Malaria scientific parallel sessions
Posted by Ilona van den Brink on 23 October 2009 at 17:21
By Lara Pandya
The morning parallel session on malaria involved various presentations spanning the three main treatment research areas of uncomplicated malaria in children, pregnancy associated malaria (PAM), and severe malaria.
The first of these research areas was addressed by Professor Umberto D’Alessandro, from the Institute of Tropical Medicine (ITM) of Antwerp, Belgium, who presented a multi-centre study that had conducted a head-to-head comparison of the safety and efficacy of four available Artemisinin Combination Therapies (ACTs), namely amodiaquine + artesunate (AQ+AS), dihydroartemisinin + piperaquine (DHA+PQ), artemether + lumefantrine (AL) or chlorproguanil-dapsone + artesunate (CDA). Over 4,000 children between the ages of 6-59 months with clinical malaria had been randomised to one of these arms and preliminary results (not yet PCR-corrected data) indicated that 71.4% children had an adequate clinical and parasitological response, 82.5% for DHA+PQ, 67.0% for AL, 71.4% for AQAS and 54.8% for CDA. Full statistical analysis will be conducted in early 2010 with the aim of producing a final report by June 2010. It should be noted that the data for CDA were obtained before CDA was withdrawn from the market for safety reasons.
The randomised trial presented by Dr Badara Cisse, from the University of Dakar, was aimed at providing efficacy and safety data of piperaquine (PQ). Study participants were administered over a 3-day period either dihydroartemisinin in combination with piperaquine (DHA+PQ), or sulfadoxine-pyrimethamine in combination with piperaquine (SP+PQ), or sulfalene-pyrimethamine in combination with amodiaquine (SP+AQ), in order to determine the best combination when used for seasonal Intermittent Preventative Treatment (IPT). 1800 children living in rural Senegal of <5 years were recruited and split across 33 clusters of 40-70 children. The results of the cross-sectional survey at the end of the transmission season indicated that PQ combinations are at least as good as SP+AQ in preventing clinical malaria; overall prevalence is much lower where PQ is a base combination compared to SP+AQ, and SP+PQ and DHA+PQ are better tolerated than SP+AQ. This study provides evidence that seasonal Intermittent Preventative Treatment in children (IPTc) with SP+PQ is highly effective and well tolerated; the combination of two long-acting drugs is optimal for malaria prevention and is most effective in the face of an emergence of resistant parasite genotypes. The study further demonstrates that amendments to age-based dosing have the potential to substantially increase dosing accuracy and improve the tolerability of for IPTc using SP+AQ. More information regarding this study can be found in a recently published article in PLoS One (http://dx.plos.org/10.1371/journal.pone.0007164).
The second of the three main areas of research on malaria was addressed by the third speaker of the day, Dr Patrice Piola of Epicentre, Kampala, Uganda. Pregnancy associated malaria (PAM) is known to be associated with low birth weight, increased maternal anaemia and severe malaria (with a mortality of 50%). Given the little data on efficacy and safety of ACTs in Africa and the known poor tolerance and adherence of quinine (SQ7), this phase IV randomised non-inferiority trial in Mbarara, Uganda, was aimed at comparing efficacy and safety of SQ7 versus AL (Coartem®) in uncomplicated malaria during pregnancy. Of the 304 women recruited for the trial, 152 were enrolled in each arm. 80% of these women were asymptomatic parasite carriers. The results of this study indicate that AL is non inferior to SQ7. Despite high efficacy in SQ7, this trial highlighted the better efficacy and higher tolerability of AL compared to SQ7, although the lumefantrine pharmacokinetic data currently being analysed are important to fully interpret these results. Furthermore, a far larger sample size will be required in order to establish safety before proceeding to a phase IV trial.
Forum participants were also made aware of the Worldwide Antimalarial Resistance Network (WWARN), which is a global collaboration working to ensure that anyone affected by malaria receives effective and safe treatment. This collaboration works towards providing comprehensive, timely and quality-assured information to track the emergence of malarial drug resistance, however, it was highlighted that the success of the network is dependent upon active participation. More information can be found at www.wwarn.com.
A good example of research in the area of severe malaria was provided by the fourth and final speaker of the morning, Dr Kamija Phiri from the College of Medicine in Malawi, whose currently ongoing study in Malawi is looking at an innovative approach in the prevention of rebound severe malaria anaemia and mortality in young children, using Intermittent Preventative Therapy post-discharge (IPT-pd). Ineffective initial treatment, leading to recrudescence, as well as new malaria episodes post-discharge negate initial improvement in haemoglobin and frequently result in rebound severe malaria and ultimately death within the first 6 months. The objective of this 3-centre randomised placebo controlled study is to investigate a means to protect children aged 4-59 months against this post-discharge mortality, particularly during the first 3 months. Owing to extended recruitment to this study, results are not yet available but will be important for informing future policy recommendations.
The afternoon parallel session on Malaria was focused largely on areas of clinical trials and baseline epidemiological studies on malaria vaccine development and building capacity at clinical trial centres in Africa.
Presentations given by Dr Sören Jepsen of the Statens Serum Institute, Dr Saadou Issifou of MRU ASH Gabon, and Dr Sanie Sesay on behalf of Dr Kalifa Bojang of the Medical Research Council (The Gambia), discussed mainly the work done so far in relation to the GMZ2 vaccine candidate (GLURP & MSP3). The Gabonese phase Ib clinical trial presented by Dr Saadou Issifou was intended to assess the safety and immunogenicity of the GMZ2 vaccine in children aged 1-5 years, the results of which confirmed that GMZ2 is safe, this being the confirmation of the safety found in adults in Gabon in a study conducted earlier. GMZ2 was also found to be well tolerated and immunogenic, as also previously demonstrated in the adult study. These findings provide a premise to underscore the need to conduct phase IIb clinical trials to evaluate the safety and efficacy of GMZ2 against P. falciparum malaria. There will also be the need for multi-centre studies to be conducted in different epidemiological set ups for immunogenicity and safety.
Furthermore, as demonstrated in the presentation given by Dr Sanie Sesay, there is a need to undertake a baseline epidemiological study in preparation for a phase IIb clinical trial of GMZ2 candidate malaria vaccine in children aged 12-84 months living in the proposed study site area of The Gambia, amongst other countries. The challenges related to site preparation, such as the need for capacity building, infrastructure upgrade, equipment provision with well planned service maintenance plans and backups, as well as the challenge of retention of staff were also highlighted and were further emphasised in the final presentation given by Sodiomon Sirima of the Centre National de Recherche et de Formation sur le Plaudisme (CNRFP). The need to establish, develop and maintain new clinical trial sites was discussed in light of declining malaria trends at established trial centres. Taking the example of Balonghin in Burkina Faso, it was noted that there was a need to look at issues and challenges of sustainability in relation to heavy equipment and infrastructure, maintenance of equipment, maintenance of the site between activities and the retention of staff. As such, a major recommendation of this session was to ensure that future capacity building is sustainable.
