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Research Summaries

Summaries of some of the applied research activities resulting from the GMP are provided below.

 


Clinical Studies

Investigations of the pathogenesis and pathology focussed on the predictors of fatal malaria, and the multiple causes of anaemia in children. Wide ranging studies on malaria in pregnancy covered causes of intra-uterine growth retardation, adverse pregnancy outcomes, and risk factors for post-natal infant mortality.

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Diagnosis

Research programmes focussed on over-diagnosis and over-treatment of malaria, the benefits of using rapid diagnostic tests, the training needed to facilitate their best use, and the application of serology for monitoring trends in endemicity.


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Epidemiology

Modelling or prediction of epidemic risk needed to be based on temporal variations in weather, other eco-epidemiological variations and variants such as immune status. Detailed investigations of the requirements for early warning systems were made. Co-infections with malaria and helminths were investigated in particular as an enhanced risk of anaemia.

Systematic reviews of changes in malaria morbidity and mortality were made, in particular in relation to countries showing decreases in malaria burden in recent years and associated with a shift in age prevalence and occurrence of asymptomatic infections.


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Treatment and Chemoprevention

Investigations into the changeover to ACTs for treatment of malaria were concerned with their effectiveness, home-based and health facility access, pre-referral administration of artesunate and the public health problems of sub-standard drugs.

The origins and evolution of drug resistant parasites were detailed.

Intermittent Preventive Treatment of children (IPTc) -now called Seasonal Malaria Chemoprevention (SMC)- has been shown to be a highly effective intervention in areas of seasonal malaria transmission.


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Social, Economic and Health Access Studies

The pros and cons of different methods of distribution of Insecticide Treated Nets (ITNs), particularly to the poorest/rural communities were compared. Intermittent Preventive Treatment in pregnancy (IPTp) is an established intervention but the benefits of treatment and the economic impact of malaria in pregnancy are still not well established. Detailed studies were made on the cost effectiveness of IPT in infants.

Access to health provision revealed that equity is a priority in the design and provision of key child survival interventions. Costs to households continue to be a major barrier to treatment and protection.


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Parasite Immunobiology

Studies covered the extensive polymorphism and antigenic variation of asexual stages of P.falciparum, the binding properties of different variants, and their association with severity of disease. A subset of variants that sequester in the placenta were investigated in detail.

Analysis of genomes of gametocytes showed that meiotic recombination was common, and that genomes are in linkage disequilibrium.  The impact of immune responses to gametocyte antigens on transmission was not clear cut; antibodies to gametocyte surface antigens were shown for the first time.


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Vaccination and Immunity

Studies as part of the phase 2 RTS,S malaria vaccine trials showed that protection is not stage specific. Early studies on other candidate vaccines investigated allelic variant specificity and target sequences that correlate with protection. Requirements for vaccination as part of an elimination strategy, and immune responses to asymptomatic infections were studied. More fundamental immunological studies focussed on innate responses, regulatory T cells and immunoglobulin switching.


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Vectors and Vector Control

Effective scale-up and distribution of ITNs and Long Lasting Insecticidal Nets (LLINs) was developed, and the length of time nets remain effective established. Detailed studies on molecular markers of insecticide resistance versus effectiveness did not give consistent results. Alternatives to pyrethroid use for Indoor Residual Spraying (IRS) and ITNs were tested.

Large variations in Entomological Inoculation Rate (EIR) in time and space were shown, and biting habits of some Anopheles species meant ITNs are of limited value if used alone. The benefits of improved house screening were shown.


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