Malaria Meets Its Match as Money and Technology Converge

Armed with an influx of funds from big donors such as the Global Fund, the Bill and Melinda Gates Foundation, the World Bank, and the U.S. President's Malaria Initiative and aided by whole gene sequencing of the Plasmodium falciparum parasite and the Anopheles gambiae mosquito, scientists are devising innovative, synergistic weapons against this deadly protozoan foe.

Effective vaccines are a key component of any malaria eradication program; but until now these have proved exceedingly difficult to develop. Why is not surprising. For starters "P. falciparum has about 5,300 different antigens and a very complicated lifecycle, spent mostly in hepatocytes and erythrocytes," according to Christian Loucq, director of the PATH Malaria Vaccine Initiative (MVI). There are also four very different malaria-causing Plasmodia to contend with in humans —P. vivax, P. malariae, and P. ovale in addition to P. falciparum, the deadliest of the four. However, progress is being made. Loucq told the audience about a number of promising vaccine candidates currently in the MVI portfolio, eight in all. One, RTS,S, invented by GlaxoSmithKline scientist Joe Cohen, has recently proved clinically safe, partially effective and immunogenic in infants, P. falciparum' s most vulnerable population. This is very good news in an area more often than not associated with failure. (http://www.malariavaccine.org/ab-current_projects.htm)

Vaccine developers need the right antigens, and molecular biochemist Susan Kraemer, at Johns Hopkins Malaria Research Institute (JHMRI), is working on protein family called 'P. falciparum erythrocyte membrane protein 1 (PfEMP1)' encoded by var genes, considered a prime target for protective immunity. Kraemer notes that, "In addition to proving useful in vaccine design, these proteins can help us understand how the parasite causes severe disease and how it evades the immune response." Kraemer's colleague at Johns Hopkins, Marcelo Jacobs-Lorena is focusing on the mosquitoes rather than the parasites. "Transmission of Plasmodium," he says, "depends on the successful differentiation of the parasite in its mosquito vector." Transgenic malaria-resistant mosquitoes are already thriving in Jacobs-Lorena's lab and even proving more fit than Plasmodium-infected controls. Jacobs-Lorena's next step is introducing the resistance genes into wild mosquito populations. (http://www.JHSPH.EDU)

"As endemic countries scale up interventions, fast, accurate and non-invasive parasite detection is necessary," says Sungano Mharakurwa, scientific director of JHMRI's field research site in Zambia. "Current definitive malaria testing requires drawing blood which is difficult in children, the de facto sentinel malaria survey group, and problematic in communities with blood taboos." Mharakurwa is using polymerase chain reaction (PCR) technology to find P. falciparum DNA fragments in saliva and urine. Proof of concept has already been demonstrated and, according to Mharakurwa, "after some technical refinements, these sharp- and needle-free detection methods are expected to be ready for drug and vaccine trials, efficacy-monitoring programs, and wide-reaching epidemiological surveys." An equally important technical achievement is David Sullivan's reliable home screening test —a urine dipstick that detects a parasite-specific protein. According to Sullivan, a JHMR physician and biochemist, " home testing will allow much greater access to malaria diagnosis and enable earlier treatment." (http://www.JHSPH.EDU)

But malaria is disease of the tropics, not ivory towers. And, in 2003, the JHBSPH brought its scientists into the war zone, establishing a research and training station in rural Zambia, where the disease has long been an inescapable fact of life and death. The Malaria Institute at Macha (MIAM), a collaborative effort with the Zambian government, the Macha Mission Hospital and the Macha Malaria Research Institute, provides the facilities and infrastructure for multifaceted malaria research. Douglas Norris, who studies mosquito biology, behavior and genetics at MIAM, told the Academy audience that "Here we study malaria with all the confounding factors of climate, movement of peoples, and cultural perceptions. It's more than a field station," he says, "MIAM has become part of the community, the majority of our staff live within a 35 km radius of the institute."

"Macha, where people live in scattered clusters of huts connected by dirt roads and Anopheles mosquitoes breed in small pools filled by periodic wet-season rains, is our best hope of conquering malaria," concluded Norris. "It's here in this living laboratory that we gain a true appreciation and understanding how people and insects interact and it's here that we'll be able to evaluate the tools and ideas needed to eradicate the disease." (http://malaria.jhsph.edu/programs/malaria_institute_macha/new_research_center/)