The effect of alpha(+)-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya

BACKGROUND: The alpha-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between alpha-thalassaemia, malaria, and other common causes of child mortality remains incomplete. METHODS AND FINDINGS: We studied the alpha+-thalassaemia-specific incidence of malaria and other common childhood diseases in two cohorts of children living on the coast of Kenya. We found no associations between alpha+-thalassaemia and the prevalence of symptomless Plasmodium falciparum parasitaemia, the incidence of uncomplicated P. falciparum disease, or parasite densities during mild or severe malaria episodes. However, we found significant negative associations between alpha+-thalassaemia and the incidence rates of severe malaria and severe anaemia (haemoglobin concentration < 50 g/l). The strongest associations were for severe malaria anaemia (> 10,000 P. falciparum parasites/mul) and severe nonmalaria anaemia; the incidence rate ratios and 95% confidence intervals (CIs) for alpha+-thalassaemia heterozygotes and homozygotes combined compared to normal children were, for severe malaria anaemia, 0.33 (95% CI, 0.15,0.73; p = 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p = 0.015). CONCLUSIONS: Our observations suggest, first that selection for alpha+-thalassaemia might be mediated by a specific effect against severe anaemia, an observation that may lead to fresh insights into the aetiology of this important condition. Second, although alpha+-thalassaemia is strongly protective against severe and fatal malaria, its effects are not detectable at the level of any other malaria outcome; this result provides a cautionary example for studies aimed at testing malaria interventions or identifying new malaria-protective genes

Ensuring sustained ACT production and reliable artemisinin supply

<p>Abstract</p> <p>Introduction</p> <p>This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal). Stability data are derived from a development project on rectal artesunate.</p> <p>Discussion</p> <p>The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than$1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar.</p> <p>A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250–300 per kg.</p> <p>Conclusion</p> <p>Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of <it>A. annua </it>and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened.</p> <p>While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would permanently discredit it and impede any progress in rolling malaria back.</p

The Use of Mosquito Nets and the Prevalence of Plasmodium falciparum Infection in Rural South Central Somalia

BACKGROUND: There have been resurgent efforts in Africa to estimate the public health impact of malaria control interventions such as insecticide treated nets (ITNs) following substantial investments in scaling-up coverage in the last five years. Little is known, however, on the effectiveness of ITN in areas of Africa that support low transmission. This hinders the accurate estimation of impact of ITN use on disease burden and its cost-effectiveness in low transmission settings. METHODS AND PRINCIPAL FINDINGS: Using a stratified two-stage cluster sample design, four cross-sectional studies were undertaken between March-June 2007 across three livelihood groups in an area of low intensity malaria transmission in South Central Somalia. Information on bed net use; age; and sex of all participants were recorded. A finger prick blood sample was taken from participants to examine for parasitaemia. Mantel-Haenzel methods were used to measure the effect of net use on parasitaemia adjusting for livelihood; age; and sex. A total of 10,587 individuals of all ages were seen of which 10,359 provided full information. Overall net use and parasite prevalence were 12.4% and 15.7% respectively. Age-specific protective effectiveness (PE) of bed net ranged from 39% among <5 years to 72% among 5-14 years old. Overall PE of bed nets was 54% (95% confidence interval 44%-63%) after adjusting for livelihood; sex; and age. CONCLUSIONS AND SIGNIFICANCE: Bed nets confer high protection against parasite infection in South Central Somalia. In such areas where baseline transmission is low, however, the absolute reductions in parasitaemia due to wide-scale net use will be relatively small raising questions on the cost-effectiveness of covering millions of people living in such settings in Africa with nets. Further understanding of the progress of disease upon infection against the cost of averting its consequent burden in low transmission areas of Africa is therefore required

Allocating Scarce Resources Strategically - An Evaluation and Discussion of the Global Fund's Pattern of Disbursements

BACKGROUND: The Global Fund is under pressure to improve its rationing of financial support. This study describes the GF's pattern of disbursements in relation to total health expenditure (THE), government health expenditure (GHE), income status and the burden of HIV/AIDS, TB and malaria. It also examines the potential for recipient countries to increase domestic public financing for health. METHODS: This is a cross-sectional study of 104 countries that received Global Fund disbursements in 2009. It analyses data on Global Fund disbursements; health financing indicators; government revenue and expenditure; and burden of disease. FINDINGS: Global Fund disbursements made up 0.37% of THE across all 104 countries; but with considerable country variation ranging from 0.002% to 53.4%. Global Fund disbursements to government amounted to 0.47% of GHE across the 104 countries, but again with considerable variation (in three countries more than half of GHE was based on Global Fund support). Although the Global Fund provides progressively more funding for lower income countries on average, there is much variation at the country such that here was no correlation between per capita GF disbursements and per capita THE, nor between per capita GF disbursement to government and per capita GHE. There was only a slight positive correlation between per capita GF disbursement and burden of disease. Several countries with a high degree of 'financial dependency' upon the Fund have the potential to increase levels of domestic financing for health. DISCUSSION: The Global Fund can improve its targeting of resources so that it better matches the pattern of global need. To do this it needs to: a) reduce the extent to which funds are allocated on a demand-driven basis; and b) align its funding model to broader health systems financing and patterns of health expenditure beyond the three diseases

The First Model-Based Geostatistical Map of Anaemia

Abdisalan Noor discusses new research in <i>PLoS Medicine<I> that used model-based geostatistics to investigate the risks of anemia among preschool-aged children in West Africa that were attributable to malnutrition, malaria, and helminth infections

A case study of transport of tropical marine boundary layer and lower tropospheric air masses to the northern midlatitude upper troposphere

Low-ozone (&lt;20 ppbv) air masses were observed in the upper troposphere in northern midlatitudes over the eastern United States and the North Atlantic Ocean on several occasions in October 1997 during the NASA Subsonic Assessment, Ozone and Nitrogen Oxide Experiment (SONEX) mission. Three cases of low-ozone air masses were shown to have originated in the tropical Pacific marine boundary layer or lower troposphere and advected poleward along a warm conveyor belt during a synoptic-scale disturbance. The tropopause was elevated in the region with the low-ozone air mass. Stratospheric intrusions accompanied the disturbances. On the basis of storm track and stratospheric intrusion climatologies, such events appear to be more frequent from September through March than the rest of the year. Copyright 2000 by the American Geophysical Union

The decline in paediatric malaria admissions on the coast of Kenya

<p>Abstract</p> <p>Background</p> <p>There is only limited information on the health impact of expanded coverage of malaria control and preventative strategies in Africa.</p> <p>Methods</p> <p>Paediatric admission data were assembled over 8.25 years from three District Hospitals; Kilifi, Msambweni and Malindi, situated along the Kenyan Coast. Trends in monthly malaria admissions between January 1999 and March 2007 were analysed using several time-series models that adjusted for monthly non-malaria admission rates and the seasonality and trends in rainfall.</p> <p>Results</p> <p>Since January 1999 paediatric malaria admissions have significantly declined at all hospitals. This trend was observed against a background of rising or constant non-malaria admissions and unaffected by long-term rainfall throughout the surveillance period. By March 2007 the estimated proportional decline in malaria cases was 63% in Kilifi, 53% in Kwale and 28% in Malindi. Time-series models strongly suggest that the observed decline in malaria admissions was a result of malaria-specific control efforts in the hospital catchment areas.</p> <p>Conclusion</p> <p>This study provides evidence of a changing disease burden on the Kenyan coast and that the most parsimonious explanation is an expansion in the coverage of interventions such as the use of insecticide-treated nets and the availability of anti-malarial medicines. While specific attribution to intervention coverage cannot be computed what is clear is that this area of Kenya is experiencing a malaria epidemiological transition.</p

Standardizing estimates of the Plasmodium falciparum parasite rate

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>parasite rate (PfPR) is a commonly reported index of malaria transmission intensity. PfPR rises after birth to a plateau before declining in older children and adults. Studies of populations with different age ranges generally report average PfPR, so age is an important source of heterogeneity in reported PfPR data. This confounds simple comparisons of PfPR surveys conducted at different times or places.</p> <p>Methods</p> <p>Several algorithms for standardizing PfPR were developed using 21 studies that stratify in detail PfPR by age. An additional 121 studies were found that recorded PfPR from the same population over at least two different age ranges; these paired estimates were used to evaluate these algorithms. The best algorithm was judged to be the one that described most of the variance when converting the PfPR pairs from one age-range to another.</p> <p>Results</p> <p>The analysis suggests that the relationship between PfPR and age is predictable across the observed range of malaria endemicity. PfPR reaches a peak after about two years and remains fairly constant in older children until age ten before declining throughout adolescence and adulthood. The PfPR pairs were poorly correlated; using one to predict the other would explain only 5% of the total variance. By contrast, the PfPR predicted by the best algorithm explained 72% of the variance.</p> <p>Conclusion</p> <p>The PfPR in older children is useful for standardization because it has good biological, epidemiological and statistical properties. It is also historically consistent with the classical categories of hypoendemic, mesoendemic and hyperendemic malaria. This algorithm provides a reliable method for standardizing PfPR for the purposes of comparing studies and mapping malaria endemicity. The scripts for doing so are freely available to all.</p

Antimalarial Drug Quality in the Most Severely Malarious Parts of Africa – A Six Country Study

A range of antimalarial drugs were procured from private pharmacies in urban and peri-urban areas in the major cities of six African countries, situated in the part of that continent and the world that is most highly endemic for malaria. Semi-quantitative thin-layer chromatography (TLC) and dissolution testing were used to measure active pharmaceutical ingredient content against internationally acceptable standards. 35% of all samples tested failed either or both tests, and were substandard. Further, 33% of treatments collected were artemisinin monotherapies, most of which (78%) were manufactured in disobservance of an appeal by the World Health Organisation (WHO) to withdraw these clinically inappropriate medicines from the market. The high persistence of substandard drugs and clinically inappropriate artemisinin monotherapies in the private sector risks patient safety and, through drug resistance, places the future of malaria treatment at risk globally