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120 YEARS OF ADVANCES FOR MILITARY AND PUBLIC HEALTH
Results of the RTS,S Phase III vaccine trial conducted in Africa were presented at the 6th Multilateral Initiative on Malaria Pan-African Malaria Conference, Oct. 8, 2013, by Dr. Lucas Otieno, principal investigator at U.S. Army Medical Research Unit-Kenya. Perhaps someday, a military-quality vaccine for malaria will be given to Soldiers deploying to malaria endemic areas of the world. U.S. Army photo
to develop a vaccine that provides sterile immunity – in other words, a vaccine that trains the immune system to kill the malaria parasite before it reaches the blood stage, which causes the symptoms and complications of malaria. “What we’re looking for in a military vaccine,” he said, “is to achieve complete protection from infection.” The safety and efficacy of the RTS,S vaccine was initially established at the WRAIR’s own laboratories using the malaria challenge model, a protocol developed by WRAIR investigators that involves the intentional infection of study subjects with the parasite, followed by a period of close observation and treatment. To date, the malaria challenge model has been used to assess candidate malaria vaccines and drugs in more than a thousand volunteer subjects. The challenge model is also being used to evaluate an experimental vaccine for another strain of the malaria parasite, P. vivax, which is not as deadly as P. falciparum but, according to Paris, causes most of the cases of malaria in the U.S. military. P. vivax tends to “hibernate” in a person’s liver, causing the disease to recur or “relapse.” “Because of its biology,” Paris said, “P. vivax presents the biggest hurdle for the elimination of malaria.” MMRP investigators today are among only a handful of scientists around the world developing an experimental P. vivax vaccine. Mild to moderate malaria caused by P. falciparum and P. vivax is treated with oral drugs. When P. falciparum developed resistance to the classic agent chloroquine at the time of the Vietnam War, WRAIR was called on to urgently deliver a new malaria prevention drug to maintain combat readiness of deployed troops and cure those who
needed treatment. WRAIR scientists invented and then co-developed a new drug named mefloquine as a chloroquine replacement. As with all drugs, resistance emerged to mefloquine over time and WRAIR physicians and scientists played an important role in the FDA approval of the next-generation malaria prophylaxis drug malarone in 2000. There are more cases in the United States of P. vivax than P. falciparum. WRAIR clinical scientists developed primaquine in the 1940s-1950s to treat the hidden P. vivax parasite in the liver, and it is still used today. WRAIR invented the potential primaquine replacement, tafenoquine, that is in advanced clinical testing today. Severe malaria is treated with intravenous drugs. Quinine is used worldwide, whereas quinidine is the only agent approved for use in the United States, although it can cause cardiac damage. For these reasons, WRAIR researchers and others have for some time focused on artemisinins. Artemisinins were widely used more than 2,000 years ago in traditional Chinese medicine, and were redeveloped by the Chinese government to treat North Vietnamese soldiers during the Vietnam War – at about the same time WRAIR researchers were developing mefloquine for U.S. troops. In the 1980s, WRAIR scientists found sweet wormwood growing on the banks of the Potomac River, extracted artemisinins, and began studying them. One of the most promising compounds to be studied by the group, artesunate, is a semi-synthetic artemisinin derivative that is water soluble and deliverable intravenously (IV). A team of WRAIR researchers led by Dr. Qigui Li and Col. Peter J. Weina, M.D., recently published that patients with severe malaria who received IV artesunate were 35 percent less likely