Cholera Vaccine Research Articles

Cholera and diarrheal diseases in Cuamba District, Niassa Province, Mozambique: Systematic healthcare facility-based surveillance strengthening, characteristics of suspected cholera and diarrheal patients, and incidence of diarrheal diseases.

Mozambique is one of the countries in Africa that is continuously at risk of cholera outbreaks due to poor sanitation, hygiene, and limited access to potable water in some districts. The Mozambique Cholera Prevention and Surveillance (MOCA) project was implemented in Cuamba District, Niassa Province to prevent and control cholera outbreaks through a preemptive cholera vaccination, strengthened surveillance system for cholera and diarrheal diseases, and better understanding of cholera-related healthcare seeking behavior of local populations, which may further guide the national cholera control and prevention strategies. This article presents the surveillance component of the MOCA project. A prospective healthcare facility (HCF)-based surveillance of cholera and diarrheal disease was conducted in six HCFs in the District of Cuamba from March 2019 to December 2020. A systematic surveillance procedure has been put in place with capacity building in selected sentinel HCFs and a basic microbiology laboratory established on-site. Patients presenting with suspected cholera or other diarrheal symptoms were eligible for enrollment. Clinical data and rectal swab samples were collected for laboratory confirmation of Vibrio Cholerae and other pathogens. A total of 419 eligible patients from six HCFs were enrolled. The median age was 19.8 years with a similar age distribution between sentinel sites. The majority were patients who exhibited diarrhea symptoms not suspected of cholera (88.8%; n = 410). Among those, 59.2% (210/397) were female and 59.9% (235/392) were 15 years and above. There were 2 cholera cases, coming outside of the catchment area. The incidence of diarrheal diseases ranged from 40-103 per 100,000 population. No Vibrio cholerae was isolated among surveillance catchment population and Escherichia coli spp. (82/277; 29.6%) was the most common pathogen isolated. Efforts were made to strengthen the systematic surveillance of suspected cholera with standardised patient screening, enrolment, and diagnostics. The first basic microbiology laboratory in Niassa Province established in Cuamba District under the MOCA project needs to be integrated into the national network of laboratories for sustainability. No reports of laboratory confirmed cholera cases from the surveillance catchment area may be highly related to the pre-emptive oral cholera vaccine (OCV) mass vaccination campaign conducted in 2018 and the use of drugs by local populations prior to visiting the sentinel HCFs. Continued systematic cholera surveillance is needed to closely monitor the cholera endemicity and epidemics, and further evaluate the long-term impact of this vaccination. High incidence of diarrheal illnesses needs to be addressed with improved water, sanitation, and hygiene (WaSH) conditions in Cuamba District. Efforts integrated with the prioritization of prevention measures are fundamental for the control of cholera in the country.

COVID-19 Vaccine Hesitancy and Associated Oral Cholera Vaccine Hesitancy in a Cholera-Endemic Country: A Community-Based Cross-Sectional Study in the Democratic Republic of Congo.

COVID-19 vaccine hesitancy and its enablers shape community uptake of non-covid vaccines such as the oral cholera vaccine (OCV) in the post-COVID-19 era. This study assessed the impact of COVID-19 vaccine hesitancy and its drivers on OCV hesitancy in a cholera-endemic region of the Democratic Republic of Congo. We conducted a community-based survey in Bukavu. The survey included demographics, intention to take OCV and COVID-19 vaccines, reasons for COVID-19 hesitancy, and thoughts and feelings about COVID-19 vaccines. Poisson regression analyses were performed. Of the 1708 respondents, 84.66% and 77.57% were hesitant to OCV alone and to both OCV and COVID-19, respectively. Hesitancy to COVID-19 vaccines rose OCV hesitancy by 12% (crude prevalence ratio, [cPR] = 1.12, 95%CI [1.03-1.21]). Independent predictors of OCV hesitancy were living in a semi-urban area (adjusted prevalence ratio [aPR] = 1.10, 95%CI [1.03-1.12]), religious refusal of vaccines (aPR = 1.06, 95%CI [1.02-1.12]), concerns about vaccine safety (aPR = 1.05, 95%CI [1.01-1.11]) and adverse effects (aPR = 1.06, 95%CI [1.01-1.12]), as well as poor vaccine literacy (aPR = 1.07, 95%CI [1.01-1.14]). Interestingly, the belief in COVID-19 vaccine effectiveness reduced OCV hesitancy by 24% (aPR = 0.76, 95%CI [0.62-0.93]). COVID-19 vaccine hesitancy and its drivers exhibited a significant domino effect on OCV uptake. Addressing vaccine hesitancy through community-based health literacy and trust-building interventions would likely improve the introduction of novel non-COVID-19 vaccines in the post-COVID-19 era.

Safety and immunogenicity of the Euvichol-S oral cholera vaccine for prevention of Vibrio cholerae O1 infection in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial

In October, 2017, WHO launched a strategy to eliminate cholera by 2030. A primary challenge in meeting this goal is the limited global supply capacity of oral cholera vaccine and the worsening of cholera outbreaks since 2021. To help address the current shortage of oral cholera vaccine, a WHO prequalified oral cholera vaccine, Euvichol-Plus was reformulated by reducing the number of components and inactivation methods. We aimed to evaluate the immunogenicity and safety of Euvichol-S (EuBiologics, Seoul, South Korea) compared with an active control vaccine, Shanchol (Sanofi Healthcare India, Telangana, India) in participants of various ages in Nepal. We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Nepal. Eligible participants were healthy individuals aged 1-40 years without a history of cholera vaccination. Individuals with a history of hypersensitivity reactions to other preventive vaccines, severe chronic disease, previous cholera vaccination, receipt of blood or blood-derived products in the past 3 months or other vaccine within 4 weeks before enrolment, and pregnant or lactating women were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block sizes of two, four, six, or eight) to one of four groups (groups A-D); groups C and D were stratified by age (1-5, 6-17, and 18-40 years). Participants in groups A-C were assigned to receive two 1·5 mL doses of Euvichol-S (three different lots) and participants in group D were assigned to receive the active control vaccine, Shanchol. All participants and site staff (with the exception of those who prepared and administered the study vaccines) were masked to group assignment. The primary immunogenicity endpoint was non-inferiority of immunogenicity of Euvichol-S (group C) versus Shanchol (group D) at 2 weeks after the second vaccine dose, measured by the seroconversion rate, defined as the proportion of participants who had achieved seroconversion (defined as ≥four-fold increase in V cholerae O1 Inaba and Ogawa titres compared with baseline). The primary immunogenicity endpoint was assessed in the per-protocol analysis set, which included all participants who received all their planned vaccine administrations, had no important protocol deviations, and who provided blood samples for all immunogenicity assessments. The primary safety endpoint was the number of solicited adverse events, unsolicited adverse events, and serious adverse events after each vaccine dose in all ages and each age stratum, assessed in all participants who received at least one dose of the Euvichol-S or Shanchol. Non-inferiority of Euvichol-S compared with Shanchol was shown if the lower limit of the 95% CI for the difference between the seroconversion rates in Euvichol-S group C versus Shanchol group D was above the predefined non-inferiority margin of -10%. The trial was registered at ClinicalTrials.gov, NCT04760236. Between Oct 6, 2021, and Jan 19, 2022, 2529 healthy participants (1261 [49·9%] males; 1268 [50·1%] females), were randomly assigned to group A (n=330; Euvichol-S lot number ES-2002), group B (n=331; Euvichol-S ES-2003), group C (n=934; Euvichol-S ES-2004]), or group D (n=934; Shanchol). Non-inferiority of Euvichol-S versus Shanchol in seroconversion rate for both serotypes at 2 weeks after the second dose was confirmed in all ages (difference in seroconversion rate for V cholerae O1 Inaba -0·00 [95% CI -1·86 to 1·86]; for V cholerae O1 Ogawa -1·62 [-4·80 to 1·56]). Treatment-emergent adverse events were reported in 244 (9·7%) of 2529 participants in the safety analysis set, with a total of 403 events; 247 events were reported among 151 (9·5%) of 1595 Euvichol-S recipients and 156 events among 93 (10·0%) of 934 Shanchol recipients. Pyrexia was the most common adverse event in both groups (57 events among 56 [3·5%] of 1595 Euvichol-S recipients and 37 events among 35 [3·7%] of 934 Shanchol recipients). No serious adverse events were deemed to be vaccine-related. A two-dose regimen of Euvichol-S vaccine was non-inferior to the active control vaccine, Shanchol, in terms of seroconversion rates 2 weeks after the second dose. The simplified formulation and production requirements of the Euvichol-S vaccine have the potential to increase the supply of oral cholera vaccine and reduce the gap between the current oral cholera vaccine supply and demand. The Bill & Melinda Gates Foundation. For the Nepali translation of the abstract see Supplementary Materials section.

Seroconversion and Kinetics of Vibriocidal Antibodies during the First 90 Days of Re-Vaccination with Oral Cholera Vaccine in an Endemic Population.

Despite the successful introduction of oral cholera vaccines, Zambia continues to experience multiple, sporadic, and protracted cholera outbreaks in various parts of the country. While vaccines have been useful in staying the cholera outbreaks, the ideal window for re-vaccinating individuals resident in cholera hotspot areas remains unclear. Using a prospective cohort study design, 225 individuals were enrolled and re-vaccinated with two doses of Shanchol™, regardless of previous vaccination, and followed-up for 90 days. Bloods were collected at baseline before re-vaccination, at day 14 prior to second dosing, and subsequently on days 28, 60, and 90. Vibriocidal assay was performed on samples collected at all five time points. Our results showed that anti-LPS and vibriocidal antibody titers increased at day 14 after re-vaccination and decreased gradually at 28, 60, and 90 days across all the groups. Seroconversion rates were generally comparable in all treatment arms. We therefore conclude that vibriocidal antibody titers generated in response to re-vaccination still wane quickly, irrespective of previous vaccination status. However, despite the observed decline, the levels of vibriocidal antibodies remained elevated over baseline values across all groups, an important aspect for Zambia where there is no empirical evidence as to the ideal time for re-vaccination.

AN OVERVIEW OF CURRENT VACCCINES FOR THE PROPHYLAXIS OF BACTERICAL INFECTIONS

Antibacterial vaccines play a central role in modern medicine by providing an effective approach to combating infectious diseases caused by bacteria. The importance of these vaccines lies in their ability to stimulate the immune system to recognise and neutralise bacterial pathogens, or exotoxins produced by them, thereby preventing, or mitigating the severity of bacterial infections. The development and widespread use of antibacterial vaccines have contributed significantly to reducing the global burden of diseases such as pneumonia, meningitis, and sepsis. Today, the global increase in vaccine-preventable diseases is a worrying trend that is closely linked to the emergence and advocacy of anti-vaccination policies. According to the latest World Health Organisation report, vaccination coverage in Serbia has declined over the past decade, jeopardising the collective immunity and led to recent outbreaks of vaccine-preventable diseases such as whooping cough and measles. Understanding the significance of antibacterial vaccines underscores their importance in promoting individual and community immunity, which ultimately leads to a healthier population and the prevention of antibiotic resistance. This paper summarises the main characteristics of the different types of antibacterial vaccines, such as whole cell vaccines, subunit vaccines and toxoid vaccines, and provides an overview of the types of bacterial antigens contained in vaccines available for mandatory immunisation (vaccines against tuberculosis, diphtheria, tetanus, pertussis, Haemophilus influenzae and pneumoccus) or for non-mandatory immunisation (meningococcal vaccine, typhoid vaccine, cholera vaccine).

MucoRice-CTB line 19A, a new marker-free transgenic rice-based cholera vaccine produced in an LED-based hydroponic system.

We previously established the selection-marker-free rice-based oral cholera vaccine (MucoRice-CTB) line 51A for human use by Agrobacterium-mediated co-transformation and conducted a double-blind, randomized, placebo-controlled phase I trial in Japan and the United States. Although MucoRice-CTB 51A was acceptably safe and well tolerated by healthy Japanese and U.S. subjects and induced CTB-specific antibodies neutralizing cholera toxin secreted by Vibrio cholerae, we were limited to a 6-g cohort in the U.S. trial because of insufficient production of MucoRice-CTB. Since MucoRice-CTB 51A did not grow in sunlight, we re-examined the previously established marker-free lines and selected MucoRice-CTB line 19A. Southern blot analysis of line 19A showed a single copy of the CTB gene. We resequenced the whole genome and detected the transgene in an intergenic region in chromosome 1. After establishing a master seed bank of MucoRice-CTB line 19A, we established a hydroponic production facility with LED lighting to reduce electricity consumption and to increase production capacity for clinical trials. Shotgun MS/MS proteomics analysis of MucoRice-CTB 19A showed low levels of α-amylase/trypsin inhibitor-like proteins (major rice allergens), which was consistent with the data for line 51A. We also demonstrated that MucoRice-CTB 19A had high oral immunogenicity and induced protective immunity against cholera toxin challenge in mice. These results indicate that MucoRice-CTB 19A is a suitable oral cholera vaccine candidate for Phase I and II clinical trials in humans, including a V. cholerae challenge study.

Enhanced cholera surveillance to improve vaccination campaign efficiency

Systematic testing for Vibrio cholerae O1 is rare, which means that the world’s limited supply of oral cholera vaccines (OCVs) may not be delivered to areas with the highest true cholera burden. Here we used a phenomenological model with subnational geographic targeting and fine-scale vaccine effects to model how expanding V. cholerae testing affected impact and cost-effectiveness for preventive vaccination campaigns across different bacteriological confirmation and vaccine targeting assumptions in 35 African countries. Systematic testing followed by OCV targeting based on confirmed cholera yielded higher efficiency and cost-effectiveness and slightly fewer averted cases than status quo scenarios targeting suspected cholera. Targeting vaccine to populations with an annual incidence rate greater than 10 per 10,000, the testing scenario averted 10.8 (95% prediction interval (PI) 9.4–12.6) cases per 1,000 fully vaccinated persons while the status quo scenario averted 6.9 (95% PI 6.0–7.8) cases per 1,000 fully vaccinated persons. In the testing scenario, testing costs increased by US$31 (95% PI 25–39) while vaccination costs reduced by US$248 (95% PI 176–326) per averted case compared to the status quo. Introduction of systematic testing into cholera surveillance could improve efficiency and reach of global OCV supply for preventive vaccination.

The surging cholera epidemic in Africa: a review of the current epidemiology, challenges and strategies for control

Africa, a known region with abundant warm coastal waters and a natural reservoir for Vibrio cholera, is known to bear the highest burden of cholera morbidity and mortality globally. Malawi is currently experiencing the deadliest cholera outbreak in two decades, and neighbouring countries, Mozambique and Zambia, have also reported significant numbers of cases. If the current trend of cholera transmission is sustained, the number of fatalities recorded in 2021, Africa’s deadliest year for cholera over the past decade, might be exceeded. This article aims to review the current epidemiology, prevention and control strategies, and treatment of cholera in Africa to highlight context-specific challenges and recommend possible solutions. The authors found out that cholera outbreaks in Africa are taking place in the midst of epidemics (measles, mumps, etc.) and natural disasters like cyclones and flooding (Mozambique, Malawi), drought (Kenya, and Ethiopia), and conflict (Cameroon, the DR Congo, Nigeria, and Ethiopia). The shortages of medical supplies like cholera kits and oral cholera vaccines in many countries due to constrained and limited resources and antibiotic resistance further make management and control difficult. The outbreak is spreading throughout the region because of poor sanitation, unsafe water supplies, and increased cross-border travel. Cholera in Africa follows a seasonal pattern, suggesting specific periods for heightened outbreak preparedness and response. The authors suggest a targeted multisectorial approach and a coordinated mechanism to respond to the epidemic through sustained political will, formidable partnerships, resource mobilisation, and the provision of technical support and advocacy at sub-national, national, and international levels.

Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.

Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

Methods for the estimation of direct and indirect vaccination effects by combining data from individual- and cluster-randomized trials.

Both individually and cluster randomized study designs have been used for vaccine trials to assess the effects of vaccine on reducing the risk of disease or infection. The choice between individually and cluster randomized designs is often driven by the target estimand of interest (eg, direct versus total), statistical power, and, importantly, logistic feasibility. To combat emerging infectious disease threats, especially when the number of events from one single trial may not be adequate to obtain vaccine effect estimates with a desired level of precision, it may be necessary to combine information across multiple trials. In this article, we propose a model formulation to estimate the direct, indirect, total, and overall vaccine effects combining data from trials with two types of study designs: individual-randomization and cluster-randomization, based on a Cox proportional hazards model, where the hazard of infection depends on both vaccine status of the individual as well as the vaccine status of the other individuals in the same cluster. We illustrate the use of the proposed model and assess the potential efficiency gain from combining data from multiple trials, compared to using data from each individual trial alone, through two simulation studies, one of which is designed based on a cholera vaccine trial previously carried out in Matlab, Bangladesh.

Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study

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. 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. 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. 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. Wellcome Trust and Gavi, the Vaccine Alliance.

A war without smoke: Infectious disease panic and its response—A case study of Macao-Portuguese government’s prevention and control of cholera from 1912 to 1949

With the time frame 1912–1949, and according to the recording in the government gazettes and Chinese press, this essay systematically discusses the powerful and effective measures and achievements in cholera prevention, epidemic prevention, and infectious disease control of the Macao-Portuguese government. Meanwhile, it analyzes and investigates the cooperation and interaction in cholera prevention between the Macao and Hong Kong governments and emphasizes the critical significance of regional developments of Macao’s cholera prevention and control, that is, with the internal control to lower incidence and external control to minimize importation and diffusion, the aim to control cholera was achieved thus allayed the public panic among Macao and perimeter zone, creating advantages to stabilize economic development, social order and peaceful living environment in Macao as well as other Cantonese regions. As one of the seaport cities that adopted the European medical system and model and implemented free cholera vaccination for all, the fighting process and measures of Macao-Portuguese government adopted to control the cholera epidemic show that cholera, a dreadful infectious disease, can be effectively managed as long as scientific and appropriate methods are taken. Sorting out the types and characteristics of infectious diseases in Macao during this period and the mechanism of combining medical and preventive treatment at that time, and analyzing the effectiveness of the administration of disease prevention and control by the Macao-Portuguese government and the limitations of governance under the conflict between Chinese and Portuguese will have important academic significance for understanding the efficiency and deficiency of Macao-Portuguese governance towards disease control, the construction, development and change of the urban public health emergency management system and the urban governance. The more important significance will bring to the urban public health emergency management system and the urban governance in modern China.

Oral killed cholera vaccines for preventing cholera.

Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria. To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults. We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL, MEDLINE; Embase; LILACS; and two trials registers (February 2023). We included randomized controlled trials (RCTs), including cluster-RCTs. There were no restrictions on the age and sex of the participants or the setting of the study. We considered any available WHO-prequalified oral killed cholera vaccine as an intervention. The control group was given a placebo, another vaccine, or no vaccine. The outcomes were related to vaccine effectiveness and safety. We included articles published in English only. Two review authors independently applied the inclusion criteria and extracted data from included studies. We assessed the risk of bias using the Cochrane ROB 1 assessment tool. We used the generic inverse variance and a random-effects model meta-analysis to estimate the pooled effect of the interventions. We assessed the certainty of the evidence using the GRADE approach. For vaccine effectiveness (VE), we converted the overall risk ratio (RR) to vaccine effectiveness using the formula: VE = (1 - RR) x 100%. Five RCTs, reported in 12 records, with 462,754 participants, met the inclusion criteria. We identified trials on whole-cell plus recombinant vaccine (WC-rBS vaccine (Dukoral)) from Peru and trials on bivalent whole-cell vaccine (BivWC (Shanchol)) vaccine from India and Bangladesh. We did not identify any trials on other BivWC vaccines (Euvichol/Euvichol-Plus), or Hillchol. Two doses of Dukoral with or without a booster dose reduces cases of cholera at two-year follow-up in a general population of children and adults, and at five-month follow-up in an adult male population (overall VE 76%; RR 0.24, 95% confidence interval (CI) 0.08 to 0.65; 2 trials, 16,423 participants; high-certainty evidence). Two doses of Shanchol reduces cases of cholera at one-year follow-up (overall VE 37%; RR 0.63, 95% CI 0.47 to 0.85; 2 trials, 241,631 participants; high-certainty evidence), at two-year follow-up (overall VE 64%; RR 0.36, 95% CI 0.16 to 0.81; 2 trials, 168,540 participants; moderate-certainty evidence), and at five-year follow-up (overall VE 80%; RR 0.20, 95% CI 0.15 to 0.26; 1 trial, 54,519 participants; high-certainty evidence). A single dose of Shanchol reduces cases of cholera at six-month follow-up (overall VE 40%; RR 0.60, 95% CI 0.47 to 0.77; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 39%; RR 0.61, 95% CI 0.53 to 0.70; 1 trial, 204,700 participants; high-certainty evidence). A single dose of Shanchol also reduces cases of severe dehydrating cholera at six-month follow-up (overall VE 63%; RR 0.37, 95% CI 0.28 to 0.50; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 50%; RR 0.50, 95% CI 0.42 to 0.60; 1 trial, 204,700 participants; high-certainty evidence). We found no differences in the reporting of adverse events due to vaccination between the vaccine and control/placebo groups. Two doses of Dukoral reduces cases of cholera at two-year follow-up. Two doses of Shanchol reduces cases of cholera at five-year follow-up, and a single dose of Shanchol reduces cases of cholera at two-year follow-up. Overall, the vaccines were safe and well-tolerated. We found no trials on other BivWC vaccines (Euvichol/Euvichol-Plus). However, BivWC products (Shanchol, Euvichol/Euvichol-Plus) are considered to produce comparable vibriocidal responses. Therefore, it is reasonable to apply the results from Shanchol trials to the other BivWC products (Euvichol/Euvichol-Plus).

Do Oral Cholera Vaccine and Water, Sanitation, and Hygiene Combine to Provide Greater Protection Against Cholera? Results From a Cluster-Randomized Trial of Oral Cholera Vaccine in Kolkata, India.

Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001). These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.

Cholera resurgence in Africa: assessing progress, challenges, and public health response towards the 2030 global elimination target.

Global efforts to combat epidemic cholera outbreaks have witnessed tremendous feats over the decades. However, sporadic outbreaks in regions, particularly across African states, mask these advancements. This regressive trend is frequently fuelled by factors retarding efforts towards optimal environmental sanitation and personal hygiene, which include ingesting infected food, drinking contaminated waters, and engaging in unhealthy environmental practices such as indiscriminate waste and sewage disposal and poor toilet practices. The ongoing efforts to achieve the Global Taskforce on Cholera Control (GTFCC) targets of a 90% reduction in cases and deaths by 2030, even in the wake of continuous outbreaks across various African regions, as reported by the World Health Organization (WHO) face a significant threat. One such effort, among others, is the AFRICHOL project, an enhanced cholera surveillance consortium launched in Africa over a decade ago as part of the GTFCC at WHO to monitor and fast-track the GTFCC's 2030 targets. It is tasked with supporting the implementation of research-based strategies for combating cholera in Africa. The prequalified oral cholera vaccines - Dukoral, Shanchol, and Euvichol - and those with recombinant DNA technology have also emerged as remarkable strides. In the face of this progress, challenges persist. Climate change, including extreme weather events and the lack of safe water, sanitation, and hygiene facilities, acts as a multiplier, amplifying existing challenges and hindering progress. Porous borders with inefficient disease surveillance networks among member states also facilitate the inter-territorial spread of the disease. Despite ongoing challenges, global targets are achievable provided strong institutional infrastructure and additional evidence-based public health initiatives are promulgated and enacted. The Global Roadmap to Ending Cholera Outbreaks by 2030 is a resourceful tool for advancing this fight and eradicating cholera.

Rapid cholera outbreak control following catastrophic landslides and floods: A case study of Bududa district, Uganda.

In June 2019, landslides and floods in Bududa district, eastern Uganda, claimed lives and led to a cholera outbreak. The affected communities had inadequate access to clean water and sanitation. To share the experience of controlling a cholera outbreak in Bududa district, after landslides and floods. A descriptive cross-sectional study was carried out in which outbreak investigation reports, weekly epidemiological data and disaster response reports were reviewed. On 4 - 5th June 2019, heavy rainfall resulted in four landslides which caused six fatalities, 27 injuries, floods and displaced 480 persons. Two weeks later, a cholera outbreak was confirmed in Bududa district. The Ministry of Health (MoH) rapidly deployed oral cholera vaccine (OCV) from local reserves and mass vaccinated 93% of the target population in 22 affected parishes. The outbreak was controlled in 10 weeks with 67 cholera cases and 1 death reported. However, WaSH conditions remained poor, with only, 24.2 % (879/3,628) of the households with washable latrines, 26.8% (1,023/3,818) had hand-washing facilities with soap and 33.6% (1617/4807) used unsafe water. The OCV stockpile by the MoH helped Uganda to control cholera promptly in Bududa district. High-risk countries should keep OCV reserves for emergencies.

The Governance of Childhood Vaccination Services in Crisis Settings: A Scoping Review.

The persistence of inadequate vaccination in crisis-affected settings raises concerns about decision making regarding vaccine selection, timing, location, and recipients. This review aims to describe the key features of childhood vaccination intervention design and planning in crisis-affected settings and investigate how the governance of childhood vaccination is defined, understood, and practised. We performed a scoping review of 193 peer-reviewed articles and grey literature on vaccination governance and service design and planning. We focused on 41 crises between 2010 and 2021. Following screening and data extraction, our analysis involved descriptive statistics and applying the governance analysis framework to code text excerpts, employing deductive and inductive approaches. Most documents related to active outbreaks in conflict-affected settings and to the mass delivery of polio, cholera, and measles vaccines. Information on vaccination modalities, target populations, vaccine sources, and funding was limited. We found various interpretations of governance, often implying hierarchical authority and regulation. Analysis of governance arrangements suggests a multi-actor yet fragmented governance structure, with inequitable actor participation, ineffective actor collaboration, and a lack of a shared strategic vision due to competing priorities and accountabilities. Better documentation of vaccination efforts during emergencies, including vaccination decision making, governance, and planning, is needed. We recommend empirical research within decision-making spaces.

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, ‘vme-VAC/MST-1’ based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine’s effects In vivo. Communicated by Ramaswamy H. Sarma

Research on cholera vaccine injection in the later period of the Republic of China

During the period of the Republic of China, cholera was one of the government-mandated infectious diseases. In response to the cholera epidemic, the Beijing municipal government and the Health Bureau established the Beijing special epidemic prevention committee to guide and supervise the implementation of epidemic prevention measures. The Beijing municipal government and the Health Bureau cooperated with medical institutions to implement cholera vaccine injection at their locations, stations, gates, schools and other public places, as well as personal residences. They strictly defined the vaccinated population and vaccination methods, and adopted the vaccination mode of combining voluntary injection and compulsory injection, effectively controlled the spreading of the cholera. The public benefit, solidarity and flexibility of its epidemic prevention work are of certain reference significance to the epidemic prevention work today and even in the future.

Effectiveness of the Euvichol® oral cholera vaccine at 2 years: A case-control and bias-indicator study in Haiti

ObjectivesThe World Health Organization recommends the use of oral cholera vaccine (OCV) in cholera control efforts. Euvichol®, pre-qualified in 2015, is the leading component of the Global OCV stockpile, but data on its field effectiveness are limited. To evaluate Euvichol® vaccine effectiveness (VE), we conducted a case-control study between September 2018 to March 2020 following an OCV campaign in November 2017 in Haiti. MethodsCases were individuals with acute watery diarrhea. Stool samples were tested by culture and real-time polymerase chain reaction of the Vibrio cholerae ctxA gene. Cases were matched to four community controls without diarrhea by residence, enrollment time, age, and gender, and interviewed for sociodemographics, risk factors, and self-reported vaccination. Cholera cases were analyzed by conditional logistic regression in the VE study. Non-cholera diarrhea cases were analyzed in a bias-indicator study. ResultsWe enrolled 15 cholera cases matched to 60 controls, and 63 non-cholera diarrhea cases matched to 249 controls. In the VE analysis, eight (53%) cases reported vaccination with any number of doses compared to 43 (72%) controls. Adjusted two-dose OCV VE was 69% (95% CI –71 to 94%). ConclusionsBetween 10-27 months after vaccination, Euvichol® was effective and similar to Shanchol™, suggesting that it can serve as one component of multi-sectoral comprehensive cholera control.