BackgroundThe global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera.Methods/Principal FindingsCountries were classified as cholera endemic, cholera non-endemic, or cholera-free based on whether a spatial regression model predicted an incidence rate over a certain threshold in at least three of five years (2008-2012). The at-risk populations were calculated for each country based on the percent of the country without sustainable access to improved sanitation facilities. Incidence rates from population-based published studies were used to calculate the estimated annual number of cases in endemic countries. The number of annual cholera deaths was calculated using inverse variance-weighted average case-fatality rate (CFRs) from literature-based CFR estimates. We found that approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases (uncertainty range: 1.3m-4.0m) occur annually in endemic countries. Among these cases, there are an estimated 95,000 deaths (uncertainty range: 21,000-143,000).Conclusion/SignificanceThe global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control.

BackgroundNewborn deaths comprise nearly half of under-5 deaths in Ghana, despite the fact that skilled birth attendants (SBAs) are present at 68% of births, which implies that evidence-based care during labor, birth and the immediate postnatal period may be deficient. We assessed the effect of a low-dose, high-frequency (LDHF) training approach on long-term evidence-based skill retention among SBAs and impact on adverse birth outcomes.MethodsFrom 2014 to 2017, we conducted a cluster-randomized trial in 40 hospitals in Ghana. Eligible hospitals were stratified by region and randomly assigned to one of four implementation waves. We assessed the relative risks (RRs) of institutional intrapartum stillbirths and 24-h newborn mortality in months 1–6 and 7–12 of implementation as compared to the historical control period, and in post-intervention facilities compared to pre-intervention facilities during the same period. All SBAs providing labor and delivery care were invited to enroll; their knowledge and skills were assessed pre- and post-training, and 1 year later.ResultsAdjusting for region and health facility type, the RR of 24-h newborn mortality in the 40 enrolled hospitals was 0·41 (95% CI 0·32–0·51; p < 0.001) in months 1–6 and 0·30 (95% CI 0·21–0·43; p < 0·001) in months 7–12 compared to baseline. The adjusted RR of intrapartum stillbirth was 0·64 (95% CI 0·53–0·77; p < 0·001) in months 1–6 and 0·48 (95% CI 0·36–0·63; p < 0·001) in months 7–12 compared to baseline. Four hundred three SBAs consented and enrolled. After 1 year, 200 SBAs assessed had 28% (95% CI 25–32; p < 0·001) and 31% (95% CI 27–36; p < 0·001) higher scores than baseline on low-dose 1 and 2 content skills, respectively.ConclusionsThis training approach results in a sustained decrease in facility-based newborn mortality and intrapartum stillbirths, and retained knowledge and skills among SBAs after a year. We recommend use of this approach for future maternal and newborn health in-service training and programs.Trial registrationRetrospectively registered on 25 September 2017 at Clinical Trials, identifier NCT03290924.Electronic supplementary materialThe online version of this article (10.1186/s12884-018-1705-5) contains supplementary material, which is available to authorized users.

BackgroundLow-dose, high-frequency (LDHF) training is a new approach best practices to improve clinical knowledge, build and retain competency, and transfer skills into practice after training. LDHF training in Ghana is an opportunity to build health workforce capacity in critical areas of maternal and newborn health and translate improved capacity into better health outcomes.MethodsThis study examined the costs of an LDHF training approach for basic emergency obstetric and newborn care and calculates the incremental cost-effectiveness of the LDHF training program for health outcomes of newborn survival, compared to the status quo alternative of no training. The costs of LDHF were compared to costs of traditional workshop-based training per provider trained. Retrospective program cost analysis with activity-based costing was used to measure all resources of the LDHF training program over a 3-year analytic time horizon. Economic costs were estimated from financial records, informant interviews, and regional market prices. Health effects from the program’s impact evaluation were used to model lives saved and disability-adjusted life years (DALYs) averted. Uncertainty analysis included one-way and probabilistic sensitivity analysis to explore incremental cost-effectiveness results when fluctuating key parameters.ResultsFor the 40 health facilities included in the evaluation, the total LDHF training cost was $823,134. During the follow-up period after the first LDHF training—1 year at each participating facility—approximately 544 lives were saved. With deterministic calculation, these findings translate to $1497.77 per life saved or $53.07 per DALY averted. Probabilistic sensitivity analysis, with mean incremental cost-effectiveness ratio of $54.79 per DALY averted ($24.42–$107.01), suggests the LDHF training program as compared to no training has 100% probability of being cost-effective above a willingness to pay threshold of $1480, Ghana’s gross national income per capita in 2015.ConclusionThis study provides insight into the investment of LDHF training and value for money of this approach to training in-service providers on basic emergency obstetric and newborn care. The LDHF training approach should be considered for expansion in Ghana and integrated into existing in-service training programs and health system organizational structures for lower cost and more efficiency at scale.

Providers, managers, and clients valued the integrated service delivery model. Trends indicated slightly higher family planning uptake in intervention facilities, but that difference was not statistically significant. Intrafacility referrals by postpartum women did not negatively affect immunization utilization rates.

SummaryBackgroundPregnancy increases the risk of harmful effects from cholera for both mothers and their fetuses. A killed oral cholera vaccine, Shanchol (Shantha Biotechnics, Hydrabad, India), can protect against the disease for up to 5 years. However, cholera vaccination campaigns have often excluded pregnant women because of insufficient safety data for use during pregnancy. We did an observational cohort study to assess the safety of Shanchol during pregnancy.MethodsThis observational cohort study was done in two adjacent districts (Nsanje and Chikwawa) in Malawi. Individuals older than 1 year in Nsanje were offered oral cholera vaccine during a mass vaccination campaign between March 30 and April 30, 2015, but no vaccines were administered in Chikwawa. We enrolled women who were exposed to oral cholera vaccine during pregnancy in Nsanje district, and women who were pregnant in Chikwawa district (and thus not exposed to oral cholera vaccine) during the same period. The primary endpoint of our analysis was pregnancy loss (spontaneous miscarriage or stillbirth), and the secondary endpoints were neonatal deaths and malformations. We evaluated these endpoints using log-binomial regression, adjusting for the imbalanced baseline characteristics between the groups. This study is registered with ClinicalTrials.gov, number NCT02499172.FindingsWe recruited 900 women exposed to oral cholera vaccine and 899 women not exposed to the vaccine between June 16 and Oct 10, 2015, and analysed 835 in each group. 361 women exposed to the vaccine and 327 not exposed to the vaccine were recruited after their pregnancies had ended. The incidence of pregnancy loss was 27·54 (95% CI 18·41–41·23) per 1000 pregnancies among those exposed to the vaccine and 21·56 (13·65–34·04) per 1000 among those not exposed. The adjusted relative risk for pregnancy loss among those exposed to oral cholera vaccine was 1·24 (95% CI 0·64–2·43; p=0·52) compared with those not exposed to the vaccine. The neonatal mortality rate was 11·78 (95% CI 5·92–23·46) per 1000 livebirths for infants whose mothers were exposed to oral cholera vaccine versus 8·91 (4·02–19·77) per 1000 livebirths for infants whose mothers were not exposed to the vaccine (crude relative risk 1·32, 95% CI 0·46–3·84; p=0·60). Only three newborn babies had malformations, two in the vaccine exposure group and one in the no-exposure group, yielding a relative risk of 2·00 (95% CI 0·18–22·04; p=0·57), although this estimate is unreliable because of the small number of outcomes.InterpretationOur study provides evidence that fetal exposure to oral cholera vaccine confers no significantly increased risk of pregnancy loss, neonatal mortality, or malformation. These data, along with findings from two retrospective studies, support use of oral cholera vaccine in pregnant women in cholera-affected regions.FundingBill & Melinda Gates Foundation.