-69.3), for the extended dose-interval, (p = 0.87). However, the Ogawa vibriocidal GMTs were significantly higher 14 days post dose two for the extended-dose interval at 87.6 (58.9-130.4) compared to the standard dose-interval group at 49.7 (34.1-72.3), p = 0.04. Vibriocidal seroconversion rates (a > 4-fold rise in vibriocidal titer) were not significantly different between dose-interval groups. This study demonstrated that vibriocidal titers 14 days after a second dose when given at an extended\ dose interval were similar to the standard dose-interval. The findings suggest that a flexible dosing schedule may be considered when epidemiologically appropriate. The trial was registered at Clinical Trials.gov (NCT03373669)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Background: In response to a cholera outbreak among mobile, difficult-to-reach fishermen on Lake Chilwa, Malawi in 2016, a novel vaccine distribution strategy exploited the proven vaccine thermostability. Fishermen, while taking the first vaccine dose under supervision, received the second dose in a sealed bag, and were told to drink it two weeks later. This study assessed short-term vaccine protection of this strategy., Methods: Patients with diarrhoea admitted to health facilities around lake were interviewed and a stool sample collected for PCR testing. Vaccine effectiveness was assessed in a case-control test-negative design by comparing cases (PCR-positive for V. cholerae O1) and controls (patients with diarrhoea but PCR-negative) and with the screening method that compared the proportions of vaccinated among cholera cases versus the general fishermen population., Results: Of 145 study participants, 120 were fishermen living on the lake. Vaccine effectiveness at three-months was 90.0% [95%CI:38.8;98.4] among fishermen and 83.3% [95%CI: 20.8; 96.5] among all participants in the case-control test-negative design, and 97.5% [95%CI: 90.9;99.3] with the screening method., Conclusion: This strategy was effective in providing short-term protection in fishermen against cholera. Further research is needed to determine the adding value of the second dose and to identify the optimal vaccination strategies for different contexts., (Copyright © 2019. Published by Elsevier Ltd.)

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., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Background: : Cholera remains a serious public health threat in Asia, Africa and in parts of the Americas. Three World health Organization (WHO) pre-qualified oral cholera vaccines are now available but their supply is limited, so current supplies must be administered strategically. This requires an improved understanding of disease transmission and control strategies., Methods: : We used demographics and disease surveillance data collected from 1991 to 2000 in Matlab, Bangladesh, to estimate the spatial and temporal extent of the zone of increased risk around cholera cases. Specifically, we compare the cholera incidence among individuals living close to cholera cases with that among individuals living close to those without medically-attended cholera in this rural endemic setting., Results: : Those living within 50 m of a confirmed cholera case had 36 times (95% confidence interval: 23-56) the risk of becoming a cholera case in the first 3 days (after case presentation) compared with risk elsewhere in the community. The relative risk gradually declined in space and time, but remained significantly high up to 450 me away within 3 days of case presentation, and up to 150 m away within 23 days from the date of presentation of the case., Conclusion: : These findings suggest that, if conducted rapidly, vaccinating individuals living close to a case (ring vaccination) could be an efficient and effective strategy to target vaccine to a high-risk population in an endemic setting., (© The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association)

Background: Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention., Methods: We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India)., Findings: Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0)., Interpretation: One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings., Funding: Médecins Sans Frontières., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy., Methods and Findings: This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals' vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5-11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%-98%) and 93% (95% CI 44%-99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child (<5 y) or was older. Of note, this study was a reanalysis of a cholera vaccine trial that used two doses; thus, a limitation of the study relates to the assumption that a single dose, if administered quickly, will induce a similar level of total and indirect protection over the short term as did two doses., Conclusions: These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective., Trial Registration: ClinicalTrials.gov NCT00289224., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: FJL received grants from the Bill and Melinda Gates Foundation. All other authors have no competing interests.