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Background: Scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool. Methods: The dynamic Plasmodium falciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings. Results: Selected (best) GLMs explained 94-97 % of variation in simulated post-intervention parasite infection prevalence, 86-97 % of variation in case incidence (three age groups, three 3-year horizons), and 74-95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5-7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached. Conclusion: Health improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control. [ABSTRACT FROM AUTHOR]

Summary: Drug-resistant malaria is a substantial problem throughout Africa and most countries must regularly adapt their antimalarial drug policies to ensure a continued coverage of effective antimalarial treatment. The timing of drug policy change can be guided by several sources of data: molecular markers of resistance, in-vitro parasite sensitivity, parasitological and clinical failure rates, and community morbidity and mortality rates. Through mathematical simulations of the spread of parasite mutations through a population exposed to high-endemic malaria, we explore the causal and chronological relations between these indicators and show which of them are obscured or confounded by other factors. Taking into account the logistical and practical advantages and disadvantages of each type of data collection, we critically appraise the value of each indicator. A major problem is shown to be that drug efficacy as perceived by people at risk will remain high even after drugs have become almost completely ineffective, resulting in a lack of community pressure for drug policy change. We show that parasitological failure is the most sensitive and timely indicator, which allows around 2–3 years for drug policy change to be implemented, so as to prevent the most rapid rise in malaria-related mortality. [Copyright &y& Elsevier]

This article presents the results of a study on estimating the number of insecticide-treated nets (ITNs) required by African households to reach continent-wide malaria coverage targets. The goal was to estimate how many ITNs were needed overall and how many are needed just to protect infants and pregnant women. Statistics show that of the 43 countries in sub-Saharan Africa that need ITNs, just 23 percent have one or more in the home. The study estimates that millions of ITNs are needed for the entire population. The estimate of ITNs needed to protect young children and pregnant women alone was about 203 million nets.

Background. The variability in CD4+ cell counts within and among human immunodeficiency virus (HIV)-positive and -negative African populations has not been explained but has important implications for understanding the incidence of HIV-related opportunistic infections, especially tuberculosis, in both individuals and populations. Methods. In HIV-negative African adults, CD4+ cell counts vary within populations (interquartile ranges [IQRs], 169–603 cells/mL) and among populations (means vary from 699 to 1244 cells/mL), with similarly wide variations in HIV-positive adults. We developed dynamic mathematical models to predict the distribution of CD4+ cell counts in HIV-positive adults using the distribution in HIV-negative adults. Results. Under the assumption that survival is independent of the CD4+ cell count before seroconversion, we fitted the observed distributions in HIV-positive adults. At a CD4+ cell count of 200 cells/mL, the median life expectancy of HIV-positive Zambians (4.0 years) was predicted to be 1.7 times that of HIV-positive South Africans (2.3 years). Conclusions. The model provides a way to estimate the changing distribution of CD4+ cell counts and, hence, the changing incidence of HIV-related opportunistic infections as the epidemic matures. This could substantially improve the planning of health services, including the need and demand for antiretroviral therapy. Better data are needed to test the model and its assumptions more rigorously and to fully understand the variability in CD4+ cell counts within and among populations. [ABSTRACT FROM AUTHOR]

To review the impact of malaria control on haemoglobin (Hb) distributions and anaemia prevalences in children under 5 in malaria-endemic Africa.Literature review of community-based studies of insecticide-treated bednets, antimalarial chemoprophylaxis and insecticide residual spraying that reported the impact on childhood anaemia. Anaemia outcomes were standardized by conversion of packed cell volumes into Hb values assuming a fixed threefold difference, and by estimation of anaemia prevalences from mean Hb values by applying normal distributions. Determinants of impact were assessed in multivariate analysis.Across 29 studies, malaria control increased Hb among children by, on average, 0.76 g/dl [95% confidence interval (CI): 0.61–0.91], from a mean baseline level of 10.5 g/dl, after a mean of 1–2 years of intervention. This response corresponded to a relative risk for Hb < 11 g/dl of 0.73 (95% CI: 0.64–0.81) and for Hb < 8 g/dl of 0.40 (95% CI: 0.25–0.55). The anaemia response was positively correlated with the impact on parasitaemia (P = 0.005,P = 0.008 andP = 0.01 for the three outcome measures), but no relationship with the type or duration of malaria intervention was apparent. Impact on the prevalence of Hb < 11 g/dl was larger in sites with a higher baseline parasite prevalence. Although no age pattern in impact was apparent across the studies, some individual trials found larger impacts on anaemia in children aged 6–35 months than in older children.In malaria-endemic Africa, malaria control reduces childhood anaemia. Childhood anaemia may be a useful indicator of the burden of malaria and of the progress in malaria control. [ABSTRACT FROM AUTHOR]

Reduction of deaths associated with malaria in children is a primary goal of malaria control programmes in Africa, but there has been little discussion about how changes in mortality will be measured. This paper assesses recent historical changes in the contribution of malaria to child survival in Africa by examining data from demographic surveillance systems (DSS) in 25 mainly rural settings. The data were adjusted for the varying sensitivity and specificity of verbal autopsies (VA) in different ranges of malaria mortality and for varying parasite prevalences. Average malaria mortality in the DSS sites in west Africa was 7·8 per 1000 child-years between 1982 and 1998; the rate did not change significantly over this period. In the sites in east and southern Africa combined, malaria mortality was 6·5 per 1000 child-years between 1982 and 1989, but it increased to 11·9 per 1000 child-years between 1990 and 1998. All-cause child mortality and non-malaria mortality, by contrast, decreased significantly over time in both regions; consequently, the proportion of deaths due to malaria rose from 18% to 23% in west African sites and from 18% to 37% in east and southern African sites between 1982–89 and 1990–98. If malaria mortality fell at a rate consistent with the Roll Back Malaria target of halving malaria mortality by the year 2010, an individual DSS of a total population of 63 500 could with adequate VA adjustment detect this reduction after 7 years. [Copyright &y& Elsevier]

Background: In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity.Methods: The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030.Results: Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST.Conclusions: Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival. [ABSTRACT FROM AUTHOR]

Background: Since 2002, development assistance for health has substantially increased, especially investments for HIV, tuberculosis (TB) and malaria control. We undertook a systematic review to assess and synthesize the existing evidence in the scientific literature on the health impacts of these investments., Methods and Findings: We systematically searched databases for peer-reviewed and grey literature, using tailored search strategies. We screened studies for study design and relevance, using predefined inclusion criteria, and selected those that enabled us to link health outcomes or impact to increased external funding. For all included studies, we recorded dataset and study characteristics, health outcomes and impacts. We analysed the data using a causal-chain framework to develop a narrative summary of the published evidence. Thirteen articles, representing 11 individual studies set in Africa and Asia reporting impacts on HIV, tuberculosis and malaria, met the inclusion criteria. Only two of these studies documented the entire causal-chain spanning from funding to programme scale-up, to outputs, outcomes and impacts. Nonetheless, overall we find a positive correlation between consecutive steps in the causal chain, suggesting that external funds for HIV, tuberculosis and malaria programmes contributed to improved health outcomes and impact., Conclusions: Despite the large number of supported programmes worldwide and despite an abundance of published studies on HIV, TB and malaria control, we identified very few eligible studies that adequately demonstrated the full process by which external funding has been translated to health impact. Most of these studies did not move beyond demonstrating statistical association, as opposed to contribution or causation. We thus recommend that funding organizations and researchers increase the emphasis on ensuring data capture along the causal pathway to demonstrate effect and contribution of external financing. The findings of these comprehensive and rigorously conducted impact evaluations should also be made publicly accessible., (Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine © The Author 2013; all rights reserved.)

Background: The variability in CD4+ cell counts within and among human immunodeficiency virus (HIV)-positive and -negative African populations has not been explained but has important implications for understanding the incidence of HIV-related opportunistic infections, especially tuberculosis, in both individuals and populations., Methods: In HIV-negative African adults, CD4+ cell counts vary within populations (interquartile ranges [IQRs], 169-603 cells/microL) and among populations (means vary from 699 to 1244 cells/microL), with similarly wide variations in HIV-positive adults. We developed dynamic mathematical models to predict the distribution of CD4+ cell counts in HIV-positive adults using the distribution in HIV-negative adults., Results: Under the assumption that survival is independent of the CD4+ cell count before seroconversion, we fitted the observed distributions in HIV-positive adults. At a CD4+ cell count of 200 cells/microL, the median life expectancy of HIV-positive Zambians (4.0 years) was predicted to be 1.7 times that of HIV-positive South Africans (2.3 years)., Conclusions: The model provides a way to estimate the changing distribution of CD4+ cell counts and, hence, the changing incidence of HIV-related opportunistic infections as the epidemic matures. This could substantially improve the planning of health services, including the need and demand for antiretroviral therapy. Better data are needed to test the model and its assumptions more rigorously and to fully understand the variability in CD4+ cell counts within and among populations.

Background: Although malaria is a leading cause of child deaths, few well-documented estimates of its direct and indirect burden exist. Our objective was to estimate the number of deaths directly attributable to malaria among children <5 years old in sub-Saharan Africa for the year 2000., Methods: We divided the population into six sub-populations and, using results of studies identified in a literature review, estimated a malaria mortality rate for each sub-population. Malaria deaths were estimated by multiplying each sub-population by its corresponding rate. Sensitivity analyses were performed to assess the impact of varying key assumptions., Results: The literature review identified 31 studies from 14 countries in middle Africa and 17 studies and reports from four countries in southern Africa. In 2000, we estimated that approximately 100 million children lived in areas where malaria transmission occurs and that 803 620 (precision estimate: 705 821-901 418) children died from the direct effects of malaria. For all of sub-Saharan Africa, including populations not exposed to malaria, malaria accounted for 18.0% (precision estimate: 15.8-20.2%) of child deaths. These estimates were sensitive to extreme assumptions about the causes of deaths with no known cause., Conclusions: These estimates, based on the best available data and methods, clearly demonstrate malaria's enormous mortality burden. We emphasize that these estimates are an approximation with many limitations and that the estimates do not account for malaria's large indirect burden. We describe information needs that, if filled, might improve the validity of future estimates.

The disability adjusted life year (DALY) approach of defining cause-specific health burdens is becoming the benchmark for international disease control prioritization. For malaria, this categorical approach may not fully capture its burden that includes chronic anemia, low birth weight, and enhancement of the severity of other childhood diseases. We investigated the extent to which malaria acts as a risk factor for all-cause mortality in African children less than five years of age from 1) ecologic associations between Plasmodium falciparum infection prevalence (PR) and under-five mortality, and 2) reductions in all-cause under-five mortality achieved in malaria intervention trials. Across 48 demographic surveillance studies, when adjusted for secular trends, PR more than doubled all-cause mortality (P = 0.0001). Trials of insecticide-treated mosquito nets generally found smaller population-attributable fractions of pediatric mortality to malaria infection, which may relate to their imperfect coverage and efficacy. In conclusion, the disability and death burden due to malaria in African children could be higher than that detectable from cause-specific DALY estimations., (Copyright 2004 The American Society of Tropical Medicine and Hygiene)