Optimal dose finding for novel antimalarial combination therapy*

A recent discussion meeting convened by the Medicines for Malaria Venture examined how best to manage the discovery and preclinical pipeline to achieve novel combination therapies which would address the key clinical needs in malaria. It became clear that dose optimisation of components within combination therapy was a key issue in achieving antimalarial efficacy and for preserving that efficacy against parasite resistance emergence. This paper outlines some of the specific issues in malaria that cause dose-ranging and dose-optimisation studies to be particularly challenging and discusses the potential of factorial study design to address such challenges

Nets, Spray or Both? The Effectiveness of Insecticide-Treated Nets and Indoor Residual Spraying in Reducing Malaria Morbidity and Child Mortality in sub-Saharan Africa.

Malaria control programmes currently face the challenge of maintaining, as well as accelerating, the progress made against malaria with fewer resources and uncertain funding. There is a critical need to determine what combination of malaria interventions confers the greatest protection against malaria morbidity and child mortality under routine conditions. This study assesses intervention effectiveness experienced by children under the age of five exposed to both insecticide-treated nets (ITNs) and indoor residual spraying (IRS), as compared to each intervention alone, based on nationally representative survey data collected from 17 countries in sub-Saharan Africa. Living in households with both ITNs and IRS was associated with a significant risk reduction against parasitaemia in medium and high transmission areas, 53% (95% CI 37% to 67%) and 31% (95% CI 11% to 47%) respectively. For medium transmission areas, an additional 36% (95% CI 7% to 53%) protection was garnered by having both interventions compared with exposure to only ITNs or only IRS. Having both ITNs and IRS was not significantly more protective against parasitaemia than either intervention alone in low and high malaria transmission areas. In rural and urban areas, exposure to both interventions provided significant protection against parasitaemia, 57% (95% CI 48% to 65%) and 39% (95% CI 10% to 61%) respectively; however, this effect was not significantly greater than having a singular intervention. Statistically, risk for all-cause child mortality was not significantly reduced by having both ITNs and IRS, and no additional protectiveness was detected for having dual intervention coverage over a singular intervention. These findings suggest that greater reductions in malaria morbidity and health gains for children may be achieved with ITNs and IRS combined beyond the protection offered by IRS or ITNs alone

Equity in health and healthcare in Malawi: analysis of trends

<p>Abstract</p> <p>Background</p> <p>Growing scientific evidence points to the pervasiveness of inequities in health and health care and the persistence of the <it>inverse care law</it>, that is the availability of good quality healthcare seems to be inversely related to the need for it in developing countries. Achievement of the Millennium Development Goals is likely to be compromised if inequities in health/healthcare are not properly addressed.</p> <p>Objective</p> <p>This study attempts to assess trends in inequities in selected indicators of health status and health service utilization in Malawi using data from the Demographic and Health Surveys of 1992, 2000 and 2004.</p> <p>Methods</p> <p>Data from Demographic and Health Surveys of 1992, 2000 and 2004 are analysed for inequities in health/healthcare using quintile ratios and concentration curves/indices.</p> <p>Results</p> <p>Overall, the findings indicate that in most of the selected indicators there are pro-rich inequities and that they have been widening during the period under consideration. Furthermore, vertical inequities are observed in the use of interventions (treatment of diarrhoea, ARI among under-five children), in that the non-poor who experience less burden from these diseases receive more of the treatment/interventions, whereas the poor who have a greater proportion of the disease burden use less of the interventions. It is also observed that the publicly provided services for some of the selected interventions (e.g. child delivery) benefit the non-poor more than the poor.</p> <p>Conclusion</p> <p>The widening trend in inequities, in particular healthcare utilization for proven cost-effective interventions is likely to jeopardize the achievement of the Millennium Development Goals and other national and regional targets. To counteract the inequities it is recommended that coverage in poor communities be increased through appropriate targeting mechanisms and effective service delivery strategies. There is also a need for studies to identify which service delivery mechanisms are effective in the Malawian context.</p

Bed net ownership, use and perceptions among women seeking antenatal care in Kinshasa, Democratic Republic of the Congo (DRC): Opportunities for improved maternal and child health

Abstract: Background: To describe malaria knowledge, attitudes toward malaria and bed net use, levels of ownership and use of bed nets, and factors associated with ownership and use among pregnant women attending their first antenatal care (ANC) visit in Kinshasa, DRC. Methods: Women attending their first ANC visit at one maternity in Kinshasa were recruited to take part in a study where they were given free insecticide treated bed nets (ITNs) and then followed up at delivery and 6 months post delivery to assess ITN use. This study describes the baseline levels of bed net ownership and use, attitudes towards net use and factors associated with net use Results: Among 351 women interviewed at baseline, 115 (33%) already owned a bed net and 86 (25%) reported to have slept under the net the previous night. Cost was reported as the reason for not owning a net by 48% of the 236 women who did not own one. In multivariable analyses, women who had secondary school or higher education were 3.4 times more likely to own a net (95% CI 1.6–7.3) and 2.8 times more likely to have used a net (95% CI 1.3–6.0) compared to women with less education Conclusion: Distribution of ITNs in antenatal clinics in this setting is needed and feasible. The potential for ITN use by this target population is high

Reductions in malaria and anaemia case and death burden at hospitals following scale-up of malaria control in Zanzibar, 1999-2008

Background: In Zanzibar, the Ministry of Health and partners accelerated malaria control from September 2003 onwards. The impact of the scale-up of insecticide-treated nets (ITN), indoor-residual spraying (IRS) and artemisinin-combination therapy (ACT) combined on malaria burden was assessed at six out of seven in-patient health facilities. Methods. Numbers of outpatient and inpatient cases and deaths were compared between 2008 and the pre-intervention period 1999-2003. Reductions were estimated by segmented log-linear regression, adjusting the effect size for time trends during the pre-intervention period. Results: In 2008, for all age groups combined, malaria deaths had fallen by an estimated 90% (95% confidence interval 55-98%)(p < 0.025), malaria in-patient cases by 78% (48-90%), and parasitologically- confirmed malaria out-patient cases by 99.5% (92-99.9%). Anaemia in-patient cases decreased by 87% (57-96%); anaemia deaths and out-patient cases declined without reaching statistical significance due to small numbers. Reductions were similar for children under-five and older ages. Among under-fives, the proportion of all-cause deaths due to malaria fell from 46% in 1999-2003 to 12% in 2008 (p < 0.01) and that for anaemia from 26% to 4% (p < 0.01). Cases and deaths due to other causes fluctuated or increased over 1999-2008, without consistent difference in the trend before and after 2003. Conclusions: Scaling-up effective malaria interventions reduced malaria-related burden at health facilities by over 75% within 5 years. In high-malaria settings, intensified malaria control can substantially contribute to reaching the Millennium Development Goal 4 target of reducing under-five mortality by two-thirds between 1990 and 2015

The use of insecticide treated nets by age: implications for universal coverage in Africa

BACKGROUND: The scaling of malaria control to achieve universal coverage requires a better understanding of the population sub-groups that are least protected and provide barriers to interrupted transmission. Here we examine the age pattern of use of insecticide treated nets (ITNs) in Africa in relation to biological vulnerabilities and the implications for future prospects for universal coverage. METHODS: Recent national household survey data for 18 malaria endemic countries in Africa were assembled to identify information on use of ITNs by age and sex. Age-structured medium variant projected population estimates for the mid-point year of the earliest and most recent national surveys were derived to compute the population by age protected by ITNs. RESULTS: All surveys were undertaken between 2005 and 2009, either as demographic health surveys (n = 12) or malaria indicator surveys (n = 6). Countries were categorized into three ITN use groups: or =20% and projected population estimates for the mid-point year of 2007 were computed. In general, the pattern of overall ITNs use with age was similar by country and across the three country groups with ITNs use initially high among children <5 years of age, sharply declining among the population aged 5-19 years, before rising again across the ages 20-44 years and finally decreasing gradually in older ages. For all groups of countries, the highest proportion of the population not protected by ITNs (38% - 42%) was among those aged 5-19 years. CONCLUSION: In malaria-endemic Africa, school-aged children are the least protected with ITNs but represent the greatest reservoir of infections. With increasing school enrollment rates, school-delivery of ITNs should be considered as an approach to reach universal ITNs coverage and improve the likelihood of impacting upon parasite transmission