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.

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.

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.

Modern History of Cholera Vaccines and the Pivotal Role of icddr,b.

The rapid spread of the seventh cholera pandemic over Asia in the 1960s led to several large field studies that revealed that the traditional injectable cholera vaccines had poor efficacy, which led the World Health Organization (WHO) in the 1970s to stop recommending cholera vaccination. At the same time, it stimulated research that has led to the development of the effective orally administered cholera vaccines (OCVs) that today are a cornerstone in WHO's strategy for Ending Cholera-A Global Roadmap to 2030. The first effective OCV, Dukoral, containing a mixture of inactivated Vibrio cholerae bacteria and cholera toxin B subunit, was licensed in 1991 and is, together with 2 similar inactivated whole-cell OCVs, Shanchol and Euvichol, currently WHO prequalified and recommended OCVs. This brief review is a personal account of the modern history of the development of these now universally recognized effective tools.

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.

Comparative whole-genome and proteomics analyses of the next seed bank and the original master seed bank of MucoRice-CTB 51A line, a rice-based oral cholera vaccine.

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.

Transient Intestinal Colonization by a Live-Attenuated Oral Cholera Vaccine Induces Protective Immune Responses in Streptomycin-Treated Mice.

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.

Pregnancy outcomes after a mass vaccination campaign with an oral cholera vaccine: a systematic review and meta-analysis.

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.

Preparation and evaluation of chitosan nanoparticles containing CtxB antigen against Vibrio cholera.

Vibrio cholera is a Gram-negative pathogen that causes diarrheal disease. The B subunit of Chlora toxin (CtxB) is one of the most important antigens of Vibrio cholera in which mediates the attachment of the bacteria to target cells. The aim of this study was to prepare chitosan nanoparticles containing CtxB and evaluate the effect of the antigen entrapment on the immunogenicity of this antigen. For this, the pET28a vector was induced using IPTG. Recombinant CtxB protein was expressed and purified using Ni-NTA column and finally was confirmed by western blotting. Following the confirmation of the protein entrapment onto the chitosan nanoparticles, the formulation was prescribed to BALB/c mice in three groups, including oral, oral-injection and injection groups. Serum and fecal IgA and IgG were evaluated by ELISA test. Finally, challenge of immunized mice was performed using Ctx toxin and rabbit ileal loop test. Using SDS-PAGE and western blotting, the 17.5 kDa recombinant CtxB was confirmed. Size electrical charge and of nanoparticles were determined and approved by Zetasizer. Nanoparticles prescription showed 1/102400 IgG endpoint titers for injection groups and 1/1600, 1/6400 for oral, oral-injection groups respectively and Serum and fecal IgA endpoint titers showed above 1/160 in all groups. Furthermore, immunized mice were able to neutralize Ctx toxin by ileal loop test. The CtxB is a suitable immunogen of V. cholera to be incorporated in both protective and preventive vaccines. Chitosan nanoparticles improve the immune responses and it may be used as a carrier for vaccine delivery.

Oral Cholera Vaccine Coverage during an Outbreak and Humanitarian Crisis, Iraq, 2015.

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.

Vaxchora: A Single-Dose Oral Cholera Vaccine.

OBJECTIVE: To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. DATA SOURCES: A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. STUDY SELECTION AND DATA EXTRACTION: Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. DATA SYNTHESIS: Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. CONCLUSION: Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

Cross-protection conferred by immunization with an rOmpH-based intranasal fowl cholera vaccine.

A previous study demonstrated that a recombinant outer membrane protein H (rOmpH)-based intranasal fowl cholera vaccine elicited efficient homologous protection against the Pasteurella multocida strain X-73 (A:1) in chickens. The present study aimed to determine the cross-protectivity against heterologous P. multocida strains. The rOmpH was purified via electroelution and formulated with two kinds of adjuvants. The vaccine formulations in a total volume of 100 µl were 100 µg rOmpH with 3 µg of Escherichia coli enterotoxin B or 10 µg of CpG ODN2007. Chickens were assigned to three experimental groups depending on bacterial strain challenge exposure as well as three control groups. The chickens were immunized intranasally three times at three-week intervals. Challenge exposures were conducted by inoculation with homologous strain X-73 or heterologous strains P-1059 (A:3) or P-1662 (A:4) at four weeks after the final immunization. The specific antibody against rOmpH was produced in vaccinated birds. Sera IgY and secretory IgA antibody titres were significantly increased (P < 0.05) post-immunization. The stimulation index values of the vaccinated groups were significantly different from stimulation index values of the non-vaccinated groups (P < 0.05). Chicken survival rates after exposure to avian P. multocida strains ranged from 70% to 100%. There was no significant difference in protection between two kinds of adjuvants in vaccine formulations. Statistical analysis indicated no significant differences in protection among avian P. multocida strains challenge exposure. We conclude that an in-house rOmpH-based intranasal fowl cholera vaccine produced efficient cross-protectivity against heterologous strains of P. multocida.

Comparison of immune responses to a killed bivalent whole cell oral cholera vaccine between endemic and less endemic settings.

Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity.

Immunogenicity of the Bivalent Oral Cholera Vaccine Shanchol in Haitian Adults With HIV Infection.

We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4(+) T-cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera.

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours.

Safety and immunogenicity assessment of an oral cholera vaccine through phase I clinical trial in Korea.

The safety, tolerability and immunogenicity of an oral cholera vaccine (OCV) was assessed in adult Korean male through an open-label, non-comparative clinical study. Two doses of vaccine with an interval of 2 weeks were given to 20 healthy subjects. A total of 7 adverse events occurred in 6 subjects. However, no clinically significant change was observed in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. The immunogenicity of OCV was evaluated by serum vibriocidal assay where anti-Vibrio cholerae O1 and O139 antibodies were measured at day 0, 14, and 28 of vaccine administration. The antibody titers ranged from < 2.5-5,120 for V. cholerae O1 Inaba, < 2.5-10,240 for V. cholerae O1 Ogawa and < 2.5-480 for V. cholerae O139. In addition, the fold increase in antibody titers ranged from 1-4,096 for O1 Inaba, 1-8,192 for O1 Ogawa, and 1-384 for O139. The seroconversion rate was 95% and 45% for O1 and O139 antibodies, respectively. Our study clearly shows that administration of two doses of OCV at a 2 week-interval increases an appropriate level of antibody titer in the serum of healthy Korean adult males (Clinical Trial Number, NCT01707537).

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

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

Knowledge and perception of a clinical trial among the participants: An experience from oral cholera vaccine study in Koshi Province, Nepal.

Clinical trials (CT) have been the cornerstones in developing medicines, vaccines, and new interventions. Despite tremendous efforts, a CT cannot succeed without participants' involvement. Various factors can affect people's attitude and participation in a CT. Hence, this study was conducted to assess the knowledge and perception of a clinical trial among the participants of a CT at B.P. Koirala Institute of Health Sciences, Dharan, Nepal. This was a population-based descriptive cross-sectional study conducted during 2021-2022. Participants involved in a phase III clinical trial were enrolled, and an in-depth interview was conducted using a semi-structured questionnaire. Demographic information, knowledge and perception about CT were assessed, and a descriptive analysis was done. Among 622 participants, the majority were males (321; 51.6%), literate (587; 94.37%), of indigenous ethnic groups (Janajatis 61.4%), and without previous experience of CT (504; 81.1%). The majority had adequate knowledge (566/622; 91%) and positive perception (595/622; 95.7%) of CT. Most participants (467; 75.1%) had participated in CT to get protection from the particular disease from the provided vaccine and (603; 96.9%) believed CT to benefit mankind. Further studies comparing pre- and post-participation knowledge and perception might be helpful for planning and better management of CTs in such settings.