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Aim To accelerate progress in reducing child mortality, many countries in sub-Saharan Africa have adopted and scaled-up integrated community case management (iCCM) programs targeting the three major infectious killers of children under-five. The programs train lay community health workers to assess, classify and treat uncomplicated cases of pneumonia with antibiotics, malaria with antimalarial drugs and diarrhea with Oral Rehydration Salts (ORS) and zinc. Although management of these conditions with the respective appropriate drugs has proven efficacious in randomized trials, the effectiveness of large iCCM scale-up programs in reducing child mortality is yet to be demonstrated. This paper reviews recent experience in documenting and attributing changes in under-five mortality to the specific interventions of a variety of iCCM programs. Methods Eight recent studies have been identified and assessed in terms of design, mortality measurement and results. Impact of the iCCM program on mortality among children age 2-59 months was assessed through a difference in differences approach using random effect Poisson regression. Results Designs used by these studies include cluster randomized trials, randomized stepped-wedge and quasi-experimental trials. Child mortality is measured through demographic surveillance or household survey with full birth history conducted at the end of program implementation. Six of the eight studies showed a higher decline in mortality among children 2-59 months in program areas compared to comparison areas, although this acceleration was statistically significant in only one study with a decline of 76% larger in intervention than in comparison areas. Conclusion Studies that evaluate large scale iCCM programs and include assessment of mortality impact must ensure an appropriate design. This includes required sample sizes and sufficient number of program and comparison districts that allow adequate inference and attribution of impact. In addition, large-scale program utilization, and a significant increase in coverage of care seeking and treatment of targeted childhood illnesses are preconditions to measurable mortality impact. Those issues need to be addressed before large investments in assessing changes in child mortality is undertaken, or the results of mortality impact evaluation will most likely be inconclusive. [ABSTRACT FROM AUTHOR]

Background: The African Health Initiative includes highly diverse partnerships in five countries (Ghana, Mozambique, Rwanda, Tanzania, and Zambia), each of which is working to improve population health by strengthening health systems and to evaluate the results. One aim of the Initiative is to generate cross-site learning that can inform implementation in the five partnerships during the project period and identify lessons that may be generalizable to other countries in the region. Collaborators in the Initiative developed a common evaluation framework as a basis for this cross-site learning. Methods: This paper describes the components of the framework; this includes the conceptual model, core metrics to be measured in all sites, and standard guidelines for reporting on the implementation of partnership activities and contextual factors that may affect implementation, or the results it produces. We also describe the systems that have been put in place for data management, data quality assessments, and cross-site analysis of results. Results and conclusions: The conceptual model for the Initiative highlights points in the causal chain between health system strengthening activities and health impact where evidence produced by the partnerships can contribute to learning. This model represents an important advance over its predecessors by including contextual factors and implementation strength as potential determinants, and explicitly including equity as a component of both outcomes and impact. Specific measurement challenges include the prospective documentation of program implementation and contextual factors. Methodological issues addressed in the development of the framework include the aggregation of data collected using different methods and the challenge of evaluating a complex set of interventions being improved over time based on continuous monitoring and intermediate results. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccines (RVV) have poor immunogenicity in low-income countries, for reasons that remain unclear. This study identified the determinants of RVV immunogenicity among infants in rural Zimbabwe. Anti-rotavirus IgA titres were measured among a sub-group of infants enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial (NCT01824940). SHINE was a cluster-randomized trial of improved infant and young child feeding, and improved water, sanitation and hygiene (WASH) in two rural Zimbabwean districts. Infants received RVV as part of the national immunisation programme. Among HIV-unexposed infants in the non-WASH trial arms, we evaluated associations between potential risk factors (vaccine schedule and dose, maternal and infant nutritional status, infant diarrhoea, and household environment) and RVV immunogenicity (seroconversion, seropositivity and geometric mean titres) using multivariable regression. Among 219 infants with seroconversion data, 43 (20%) successfully seroconverted and 176 (80%) failed to seroconvert to RVV. Seroconversion was positively associated with a higher length-for-age Z-score (LAZ) around the time of vaccination (adjusted RR 1.27 (95% CI 1.04, 1.55), P = 0.021), and negatively associated with concurrent OPV and RVV administration (adjusted RR 0.36 (0.19, 0.71), P = 0.003). Among 472 infants with post-vaccination titres, a higher LAZ score was associated with increased seropositivity (aRR 1.21 (95% CI 1.06, 1.38), P = 0.004), and higher birthweight was associated with increased IgA titres (0.45 (95%CI 0.18, 1.09) U/mL greater per 100 g gain in birthweight; P = 0.001). Infant ponderal and linear growth were positively associated with RVV immunogenicity, while concurrent administration of OPV was negatively associated with RVV immunogenicity. Together, these findings suggest that improving foetal growth and separating RVV and OPV administration are plausible approaches to increasing RVV immunogenicity. [ABSTRACT FROM AUTHOR]

First generation candidate vaccines against leishmaniasis, prepared using inactivated whole parasites as their main ingredient, were considered as promising because of their relative ease of production and low cost. These vaccines have been the subject of many investigations over several decades and are the only leishmaniasis vaccine candidates which have undergone phase 3 clinical trial evaluation. Although the studies demonstrated the safety of the vaccines and several studies showed reasonable immunogenicity and some indication of protection, an efficacious prophylactic vaccine is yet to be identified. Despite this overall failure, these trials contributed significantly to increasing knowledge on human leishmaniasis immunology. To provide a collective view, this review discusses the methods and findings of field efficacy trials of first generation leishmaniasis vaccine clinical trials conducted in the Old and New Worlds.