Oral killed cholera vaccines for preventing cholera.

BACKGROUND: Cholera causes acute watery diarrhoea and death if not properly treated. Outbreaks occur in areas with poor sanitation, including refugee camps. Several vaccines have been developed and tested over the last 50 years. This is an update of a Cochrane review, originally published in 1998, which explored the effects of all vaccines for preventing cholera. This review examines oral vaccines made from killed bacteria. OBJECTIVES: To assess the effectiveness and safety of the available World Health Organization (WHO)-prequalified oral killed cholera vaccines among children and adults. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL, MEDLINE; Embase; LILACS; and two trials registers (February 2023). SELECTION CRITERIA: We included randomized controlled trials (RCTs), including cluster-RCTs. There were no restrictions on the age and sex of the participants or the setting of the study. We considered any available WHO-prequalified oral killed cholera vaccine as an intervention. The control group was given a placebo, another vaccine, or no vaccine. The outcomes were related to vaccine effectiveness and safety. We included articles published in English only. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and extracted data from included studies. We assessed the risk of bias using the Cochrane ROB 1 assessment tool. We used the generic inverse variance and a random-effects model meta-analysis to estimate the pooled effect of the interventions. We assessed the certainty of the evidence using the GRADE approach. For vaccine effectiveness (VE), we converted the overall risk ratio (RR) to vaccine effectiveness using the formula: VE = (1 - RR) x 100%. MAIN RESULTS: Five RCTs, reported in 12 records, with 462,754 participants, met the inclusion criteria. We identified trials on whole-cell plus recombinant vaccine (WC-rBS vaccine (Dukoral)) from Peru and trials on bivalent whole-cell vaccine (BivWC (Shanchol)) vaccine from India and Bangladesh. We did not identify any trials on other BivWC vaccines (Euvichol/Euvichol-Plus), or Hillchol. Two doses of Dukoral with or without a booster dose reduces cases of cholera at two-year follow-up in a general population of children and adults, and at five-month follow-up in an adult male population (overall VE 76%; RR 0.24, 95% confidence interval (CI) 0.08 to 0.65; 2 trials, 16,423 participants; high-certainty evidence). Two doses of Shanchol reduces cases of cholera at one-year follow-up (overall VE 37%; RR 0.63, 95% CI 0.47 to 0.85; 2 trials, 241,631 participants; high-certainty evidence), at two-year follow-up (overall VE 64%; RR 0.36, 95% CI 0.16 to 0.81; 2 trials, 168,540 participants; moderate-certainty evidence), and at five-year follow-up (overall VE 80%; RR 0.20, 95% CI 0.15 to 0.26; 1 trial, 54,519 participants; high-certainty evidence). A single dose of Shanchol reduces cases of cholera at six-month follow-up (overall VE 40%; RR 0.60, 95% CI 0.47 to 0.77; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 39%; RR 0.61, 95% CI 0.53 to 0.70; 1 trial, 204,700 participants; high-certainty evidence). A single dose of Shanchol also reduces cases of severe dehydrating cholera at six-month follow-up (overall VE 63%; RR 0.37, 95% CI 0.28 to 0.50; 1 trial, 204,700 participants; high-certainty evidence), and at two-year follow-up (overall VE 50%; RR 0.50, 95% CI 0.42 to 0.60; 1 trial, 204,700 participants; high-certainty evidence). We found no differences in the reporting of adverse events due to vaccination between the vaccine and control/placebo groups. AUTHORS' CONCLUSIONS: Two doses of Dukoral reduces cases of cholera at two-year follow-up. Two doses of Shanchol reduces cases of cholera at five-year follow-up, and a single dose of Shanchol reduces cases of cholera at two-year follow-up. Overall, the vaccines were safe and well-tolerated. We found no trials on other BivWC vaccines (Euvichol/Euvichol-Plus). However, BivWC products (Shanchol, Euvichol/Euvichol-Plus) are considered to produce comparable vibriocidal responses. Therefore, it is reasonable to apply the results from Shanchol trials to the other BivWC products (Euvichol/Euvichol-Plus).

Closing the gaps in tobacco endgame evidence: a scoping review.

OBJECTIVE: Tobacco endgame policies aim to rapidly and permanently reduce smoking to minimal levels. We reviewed evidence syntheses for: (1) endgame policies, (2) evidence gaps, and (3) future research priorities. DATA SOURCES: Guided by JBI scoping review methodology, we searched five databases (PubMed, CINAHL, Scopus, Embase and Web of Science) for evidence syntheses published in English since 1990 on 12 policies, and Google for publications from key national and international organisations. Reference lists of included publications were hand searched. STUDY SELECTION: Two reviewers independently screened titles and abstracts. Inclusion criteria were broad to capture policy impacts (including unintended), feasibility, public and stakeholder acceptability and other aspects of policy implementation. DATA EXTRACTION: We report the results according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SYNTHESIS: Eight policies have progressed to evidence synthesis stage (49 publications): mandatory very low nicotine content (VLNC) standard (n=26); product standards to substantially reduce consumer appeal or remove the most toxic products from the market (n=1); moving consumers to reduced risk products (n=8); tobacco-free generation (n=4); ending sales (n=2); sinking lid (n=2); tax increases (n=7); and restrictions on tobacco retailers (n=10). Based on published evidence syntheses, the evidence base was most developed for a VLNC standard, with a wide range of evidence synthesised. CONCLUSIONS: VLNC cigarettes have attracted the most attention, in terms of synthesised evidence. Additional focus on policies that reduce the availability of tobacco is warranted given these measures are being implemented in some jurisdictions.

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 .

The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys.

INTRODUCTION: Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12-27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies. METHODS/DESIGN: Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN 12131979. ETHICS REFERENCES: Oxford (Oxford Tropical Research Ethics Committee 39-15).Bangladesh (icddr,b Institutional Review Board PR-15119).Malawi (National Health Sciences Research Committee 15/5/1599).Nepal (Nepal Health Research Council 306/2015).