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Daily report - Thursday 5 November 2009

Source: TropIKA.net editorial team

Dr. Hans Rietveld, director of Global Access & Marketing at the Novartis Malaria Initiative, talked about how Novartis is contributing to the fight against malaria through partnerships. How, Rietveld asked, would the picture of malaria look today without Novartis, maker of Coartem, the most widely prescribed artemisinin combination therapy in the world?

The story of Coartem (Artemether/Lumefantrin), he said, is a story of innovation through unique collaborations with Chinese partners—namely Professor Zhou Yi-Quing, the Chinese scientist credited with isolating the active compound from Artemisinin annua. Dr. Yi-Quing and his team at the Microbiology and Epidemiology Institute in Beijing was awarded the “Inventor of the Year” Award for 2009 from the EU Patent Office.

More than 280 million Coartem treatments have been delivered to the public sector since 2001. Today, it is used in more than 60 countries worldwide..That access is accompanied by a holistic approach to control, combining training support for healthcare professionals, the passing on of economies of scale, and financial support to motivate farmers to cultivate Artemisinin annua.

Dr. Bernhards Ogutu of KEMRI (Kenya Medical Research Institute) discussed the importance of data collection and the collection of accurate data, putting special emphasis on malaria immunity and risk, parasite prevalence, and other measures of the epidemiology. As it is, existing data is inadequate, he said. Dr. John Waitumbi of KEMRI/WRP talked about the three syndromes of malaria--anemia, cerebral malaria, and placental malaria--and attempted to shed some light on the question of how the same parasite can cause different symptoms. Waitumbi suggested that this may be explained by adhesion molecules, such as iRBCs and ligands on many target host cells, and the mechanical occlusion of vasculature.

Dr. Sue Pierce of the US National Institute of Allergy and Infectious Diseases discussed the naturally acquired malaria immunity that leaves children under 5 susceptible to severe infection, children under 10 to mild uncomplicated infection, and adults very well protected. Antibodies can control malaria. So what do we know about antibody immunity acquisition?

A study in Kambila, Mali revealed some important insights. The study followed a cohort of 225 children under 7 zears. Measures of antibody reactivity were taken before and after the malaria season, indicating that antibody reactivity increased with age and was higher overall after the season. But acquisition of antibody immunity was very slow. Like antibodies, memory B cells and long-lived plasma cells accumulate gradually with age. There may be some malaria-induced problem, a mechanism that blocks selection of cells into these pools.

The final presentation by Dr. Salim Abdullah, director of the Ifakara Health Institute, was a brief evaluation of malaria vaccines in Africa. Dr. Abdullah talked about the three target areas of current malaria vaccine research, including pre-erythrocytic, blood stage, and transmission blocking vaccines. With regard to pre-erythrocytic vaccines such as the RTS,S, which is now entering Phase III trials, “we know that these will offer some protection in high transmission areas,” he said. “But how to evaluate efficacy is still challenging due to its large population needs.

Symposium 32 dealt with capacity building for clinical trials in Africa, which should focus on infrastructural capacity at the trial sites; most existing facilities in Africa were not designed for clinical trials. There is also the need for laboratory equipment and human resource development in the areas of laboratory training and GCP. Capacity building at a site is not an event but a continuous process; some equipment need regular replacement and maintenance to meet standard practice for laboratory accreditation.

For effective capacity building for clinical trials, African collaborators should not only be trained to implement protocols and use prepared case record forms but should be involved from the stage of trial planning through design, implementation, control and completion of the trials.

Financial capacity building should allow for supportive functioning of the research centers. For example, administrative fee rates are usually dictated by the sponsor, often to the dissatisfaction of African partners.

Symposium 33 covered health research ethics. Malaria trials are starting to look at more complex areas of science such as genomics. But AMANET’s Aceme Nyika said that investigators shouldn’t use the complexity of genetics to avoid proper informed consent - participants don’t need to understand the science of genes or phenotypes to understand that they can inherit disease, or that DNA tests can tell them about disease.

It’s a positive thing that collaborations between developed and developing countries are growing, said Jerome Singh who heads the bioethics advisory of the Gates’ Grand Challenges in Global Health, but these alliances need to be equal. Too often, he said, developed country authors are the PIs with their developing country counterparts acting more like technicians.

Investigators in the developing world need to educate themselves on issues like intellectual property so that when it comes to drawing up material transfer agreements that dictate the sharing of research materials, both parties benefit.

ACTs are still not getting to everyone in Africa who needs them, and this was the topic of Symposium 34. The ACT consortium of 17 institutions has been set up to deal with problems of ACT delivery in Africa. These problems include lack of access, poor drug quality, and over-diagnosis of malaria. The consortium has research to address this issue in Afghanistan, Cameroon, Ghana, Malawi, Nigeria, South Africa, Tanzania, and Uganda.

Symposium 35 was about modeling malaria dynamics, an area of untapped potential for malaria control programs. In recent years, modelers have looked beyond transmission dynamics and have addressed other topics such as drug resistance, insecticide resistance, and cost-effectiveness of different interventions. Assumptions that are acceptable for control are not acceptable for elimination; in the latter, low prevalence systems unmask other previously insignificant factors which must be accounted for.

Symposium 36 discussed the need for vector control efforts to be integrated into country disease programs. Integrated Vector management (IVM), a national decision-making process for optimal implementation of vector control methods. Malaria control must involve all stakeholders to facilitate implementation. No single actor can do this alone.

Symposium 37 looked at the use of Rapid Diagnostic Test (RDTs) for malaria at the community level. A recent study showed that RDTs can improve significantly the accuracy of diagnosis leading to appropriate treatment and therefore early remission of symptoms compared to presumptive treatment (91.0% versus 83.2%, p<0.001) within three days post treatment. The use of RDTs can also reduce the administration of ACTs by 10% and antibiotics by 13%. Trained community health workers can reach children in hard-to-reach areas with anti-malarials, antibiotics and oral rehydration therapy to help reduce child mortality and help achieve MDG4.

Symposium 38 was also devoted to AntiMAL, an integrated project comprising leading groups of researchers with expertise in malaria biology, chemotherapy and drug development. The project’s aim is to exploit new scientific and political opportunities to secure the development of a portfolio of viable novel antimalarial drugs. Researchers at AntiMAL are synthesizing molecules that they hope will be more efficacious and less toxic than those currently on the market. Synthetic formulations are less costly to develop than the currently available drugs and compare well with current antimalarials in terms of their pharmacokinetic properties.

Symposium 39 discussed Oxford University-U.S. Military vectored vaccines for malaria, with emphasis on the role of African scientists in the ongoing malaria vaccine trials. Active participation of African scientists and communities in the trials would build confidence in both the trials and their results. Phase I trials of Ad.35.CS.01, an NIAID malaria vaccine candidate, showed promising safety and reactogenecity with ascending dosage.

Parasite genetics was the theme of Scientific Session 24. Studies of P. falciparum kinases that regulate essential pathways of the parasites identified aurora-related protein kinase (Pferk1) mitotic regulator and a potential drug target.

Another recent study revealed the existence of apoptotic machinery in P. falciparum in vitro operating in tandem with parasite density, providing insights on parasite survival tactics and new areas of exploration for potential drug targets. A better understanding of the blood and liver stage interactions will probably explain the partial protection from severe infection observed in high transmission areas.

Scientific session 25 looked at vector ecology. Scientists have known for some time that human modification of the environment can alter malaria endemicity. For example, when pits were dug to house water taps at the Kakuma refugee camp in Kenya, malaria became much more endemic. Urbanisation is a good example of how malaria dynamics can change. By the year 2030, half of Africa's population are estimated to be urban dwellers. What researchers want to find out is which molecular forms of the A.gambiae mosquito is found in urban areas and which in rural ones. A study in Younde in Cameroon found that the M molecular form was found in urban environments and the S form in rural areas.

Scientific session 26 focused on drugs and resistance. The use of Coartem may lead to selection of chloroquine sensitive parasites. The use of Coartem may lead to increased chloroquine sensitivity in parasites due to the presence of lumefentrine, which has inverse relationship with chloroquine.

The use of sulphadoxine/pyrimethamine (SP) in Intermittent Preventive Treatment in pregnancy in Gabon could soon be compromised by the prevalence of resistant parasites found in blood samples taken from pregnant women. Drug resistance molecular studies should be incorporated in malaria surveillance. Tests should be conducted to find out if artemisinin resistance has spread outside of Asia. As yet, there is no validated molecular marker for artemisinin resistance.

Symposium 27 featured an integrated immunoepidemiologal approach now being used in the development of malaria vaccines. The approach involves selection and validation of candidate antigens based on immune responses in populations with different protection levels, and determination of the balance between protection and development of severe disease resulting from immune responses based on studies in people residing in endemic areas with acquired partial protective immunity. The integrated approach is being applied in Senegal in studying immune responses to candidate vaccine antigens MSP3 and LSA3.

Scientific Session 28, on epidemiology and transmission, reported that the primary factor underlying the decreased efficacy of AQ + SP may be attributable to declining immunity rather than increasing parasite resistance. The use of verbal autopsy in determining malaria specific mortality may underestimate the impact of interventions on malaria specific mortality.

A system of transmitting malaria information using cellular phones in Zanzibar has proven capable of gathering weekly surveillance data from peripheral health facilities and demonstrates high completeness of reporting. Interruption of malaria transmission in areas of acute seasonal transmission may be possible with widespread annual household IRS and the use of ACTs as front-line antimalarials.

A roundtable dialogue with malaria funders kicked off in Scientific Session 32. The key funding agencies represented were Fogarty International, MIM, NIAID, Wellcome Trust, TDR, EDCTP, and PMI. They talked about their very different research priorities; for example, PMI prefers to set up ongoing programmes on monitoring and evaluation, and drug surveillance. The EDCTP, meanwhile, funds phase II and III trials on drugs and vaccines.

Scientific session 33 focused on vectors and the development of resistance. A study in Burkina Faso indicates that A. arabiensis would be a good vector to consider for control strategies. Scientists are also developing new software for monitoring and evaluation of vectors - the Malaria Decision Support System, which allows for integration of different data sets, is being tested in three southern African countries. Speakers said that indoor residual spraying plays and important role in malaria control even in areas of low transmission.

The Controversy session was chaired by Prof Wen KilamaProf and pitted Dr. Louis Miller agaist Dr. Rose Leke on the subject of African malaria research in the 21st Century. Dr. Miller said the MIM secretariat should remain in Africa. There should be increased MIM/TDR investigator-initiated grants with a strong capacity building component. African scientists interested in basic research for solving the malaria burden should be supported. African scientists should identify young bright scientists, train and mentor them.

Dr. Leke asserted that research should be moved from the bench to industry in order to develop tools to reduce the malaria burden. Evidence-based research on the impact of ITN distribution and use, insecticides and resistance, residual spraying and larvicides is critical. Research is also required on malaria vaccines, antimalarial treatment and drug resistance and ACT availability and affordability. Diagnosis, malaria and co-infections and climate change should also be researched further. African scientists in the diaspora should be encouraged to return to Africa to bring new expertise and forge new collaborations. Capacity building should be emphasized and there should be increased communication between the African scientists, policy makers and the political leadership to increase research funding.

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