Attitude towards cholera vaccination and its related factors in Jordan amid the 2022 Middle East outbreak.

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.

Coverage of Two-Dose Preemptive Cholera Mass Vaccination Campaign in High-Priority Hotspots in Shashemene, Oromia Region, Ethiopia.

BACKGROUND: Cholera is a public health priority in Ethiopia. The Ethiopian National Cholera Plan elaborates a multi-year scheme of oral cholera vaccine (OCV) use. Aligned with this, a preemptive OCV campaign was conducted under our Ethiopia Cholera Control and Prevention project. Here, we present the OCV vaccination outcomes. METHOD: Cholera high-priority hotspots in the Oromia Region, Shashemene Town (ST) and Shashemene Woreda (SW), were selected. Four kebelles (Abosto, Alelu, Arada, and Awasho) in ST and 4 clusters (Faji Gole, Harabate, Toga, and Chabi) in SW were study sites with OCV areas nested within. A total of 40 000 and 60 000 people in ST and SW, respectively, were targeted for a 2-dose OCV (Euvichol-Plus) campaign in 11-15 May (first round [R1]) and 27-31 May (second round [R2]) 2022. Daily administrative OCV coverage and a coverage survey in 277 randomly selected households were conducted. RESULTS: The administrative OCV coverage was high: 102.0% for R1 and 100.5% for R2 in ST and 99.1% (R1) and 100.0% (R1) in SW. The coverage survey showed 78.0% (95% confidence interval [CI]: 73.1-82.9) of household members with 2-dose OCV and 16.8% (95% CI: 12.4-21.3) with no OCV in ST; and 83.1% (95% CI: 79.6-86.5) with 2-dose OCV and 11.8% (95% CI: 8.8-14.8) with no OCV in SW. The 2-dose coverages in 1-4-, 5-14-, and ≥15-year age groups were 88.3% (95% CI: 70.6-96.1), 88.9% (95% CI: 82.1-95.7), and 71.3% (95% CI: 64.2-78.3), respectively, in ST and 78.2% (95% CI: 68.8-87.7), 91.0% (95% CI: 86.6-95.3), and 78.7% (95% CI: 73.2-84.1) in SW. CONCLUSIONS: High 2-dose OCV coverage was achieved. Cholera surveillance is needed to assess the vaccine impact and effectiveness.

Early use of oral cholera vaccines as a prime control measure during outbreaks: Necessary but not sufficient.

INTRODUCTION: Despite being a preventable and treatable disease, cholera remains a public health problem in Sudan. The objective of the outbreak investigation was to identify associated risk factors that would help institute appropriate control measures. MATERIAL AND METHODS: A case control study design was chosen to identify the risk factors for cholera in Gadarif State. RESULTS: Multi-variate analysis of identified two risk factors and three preventive factors for cholera in Gadarif City. RISK FACTORS: Buying foods or drinks from street vendors (OR = 71.36), 95 % CI: 16.58-307.14), living in an urban setting (Gadarif City) (OR = 5.38), 95 % CI: 2.10-13.81); and the preventive factors were: Washing hands with water after defecation but without soap (OR = 0.16), 95 % CI: 0.04-0.63) or with soap (OR = 0.01), 95 % CI: 0.00-0.03), washing hands before eating (OR = 0.15), 95 % CI: 0.05-0.51) and taking Oral Cholera Vaccine (OCV) (OR = 0.19, 95 % CI: 0.08-0.44). The effectiveness of OCV (VE) was (Unadjusted VE: 80 %, 95 % CI: 69 %-87 %) or (Adjusted VE = 81.0 %, 95 % CI: 56.0 %-92.0 %). DISCUSSION: Cholera outbreaks, especially in the setting of a complex humanitarian crises, can spread rapidly, resulting in many deaths, and quickly become a public health crisis. Implementation of a community-wide vaccination campaign using OCV as early as possible during the outbreak while implementing other control measures to target hotspots and at-risk populations would expedite halting outbreaks of cholera and save lives.

The reactive cholera vaccination campaign in urban Dhaka in 2022: experience, lessons learned and future directions.

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.

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.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Towards cholera elimination in Zanzibar: analysis of evidences on what have worked.

Cholera, an enteric disease caused by Vibrio cholera claims thousands of lives yearly. The disease is a disease of inequality that affect populations which have poor access to safe water and sanitation facilities. Zanzibar, an archipelago in the Indian ocean which is part of the United Republic of Tanzania has been affected by recurrent cholera outbreak for the past decades. A multi-sectoral and multi-year three pillar approach namely Enabling Environment, Prevention and Response, for the elimination of cholera were initiated by the stewardship of the government, engagement of the community and technical and financial support of partners. The approach has enabled Zanzibar to interrupt the recurrent cholera outbreak for the past five years. The analysis of evidences have proven that creating an enabling environment through multi-sectoral involvement, mobilizing communities, intensifying surveillance complemented by the traditional disease prevention and control interventions has resulted to interruption of cholera transmission in the country.

Comparison of O-specific polysaccharide responses in patients following infection with Vibrio cholerae O139 versus vaccination with a bivalent (O1/O139) oral killed cholera vaccine in Bangladesh.

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.

Oral cholera vaccine coverage evaluation survey: Forcibly Displaced Myanmar Nationals and host community in Cox's Bazar, Bangladesh.

Introduction: Cholera 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. Methods: In 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. Results: According 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. Discussion: Our 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 interplay between WASH practices and vaccination with oral cholera vaccines in protecting against cholera in urban Bangladesh: Reanalysis of a cluster-randomized trial.

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.

Coverage survey and lessons learned from a pre-emptive cholera vaccination campaign in urban and rural communities affected by landslides and floods in Freetown Sierra Leone.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Challenges, best practices, and lessons learned from oral cholera mass vaccination campaign in urban Cameroon during the COVID-19 era.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: Proper communication will always brave the odds of hesitancy and favor mass population vaccination to thwart hesitancy and consolidate herd immunity.

Diagnosis, Management, and Future Control of Cholera.

Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. The disease is transmitted fecally-orally via contaminated food or water. Severe dehydrating cholera can progress to hypovolemic shock due to the rapid loss of fluids and electrolytes, which requires a rapid infusion of intravenous (i.v.) fluids. The case fatality rate exceeds 50% without proper clinical management but can be less than 1% with prompt rehydration and antibiotics. Oral cholera vaccines (OCVs) serve as a major component of an integrated control package during outbreaks or within zones of endemicity. Water, sanitation, and hygiene (WaSH); health education; and prophylactic antibiotic treatment are additional components of the prevention and control of cholera. The World Health Organization (WHO) and the Global Task Force for Cholera Control (GTFCC) have set an ambitious goal of eliminating cholera by 2030 in high-risk areas.

Travel vaccines are strongly associated to reduced mortality in prostate cancer patients - a real effect or residual confounding?

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.

Oral MucoRice-CTB vaccine is safe and immunogenic in healthy US adults.

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.

Oral Cholera Vaccine Efficacy and Effectiveness.

Although measuring vaccine efficacy through the conventional phase III study design, randomized, double-blinded controlled trial serves as the "gold standard", effectiveness studies, conducted in the context of a public health program, seek to broaden the understanding of the impact of a vaccine in a real world setting including both individual and population level impacts. Cholera is an acute diarrheal infection caused by the ingestion of food or water contaminated with the bacterium Vibrio cholerae. Since the 1980s, either killed or live oral cholera vaccines (OCVs) have been developed and efficacy and effectiveness studies have been conducted on OCV. Although the results of OCV effectiveness studies sometimes showed outliers, the tendency seen is for effectiveness of the vaccine used in public health settings to be somewhat higher than estimated in randomized controlled trials due to the influence of indirect herd protection. Efficacy and Effectiveness studies both generate important information about the vaccine performance characteristics and its impact when used in real world populations at risk for the disease.

Challenges for Programmatic Implementation of Oral Cholera Vaccine in India.

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.

Mathematical Modeling of Endemic Cholera Transmission.

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.

Assessment of Vaccine Herd Protection: Lessons Learned From Cholera and Typhoid Vaccine Trials.

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.

Serum vibriocidal responses when second doses of oral cholera vaccine are delayed 6 months in Zambia.

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).

Cholera Hot-Spots and Contextual Factors in Burundi, Planning for Elimination.

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.