Thomas P. Eisele

Global, regional, and national causes of child mortality in 2008: a systematic analysis

BACKGROUND Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in children younger than 5 years. METHODS We used multicause proportionate mortality models to estimate deaths in neonates aged 0-27 days and children aged 1-59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world. FINDINGS Of the estimated 8.795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5.970 million), with the largest percentages due to pneumonia (18%, 1.575 million, uncertainty range [UR] 1.046 million-1.874 million), diarrhoea (15%, 1.336 million, 0.822 million-2.004 million), and malaria (8%, 0.732 million, 0.601 million-0.851 million). 41% (3.575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1.033 million, UR 0.717 million-1.216 million), birth asphyxia (9%, 0.814 million, 0.563 million-0.997 million), sepsis (6%, 0.521 million, 0.356 million-0.735 million), and pneumonia (4%, 0.386 million, 0.264 million-0.545 million). 49% (4.294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China. INTERPRETATION These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions. FUNDING WHO, UNICEF, and Bill & Melinda Gates Foundation.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542–753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea pneumonia and malaria.

BackgroundZinc 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 methodsA 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.ResultsThe 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)ConclusionZinc supplementation results in reductions in diarrhea and pneumonia mortality.

Protective efficacy of interventions for preventing malaria mortality in children in Plasmodium falciparum endemic areas

Background Insecticide-treated mosquito nets (ITNs) and indoor-residual spraying (IRS) are recommended strategies for preventing malaria in children. While their impact on all-cause child mortality is well documented, their impact on reducing malaria-attributable mortality has not been quantified. While the impact of intermittent preventive therapy in pregnant women (IPTp) and ITNs in pregnancy for improving birth outcomes is also well established, their impact on preventing neonatal or child mortality has not been quantified. Methods We performed two systematic literature reviews in Plasmodium falciparum endemic settings; one to estimate the effect of ITNs and IRS on preventing malaria-attributable mortality in children 1–59 months, and another to estimate the effect of ITNs and IPTp on preventing neonatal and child mortality through improvements in birth outcomes. Results We estimate the protective efficacy (PE) of ITNs and IRS on reducing malaria-attributable mortality 1–59 months to be 55%, with a range of 49–61%, in P. falciparum settings. We estimate malaria prevention interventions in pregnancy (IPTp and ITNs) to have a pooled PE of 35% (95% confidence interval: 23–45%) on reducing the prevalence of low birth weight (LBW) in the first or second pregnancy in areas of stable P. falciparum transmission. Conclusion This systematic review quantifies the PE of ITNs for reducing malaria-attributable mortality in children, and the PE of IPTp and ITNs during pregnancy for reducing LBW. It is assumed the impact of IRS is equal to that of ITNs on reducing malaria-attributable mortality in children. These data will be used in the Lives Saved Tool (LiST) model for estimating the impact of malaria prevention interventions. These data support the continued scale-up of these malaria prevention interventions in endemic settings that will prevent a considerable number of child deaths due directly and indirectly to malaria.

Malaria prevention in pregnancy, birthweight, and neonatal mortality: a meta-analysis of 32 national cross-sectional datasets in Africa

BACKGROUND Low birthweight is a significant risk factor for neonatal and infant death. A prominent cause of low birthweight is infection with Plasmodium falciparum during pregnancy. Antimalarial intermittent preventive therapy in pregnancy (IPTp) and insecticide-treated mosquito nets (ITNs) significantly reduce the risk of low birthweight in regions of stable malaria transmission. We aimed to assess the effectiveness of malaria prevention in pregnancy (IPTp or ITNs) at preventing low birthweight and neonatal mortality under routine programme conditions in malaria endemic countries of Africa. METHODS We used a retrospective birth cohort from national cross-sectional datasets in 25 African countries from 2000-10. We used all available datasets from multiple indicator cluster surveys, demographic and health surveys, malaria indicator surveys, and AIDS indicator surveys that were publically available as of 2011. We tried to limit confounding bias through exact matching on potential confounding factors associated with both exposure to malaria prevention (ITNs or IPTp with sulfadoxine-pyrimethamine) in pregnancy and birth outcomes, including local malaria transmission, neonatal tetanus vaccination, maternal age and education, and household wealth. We used a logistic regression model to test for associations between malaria prevention in pregnancy and low birthweight, and a Poisson model for the outcome of neonatal mortality. Both models incorporated the matched strata as a random effect, while accounting for additional potential confounding factors with fixed effect covariates. FINDINGS We analysed 32 national cross-sectional datasets. Exposure of women in their first or second pregnancy to full malaria prevention with IPTp or ITNs was significantly associated with decreased risk of neonatal mortality (protective efficacy [PE] 18%, 95% CI 4-30; incidence rate ratio [IRR] 0·820, 95% CI 0·698-0·962), compared with newborn babies of mothers with no protection, after exact matching and controlling for potential confounding factors. Compared with women with no protection, exposure of pregnant women during their first two pregnancies to full malaria prevention in pregnancy through IPTp or ITNs was significantly associated with reduced odds of low birthweight (PE 21%, 14-27; IRR 0·792, 0·732-0·857), as measured by a combination of weight and birth size perceived by the mother, after exact matching and controlling for potential confounding factors. INTERPRETATION Malaria prevention in pregnancy is associated with substantial reductions in neonatal mortality and low birthweight under routine malaria control programme conditions. Malaria control programmes should strive to achieve full protection in pregnant women by both IPTp and ITNs to maximise their benefits. Despite an attempt to mitigate bias and potential confounding by matching women on factors thought to be associated with access to malaria prevention in pregnancy and birth outcomes, some level of confounding bias possibly remains.

Estimates of child deaths prevented from malaria prevention scale-up in Africa 2001-2010

BackgroundFunding from external agencies for malaria control in Africa has increased dramatically over the past decade resulting in substantial increases in population coverage by effective malaria prevention interventions. This unprecedented effort to scale-up malaria interventions is likely improving child survival and will likely contribute to meeting Millennium Development Goal (MDG) 4 to reduce the < 5 mortality rate by two thirds between 1990 and 2015.MethodsThe Lives Saved Tool (LiST) model was used to quantify the likely impact that malaria prevention intervention scale-up has had on malaria mortality over the past decade (2001-2010) across 43 malaria endemic countries in sub-Saharan African. The likely impact of ITNs and malaria prevention interventions in pregnancy (intermittent preventive treatment [IPTp] and ITNs used during pregnancy) over this period was assessed.ResultsThe LiST model conservatively estimates that malaria prevention intervention scale-up over the past decade has prevented 842,800 (uncertainty: 562,800-1,364,645) child deaths due to malaria across 43 malaria-endemic countries in Africa, compared to a baseline of the year 2000. Over the entire decade, this represents an 8.2% decrease in the number of malaria-caused child deaths that would have occurred over this period had malaria prevention coverage remained unchanged since 2000. The biggest impact occurred in 2010 with a 24.4% decrease in malaria-caused child deaths compared to what would have happened had malaria prevention interventions not been scaled-up beyond 2000 coverage levels. ITNs accounted for 99% of the lives saved.ConclusionsThe results suggest that funding for malaria prevention in Africa over the past decade has had a substantial impact on decreasing child deaths due to malaria. Rapidly achieving and then maintaining universal coverage of these interventions should be an urgent priority for malaria control programmes in the future. Successful scale-up in many African countries will likely contribute substantially to meeting MDG 4, as well as succeed in meeting MDG 6 (Target 1) to halt and reverse malaria incidence by 2015.

Rolling out insecticide treated nets in Eritrea: examining the determinants of possession and use in malarious zones during the rainy season.

Objective  This paper describes determinants of insecticide treated net (ITN) ownership and use in malarious areas of Eritrea. With ITN distribution and re‐treatment now free for all living in these areas, we examine barriers (other than cost) to access and use of ITNs. We explore the differences between use of an ITN as a proportion of all households in the survey (the roll back malaria indicator), and use of an ITN as a proportion of those households who already own an ITN.

Coverage of intermittent preventive treatment and insecticide-treated nets for the control of malaria during pregnancy in sub-Saharan Africa: a synthesis and meta-analysis of national survey data 2009-11.

BACKGROUND Pregnant women in malaria-endemic countries in sub-Saharan Africa are especially vulnerable to malaria. Recommended prevention strategies include intermittent preventive treatment with two doses of sulfadoxine-pyrimethamine and the use of insecticide-treated nets. However, progress with implementation has been slow and the Roll Back Malaria Partnership target of 80% coverage of both interventions by 2010 has not been met. We aimed to review the coverage of intermittent preventive treatment, insecticide-treated nets, and antenatal care for pregnant women in sub-Saharan Africa and to explore associations between coverage and individual and country-level factors, including the role of funding for malaria prevention. METHODS We used data from nationally representative household surveys from 2009-11 to estimate coverage of intermittent preventive treatment, use of insecticide-treated nets, and attendance at antenatal clinics by pregnant women in sub-Saharan Africa. Using demographic data for births and published data for malaria exposure, we also estimated the number of malaria-exposed births (livebirths and stillbirths combined) for 2010 by country. We used meta-regression analysis to investigate the factors associated with coverage of intermittent preventive treatment and use of insecticide-treated nets. RESULTS Of the 21·4 million estimated malaria-exposed births across 27 countries in 2010, an estimated 4·6 million (21·5%, 95% CI 19·3-23·7) were born to mothers who received intermittent preventive treatment. Insecticide-treated nets were used during pregnancy for 10·5 million of 26·9 million births across 37 countries (38·8%, 34·6-43·0). Antenatal care was attended at least once by 16·3 of 20·8 million women in 2010 (78·3%, 75·2-81·4; n=26 countries) and at least twice by 14·7 of 19·6 million women (75·1%, 72·9-77·3; n=22 countries). For the countries with previous estimates for 2007, coverage of intermittent preventive treatment increased from 13·1% (11·9-14·3) to 21·2% (18·9-23·5; n=14 countries) and use of insecticide-treated nets increased from 17·9% (15·1-20·7) to 41·6% (37·2-46·0; n=24 countries) in 2010. A fall in coverage by more than 10% was seen in two of 24 countries for intermittent preventive treatment and in three of 30 countries for insecticide-treated nets. High disbursement of funds for malaria control and a long time interval since adoption of the relevant policy were associated with the highest coverage of intermittent preventive treatment. High disbursement of funds for malaria control and high total fertility rate were associated with the greatest use of insecticide-treated nets, whereas a high per-head gross domestic product (GDP) was associated with less use of nets than was a lower GDP. Coverage of intermittent preventive treatment showed greater inequity overall than use of insecticide-treated nets, with richer, educated, and urban women more likely to receive preventive treatment than their poorer, uneducated, rural counterparts. INTERPRETATION Although coverage of intermittent preventive treatment and use of insecticide-treated nets by pregnant women has increased in most countries, coverage remains far below international targets, despite fairly high rates of attendance at antenatal clinics. The effect of the implementation of WHOs 2012 policy update for intermittent preventive treatment, which aims to simplify the message and align preventive treatment with the focused antenatal care schedule, should be assessed to find out whether it leads to improvements in coverage. FUNDING Bill & Melinda Gates Foundation.

Household Possession and Use of Insecticide-Treated Mosquito Nets in Sierra Leone 6 Months after a National Mass-Distribution Campaign

Background In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. Methods We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. Results The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥1∶2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. Conclusions The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.

Protective efficacy of malaria case management for preventing malaria mortality in children: a systematic review for the Lives Saved Tool

BackgroundThe 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.MethodsWe 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.ResultsBased 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.ConclusionsThis 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 <5. These data will be used in the Lives Saved Tool (LiST) model for estimating the impact of scaling-up these interventions against malaria. However, in order to estimate the reduction in child mortality due to scale-up of these interventions, it is imperative to develop standardized indicators to measure population coverage of these interventions.