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Background: An outbreak of cholera was reported in the Middle East by the second half of 2022. Raising public awareness and vaccination against cholera represent critical factors in the preventive efforts. The current study aimed to assess the knowledge of cholera and attitude towards its vaccination among a sample of the general public residing in Jordan. Methods: An online self-administered questionnaire was distributed to the residents in Jordan using a snowball convenience-based sampling approach. The questionnaire based on previously published studies included items to evaluate sociodemographic variables, knowledge about cholera symptoms, transmission, and prevention and the willingness to accept cholera vaccination. Additionally, four items based on the validated 5 C scale in Arabic were included to assess the psychological factors influencing attitude to cholera vaccination. Results: The final study sample comprised 1339 respondents, of whom 1216 (90.8%) heard of cholera before the study. Among those who heard of cholera, and on a scale from 0 to 20, the overall mean cholera Knowledge score (K-score) was 12.9 ± 3.8. In multivariate analysis, being over 30 years old and occupation as healthcare workers or students in healthcare-related colleges were significantly associated with a higher K-score compared to younger individuals and students in non-healthcare-related colleges. Overall, the acceptance of cholera vaccination if cases are recorded in Jordan, and if the vaccine is safe, effective, and provided freely was reported among 842 participants (69.2%), while 253 participants were hesitant (20.8%) and 121 participants were resistant (10.0%). In linear regression, the significant predictors of cholera vaccine acceptance were solely the three psychological factors namely high confidence, low constraints, and high collective responsibility. Conclusions: In this study, the identified gaps in cholera knowledge emphasize the need to enhance educational initiatives. Although cholera vaccine acceptance was relatively high, a significant minority of the respondents exhibited vaccination hesitancy or resistance. The evident correlation between the psychological determinants and attitudes toward cholera vaccination emphasizes the need to consider these factors upon designing public health campaigns aimed at cholera prevention. The insights of the current study highlight the importance of addressing both knowledge gaps and psychological barriers to optimize cholera control strategies. [ABSTRACT FROM AUTHOR]

Abstract Background An outbreak of cholera was reported in the Middle East by the second half of 2022. Raising public awareness and vaccination against cholera represent critical factors in the preventive efforts. The current study aimed to assess the knowledge of cholera and attitude towards its vaccination among a sample of the general public residing in Jordan. Methods An online self-administered questionnaire was distributed to the residents in Jordan using a snowball convenience-based sampling approach. The questionnaire based on previously published studies included items to evaluate sociodemographic variables, knowledge about cholera symptoms, transmission, and prevention and the willingness to accept cholera vaccination. Additionally, four items based on the validated 5 C scale in Arabic were included to assess the psychological factors influencing attitude to cholera vaccination. Results The final study sample comprised 1339 respondents, of whom 1216 (90.8%) heard of cholera before the study. Among those who heard of cholera, and on a scale from 0 to 20, the overall mean cholera Knowledge score (K-score) was 12.9 ± 3.8. In multivariate analysis, being over 30 years old and occupation as healthcare workers or students in healthcare-related colleges were significantly associated with a higher K-score compared to younger individuals and students in non-healthcare-related colleges. Overall, the acceptance of cholera vaccination if cases are recorded in Jordan, and if the vaccine is safe, effective, and provided freely was reported among 842 participants (69.2%), while 253 participants were hesitant (20.8%) and 121 participants were resistant (10.0%). In linear regression, the significant predictors of cholera vaccine acceptance were solely the three psychological factors namely high confidence, low constraints, and high collective responsibility. Conclusions In this study, the identified gaps in cholera knowledge emphasize the need to enhance educational initiatives. Although cholera vaccine acceptance was relatively high, a significant minority of the respondents exhibited vaccination hesitancy or resistance. The evident correlation between the psychological determinants and attitudes toward cholera vaccination emphasizes the need to consider these factors upon designing public health campaigns aimed at cholera prevention. The insights of the current study highlight the importance of addressing both knowledge gaps and psychological barriers to optimize cholera control strategies.

Background: In 2019–2020, preventative Oral Cholera Vaccine campaigns were conducted in 24/32 non-contiguous health areas of Goma, DR Congo. In August 2022, we measured coverage and factors potentially influencing success of the delivery strategy. Methods: We used random geo-sampled stratified cluster survey to estimate OCV coverage and assess population movement, diarrhea history, and reasons for non-vaccination. Results: 603 households were visited. Coverage with at least one dose was 46.4 % (95 %CI: 41.8–51.0), and 50.1 % (95 %CI: 45.4–54.8) in areas targeted by vaccination compared to 26.3 % (95 %CI: 19.2–34.9) in non-targeted areas. Additionally, 7.0 % of participants reported moving from outside Goma since 2019, and 5.4 % reported history of severe diarrhea. Absence and unawareness were the main reasons for non-vaccination. Conclusion: Results suggest that targeting non-contiguous urban areas had a coverage-diluting effect. Targeting entire geographically contiguous areas, adapted distribution, and regular catch-up campaigns are operational recommendations to reach higher coverages arising from the study.

Introduction: An upsurge of diarrheal cases occurred in Dhaka, Bangladesh, with approximately 30% of the cases being identified as cholera in 2022. To combat this situation, a reactive Oral Cholera Vaccination campaign was organized in five highly cholera-affected areas of Dhaka city. The paper is a descriptive tale of experience gathering, organization and implementation of reactive oral cholera vaccination campaign. Study design: This is a descriptive report of a reactive oral cholera vaccination campaign. Methods: Population density maps were generated using GIS technology before launching the campaign. The target population comprised individuals aged over one year, excluding pregnant women, totaling 2,374,976 people residing in above mentioned areas. The campaign utilized Euvichol-Plus, an OCV with adherence to the necessary cold chain requirements. Total 700 teams, each consisting of six members, were deployed across the five zones. The campaign was conducted in two rounds, where first round took place in June–July 2022, followed by second round in August 2022. During the campaign, data on adverse events following immunization (AEFI) was collected. Expert teams from various government and non-government organizations monitored regularly and ensured the campaign's success. Results: The first round achieved a coverage rate of 99%, whereas in the second round, 86.3% of individuals among the first dose recipients. During the campaigns, a total of 57 AEFIs were reported. Conclusions: This campaign serves as a model for a multispectral approach in combating cholera epidemics, highlighting the collaborative efforts of policymakers, health authorities, local communities, and health partners.

ABSTRACT Cholera caused by Vibrio cholerae O139 emerged in the early 1990s and spread rapidly to 11 Asian countries before receding for unclear reasons. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). V. cholerae O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting V. cholerae O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by V. cholerae O139. We compared these responses to those of age-gender-blood group-matched recipients of the bivalent oral cholera vaccine (OCV O1/O139). We found prominent OSP, LPS, and vibriocidal responses in patients, with a high correlation between these responses. OSP responses primarily targeted the terminal tetrasaccharide of OSP. Vaccinees developed OSP, LPS, and vibriocidal antibody responses, but of significantly lower magnitude and responder frequency (RF) than matched patients. We separately analyzed responses in pediatric vaccinees born after V. cholerae O139 had receded in Bangladesh. We found that OSP responses were boosted in children who had previously received a single dose of bivalent OCV 3 yr previously but not in vaccinated immunologically naïve children. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 despite the presence of capsules, that vaccination with bivalent OCV is poorly immunogenic in the short term in immunologically naïve individuals, but that OSP-specific immune responses can be primed by previous exposure, although whether such responses can protect against O139 cholera is uncertain. IMPORTANCE Cholera is a severe dehydrating illness in humans caused by Vibrio cholerae serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of V. cholerae LPS. Yet, little is known about immunity to O139 OSP. In this study, we assessed immune responses targeting OSP in patients from an endemic region with cholera caused by V. cholerae O139. We compared these responses to those of the age-gender-blood group-matched recipients of the bivalent oral cholera vaccine. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 and that the OSP responses primarily target the terminal tetrasaccharide of OSP. Our results further suggest that vaccination with the bivalent vaccine is poorly immunogenic in the short term for inducing O139-specific OSP responses in immunologically naïve individuals, but OSP-specific immune responses can be primed by previous exposure or vaccination.

BACKGROUND: We have previously developed a rice-based oral vaccine against cholera diarrhea, MucoRice-CTB. Using Agrobacterium-mediated co-transformation, we produced the selection marker-free MucoRice-CTB line 51A, which has three copies of the cholera toxin B subunit (CTB) gene and two copies of an RNAi cassette inserted into the rice genome. We determined the sequence and location of the transgenes on rice chromosomes 3 and 12. The expression of alpha-amylase/trypsin inhibitor, a major allergen protein in rice, is lower in this line than in wild-type rice. Line 51A was self-pollinated for five generations to fix the transgenes, and the seeds of the sixth generation produced by T5 plants were defined as the master seed bank (MSB). T6 plants were grown from part of the MSB seeds and were self-pollinated to produce T7 seeds (next seed bank; NSB). NSB was examined and its whole genome and proteome were compared with those of MSB. RESULTS: We re-sequenced the transgenes of NSB and MSB and confirmed the positions of the three CTB genes inserted into chromosomes 3 and 12. The DNA sequences of the transgenes were identical between NSB and MSB. Using whole-genome sequencing, we compared the genome sequences of three NSB with three MSB samples, and evaluated the effects of SNPs and genomic structural variants by clustering. No functionally important mutations (SNPs, translocations, deletions, or inversions of genic regions on chromosomes) between NSB and MSB samples were detected. Analysis of salt-soluble proteins from NSB and MSB samples by shot-gun MS/MS detected no considerable differences in protein abundance. No difference in the expression pattern of storage proteins and CTB in mature seeds of NSB and MSB was detected by immuno-fluorescence microscopy. CONCLUSIONS: All analyses revealed no considerable differences between NSB and MSB samples. Therefore, NSB can be used to replace MSB in the near future.

IntroductionCholera remains a significant public health concern in many parts of the world, particularly in areas with poor sanitation and hygiene. Bangladesh and other impoverished nations have been severely affected by cholera outbreaks, especially in areas with a high population density. In order to mitigate the spread of cholera, oral cholera vaccines (OCVs) are recommended as a prophylactic measure. In May 2018, 775,666 of the Forcibly Displaced Myanmar Nationals (FDMN) in the registered and makeshift camps and 103,605 of the residents in the host community received two doses of OCV ShancholTM in Cox's Bazar, Bangladesh, because the conditions in the area favored the transmission of cholera and other waterborne diseases. This study aimed to assess the coverage of OCV among the FDMN and the host community in Cox's Bazar.MethodsIn August 2018, we enrolled 4,240 respondents for this study following the “World Health Organization (WHO) Vaccination Coverage Cluster Surveys: Reference Manual (2018).” The coverage survey was conducted with three strata of the population: the host community from the Teknaf Upazila, the registered camp, and the makeshift camp from the Ukhia Upazila. We collected information regarding OCV coverage, demographic characteristics, and knowledge and behaviors of people toward the vaccine. The data were analyzed using descriptive statistics.ResultsAccording to our study, the overall OCV coverage was 85%, with 68% in the host community, 91% in the registered camp, and 98% in the makeshift camp. The lower coverage in the host community was due to residents unaware of the vaccination campaign, the unavailability of vaccines, and unaware where to go for vaccination.DiscussionOur findings demonstrate that the OCV campaign in the FDMN camps was successful, reaching over 90% coverage, while coverage in the host community was much lower. In order to make sure that OCV vaccination efforts are reaching the target population and having the desired impact, our study emphasizes the need to inform the target population of when and where to get vaccinated.

The paper presents a review of the data on the methods of isolation and control of Vibrio cholerae antigens – cholerogen-anatoxin and O-antigens of Inaba and Ogawa – components of the oral bivalent chemical cholera vaccine produced by the RusRAPI “Microbe”, the only prophylactic drug against cholera registered in the territory of the Russian Federation. Currently, the vaccine is produced using the method of segregated manufacturing of cholerogenanatoxin and O-antigens Inaba and Ogawa with step-by-step control of their main properties, which ensures the production of a high-quality finished product. Ultrafiltration is an effective method for concentrating a semi-finished product, which helps to reduce losses and increases the yield of the final product. It remains promising to develop a method for gentle steril ization of O-antigens to maximize the preservation of specific activity. To control the specific activity of the antigenic components and the finished vaccine preparation, a complex of in vivo and in vitro methods is applied. However, the multi-stage process and duration, the use of several types of laboratory animals, as well as modern WHO requirements determine the need for the introduction of alternative in vitro control methods. The use of cell cultures as a replacement for the biological method appears prospective, and demonstrates a positive correlation with animal tests. To assess the activity of antigens, the use of an immunochemical method – dot-immunoassay with gold nanoparticles – is put forward, which will make it possible to harmonize the control method at all stages of the production process, as well as to determine the serovar specificity of Vibrio cholerae O-antigens. The development of molecular-genetic, microbiological, immunochemical methods is relevant for a more complete and comprehensive control of the main immunogens of industrial strains of cholera vibrio. The introduction of promising methods for obtaining antigens and monitoring their properties will allow for a more complete characterization of the component composition of the finished dosage form of the chemical cholera vaccine.

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic. [ABSTRACT FROM AUTHOR]

• Combine door-to-door with fixed or semi-fixed vaccination teams. • Allow for extended immunization period and self-administered second dose. • Vaccinate frontline health workers since they are at great risk of exposure. • Strengthen supervision of the vaccination teams. On 14 August 2017, massive landslides and floods hit Freetown (Sierra Leone). More than 1,000 people lost their lives while approximately 6,000 people were displaced. The areas most affected included parts of the town with challenged access to basic water and sanitation facilities, with communal water sources likely contaminated by the disaster. To avert a possible cholera outbreak following this emergency, the Ministry of Health and Sanitation (MoHS), supported by the World Health Organization (WHO) and international partners, including Médecins Sans Frontières (MSF) and UNICEF, launched a two-dose pre-emptive vaccination campaign using Euvichol™, an oral cholera vaccine (OCV). We conducted a stratified cluster survey to estimate vaccination coverage during the OCV campaign and also monitor adverse events. The study population – subsequently stratified by age group and residence area type (urban/rural) – included all individuals aged 1 year or older, living in one of the 25 communities targeted for vaccination. In total 3,115 households were visited, 7,189 individuals interviewed; 2,822 (39%) people in rural and 4,367 (61%) in urban areas. The two-dose vaccination coverage was 56% (95% confidence interval (CI): 51.0–61.5), 44% (95%CI: 35.2–53.0) in rural and 57% (95%CI: 51.6–62.8) in urban areas. Vaccination coverage with at least one dose was 82% (95%CI: 77.3–85.5), 61% (95%CI: 52.0–70.2) in rural and 83% (95%CI: 78.5–87.1) in urban areas. The Freetown OCV campaign exemplified a timely public health intervention to prevent a cholera outbreak, even if coverage was lower than expected. We hypothesised that vaccination coverage in Freetown was sufficient in providing at least short-term immunity to the population. However, long-term interventions to ensure access to safe water and sanitation are needed. [ABSTRACT FROM AUTHOR]

Since 1971, Cameroon has been facing an ever-growing series of cholera epidemics; despite all the efforts made by the government to address this substantial public health problem. In 2020, in addition to the COVID-19 pandemic, Cameroon recorded a high cholera case fatality rate of 5.3% following epidemics noted in the South, Littoral, and South-West regions which is far higher than the 1% World Health Organization acceptable rate. The Ministry of Public Health organized a reactive vaccination campaign against cholera to address the high mortality rate in the affected health districts. The first round was in August 2020 and the second in March 2021. We conducted a cross-sectional study and reviewed this vaccination campaign's challenges, best practices, and lessons. The vaccination coverage for the two doses of the oral cholera vaccine was 80.4%, with a refusal rate as high as 67%. People 20 years and above recorded the lowest vaccination coverage. The main challenge was misinformation about the cholera vaccine. The best practice was thorough population sensitization through community actors. Proper communication will always brave the odds of hesitancy and favor mass population vaccination to thwart hesitancy and consolidate herd immunity. [ABSTRACT FROM AUTHOR]

Repurposing of existing drugs and vaccines for diseases that they were not originally intended for is a promising research field. Recently there has been evidence that oral cholera vaccine might be used in the treatment of inflammatory disease and some common cancers. Specifically, Ji et al showed that the administration of cholera vaccine after a prostate cancer diagnosis reduced prostate cancer specific mortality rates by almost 50%. In a cohort of men from Stockholm, Sweden, with more detailed cancer data and a higher coverage of exposure to vaccine, we replicated these findings using a marginal structural Cox model. We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46, 95% CI 0.31–0.69, p-value 0.0001) even after adjusting for all known confounders. However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding. [ABSTRACT FROM AUTHOR]

MucoRice-CTB is a promising cold-chain-free oral cholera vaccine candidate. Here, we report a double-blind, randomized, placebo-controlled, phase I study conducted in the USA in which vaccination with the 6-g dose of MucoRice-CTB induced cross-reactive antigen-specific antibodies against the B subunit of cholera toxin (CTB) and enterotoxigenic Escherichia coli heat-labile enterotoxin without inducing serious adverse events. This dosage was acceptably safe and tolerable in healthy men and women. In addition, it induced a CTB-specific IgA response in the saliva of two of the nine treated subjects; in one subject, the immunological kinetics of the salivary IgA were similar to those of the serum CTB-specific IgA. Antibodies from three of the five responders to the vaccine prevented CTB from binding its GM1 ganglioside receptor. These results are consistent with those of the phase I study in Japan, suggesting that oral MucoRice-CTB induces neutralizing antibodies against diarrheal toxins regardless of ethnicity. [ABSTRACT FROM AUTHOR]

Abstract Background We have previously developed a rice-based oral vaccine against cholera diarrhea, MucoRice-CTB. Using Agrobacterium-mediated co-transformation, we produced the selection marker–free MucoRice-CTB line 51A, which has three copies of the cholera toxin B subunit (CTB) gene and two copies of an RNAi cassette inserted into the rice genome. We determined the sequence and location of the transgenes on rice chromosomes 3 and 12. The expression of alpha-amylase/trypsin inhibitor, a major allergen protein in rice, is lower in this line than in wild-type rice. Line 51A was self-pollinated for five generations to fix the transgenes, and the seeds of the sixth generation produced by T5 plants were defined as the master seed bank (MSB). T6 plants were grown from part of the MSB seeds and were self-pollinated to produce T7 seeds (next seed bank; NSB). NSB was examined and its whole genome and proteome were compared with those of MSB. Results We re-sequenced the transgenes of NSB and MSB and confirmed the positions of the three CTB genes inserted into chromosomes 3 and 12. The DNA sequences of the transgenes were identical between NSB and MSB. Using whole-genome sequencing, we compared the genome sequences of three NSB with three MSB samples, and evaluated the effects of SNPs and genomic structural variants by clustering. No functionally important mutations (SNPs, translocations, deletions, or inversions of genic regions on chromosomes) between NSB and MSB samples were detected. Analysis of salt-soluble proteins from NSB and MSB samples by shot-gun MS/MS detected no considerable differences in protein abundance. No difference in the expression pattern of storage proteins and CTB in mature seeds of NSB and MSB was detected by immuno-fluorescence microscopy. Conclusions All analyses revealed no considerable differences between NSB and MSB samples. Therefore, NSB can be used to replace MSB in the near future.

Cholera is both an endemic and epidemic disease in many low and middle-income countries (LMICs). Strategies for cholera control include improving water, sanitation, and hygiene; providing early and effective treatment; and deploying oral cholera vaccine (OCV). This last strategy is relatively new, and countries considering its introduction are interested in knowing the potential cost not only of the vaccine, but also the cost of introduction. This paper describes the costing of OCV introduction in LMICs using a publicly available Excel-based tool known as the CholTool. It includes estimates of delivery cost categories which cover not only the service delivery costs (e.g. vaccine procurement, handling, storage, and transport; vaccination administration, monitoring supervision, and field support), but also the programmatic costs associated with introducing a new vaccine (i.e. microplanning, communication and training materials development, sensitization/social mobilization, and personnel training) to ensure that a comprehensive estimate is provided with health payer perspective. CholTool takes the user through a structured sequence of interlinked modules containing input parameter cells (assumptions), decision cells (variable selections), and formulas (calculations) to produce customized cost estimates based on standardized methods. The tool provides both financial and economic cost estimates, to ensure that both costs are available for consideration. Four examples of applications of CholTool are presented in three countries- one in Ethiopia, two in Malawi and one in Nepal. The estimates of economic delivery cost per dose (including service delivery and programmatic costs) were (in USD 2016): $2.89 in Ethiopia, $3.04 in Malawi1, $3.35 in Malawi2 and $3.06 in Nepal. A cost projection conducted before the campaign using the tool and a retrospective costing using the tool in Nepal resulted in no significant difference between economic delivery costs per dose.

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss 2 examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that nonvaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the "herd immunity" threshold needed to stop transmission and achieve elimination. [ABSTRACT FROM AUTHOR]

Cholera remains a major contributor of diarrheal diseases and leads to substantial morbidity and mortality, particularly in low socioeconomic settings. Nonavailability of a national cholera control plan in India, compounded by underreporting of cholera cases and deficient accurate cholera hotspot estimates, has made cholera control a challenge. Obstacles in the programmatic introduction of oral cholera vaccine (OCV) lie within the infrastructure-stockpile, costing, distribution system, cold-chain mechanism, vaccine logistics, and lack of strengthened surveillance systems for adverse events following immunization. Sustained political commitment along with collaboration of people working in the media will also determine the policy outcome of OCV introduction in India. [ABSTRACT FROM AUTHOR]

Vaccine herd protection is the extension of the defense conferred by immunization beyond the vaccinated to unvaccinated persons in a population, as well as the enhancement of the protection among the vaccinated, due to vaccination of the surrounding population. Vaccine herd protection has traditionally been inferred from observations of disease trends after inclusion of a vaccine in national immunization schedules. Rather than awaiting outcomes of widescale vaccine deployment, earlier-stage evaluation of vaccine herd protection during trials or mass vaccination projects could help inform policy decisions about potential vaccine introduction. We describe the components, influencing factors, and implications of vaccine herd protection and discuss various methods for assessing herd protection, using examples from cholera and typhoid vaccine studies. [ABSTRACT FROM AUTHOR]

Cholera remains a public health threat among the least privileged populations and regions affected by conflicts and natural disasters. Together with Water, Sanitation and Hygiene practices, use of oral cholera vaccines (OCVs) is a key tool to prevent cholera. Bivalent whole-cell killed OCVs have been extensively used worldwide and found effective in protecting populations against cholera in endemic and outbreak settings. No cholera vaccine had been available for United States (US) travelers at risk for decades until 2016 when CVD 103-HgR (Vaxchora™), an oral live attenuated vaccine, was licensed by the US FDA. A single dose of Vaxchora™ protected US volunteers against experimental challenge 10 days and 3 months after vaccination. However, use of Vaxchora™ poses several challenges in resource poor settings as it requires reconstitution, is age-restricted to 18 to 64 years, has no data in populations endemic for cholera, and faces challenges related to cold chain and cost.

Objective: To assess the extent of existing published evidence on cholera and to characterize the epidemiologic data of cholera in Nepal. Methods: We conducted a literature scoping review by summarizing published literature reporting on cholera in Nepal from January 1946 to March 2019 in online databases: MEDLINE, Embase, Cochrane, and Global Health. Additionally, we reviewed national surveillance data on clinically diagnosed and laboratory confirmed cholera reported by the Ministry of Health and Population. Results: Most of the published studies were conducted predominantly in Kathmandu Valley during the rainy season; however, outbreaks have been reported in other parts of Nepal including Terai, Hilly and Mountain regions. Our literature review exhibited that all age groups were affected by cholera, but particularly children and young adults were at-risk age groups in Nepal. Vibrio cholerae serogroup O1, biotype El Tor, serotype Ogawa has been predominantly isolated with an emergence of resistant strains since 1996. Two mass vaccination campaigns using oral cholera vaccines were conducted: Rautahat district in 2014 and Banke district in 2017. Conclusions: Capacity building for a nation wide systematic cholera surveillance with rapid and reliable diagnosis is needed to better estimate the burden of cholera and identify geographically at-risk areas associated with the disease in Nepal. It is essential for developing an adequate policy on oral cholera vaccine introduction and effective water, sanitation and hygiene interventions.

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). [ABSTRACT FROM AUTHOR]

Background In mid-2016, a cholera outbreak occurred in Kathmandu Valley, Nepal. This retrospective study aims to determine if a reactive, ring vaccination strategy would have been useful in preventing cholera transmission during that outbreak. Methods Data on cholera cases were collected as part of hospital-based surveillance in the Kathmandu Valley in 2016. Global Positioning System (GPS) coordinates were obtained during household visits. Geographic clusters of cases were visually determined and tested statistically for clustering. Cluster size was determined based on the distribution of cases around the index case. Results GPS coordinates for 69 cases were analysed. Six geographic clusters were identified, all of which showed significant clustering of cases. Approximately 85% of cases within a cluster occurred more than 7 d after the index case. The median ring size was 1 km, with a population of 14 000 people. Conclusions Cholera cases were clustered in space and the majority of cases occurred over 1 week after the initial cases in the cluster, allowing for an opportunity to prevent transmission through the use of the vaccine soon after the initial case was identified. A ring vaccination strategy may be especially useful for large urban areas with recurrent seasonal outbreaks but where the specific locations for such outbreaks are not predictable. [ABSTRACT FROM AUTHOR]

Cameroon chose Oral Cholera Vaccine (OCV) mass vaccination campaign in addition to other interventions to respond to outbreaks since 2015. There is still a persistent controversy on the effectiveness of reactive OCV mass vaccination campaign. This article aimed to share evidence-based observations on the effect of a reactive single-dose OCV mass vaccination campaign on cholera cases in Cameroon. Health area centered risk analysis was used to identify nine high risk health areas among four health districts in the |North Region as hotspots. About 537,274 people at risk of cholera transmission one year of age and above including pregnant women were eligible to receive OCV. A total of 537,279 doses of OCV was deployed for vaccination from August 1–5, 2019 through door-to-door strategy for urban health districts, and fixed/ temporary fixed posts strategies for rural health districts. The overall vaccination coverage was 99.9%. Vaccine wastage rate was less than 0.5% (0.0011%). Independent monitoring showed vaccination coverage at 97.2%. The 2019 epidemic curve went down after OCV intervention on the contrary to that in the year 2018 at the same period. After OCV intervention, cholera cases dropped from about 10.5 to 9.3 cases per week at the regional level while at the district level, they dropped from 5.3 to 2.1, 2.2 to 1.7, 0.6 to 0 and 1.7 to 1.5 cases per week respectively for Garoua, Garoua II, Tchollire and Pitoa. Though not statistically significant (p = 1.4, α = 0.05), cases per 1000 population seemed to remain unchanged among OCV zones (0.32/1000) and non-OCV zones (0.31/1000) in 2018 while they increased from 0.37 (OCV zones) to 0.53 (non-0CV zones) cases per 1000 population in 2019. There might have been a general trend in the reduction of the number of new cases after a reactive single-dose OCV campaign. [ABSTRACT FROM AUTHOR]

Introduction: An upsurge of diarrheal cases occurred in Dhaka, Bangladesh, with approximately 30% of the cases being identified as cholera in 2022. To combat this situation, a reactive Oral Cholera Vaccination campaign was organized in five highly cholera-affected areas of Dhaka city. The paper is a descriptive tale of experience gathering, organization and implementation of reactive oral cholera vaccination campaign., Study Design: This is a descriptive report of a reactive oral cholera vaccination campaign., Methods: Population density maps were generated using GIS technology before launching the campaign. The target population comprised individuals aged over one year, excluding pregnant women, totaling 2,374,976 people residing in above mentioned areas. The campaign utilized Euvichol-Plus, an OCV with adherence to the necessary cold chain requirements. Total 700 teams, each consisting of six members, were deployed across the five zones. The campaign was conducted in two rounds, where first round took place in June-July 2022, followed by second round in August 2022. During the campaign, data on adverse events following immunization (AEFI) was collected. Expert teams from various government and non-government organizations monitored regularly and ensured the campaign's success., Results: The first round achieved a coverage rate of 99%, whereas in the second round, 86.3% of individuals among the first dose recipients. During the campaigns, a total of 57 AEFIs were reported., Conclusions: This campaign serves as a model for a multispectral approach in combating cholera epidemics, highlighting the collaborative efforts of policymakers, health authorities, local communities, and health partners., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germfree mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. In this study, we leveraged antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single-dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin-treated adult mice within 2 weeks after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV-vaccinated dams were also significantly more protected from choleric disease than pups from inactivated-HaitiV-vaccinated dams. Our findings establish the benefits of antibiotic-treated mice for live-OCV studies as well as their limitations and underscore the immunogenicity of HaitiV. IMPORTANCE Oral cholera vaccines (OCVs) are being deployed to combat cholera, but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations, but small-animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live-OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated HaitiV did not. These findings demonstrate HaitiV's immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs. [ABSTRACT FROM AUTHOR]

Cholera remains an important global health problem with up to 4 million cases and 140,000 deaths annually. Oral cholera vaccines (OCVs) are now a cornerstone of the WHOs "Ending Cholera – A Global Roadmap to 2030" global program for the eventual elimination of cholera. There are currently three WHO prequalified OCVs available, Dukoral®, Shanchol® and Euvichol-Plus®. These vaccines are effective but due to a multiple strain composition and two different methods of inactivation, are complex and costly to manufacture. We describe here the characterization and industrial scale development of Hillchol®; a novel, likely affordable single-component OCV for low and middle-income countries. Hillchol® consists of formalin-inactivated bacteria of a stable recombinant Vibrio cholerae O1 El Tor Hikojima serotype strain expressing approximately 50% each of Ogawa and Inaba O1 LPS antigens. The novel OCV can be manufactured on an industrial scale at a low cost. Hillchol® was well tolerated in animal toxicology studies and shown to have non-inferior oral immunogenicity in mice for both intestinal-mucosal and serological immune responses when compared with a WHO-prequalified OCV. The optimized production of this single component OCV will reduce cost of OCV production and thus substantially increase vaccine availability. Based on these results, Hillchol® has been produced at a GMP facility and used successfully for clinical phase I/II studies. [ABSTRACT FROM AUTHOR]

World Health Organization recommends oral cholera vaccine (OCV) to prevent and control cholera, but requires cost-effectiveness evidence. This review aimed to provide a critical appraisal and summary of global economic evaluation (EE) studies involving OCV to guide future EE study. Full EE studies, published from inception to December 2015, evaluating OCV against cholera disease were included. The included studies were appraised using WHO guide for standardization of EE of immunization programs. Out of 14 included studies, almost all (13/14) were in low- and middle-income countries. Most studies (11/14) evaluated mass vaccination program. Most of the studies (9/14) incorporated herd protective effect. The most common influential parameters were cholera incidence, OCV coverage, herd protection and OCV price. OCV vaccination is likely to be cost-effective when targeted at the population with high-risk of cholera and poor access to health care facilities when herd protection effect is incorporated and OCV price is low.

Background: Cholera is known to be transmitted from person to person, and inactivated oral cholera vaccines (OCVs) have been shown to confer herd protection via interruption of this transmission. However, the geographic dimensions of chains of person-to-person transmission of cholera are uncertain. The ability of OCVs to confer herd protection was used to define these dimensions in two cholera-endemic settings, one in rural Bangladesh and the other in urban India. Methods: Two large randomized, placebo-controlled trials of inactivated OCVs, one in rural Matlab, Bangladesh and the other in urban Kolkata, India, were reanalyzed. Vaccine herd protection was evaluated by relating the risk of cholera in placebo recipients to vaccine coverage of surrounding residents residing within concentric rings. In Matlab, concentric rings in 100-m increments up to 700 m were evaluated; in Kolkata, 50-m increments up to 350 m were evaluated. Results: One hundred and eight cholera cases among 24 667 placebo recipients were detected during 1 year of post-vaccination follow-up at Matlab; 128 cholera cases among 34 968 placebo recipients were detected during 3 years of follow-up in Kolkata. Consistent inverse relationships were observed between vaccine coverage of the ring and the risk of cholera in the central placebo recipient for rings with radii up to 500 m in Matlab and up to 150 m in Kolkata. Conclusions: These results suggest that the dimensions of chains of person-to-person transmission in endemic settings can be quite large and may differ substantially from setting to setting. Using OCVs as ‘probes’ to define these dimensions can inform geographical targeting strategies for the deployment of these vaccines in endemic settings.

Background: Cholera has harmful effects on the fetus but safety data on the oral cholera vaccine in pregnant women are controversial.Objectives: We conducted the first meta-analysis of studies in pregnant women comparing the effect of oral cholera vaccination on pregnancy outcomes with unvaccinated women. Outcomes of interest were adverse pregnancy outcome, miscarriage, stillbirth, preterm delivery, low birthweight, abortion and malformation.Search Strategy: The search was run in MEDLINE/PubMed, SCOPUS and Embase databases from inception up to December 2019.Selection Criteria: Inclusion criteria were: (1) studies that investigated the association between oral cholera vaccines and adverse pregnancy outcomes; (2) studies that reported outcomes with appropriate estimates; and (3) studies that contained an unvaccinated control group.Data Collection and Analysis: A random-effects model (DerSimonian and Laird) was run to evaluate the overall treatment effect (relative risk, RR). The PRISMA statement was followed in reporting this meta-analysis.Main Results: Five studies included in meta-analysis with 5584 women (2920 exposed and 2664 not exposed). No significant increase in adverse pregnancy outcome (RR 1.03, 95% CI 0.79-1.34), miscarriage (RR 1.15, 95% CI 0.84-1.57) or stillbirth (RR 1.11, 95% CI 0.69-1.80) following cholera vaccine administration was found compared with control group. There was also no association with an increased risk of preterm delivery (RR 0.61, 95% CI 0.35-1.06) low birthweight (RR 0.84, 95% CI 0.56- 1.26), accidental abortion (RR 1.02, 95% CI 0.77-1.35) or malformation (RR 0.70, 95% CI 0.22-2.25).Conclusions: This study shows no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm.Tweetable Abstract: There is no evidence of an association between oral cholera vaccination and adverse pregnancy outcomes. The findings do not rigorously exclude the possibility that the vaccine protocol may result in some degree of harm. [ABSTRACT FROM AUTHOR]

The first oral cholera vaccination (OCV) campaign in Somalia was implemented between March and October 2017. It was the first time the Ministry of Health had introduced and used OCV as part of the cholera prevention and control strategies. The Ministry of Health aimed to cover 1.1 million people ≥ 1 year with 2 doses of the OCV in 11 high-risk districts. Overall, 2-dose administrative OCV coverage in all targeted districts was 95.5%. Following the campaign, a random sample survey was conducted in 9 out of 11districts to evaluate coverage, awareness, reasons for non-vaccination, the water and sanitation status of households, and any resulting adverse events. The survey was conducted in 2 phases. Of the 3,715 eligible individuals in the first phase, 92.5% (95% CI 91.4–93.6%) received 2 doses of the OCV and 7.0% (95% CI 6.0–8.2%) 1 dose. In the second phase, of 1,926 individuals, 94.1% (95% CI 92.9–95.1%) received 2 doses and 2.6% (95% CI 2.0–3.4%) 1 dose. Despite challenges, this experience shows that OCV campaigns can be implemented in acute humanitarian settings through existing immunization structures. [ABSTRACT FROM AUTHOR]

Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs. In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD. The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings. [ABSTRACT FROM AUTHOR]

Cholera remains a major global public health problem that is primarily linked to insufficient access to safe water and proper sanitation. Oral Cholera Vaccine (OCV) has been recommended as an additional public health tool along with WASH in cholera endemic countries and in areas at risk for outbreaks. The new generation OCV is safe and offers good protection in older children and adults while limited protection in younger children less than five years of age has been observed. The combination of direct vaccine protection and vaccine herd immunity effects makes OCV highly cost-effective and, therefore, attractive for use in developing countries. Additionally, in recent studies OCV was safe in pregnant women, supporting its use in pregnant women in cholera endemic countries. However, knowledge need to be developed for current vaccines for their prolonged duration of protection and vaccines need improvements for better immune response in younger children. A single dose vaccination regimen would be more cost-effective and easier to deliver. Recent approaches have focused on designing genetically attenuated cholera strains for use in single-dose cholera vaccines. The global demand for OCV has been boosted by the WHO recommendation to use OCV and is driven largely by epidemics and outbreaks and has been increasing due to the availability of cheaper easy-to-use vaccines, feasibility of mass OCV vaccination campaigns, demonstration of protection to underserved population in precarious situations, and vaccine costs being borne by Gavi (Vaccine Alliance). For rapid access in emergency and equitable distribution of OCV in cholera-endemic low-income countries, a global OCV stockpile was established in 2013 with support from the Global Alliance for Vaccines and Immunization. The three WHO-prequalified vaccines are Dukoral®, Shanchol™, Euvichol® (and Euvichol® Plus presentation), the latter two being included in the stockpile. [ABSTRACT FROM AUTHOR]

Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. However, policy directions are currently unavailable in India to guide the vaccine delivery. We conducted a scoping review to inform the policy about the scopes and challenges of different strategic choices of OCV delivery in India in light of current evidences, highlighting the scope of new research. Adopting the Arksey and O'Malley Framework for review, we searched for literatures on "efficacy", "effectiveness", and "cost" of oral cholera vaccine delivery through different strategies in Pubmed and Scopus. We found that the protective efficacy of OCV depends on its coverage. Evidence on effectiveness of OCV are available for both reactive and pre-vaccination campaigns. Reactive high-risk vaccination is more effective than reactive ring and mass vaccination. Pre-vaccination campaigns are more effective than reactive vaccination when vaccine availability is adequate. Pre-vaccination through school campaigns in 1–14 years age group have been cost effective in India. Vaccination campaigns in under-5 children are also cost effective in spite of low efficacy due to the scope of averting a higher number of cases. However, no evidence is available regarding efficacy and effectiveness of OCV in children <1 year as well as the effectiveness of delivering OCV through routine immunization. Little evidence exist to depict mass-campaign as more economic and effective than routine expanded programme on immunization (EPI) session for delivery of OCV. Considering operational feasibility, it needs to be explored whether OCV delivery strategy is compatible with India's current EPI, if it can be introduced in routine immunization at measles containing vaccine age-schedule, optionally preceded by a campaign in targeted hot-spots in the 1–14 year age-group. Safety and efficacy data of OCV during infancy as well as hot-spot surveillance are pre-requisites for formulation of such EPI policy. [ABSTRACT FROM AUTHOR]

The Republic of Burundi first reported cholera cases in 1978 and outbreaks have been occurring nearly every year since then. From 2008–2020, 6949 cases and 43 deaths were officially reported. To evaluate Burundi’s potential to eliminate cholera, we identified hotspots using cholera incidence and disease persistence as suggested by the Global Task Force for Cholera Control. The mean annual incidence for each district that reported cholera ranged from 0.29 to 563.14 cases per 100,000 population per year from 2014–2020. Ten of 12 Health Districts which recorded cholera cases reported a mean annual incidence ≥5 per 100,000 for this time period. Cholera cases occur during the second half of the year in the areas near Lake Tanganyika and along the Ruzizi River, with the highest risk district being Bujumbura Centre. Additional research is needed to understand the role of Lake Tanganyika; risks associated with fishing; migration patterns; and other factors that may explain cholera’s seasonality. Due to the consistent epidemiological pattern and the relatively small area affected by cholera, control and elimination are feasible with an integrated program of campaigns using oral cholera vaccine over the short term and community-based interventions including WASH activities for sustained control.

Individual resistance to cholera infection and disease depends on both innate host factors and adaptive immunity acquired by a previous infection or vaccination. Locally produced, intestinal-mucosal secretory IgA (SIgA) antibodies against bacterial surface lipopolysaccharide (LPS) O antigens and/or secreted cholera toxins are responsible for the protective adaptive immunity, in conjunction with an effective mucosal immunologic memory that can elicit a rapid anamnestic SIgA antibody response upon re-exposure to the antigen/pathogen even many years later. Oral cholera vaccines (OCVs), based on inactivated Vibrio cholerae whole-cell components, either together with the cholera toxin B subunit (Dukoral™) or administered alone (Shanchol™/Euvichol-Plus™) were shown to be consistently safe and effective in large field trials in all settings. These OCVs are recommended by the World Health Organisation (WHO) for the control of both endemic cholera and epidemic cholera outbreaks. OCVs are now a cornerstone in WHO’s global strategy found in “Ending Cholera: A Global Roadmap to 2030.” However, the forecasted global demands for OCV, estimated by the Global Alliance for Vaccines and Immunization (GAVI) to 1.5 billion doses for the period 2020–2029, markedly exceed the existing manufacturing capacity. This calls for an increased production capacity of existing OCVs, as well as the rapid introduction of additional and improved vaccines under development.

Introduction: Cholera’s impact is greatest in resource-limited countries. In the last decade several large epidemics have led to a global push to improve and implement the tools for cholera prevention and control. Areas covered: PubMed, Google Scholar and the WHO website were searched to review the literature and summarize the current status of cholera vaccines to make recommendations on improving immunization approaches to cholera. Oral cholera vaccines (OCVs) have demonstrated their effectiveness in endemic, outbreak response and emergency settings, highlighting their potential for wider adoption. While two doses of the currently available OCVs are recommended by manufacturers, a single dose would be easier to implement. Encouragingly, recent studies have shown that cold chain requirements may no longer be essential. The establishment of the global OCV stockpile in 2013 has been a major advance in cholera preparedness. New killed and live-attenuated vaccines are being actively explored as candidate vaccines for endemic settings and/or as a traveller’s vaccine. The recent advances in cholera vaccination approaches should be considered in the global cholera control strategy. Expert commentary: The development of affordable cholera vaccines is a major success to improve cholera control. New vaccines and country specific interventions will further reduce the burden of this disease globally.

During November–December 2015, as part of the 2015 cholera outbreak response in Iraq, the Iraqi Ministry of Health targeted ≈255,000 displaced persons >1 year of age with 2 doses of oral cholera vaccine (OCV). All persons who received vaccines were living in selected refugee camps, internally displaced persons camps, and collective centers. We conducted a multistage cluster survey to obtain OCV coverage estimates in 10 governorates that were targeted during the campaign. In total, 1,226 household and 5,007 individual interviews were conducted. Overall, 2-dose OCV coverage in the targeted camps was 87% (95% CI 85%–89%). Two-dose OCV coverage in the 3 northern governorates (91%; 95% CI 87%–94%) was higher than that in the 7 southern and central governorates (80%; 95% CI 77%–82%). The experience in Iraq demonstrates that OCV campaigns can be successfully implemented as part of a comprehensive response to cholera outbreaks among high-risk populations in conflict settings.

Cholera caused by Vibrio cholerae O139 emerged in the early 1990s and spread rapidly to 11 Asian countries before receding for unclear reasons. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). V. cholerae O139 also expresses the OSP-capsule. We, therefore, assessed antibody responses targeting V. cholerae O139 OSP, LPS, capsule, and vibriocidal responses in patients in Bangladesh with cholera caused by V. cholerae O139. We compared these responses to those of age-gender-blood group-matched recipients of the bivalent oral cholera vaccine (OCV O1/O139). We found prominent OSP, LPS, and vibriocidal responses in patients, with a high correlation between these responses. OSP responses primarily targeted the terminal tetrasaccharide of OSP. Vaccinees developed OSP, LPS, and vibriocidal antibody responses, but of significantly lower magnitude and responder frequency (RF) than matched patients. We separately analyzed responses in pediatric vaccinees born after V. cholerae O139 had receded in Bangladesh. We found that OSP responses were boosted in children who had previously received a single dose of bivalent OCV 3 yr previously but not in vaccinated immunologically naïve children. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 despite the presence of capsules, that vaccination with bivalent OCV is poorly immunogenic in the short term in immunologically naïve individuals, but that OSP-specific immune responses can be primed by previous exposure, although whether such responses can protect against O139 cholera is uncertain. IMPORTANCE Cholera is a severe dehydrating illness in humans caused by Vibrio cholerae serogroups O1 or O139. Protection against cholera is serogroup-specific, which is defined by the O-specific polysaccharide (OSP) of V. cholerae LPS. Yet, little is known about immunity to O139 OSP. In this study, we assessed immune responses targeting OSP in patients from an endemic region with cholera caused by V. cholerae O139. We compared these responses to those of the age-gender-blood group-matched recipients of the bivalent oral cholera vaccine. Our results suggest that OSP-specific responses occur during cholera caused by V. cholerae O139 and that the OSP responses primarily target the terminal tetrasaccharide of OSP. Our results further suggest that vaccination with the bivalent vaccine is poorly immunogenic in the short term for inducing O139-specific OSP responses in immunologically naïve individuals, but OSP-specific immune responses can be primed by previous exposure or vaccination., Competing Interests: The authors declare no conflict of interest.

Cholera is a disease of poverty and occurs where there is a lack of access to clean water and adequate sanitation. Since improved water supply and sanitation infrastructure cannot be implemented immediately in many high-risk areas, vaccination against cholera is an important additional tool for prevention and control. We describe the development of licensed and recommended inactivated oral cholera vaccines (OCVs), including the results of safety, efficacy and effectiveness studies and the creation of the global OCV stockpile. Over the years, the public health strategy for oral cholera vaccination has broadened—from purely pre-emptive use to reactive deployment to help control outbreaks. Limited supplies of OCV doses continues to be an important problem. We discuss various innovative dosing and delivery approaches that have been assessed and implemented and evidence of herd protection conferred by OCVs. We expect that the demand for OCVs will continue to increase in the coming years across many countries.

• Seroconversion after Dukoral 57% in renal transplant recipients and 81% in controls. • Vaccine response most suppressed by mycophenolate followed by calcineurin inhibitor. • Do not discard oral vaccines in immunosuppressed patients. The evidence for recommendations regarding vaccination in solid organ transplant recipients is sparse. There is little data comparing vaccine responses between groups on different immunosuppressive drugs. This study was conducted to evaluate the antibody response to Dukoral® oral cholera vaccine in renal transplant recipients (RTR). In a single-center non-randomized controlled clinical trial, healthy volunteers (n = 21) and renal transplant recipients (n = 30) were vaccinated with the oral whole cell/recombinant B subunit cholera vaccine Dukoral® (Valneva Inc., Vienna, Austria). The RTR were stratified according to their maintenance immunosuppressive therapy: either prednisone and a calcineurin inhibitor (cyclosporine A or tacrolimus; P/CNI group; n = 15) or prednisone and mycophenolate (P/MMF group; n = 15). All volunteers ingested Dukoral® at baseline and at day 14. Serum samples were drawn at day 0 and day 21. The primary outcome was seroconversion, defined as either a 3-fold IgA serum titer increase in anti-cholera toxin B antibodies and/or a 4-fold rise in the serum vibriocidal titer. Follow-up was complete. Seroconversion after vaccination was 57% (standard error, SE 9%) in RTR and 81% (SE 9%) in healthy controls (Relative Risk, RR 0.70; 95% CI 0.48–1.02). When stratified according to maintenance immunosuppression, the seroconversion rate was 67% (SE 12%) in the P/CNI group (RR compared with controls 0.82; 95% CI 0.55–1.25) and 47% (SE 13%) in the P/MMF group (RR compared with controls 0.58; 95% CI 0.32–1.03). Adverse events were mild to moderate and transient. The response to Dukoral was weaker and the seroconversion rate was lower in renal transplant recipients than in healthy controls. In particular, those using mycophenolate had a poor response. Nevertheless, more than half of the transplant recipients seroconverted. Therefore oral vaccines should not be discarded as a potential tool for protection of solid organ transplant recipients. This trial is registered in clinicaltrials.gov under NCT01109914. [ABSTRACT FROM AUTHOR]

Background Past research has suggested that the most cost-effective approach to using oral cholera vaccines (OCVs) to control endemic cholera may be to target only children <15 y of age. However, the assumption that vaccination of children with OCVs protects unvaccinated adults has never been tested. Methods We reanalyzed the data of an OCV trial in Bangladesh in which children 2–15 y of age and women >15 y of age were allocated to OCV or placebo and assessed herd protection by relating the risk of cholera in each nonvaccinated adult (>15 y) to OCV coverage (OCVC) of residents residing in virtual clusters within 500 m of the residence of that unvaccinated adult. Results The risk of cholera in unvaccinated adults decreased by 14% with each 10% increase of OCVC of all targeted age groups (95% 7 to 21%, p=0.0004). Also, the risk of cholera in unvaccinated adults decreased by 13% with each 10% increase in OCVC of children 2–15 y of age (95% CI 6 to 20%, p=0.0007). A high correlation between levels of OCVC of children and adult females precluded an assessment of the herd protection of unvaccinated adults by vaccinating children <16 y of age, independent of concomitant vaccination of adult women. Conclusions Unvaccinated adults benefitted from herd protection conferred by OCVs in this trial. Vaccination of children may be sufficient to confer this protection, but this possibility needs to be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Highlights • Oral cholera vaccine is considered as an important public health tool for cholera control. • Maintaining cold chain and experienced human resources are major challenges for vaccination. • Self administration strategy is a novel approach for delivery of oral cholera vaccine. • The alternative strategy of vaccination will be useful to increase coverage and vaccine delivery. Abstract Cholera remains a major public health problem in many developing countries including Bangladesh. The oral cholera vaccine (OCV) is now considered a key component of the public health response to cholera. Although maintaining cold chain and organizing human resource are the major challenges of vaccine delivery to the community. Here we applied an innovative approach to second dose OCV delivery to minimize financial and logistic burdens. The purpose of this study was to assess the feasibility and compliance of second dose self-administration when the second dose was provided in a plastic bag to first dose vaccine recipients as OCV is stable for up to 42 days at ambient temperatures. We aimed to deploy vaccines (N = 112,000) left over from other studies to 56,000 people aged ≥ one year living in Mirpur, Dhaka to see the feasibility of self-administration strategy. During vaccination, the first OCV dose (OCV1) was given from fixed sites and the second dose (OCV2) was provided in a plastic zip-lock bag for the participant to take the vaccine two weeks later at home. Participants were instructed to keep the vaccine away from light and in a dry cool place. Empty vials were collected following the end date of the scheduled second vaccination. Of the targeted population, 41,694 (74%) received the first OCV dose whereas an estimated 38,852 (93% of those receiving the first dose) received the second dose which represents a 7% drop out rate from OCV1 to OCV2. However the average two dose coverage was 69%. A survey of a subsample 2990 (from 8551) randomly selected households revealed that almost all respondents (98.75%) appreciated this new self-administration strategy and considered the strategy to be more practical and convenient than the usual method. This simplified, self-administered delivery strategy provides an ideal alternative for second-dose OCV delivery in hard-to-reach populations and resource-poor settings. [ABSTRACT FROM AUTHOR]

Cholera is endemic in approximately 50 countries, primarily in Africa and South and Southeast Asia, and in these areas, it remains a disease associated with poverty. In developed nations, cholera is rare, and cases are typically imported from endemic areas by returning travellers. Cholera is readily preventable with the tools available to modern medicine. In developing nations, cholera transmission can be prevented through improved water, sanitation, and hygiene services and the use of oral cholera vaccines (OCVs). For travellers, risk can be mitigated by practicing regular hand hygiene and consuming food and water from safe sources. OCVs should be considered for high-risk travellers likely to be exposed to cholera patients or contaminated water and food. There are currently three World Health Organization pre-qualified OCVs, which are based on killed whole-cell strains of Vibrio cholerae. These established vaccines offer significant protection in adults and children for up to 2 years. A novel live attenuated vaccine that provides rapid-onset protection in adults and children is licensed in the USA and Europe only. Live attenuated OCVs may mimic the natural infection of V. cholerae more closely, generating rapid immune responses without the need for repeat dosing. These potential benefits have prompted the ongoing development of several additional live attenuated vaccines. The objective of this article is to provide a general review of the current landscape of OCVs, including a discussion of their appropriate use in international travellers.