Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.

BACKGROUND: A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up. METHODS: In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207. FINDINGS: Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy -13%, -68 to 25) or severe cholera episodes (-44%, -220 to 35). INTERPRETATION: A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group. FUNDING: Bill & Melinda Gates Foundation to the International Vaccine Institute.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.

BACKGROUND: A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic. METHODS: Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline. RESULTS: A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups. CONCLUSIONS: A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).

Strategies for providing healthcare services to street-dwellers in Dhaka city: evidence from an operations research.

BACKGROUND: In almost every major urban city, thousands of people live in overcrowded slums, streets, or other public places without any health services. Bangladesh has experienced one of the highest rates of urban population growth in the last three decades compared to the national population growth rate. The numbers of the urban poor and street-dwellers are likely to increase at least in proportion to the overall population growth of the country. The street-dwellers in Bangladesh are extremely vulnerable in terms of their health needs and healthcare-seeking behaviours. In Bangladesh, there is no health service-delivery mechanism targeting this marginalized group of people. This study, therefore, assessed the effectiveness of two models to provide primary healthcare (PHC) services to street-dwellers. METHODS: This study of experimental pre-post design tested two models, such as static clinic and satellite clinics, for providing PHC services to street-dwellers in the evening through paramedics in Dhaka city during May 2009-April 2010. Both quantitative and qualitative techniques were used for collecting data. Data were analyzed comparing before and after the implementation of the clinics for the assessment of selected health and family-planning indicators using the statistical t-test. Services received from the model l and model 2 clinics were also compared by calculating the absolute difference to determine the relative effectiveness of one model over another. RESULTS: The use of healthcare services by the street-dwellers increased at endline compared to baseline in both the model clinic areas, and the difference was highly significant (p < 0.001). Institutional delivery among the female street-dwellers increased at endline compared to baseline in both the clinic areas. The use of family-planning methods among females also significantly (p < 0.001) increased at endline compared to baseline in both the areas. CONCLUSIONS: As the findings of the study showed the promise of this approach, the strategies could be implemented in all other cities of Bangladesh and in other countries which encounter similar problems.

Programmatic aspects of dropouts in child vaccination in Bangladesh: findings from a prospective study.

The present study investigated prospectively programmatic factors relating to dropouts in child vaccination in 6 subdistricts of Bangladesh. A cross-sectional survey (n = 2700) was conducted estimating overall coverage of immunization using cluster sampling. The eligible subsample of children (n = 1064) was followed up prospectively to understand reasons for dropouts. In-depth interviews (n = 73) with mothers/caregivers and service providers were done and EPI (Expanded Programme on Immunization) sessions were observed (n = 131). Irregular EPI sessions were the prime cause of dropouts particularly in low-performing subdistricts. The other programmatic factors linked with dropouts were (a) no reminder about subsequent session/doses, (b) unfriendly behavior or absence of vaccinator, ( c) refusal due to lost card or vaccine exhausted, and (d) short duration of sessions. Providers highlighted constraints such as financial problems for transportation, particularly in the hard-to-reach areas and vacancies of the posts of health assistants. The barriers to completing full schedules of vaccination can be removed to a large extent through programmatic adjustments.