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

<p>Abstract</p> <p>Background</p> <p>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 <it>Plasmodium falciparum</it> 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.</p> <p>Methods</p> <p>We performed systematic literature reviews of published studies in <it>P. falciparum</it> 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.</p> <p>Results</p> <p>Based on multiple data sources, we estimate the PE of ACT treatment of uncomplicated <it>P. falciparum</it> 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 <it>P. falciparum</it> 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.</p> <p>Conclusions</p> <p>This systematic review quantifies the PE of ACT used for treating uncomplicated malaria and effective case management including parenteral quinine for treating severe <it>P. falciparum</it> 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.</p

Is the Scale Up of Malaria Intervention Coverage Also Achieving Equity?

Malaria in Africa is most severe in young children and pregnant women, particularly in rural and poor households. In many countries, malaria intervention coverage rates have increased as a result of scale up; but this may mask limited coverage in these highest-risk populations. Reports were reviewed from nationally representative surveys in African malaria-endemic countries from 2006 through 2008 to understand how reported intervention coverage rates reflect access by the most at-risk populations.Reports were available from 27 Demographic and Health Surveys (DHSs), Multiple Indicator Cluster Surveys (MICSs), and Malaria Indicator Surveys (MISs) during this interval with data on household intervention coverage by urban or rural setting, wealth quintile, and sex. Household ownership of insecticide-treated mosquito nets (ITNs) varied from 5% to greater than 60%, and was equitable by urban/rural and wealth quintile status among 13 (52%) of 25 countries. Malaria treatment rates for febrile children under five years of age varied from less than 10% to greater than 70%, and while equitable coverage was achieved in 8 (30%) of 27 countries, rates were generally higher in urban and richest quintile households. Use of intermittent preventive treatment in pregnant women varied from 2% to more than 60%, and again tended to be higher in urban and richest quintile households. Across all countries, there were no significant male/female inequalities seen for children sleeping under ITNs or receiving antimalarial treatment for febrile illness. Parasitemia and anemia rates from eight national surveys showed predominance in poor and rural populations.Recent efforts to scale up malaria intervention coverage have achieved equity in some countries (especially with ITNs), but delivery methods in other countries are not addressing the most at-risk populations. As countries seek universal malaria intervention coverage, their delivery systems must reach the rural and poor populations; this is not a small task, but it has been achieved in some countries

Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa

OBJECTIVE To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS All methods require a plausibility argument - i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added

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

Funding 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.\ud The 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. The 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. The 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

Caution is required when using health facility-based data to evaluate the health impact of malaria control efforts in Africa

The global health community is interested in the health impact of the billions of dollars invested to fight malaria in Africa. A recent publication used trends in malaria cases and deaths based on health facility records to evaluate the impact of malaria control efforts in Rwanda and Ethiopia. Although the authors demonstrate the use of facility-based data to estimate the impact of malaria control efforts, they also illustrate several pitfalls of such analyses that should be avoided, minimized, or actively acknowledged. A critique of this analysis is presented because many country programmes and donors are interested in evaluating programmatic impact with facility-based data. Key concerns related to: 1) clarifying the objective of the analysis; 2) data validity; 3) data representativeness; 4) the exploration of trends in factors that could influence malaria rates and thus confound the relationship between intervention scale-up and the observed changes in malaria outcomes; 5) the analytic approaches, including small numbers of patient outcomes, selective reporting of results, and choice of statistical and modeling methods; and 6) internal inconsistency on the strength and interpretation of the data. In conclusion, evaluations of malaria burden reduction using facility-based data could be very helpful, but those data should be collected, analysed, and interpreted with care, transparency, and a full recognition of their limitations

Malaria indicator survey 2007, Ethiopia: coverage and use of major malaria prevention and control interventions

<p>Abstract</p> <p>Background</p> <p>In 2005, a nationwide survey estimated that 6.5% of households in Ethiopia owned an insecticide-treated net (ITN), 17% of households had been sprayed with insecticide, and 4% of children under five years of age with a fever were taking an anti-malarial drug. Similar to other sub-Saharan African countries scaling-up malaria interventions, the Government of Ethiopia set an ambitious national goal in 2005 to (i) provide 100% ITN coverage in malarious areas, with a mean of two ITNs per household; (ii) to scale-up indoor residual spraying of households with insecticide (IRS) to cover 30% of households targeted for IRS; and (iii) scale-up the provision of case management with rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT), particularly at the peripheral level.</p> <p>Methods</p> <p>A nationally representative malaria indicator survey (MIS) was conducted in Ethiopia between September and December 2007 to determine parasite and anaemia prevalence in the population at risk and to assess coverage, use and access to scaled-up malaria prevention and control interventions. The survey used a two-stage random cluster sample of 7,621 households in 319 census enumeration areas. A total of 32,380 people participated in the survey. Data was collected using standardized Roll Back Malaria Monitoring and Evaluation Reference Group MIS household and women's questionnaires, which were adapted to the local context.</p> <p>Results</p> <p>Data presented is for households in malarious areas, which according to the Ethiopian Federal Ministry of Health are defined as being located <2,000 m altitude. Of 5,083 surveyed households, 3,282 (65.6%) owned at least one ITN. In ITN-owning households, 53.2% of all persons had slept under an ITN the prior night, including 1,564/2,496 (60.1%) children <5 years of age, 1,891/3,009 (60.9%) of women 15 - 49 years of age, and 166/266 (65.7%) of pregnant women. Overall, 906 (20.0%) households reported to have had IRS in the past 12 months. Of 747 children with reported fever in the two weeks preceding the survey, 131 (16.3%) sought medical attention within 24 hours. Of those with fever, 86 (11.9%) took an anti-malarial drug and 41 (4.7%) took it within 24 hours of fever onset. Among 7,167 surveyed individuals of all ages, parasitaemia as estimated by microscopy was 1.0% (95% CI 0.5 - 1.5), with 0.7% and 0.3% due to <it>Plasmodium falciparum </it>and <it>Plasmodium vivax</it>, respectively. Moderate-severe anaemia (haemoglobin <8 g/dl) was observed in 239/3,366 (6.6%, 95% CI 4.9-8.3) children <5 years of age.</p> <p>Conclusions</p> <p>Since mid-2005, the Ethiopian National Malaria Control Programme has considerably scaled-up its malaria prevention and control interventions, demonstrating the impact of strong political will and a committed partnership. The MIS showed, however, that besides sustaining and expanding malaria intervention coverage, efforts will have to be made to increase intervention access and use. With ongoing efforts to sustain and expand malaria intervention coverage, to increase intervention access and use, and with strong involvement of the community, Ethiopia expects to achieve its targets in terms of coverage and uptake of interventions in the coming years and move towards eliminating malaria.</p

The relative contribution of climate variability and vector control coverage to changes in malaria parasite prevalence in Zambia 2006-2012

BACKGROUND: Four malaria indicator surveys (MIS) were conducted in Zambia between 2006 and 2012 to evaluate malaria control scale-up. Nationally, coverage of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) increased over this period, while parasite prevalence in children 1-59 months decreased dramatically between 2006 and 2008, but then increased from 2008 to 2010. We assessed the relative effects of vector control coverage and climate variability on malaria parasite prevalence over this period. METHODS: Nationally-representative MISs were conducted in April-June of 2006, 2008, 2010 and 2012 to collect household-level information on malaria control interventions such as IRS, ITN ownership and use, and child parasite prevalence by microscopic examination of blood smears. We fitted Bayesian geostatistical models to assess the association between IRS and ITN coverage and climate variability and malaria parasite prevalence. We created predictions of the spatial distribution of malaria prevalence at each time point and compared results of varying IRS, ITN, and climate inputs to assess their relative contributions to changes in prevalence. RESULTS: Nationally, the proportion of households owning an ITN increased from 37.8 % in 2006 to 64.3 % in 2010 and 68.1 % in 2012, with substantial heterogeneity sub-nationally. The population-adjusted predicted child malaria parasite prevalence decreased from 19.6 % in 2006 to 10.4 % in 2008, but rose to 15.3 % in 2010 and 13.5 % in 2012. We estimated that the majority of this prevalence increase at the national level between 2008 and 2010 was due to climate effects on transmission, although there was substantial heterogeneity at the provincial level in the relative contribution of changing climate and ITN availability. We predict that if climate factors preceding the 2010 survey were the same as in 2008, the population-adjusted prevalence would have fallen to 9.9 % nationally. CONCLUSIONS: These results suggest that a combination of climate factors and reduced intervention coverage in parts of the country contributed to both the reduction and rebound in malaria parasite prevalence. Unusual rainfall patterns, perhaps related to moderate El Niño conditions, may have contributed to this variation. Zambia has demonstrated considerable success in scaling up vector control. This analysis highlights the importance of accounting for climate variability when using cross-sectional data for evaluation of malaria control efforts

Scaling Up Malaria Control in Zambia: Progress and Impact 2005–2008

Zambia national survey, administrative, health facility, and special study data were used to assess progress and impact in national malaria control between 2000 and 2008. Zambia malaria financial support expanded from US$9 million in 2003 to US$ ~40 million in 2008. High malaria prevention coverage was achieved and extended to poor and rural areas. Increasing coverage was consistent in time and location with reductions in child (age 6–59 months) parasitemia and severe anemia (53% and 68% reductions, respectively, from 2006 to 2008) and with lower post-neonatal infant and 1–4 years of age child mortality (38% and 36% reductions between 2001/2 and 2007 survey estimates). Zambia has dramatically reduced malaria transmission, disease, and child mortality burden through rapid national scale-up of effective interventions. Sustained progress toward malaria elimination will require maintaining high prevention coverage and further reducing transmission by actively searching for and treating infected people who harbor malaria parasites