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Abstract Background Insecticide-treated mosquito nets (ITNs) and indoor-residual spraying have been scaled-up across sub-Saharan Africa as part of international efforts to control malaria. These interventions have the potential to significantly impact child survival. The Lives Saved Tool (LiST) was developed to provide national and regional estimates of cause-specific mortality based on the extent of intervention coverage scale-up. We compared the percent reduction in all-cause child mortality estimated by LiST against measured reductions in all-cause child mortality from studies assessing the impact of vector control interventions in Africa. Methods We performed a literature search for appropriate studies and compared reductions in all-cause child mortality estimated by LiST to 4 studies that estimated changes in all-cause child mortality following the scale-up of vector control interventions. The following key parameters measured by each study were applied to available country projections: baseline all-cause child mortality rate, proportion of mortality due to malaria, and population coverage of vector control interventions at baseline and follow-up years. Results The percent reduction in all-cause child mortality estimated by the LiST model fell within the confidence intervals around the measured mortality reductions for all 4 studies. Two of the LiST estimates overestimated the mortality reductions by 6.1 and 4.2 percentage points (33% and 35% relative to the measured estimates), while two underestimated the mortality reductions by 4.7 and 6.2 percentage points (22% and 25% relative to the measured estimates). Conclusions The LiST model did not systematically under- or overestimate the impact of ITNs on all-cause child mortality. These results show the LiST model to perform reasonably well at estimating the effect of vector control scale-up on child mortality when compared against measured data from studies across a range of malaria transmission settings. The LiST model appears to be a useful tool in estimating the potential mortality reduction achieved from scaling-up malaria control interventions.

Abstract Background Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality. Methods We undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model. Results A total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55). Conclusions The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.

Abstract Background Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation. Data sources/ review methods A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed. Results The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model. The impact on diarrhea-specific mortality of zinc alone was a non-significant 18% reduction (RR = 0.82; 95% CI: 0.64, 1.05) and 15% for pneumonia-specific mortality (RR = 0.85; 95% CI: 0.65, 1.11). The incidence of diarrhea showed a 13% reduction with preventive zinc supplementation (RR = 0.87; 95% CI: 0.81, 0.94) and a 19% reduction in pneumonia morbidity (RR = 0.81; 95% CI: 0.73, 0.90). Keeping in mind the direction of effect of zinc supplementation in reducing diarrhea and pneumonia related morbidity and mortality; we considered all the outcomes for selection of effectiveness estimate for inclusion in the LiST model. After application of the CHERG rules with consideration to quality of evidence and rule # 6, we used the most conservative estimates as a surrogate for mortality. We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15% for inclusion in the LiST tool. Preventive zinc supplementation had no effect on malaria specific mortality (RR = 0.90; 95% CI: 0.77, 1.06) or incidence of malaria (RR=0.92; 95 % CI 0.82-1.04) Conclusion Zinc supplementation results in reductions in diarrhea and pneumonia mortality.

Abstract Background The Lives Saved Tool (LiST) model was developed to estimate the impact of the scale-up of child survival interventions on child mortality. New advances in antimalarials have improved their efficacy of treating uncomplicated and severe malaria. Artemisinin-based combination therapies (ACTs) for uncomplicated Plasmodium falciparum malaria and parenteral or rectal artemisinin or quinine for severe malaria syndromes have been shown to be very effective for the treatment of malaria in children. These interventions are now being considered for inclusion in the LiST model. However, for obvious ethical reasons, their protective efficacy (PE) compared to placebo is unknown and their impact on reducing malaria-attributable mortality has not been quantified. Methods We performed systematic literature reviews of published studies in P. falciparum endemic settings to determine the protective efficacy (PE) of ACT treatment against malaria deaths among children with uncomplicated malaria, as well as the PE of effective case management including parenteral quinine against malaria deaths among all hospitalized children. As no randomized placebo-controlled trials of malaria treatment have been conducted, we used multiple data sources to ascertain estimates of PE, including a previously performed Delphi estimate for treatment of uncomplicated malaria. Results Based on multiple data sources, we estimate the PE of ACT treatment of uncomplicated P. falciparum malaria on reducing malaria mortality in children 1–23 months to be 99% (range: 94-100%), and in children 24-59 months to be 97% (range: 86-99%). We estimate the PE of treatment of severe P. falciparum malaria with effective case management including intravenous quinine on reducing malaria mortality in children 1-59 months to be 82% (range: 63-94%) compared to no treatment. Conclusions This systematic review quantifies the PE of ACT used for treating uncomplicated malaria and effective case management including parenteral quinine for treating severe P. falciparum malaria for preventing malaria mortality in children

Abstract Background A critical challenge in the health sector in developing countries is to ensure the quality and effectiveness of surveillance and public health response in an environment of decentralization. In Georgia, a country where there has been extensive decentralization of public health responsibilities over the last decade, an intervention was recently piloted to strengthen district-level local vaccine-preventable disease surveillance and response activities through improved capacity to analyze and use routinely collected data. The purpose of the study is 1) to assess the effectiveness of the intervention on motivation and perceived capacity to analyze and use information at the district-level, and 2) to assess the role that individual- and system-level factors play in influencing the effectiveness of the intervention. Methods A pre-post quasi-experimental research design is used for the quantitative evaluation. Data come from a baseline and two follow-up surveys of district-level health staff in 12 intervention and 3 control Center of Public Health (CPH) offices. These data were supplemented by record reviews in CPH offices as well as focus group discussions among CPH and health facility staff. Results The results of the study suggest that a number of expected improvements in perceived data availability and analysis occurred following the implementation of the intervention package, and that these improvements in analysis could be attributable to the intervention package. However, the study results also suggest that there exist several health systems barriers that constrained the effectiveness of the intervention in influencing the availability of data, analysis and response. Conclusion To strengthen surveillance and response systems in Georgia, as well as in other countries, donor, governments, and other stakeholders should consider how health systems factors influence investments to improve the availability of data, analysis, and response. Linking the intervention to broader health sector reforms in management processes and organizational culture will be critical to ensure that efforts designed to promote evidence-based decision-making are successful, especially as they are scaled up to the national level.