Developing digital tools for health surveys in low- and middle-income countries: Comparing findings of two mobile phone surveys with a nationally representative in-person survey in Bangladesh.

Non-communicable disease (NCD) risk factor data from low- and middle-income countries (LMICs) are inadequate, mostly due to the cost and burden of collecting in-person population-level estimates. High-income countries regularly use phone-based surveys, and with increasing mobile phone subscription in developing countries, mobile phone surveys (MPS) could complement in-person surveys in LMICs. We compared the representativeness and prevalence estimates of two MPS (i.e., interactive voice response (IVR) and computer-assisted telephone interview (CATI)) with a nationally representative household survey in Bangladesh-the STEPwise approach to NCD risk factor surveillance (STEPs) 2018. This cross-sectional study included 18-69-year-old respondents. CATI and IVR recruitments were done by random digit dialing, while STEPs used multistage cluster sampling design. The prevalence of NCD risk factors related to tobacco, alcohol, diet, and hypertension was reported and compared by prevalence differences (PD) and prevalence ratios (PR). We included 2355 (57% males), 1942 (62% males), and 8185 (47% males) respondents in the CATI, IVR, and STEPs, respectively. CATI (28%) and IVR (52%) had a higher proportion of secondary/above-educated people than STEPs (13%). Most prevalence estimates differed by survey mode; however, CATI estimates were closer to STEPs than IVR. For instance, in CATI, IVR, and STEPs, respectively, the prevalence was 21.4%, 17.9%, and 23.5% for current smoking; and 1.6%, 2.2%, and 1.5% for alcohol drinking in past month. Compared to STEPs, the PD ranged from '-56.6% to 0.4%' in CATI and '-41.0% to 8.4%' in IVR; the PR ranged from '0.3 to 1.1' in CATI and '0.3 to 1.6' in IVR. There were some differences and some similarities in NCD indicators produced by MPS and STEPs with differences likely due to differences in socioeconomic characteristics between survey participants.

Effect of the Data Collection Method on Mobile Phone Survey Participation in Bangladesh and Tanzania: Secondary Analyses of a Randomized Crossover Trial.

BACKGROUND: Mobile phone surveys provide a novel opportunity to collect population-based estimates of public health risk factors; however, nonresponse and low participation challenge the goal of collecting unbiased survey estimates. OBJECTIVE: This study compares the performance of computer-assisted telephone interview (CATI) and interactive voice response (IVR) survey modalities for noncommunicable disease risk factors in Bangladesh and Tanzania. METHODS: This study used secondary data from a randomized crossover trial. Between June 2017 and August 2017, study participants were identified using the random digit dialing method. Mobile phone numbers were randomly allocated to either a CATI or IVR survey. The analysis examined survey completion, contact, response, refusal, and cooperation rates of those who received the CATI and IVR surveys. Differences in survey outcomes between modes were assessed using multilevel, multivariable logistic regression models to adjust for confounding covariates. These analyses were adjusted for clustering effects by mobile network providers. RESULTS: For the CATI surveys, 7044 and 4399 phone numbers were contacted in Bangladesh and Tanzania, respectively, and 60,863 and 51,685 phone numbers, respectively, were contacted for the IVR survey. The total numbers of completed interviews in Bangladesh were 949 for CATI and 1026 for IVR and in Tanzania were 447 for CATI and 801 for IVR. Response rates for CATI were 5.4% (377/7044) in Bangladesh and 8.6% (376/4391) in Tanzania; response rates for IVR were 0.8% (498/60,377) in Bangladesh and 1.1% (586/51,483) in Tanzania. The distribution of the survey population was significantly different from the census distribution. In both countries, IVR respondents were younger, were predominantly male, and had higher education levels than CATI respondents. IVR respondents had a lower response rate than CATI respondents in Bangladesh (adjusted odds ratio [AOR]=0.73, 95% CI 0.54-0.99) and Tanzania (AOR=0.32, 95% CI 0.16-0.60). The cooperation rate was also lower with IVR than with CATI in Bangladesh (AOR=0.12, 95% CI 0.07-0.20) and Tanzania (AOR=0.28, 95% CI 0.14-0.56). Both in Bangladesh (AOR=0.33, 95% CI 0.25-0.43) and Tanzania (AOR=0.09, 95% CI 0.06-0.14), there were fewer completed interviews with IVR than with CATI; however, there were more partial interviews with IVR than with CATI in both countries. CONCLUSIONS: There were lower completion, response, and cooperation rates with IVR than with CATI in both countries. This finding suggests that, to increase representativeness in certain settings, a selective approach may be needed to design and deploy mobile phone surveys to increase population representativeness. Overall, CATI surveys may offer a promising approach for surveying potentially under-represented groups like women, rural residents, and participants with lower levels of education in some countries.

Promised and Lottery Airtime Incentives to Improve Interactive Voice Response Survey Participation Among Adults in Bangladesh and Uganda: Randomized Controlled Trial.

BACKGROUND: Increased mobile phone penetration allows the interviewing of respondents using interactive voice response surveys in low- and middle-income countries. However, there has been little investigation of the best type of incentive to obtain data from a representative sample in these countries. OBJECTIVE: We assessed the effect of different airtime incentives options on cooperation and response rates of an interactive voice response survey in Bangladesh and Uganda. METHODS: The open-label randomized controlled trial had three arms: (1) no incentive (control), (2) promised airtime incentive of 50 Bangladeshi Taka (US $0.60; 1 BDT is approximately equivalent to US $0.012) or 5000 Ugandan Shilling (US $1.35; 1 UGX is approximately equivalent to US $0.00028), and (3) lottery incentive (500 BDT and 100,000 UGX), in which the odds of winning were 1:20. Fully automated random-digit dialing was used to sample eligible participants aged ≥18 years. The risk ratios (RRs) with 95% confidence intervals for primary outcomes of response and cooperation rates were obtained using log-binomial regression. RESULTS: Between June 14 and July 14, 2017, a total of 546,746 phone calls were made in Bangladesh, with 1165 complete interviews being conducted. Between March 26 and April 22, 2017, a total of 178,572 phone calls were made in Uganda, with 1248 complete interviews being conducted. Cooperation rates were significantly higher for the promised incentive (Bangladesh: 39.3%; RR 1.38, 95% CI 1.24-1.55, P<.001; Uganda: 59.9%; RR 1.47, 95% CI 1.33-1.62, P<.001) and the lottery incentive arms (Bangladesh: 36.6%; RR 1.28, 95% CI 1.15-1.45, P<.001; Uganda: 54.6%; RR 1.34, 95% CI 1.21-1.48, P<.001) than those for the control arm (Bangladesh: 28.4%; Uganda: 40.9%). Similarly, response rates were significantly higher for the promised incentive (Bangladesh: 26.5%%; RR 1.26, 95% CI 1.14-1.39, P<.001; Uganda: 41.2%; RR 1.27, 95% CI 1.16-1.39, P<.001) and lottery incentive arms (Bangladesh: 24.5%%; RR 1.17, 95% CI 1.06-1.29, P=.002; Uganda: 37.9%%; RR 1.17, 95% CI 1.06-1.29, P=.001) than those for the control arm (Bangladesh: 21.0%; Uganda: 32.4%). CONCLUSIONS: Promised or lottery airtime incentives improved survey participation and facilitated a large sample within a short period in 2 countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT03773146; http://clinicaltrials.gov/ct2/show/NCT03773146.

Frequency and patterns of exposure to live poultry and the potential risk of avian influenza transmission to humans in urban Bangladesh.

Avian influenza is endemic in Bangladesh, where greater than 90% of poultry are marketed through live poultry markets (LPMs). We conducted a population-based cross-sectional mobile telephone survey in urban Dhaka, Bangladesh to investigate the frequency and patterns of human exposure to live poultry in LPMs and at home. Among 1047 urban residents surveyed, 74.2% (95% CI 70.9-77.2) reported exposure to live poultry in the past year, with the majority of exposure occurring on a weekly basis. While visiting LPMs was less common amongst females (40.3%, 95% CI 35.0-45.8) than males (58.9%, 95% CI 54.0-63.5), females reported greater poultry exposure through food preparation, including defeathering (13.2%, 95% CI 9.5-17.9) and eviscerating (14.8%, 95% CI 11.2-19.4) (p < 0.001). A large proportion of the urban population is frequently exposed to live poultry in a setting where avian influenza viruses are endemic in LPMs. There is thus not only ample opportunity for spillover of avian influenza infections into humans in Dhaka, Bangladesh, but also greater potential for viral reassortment which could generate novel strains with pandemic potential.

Population Health Surveillance Using Mobile Phone Surveys in Low- and Middle-Income Countries: Methodology and Sample Representativeness of a Cross-sectional Survey of Live Poultry Exposure in Bangladesh.

BACKGROUND: Population-based health surveys are typically conducted using face-to-face household interviews in low- and middle-income countries (LMICs). However, telephone-based surveys are cheaper, faster, and can provide greater access to hard-to-reach or remote populations. The rapid growth in mobile phone ownership in LMICs provides a unique opportunity to implement novel data collection methods for population health surveys. OBJECTIVE: This study aims to describe the development and population representativeness of a mobile phone survey measuring live poultry exposure in urban Bangladesh. METHODS: A population-based, cross-sectional, mobile phone survey was conducted between September and November 2019 in North and South Dhaka City Corporations (DCC), Bangladesh, to measure live poultry exposure using a stratified probability sampling design. Data were collected using a computer-assisted telephone interview platform. The call operational data were summarized, and the participant data were weighted by age, sex, and education to the 2011 census. The demographic distribution of the weighted sample was compared with external sources to assess population representativeness. RESULTS: A total of 5486 unique mobile phone numbers were dialed, with 1047 respondents completing the survey. The survey had an overall response rate of 52.2% (1047/2006) and a co-operation rate of 89.0% (1047/1176). Initial results comparing the sociodemographic profile of the survey sample to the census population showed that mobile phone sampling slightly underrepresented older individuals and overrepresented those with higher secondary education. After weighting, the demographic profile of the sample population matched well with the latest DCC census population profile. CONCLUSIONS: Probability-based mobile phone survey sampling and data collection methods produced a population-representative sample with minimal adjustment in DCC, Bangladesh. Mobile phone-based surveys can offer an efficient, economic, and robust way to conduct surveillance for population health outcomes, which has important implications for improving population health surveillance in LMICs.

A cost study for mobile phone health surveys using interactive voice response for assessing risk factors of noncommunicable diseases.

BACKGROUND: This is the first study to examine the costs of conducting a mobile phone survey (MPS) through interactive voice response (IVR) to collect information on risk factors for noncommunicable diseases (NCD) in three low- and middle-income countries (LMIC); Bangladesh, Colombia, and Uganda. METHODS: This is a micro-costing study conducted from the perspective of the payer/funder with a 1-year horizon. The study evaluates the fixed costs and variable costs of implementing one nationally representative MPS for NCD risk factors of the adult population. In this costing study, we estimated the sample size of calls required to achieve a population-representative survey and associated incentives. Cost inputs were obtained from direct economic costs incurred by a central study team, from country-specific collaborators, and from platform developers who participated in the deployment of these MPS during 2017. Costs were reported in US dollars (USD). A sensitivity analysis was conducted assessing different scenarios of pricing and incentive strategies. Also, costs were calculated for a survey deployed targeting only adults younger than 45 years. RESULTS: We estimated the fixed costs ranging between $47,000 USD and $74,000 USD. Variable costs were found to be between $32,000 USD and $129,000 USD per nationally representative survey. The main cost driver was the number of calls required to meet the sample size, and its variability largely depends on the extent of mobile phone coverage and access in the country. Therefore, a larger number of calls were estimated to survey specific harder-to-reach sub-populations. CONCLUSION: Mobile phone surveys have the potential to be a relatively less expensive and timely method of collecting survey information than face-to-face surveys, allowing decision-makers to deploy survey-based monitoring or evaluation programs more frequently than it would be possible having only face-to-face contact. The main driver of variable costs is survey time, and most of the variability across countries is attributable to the sampling differences associated to reaching out to population subgroups with low mobile phone ownership or access.

Epidemiology of Cholera in Bangladesh: Findings From Nationwide Hospital-based Surveillance, 2014-2018.

BACKGROUND: Despite advances in prevention, detection, and treatment, cholera remains a major public health problem in Bangladesh and little is known about cholera outside of limited historical sentinel surveillance sites. In Bangladesh, a comprehensive national cholera control plan is essential, although national data are needed to better understand the magnitude and geographic distribution of cholera. METHODS: We conducted systematic hospital-based cholera surveillance among diarrhea patients in 22 sites throughout Bangladesh from 2014 to 2018. Stool specimens were collected and tested for Vibrio cholerae by microbiological culture. Participants' socioeconomic status and clinical, sanitation, and food history were recorded. We used generalized estimating equations to identify the factors associated with cholera among diarrhea patients. RESULTS: Among 26 221 diarrhea patients enrolled, 6.2% (n = 1604) cases were V. cholerae O1. The proportion of diarrhea patients positive for cholera in children <5 years was 2.1% and in patients ≥5 years was 9.5%. The proportion of cholera in Dhaka and Chittagong Division was consistently high. We observed biannual seasonal peaks (pre- and postmonsoon) for cholera across the country, with higher cholera positivity during the postmonsoon in western regions and during the pre-monsoon season in eastern regions. Cholera risk increased with age, occupation, and recent history of diarrhea among household members. CONCLUSIONS: Cholera occurs throughout a large part of Bangladesh. Cholera-prone areas should be prioritized to control the disease by implementation of targeted interventions. These findings can help strengthen the cholera-control program and serve as the basis for future studies for tracking the impact of cholera-control interventions in Bangladesh.

Effect of airtime incentives on response and cooperation rates in non-communicable disease interactive voice response surveys: randomised controlled trials in Bangladesh and Uganda.

BACKGROUND: The global proliferation of mobile phones offers opportunity for improved non-communicable disease (NCD) data collection by interviewing participants using interactive voice response (IVR) surveys. We assessed whether airtime incentives can improve cooperation and response rates for an NCD IVR survey in Bangladesh and Uganda. METHODS: Participants were randomised to three arms: a) no incentive, b) 1X incentive or c) 2X incentive, where X was set to airtime of 50 Bangladesh Taka (US$0.60) and 5000 Ugandan Shillings (UGX; US$1.35). Adults aged 18 years and older who had a working mobile phone were sampled using random digit dialling. The primary outcomes, cooperation and response rates as defined by the American Association of Public Opinion Research, were analysed using log-binomial regression model. RESULTS: Between 14 June and 14 July 2017, 440 262 phone calls were made in Bangladesh. The cooperation and response rates were, respectively, 28.8% (353/1227) and 19.2% (580/3016) in control, 39.2% (370/945) and 23.9% (507/2120) in 50 Taka and 40.0% (362/906) and 24.8% (532/2148) in 100 Taka incentive groups. Cooperation and response rates, respectively, were significantly higher in both the 50 Taka (risk ratio (RR) 1.36, 95% CI 1.21 to 1.53) and (RR 1.24, 95% CI 1.12 to 1.38), and 100 Taka groups (RR 1.39, 95% CI 1.23 to 1.56) and (RR 1.29, 95% CI 1.16 to 1.43), as compared with the controls. In Uganda, 174 157 phone calls were made from 26 March to 22 April 2017. The cooperation and response rates were, respectively, 44.7% (377/844) and 35.2% (552/1570) in control, 57.6% (404/701) and 39.3% (508/1293) in 5000 UGX and 58.8% (421/716) and 40.3% (535/1328) in 10 000 UGX groups. Cooperation and response rates were significantly higher, respectively in the 5000 UGX (RR 1.29, 95% CI 1.17 to 1.42) and (RR 1.12, 95% CI 1.02 to 1.23), and 10 000 UGX groups (RR 1.32, 95% CI 1.19 to 1.45) and (RR 1.15, 95% CI 1.04 to 1.26), as compared with the control group. CONCLUSION: In two diverse settings, the provision of an airtime incentive significantly improved both the cooperation and response rates of an IVR survey, with no significant difference between the two incentive amounts. TRIAL REGISTRATION NUMBER: NCT03768323.

Safety of a bivalent, killed, whole-cell oral cholera vaccine in pregnant women in Bangladesh: evidence from a randomized placebo-controlled trial.

BACKGROUND: Cholera increases the risk of harmful effects on foetuses. We prospectively followed pregnant women unaware of their pregnancy status who received a study agent in a clinical trial evaluating the association between exposure to an oral cholera vaccine (OCV) and foetal survival. METHODS: Study participants were selected from a randomized placebo-controlled trial conducted in Dhaka, Bangladesh. The vaccination campaign was conducted between January 10 and February 4, 2014. We enrolled women who were exposed to an OCV or placebo during pregnancy (Cohort 1) and women who were pregnant after the vaccination was completed (Cohort 2). Our primary endpoint was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were preterm delivery and low birth weight. We employed a log-binomial regression to calculate the relative risk of having adverse outcomes among OCV recipients compared to that among placebo recipients. RESULT: There were 231 OCV and 234 placebo recipients in Cohort 1 and 277 OCV and 299 placebo recipients in Cohort 2. In Cohort 1, the incidence of pregnancy loss was 113/1000 and 115/1000 among OCV and placebo recipients, respectively. The adjusted relative risk for pregnancy loss was 0.97 (95% CI: 0.58-1.61; p = 0.91) in Cohort 1. We did not observe any variation in the risk of pregnancy loss between the two cohorts. The risks for preterm delivery and low birth weight were not significantly different between the groups in both cohorts. CONCLUSIONS: Our study provides additional evidence that exposure to an OCV during pregnancy does not increase the risk of pregnancy loss, preterm delivery, or low birth weight, suggesting that pregnant women in cholera-affected regions should not be excluded in a mass vaccination campaign. TRIAL REGISTRATION: The study is registered at ( http://clinicaltrials.gov ). Identifier: NCT02027207 .

Does mobile phone survey method matter? Reliability of computer-assisted telephone interviews and interactive voice response non-communicable diseases risk factor surveys in low and middle income countries.

INTRODUCTION: Increased mobile phone subscribership in low- and middle-income countries (LMICs) provides novel opportunities to track population health. The objective of this study was to examine reliability of data in comparing participant responses collected using two mobile phone survey (MPS) delivery modalities, computer assisted telephone interviews (CATI) and interactive voice response (IVR) in Bangladesh (BGD) and Tanzania (TZA). METHODS: Using a cross-over design, we used random digit dialing (RDD) to call randomly generated mobile phone numbers and recruit survey participants to receive either a CATI or IVR survey on non-communicable disease (NCD) risk factors, followed 7 days later by the survey mode not received during first contact; either IVR or CATI. Respondents who received the first survey were designated as first contact (FC) and those who consented to being called a second time and subsequently answered the call were designated as follow-up (FU). We used the same questionnaire for both contacts, with response options modified to suit the delivery mode. Reliability of responses was analyzed using the Cohen's kappa statistic for percent agreement between two modes. RESULTS: Self-reported data on demographic characteristics and NCD behavioral risk factors were collected from 482 (CATI-FC) and 653 (IVR-FC) age-eligible and consenting respondents in BGD, and from 387 (CATI-FC) and 674 (IVR-FC) respondents in TZA respectively. Survey follow-up rates were 30.7% (n = 482) for IVR-FU and 53.8% (n = 653) for CATI-FU in BGD; and 42.4% (n = 387) for IVR-FU and 49.9% (n = 674) for CATI-FU in TZA respectively. Overall, there was high consistency between delivery modalities for alcohol consumption in the past 30 days in both countries (kappa = 0.64 for CATI→IVR (BGD), kappa = 0.54 for IVR→CATI (BGD); kappa = 0.66 for CATI→IVR (TZA), kappa = 0.76 for IVR→CATI (TZA)), and current smoking (kappa = 0.68 for CATI→IVR (BGD), kappa = 0.69 for IVR→CATI (BGD); kappa = 0.39 for CATI→IVR (TZA), kappa = 0.50 for IVR→CATI (TZA)). There was moderate to substantial consistency in both countries for history of checking for hypertension and diabetes with kappa statistics ranging from 0.43 to 0.67. There was generally lower consistency in both countries for physical activity (vigorous and moderate) with kappa statistics ranging from 0.10 to 0.41, weekly fruit and vegetable with kappa ranging from 0.08 to 0.45, consumption of foods high in salt and efforts to limit salt with kappa generally below 0.3. CONCLUSIONS: The study found that when respondents are re-interviewed, the reliability of answers to most demographic and NCD variables is similar whether starting with CATI or IVR. The study underscores the need for caution when selecting questions for mobile phone surveys. Careful design can help ensure clarity of questions to minimize cognitive burden for respondents, many of whom may not have prior experience in taking automated surveys. Further research should explore possible differences and determinants of survey reliability between delivery modes and ideally compare both IVR and CATI surveys to in-person face-to-face interviews. In addition, research is needed to better understand factors that influence survey cooperation, completion, refusal and attrition rates across populations and contexts.

Organization and implementation of an oral cholera vaccination campaign in an endemic urban setting in Dhaka, Bangladesh.

Bangladesh has historically been cholera endemic, with seasonal cholera outbreaks occurring each year. In collaboration with the government of Bangladesh, the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) initiated operational research to test strategies to reach the high-risk urban population with an affordable oral cholera vaccine (OCV) "ShancholTM" and examine its effectiveness in reducing diarrhea due to cholera. Here we report a sub-analysis focusing on the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. We described how the vaccination program was planned, prepared and implemented using different strategies to deliver oral cholera vaccine to a high-risk urban population in Dhaka, Bangladesh based on administrative data and observations made during the program. The objective of this study is to evaluate the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. OCV administration by trained local volunteers through outreach sites and mop-up activities yielded high coverage of 82% and 72% of 172,754 targeted individuals for the first and second dose respectively, using national Expanded Program on Immunization (EPI) campaign mechanisms without disrupting routine immunization activities. The cost of delivery was low. Safety and cold chain requirements were adequately managed. The adopted strategies were technically and programmatically feasible. Current evidence on implementation strategies in different settings together with available OCV stockpiles should encourage at-risk countries to use OCV along with other preventive and control measures.

Feasibility, coverage and cost of oral cholera vaccination conducted by icddr,b using the existing national immunization service delivery mechanism in rural setting Keraniganj, Bangladesh.

Background: Cholera is a considerable health burden in developing country settings including Bangladesh. The oral cholera vaccine (OCV) is a preventative tool to control the disease. The objective of this study was to describe whether the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), could provide the OCV to rural communities using existing government infrastructure. Methods: The study was conducted in rural sub-district Keraniganj, 20 km from the capital city Dhaka. All listed participants one year and above in age (excluding pregnant women) were offered two doses of OCV at a 14 day interval. Existing government facilities were used to deliver and also maintain the cold chain required for the vaccine. All events related to vaccination were recorded at the 17 vaccination sites to evaluate the coverage and feasibility of OCV program. Results: A total of 29,029 individuals received the 1st dose (90% of target) and 26,611 individuals received the 2nd dose (83% of target and 92% of 1st dose individuals) of OCV. The highest vaccination coverage was in younger children (1-9 years) and the lowest was amongst 18-29-year age group. Somewhat better coverage was seen amongst the female participants than males (92% vs. 88% for the 1st dose and 93% vs. 90% for the 2nd dose). The cost of vaccine cost was calculated as US$1.00 per dose plus freight, insurance, and transportation and the total vaccine delivery cost was US$70,957. Conclusion: This was a project undertaken using existing public health program resources to collect empirical evidence on the use of a mass OCV campaign in the rural setting. Mass vaccination with the OCV is feasible in the rural setting using existing governmental vaccine delivery systems in Bangladesh.

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.

Safety of the oral cholera vaccine in pregnancy: Retrospective findings from a subgroup following mass vaccination campaign in Dhaka, Bangladesh.

BACKGROUND: Pregnant women are vulnerable to complications of cholera. Killed oral cholera vaccines (OCV) are not recommended for pregnant women though there is no evidence of harmful effects during pregnancy. We evaluated the effect of a killed OCV, Shanchol™, on pregnancy outcomes during an effectiveness trial of the vaccine in urban Bangladesh. METHODOLOGY: Individuals ⩾1year were invited to participate in the trial, conducted in 2011 in Dhaka, Bangladesh. Pregnancy by history was an exclusion criterion and all women of reproductive age (15-49years) were verbally questioned about pregnancy at enrollment and prior to vaccination. Out of 48,414 women of reproductive age 286 women received the OCV unknowingly while pregnant. Out of these, we could recruit 69 women defined as exposed to OCV. Accordingly, we selected 69 pregnant women randomly from those who did not take the OCV (non-exposed to OCV). We evaluated adverse pregnancy outcome (spontaneous miscarriages, still births, or congenital malformations) between those who were exposed to OCV and those who were not exposed to OCV. RESULTS: About 16% of pregnant women exposed to OCV had pregnancy loss, as compared to 12% of unvaccinated pregnant women (P=0.38). One congenital anomaly was observed and occurred in women non-exposed to OCV group. Models that adjusted for baseline characteristics that were unbalanced between the exposed and non-exposed groups, revealed a no elevation of risk of adverse pregnancy outcomes in vaccinees versus non-vaccinees (Adj. OR (95% CI): 0.45 (0.11-1.88). CONCLUSIONS: No excess of adverse fetal outcomes associated with receipt of OCV was observed in this study. TRIAL REGISTRATION: Clinical Trials.gov number NCT01339845.

Estimating the cost of cholera-vaccine delivery from the societal point of view: A case of introduction of cholera vaccine in Bangladesh.

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, "Introduction of Cholera Vaccine in Bangladesh (ICVB)", was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future.

Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh: a cluster randomised open-label trial.

BACKGROUND: Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting. METHODS: We did this cluster-randomised open-label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845. FINDINGS: Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-related serious adverse events. INTERPRETATION: Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations. FUNDING: Bill & Melinda Gates Foundation.

Diarrheal Illness and Healthcare Seeking Behavior among a Population at High Risk for Diarrhea in Dhaka, Bangladesh.

Diarrhea remains one of the major causes of death in Bangladesh. We studied diarrheal disease risk and healthcare seeking behavior among populations at high risk for diarrhea in Dhaka, Bangladesh. Data were obtained from a cross-sectional survey conducted during April and September 2010. The prevalence of diarrhea was calculated by age-group and sex. A generalized estimating equation with logit link function was used to predict diarrheal disease risk and seeking care from a professional healthcare provider. Of 316,766 individuals, 10% were young children (<5 years). The prevalence of diarrhea was 16 per 1000 persons among all ages; young children accounted for 44 per 1000 persons. Prevalence of diarrhea was significantly higher (p=.003) among younger males (<15 years) compared to that among younger females. In contrast, prevalence of diarrhea was significantly higher (p<.0001) among older females (≥15 years) compared to that among older males. An increased risk for diarrhea was observed in young children, males, and those staying in rented houses, lower family members in the house, using non-sanitary toilets, living in the area for short times, living in a community with less educated persons, living in a community with less use of safe water source for drinking, or living close to the hospital. About 80% of those with diarrhea sought care initially from a non-professional healthcare provider. Choice of the professional healthcare provider was driven by age of the patient, educational status of the household head, and hygienic practices by the household. The study reaffirms that young children are at greater risk for diarrhea. Like other developing countries most people in this impoverished setting of Dhaka are less likely to seek care from a professional healthcare provider than from a non-professional healthcare provider, which could be attributed to a higher number of diarrheal deaths among young children in Bangladesh. Dissemination of information on health education, increasing the supply of skilled healthcare providers, and low-cost and quality healthcare services may encourage more people to seek care from professional healthcare providers, thus may help reduce child mortality in the country. Further studies are warranted to validate the results.

Coverage and acceptability of cholera vaccine among high-risk population of urban Dhaka, Bangladesh.

The oral cholera vaccine (Shanchol), along with other interventions, is a potential new measure to prevent or control cholera. A mass cholera-vaccination programme was launched in urban Dhaka, Bangladesh, during February-April 2011 targeting about 173,041 people who are at high risk of cholera. This cross-sectional, descriptive study assessed the coverage and acceptability of the vaccine. The study used a quantitative household survey and qualitative data-collection techniques comprising focus-group discussions, in-depth interviews, and observations for assessment. The findings revealed that 88% of the target population received the first dose of the vaccine, and 79% received the second dose. Absence of persons at home was a prominent cause of not administering the first (71%) and the second dose (67%). Thirty-three percent of the respondents (n=9308) did not like the taste of the vaccine. Only 1.3% and 3% recipients of the first dose and the second dose of the vaccine respectively reported adverse effects within 28 days of vaccination, and the adverse effects included vomiting or vomiting tendency and diarrhoea. To improve the coverage of the cholera vaccine, exploration of effective solutions to reach the unvaccinated population is required. The vaccine may be more acceptable to the community through changing its taste.

Cost of illness for cholera in a high risk urban area in Bangladesh: an analysis from household perspective.

BACKGROUND: Cholera poses a substantial health burden to developing countries such as Bangladesh. In this study, the objective is to estimate the economic burden of cholera treatments incurred by households. The study was carried out in the context of a large vaccine trial in an urban area of Bangladesh. METHODS: The study used a combination of prospective and retrospective incidence-based cost analyses of cholera illness per episode per household. A total of 394 confirmed cholera hospitalized cases were identified and treated in the study area during June-October 2011. Households with cholera patients were interviewed within 15 days after discharge from hospitals or clinics. To estimate the total cost of cholera illness a structured questionnaire was used, which included questions on direct medical costs, non-medical costs, and the indirect costs of patients and caregivers. RESULTS: The average total household cost of treatment for an episode of cholera was US$30.40. Total direct and indirect costs constituted 24.6% (US$7.40) and 75.4% (US$23.00) of the average total cost, respectively. The cost for children under 5 years of age (US$21.50) was higher than that of children aged 5-14 years (US$17.50). The direct cost of treatment was similar for male and female patients, but the indirect cost was higher for males. CONCLUSION: Our study suggests that by preventing one cholera episode (3 days on an average), we can avert a total cost of 2,278.50 BDT (US$30.40) per household. Among medical components, medicines are the largest cost driver. No clear socioeconomic gradient emerged from our study, but limited demographic patterns were observed in the cost of illness. By preventing cholera cases, large production losses can be reduced.

Coverage and cost of a large oral cholera vaccination program in a high-risk cholera endemic urban population in Dhaka, Bangladesh.

A feasibility study of an oral cholera vaccine was carried out to test strategies to reach high-risk populations in urban Mirpur, Dhaka, Bangladesh. The study was cluster randomized, with three arms: vaccine, vaccine plus safe water and hand washing practice, and no intervention. High risk people of age one year and above (except pregnant woman) from the two intervention arms received two doses of the oral cholera vaccine, Shanchol™. Vaccination was conducted between 17th February and 16th April 2011, with a minimum interval of fourteen days between two doses. Interpersonal communication preceded vaccination to raise awareness amongst the target population. The number of vaccine doses used, the population vaccinated, left-out, drop out, vaccine wastage and resources required were documented. Fixed outreach site vaccination strategy was adopted as the mode of vaccine delivery. Additionally, mobile vaccination sites and mop-up activities were carried out to reach the target communities. Of the 172,754 target population, 141,839 (82%) and 123,666 (72%) received complete first and second doses of the vaccine, respectively. Dropout rate from the first to the second dose was 13%. Two complete doses were received by 123,661 participants. Vaccine coverage in children was 81%. Coverage was significantly higher in females than in males (77% vs. 66%, P<0.001). Vaccine wastage for delivering the complete doses was 1.2%. The government provided cold-chain related support at no cost to the project. Costs for two doses of vaccine per-person were US$3.93, of which US$1.63 was spent on delivery. Cost for delivering a single dose was US$0.76. We observed no serious adverse events. Mass vaccination with oral cholera vaccine is feasible for reaching high risk endemic population through the existing national immunization delivery system employed by the government.