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Plenary Session 4

Source: TropIKA

Date: 5 November 2009

Overview

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 in Artemisinin annua. Dr. Yi-Quing and his team at the Microbiology and Epidemiology Institute in Beijing were awarded the “Inventor of the Year” Award for 2009 from the EU Patent Office.

The packaging of Coartem is designed to improve dispensing and enhance compliance through pictorial instructions, explaining the need to continue to the end of the 3-day therapy course. 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, and as a result Novartis boasts the largest access to malaria medicine program in Africa. 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 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. Reliable information on causes of death and estimation of disease burden is severely lacking. Among the many determinants of epidemiology, Ogutu added, the most important may be the human environment and understanding, for example, the reasons behind the shift in age of severe malaria.

Malaria pathogenesis was the subject of a presentation given by John Waitumbi, at KEMRI/WRP. He 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.

The aetiology of malaria is multi-factorial, said Waitumbi. It is immune mediated and includes haemolysis, bone marrow depression, altered cytokine balance, and nutritional deficiency, all in the context of red blood cell polymorphisms. Malaria anaemia, he noted, does not occur everywhere there is malaria, and there is a new school of thought that it is no different than the anaemia caused by lack of iron in other diseases. This might have to do with complement receptor 1 (CR1). Studies have demonstrated that children with severe malaria have reduced expression of CR1, and that expression levels of CR1 on RBC are age-related. They are lowest when children are most susceptible to infection and increase with age in endemic areas.

Dr. Waitumbi explained that measuring iron status in children is problematic due to the overlapping symptoms of malaria and other diseases. He said that better biomarkers of iron are needed and suggested Chr (reticulocyte hemoglobin content) as a potential candidate.

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 7years. 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.

Many questions remain to be answered. To really understand natural acquisition, it is critical that the malaria community attract more immunologists to the field. The NIH is doing just that through a new Malaria Infection Biology (MIB) Research and Training program ((link to MIB Program to www3.niaid.nih.gov/labs/training/mibProgram ), aimed at training top young scientists at the intersection of malaria biology and immunology.

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.

There are currently very few vaccine candidates in the pipeline in any of the target areas. Many of the products are still in the pre-clinical stages, he said, and “we have learned from the testing what it takes to get them to the market.” As evidenced by the regional differences in immune responses to the Spf66 vaccine—which was significantly protective in Colombia, borderline in Tanzania, and ineffective in Gambia and Thailand--researchers will need to have region-specific information.

A key question, he said, is the meaning of "partially effective". What does it mean to have a vaccine that is 40% effective? Does it offer zero protection to 60% of the population? Or is it preferable that everyone who is vaccinated has 40% lower protection than those who are not vaccinated? “We don’t know which model provides best scenario.” In concluding, Abdullah said that much progress has been made in the past ten years, capacity is being developed across Africa, and there remains great hope for a first generation vaccine.

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