The New Drug War Against Malaria

To date, we have spent roughly $2 billion a year on malaria control, a disease that has existed for 4700 years. And yet the best scientists in the world, bankrolled by the best foundations, have been unsuccessful. Why?

One main reason is that the vast majority of funding is going to vector control for insecticide-treated nets instead of further research into understanding the parasite itself and development of new drugs. While malaria control interventions seem to work, it has not proven sufficient against the constantly evolving parasite. According to the CDC, the insecticide-treated nets reduced child mortality from malaria by 20%. However, these bed nets do not protect children and others at risk of malaria when they are not sleeping under them. Furthermore, alarming new evidence points to the fact that current drugs are not working as well as they should against the parasite. Therefore, more consistent protection in the form of prophylactic vaccines and effective novel therapeutics are needed to combat the parasite.

not good enough

not good enough

To much of the Western world, malaria is a forgotten disease. Yet each year, malaria infects 500 million people globally and claims nearly a million lives. With 90% of these fatal cases occurring in Africa, the disease is taking the lives of mostly children and pregnant women.  People living in endemic countries can be infected several times during their lives. For young adults supporting their families, malaria can prevent them from working for several days. For a traveler with no immunity, the initial flu-like symptoms can be misleading. The disease is caused by the plasmodium parasite transmitted by female Anopheles mosquitoes. The parasite enters the bloodstream and travels to the liver, where it matures. About a week later, the parasite reenters the bloodstream and hijacks red blood cells causing symptoms including chills, fever, anemia and jaundice with severe cases leading to kidney or liver failure, coma and death. Significant evidence suggests the disease is outgrowing our means to combat it.

A study published in the New England Medical Journal last year showed evidence of emerging artemisinin-resistant malaria along the Thai-Cambodian border, a hotspot for drug-resistant strains. Combination therapies using artemisinin, a potent drug derived from the herbal plant Artemisia annua, are the recommended treatment for the Plasmodium falciparum malaria parasite, the most deadly strain that kills 90% of infected individuals. Since the 1950s, Pailin, the gem-mining town in western Cambodia, has been the epicenter for drug-resistant malaria strains.  During the Khmer Rouge era, people purchased cheap monotherapy drugs in the black markets. Monotherapy, the use of one drug, has consequently led to the failing potency of these treatments. Resistance to anti-malarial drugs chloroquine and sulfadoxine-pyrimethamine developed first, followed by mefloquine. Exacerbating the problem, migrant gem miners in Pailin carried the resistant strains with them. Eventually, resistance to chloroquine and sulfadoxine-pyrimethamine radiated out of Cambodia, reaching Africa by the 1990s.


Malaria burden worldwide

With the emerging resistance to current anti-malarial treatment, an international collaboration led by R. Kiplin Guy at St. Jude’s Children’s Research Hospital has identified possible starting points for new drugs. In a phone interview, Dr. Guy explained that they applied a pharmacological approach and assessed how chemicals interacted with the parasite. Published in the May 20 issue of Nature this year, the study released data showing promising candidates for further drug development against drug-resistant Plasmodium falciparum parasites.   Researchers screened a library of 310,000 chemical compounds yielding 1,100 confirmed “hits” against drug-resistant parasites. Further screening revealed detailed profiling of 172 structurally unique compounds that could potentially lead to new malaria drugs. A majority of these chemical compounds can selectively target Plasmodium falciparum without harming humans and interact with the parasite differently from previous drugs. One of these compounds was further evaluated in mice infected with malaria, which successfully stopped the growth of the parasite. The study provides a collection of novel chemical structures leading to the basis for completely new antimalarial drugs and possible alternatives to artemisinin. However, Dr. Guy projects it will be about another 6 years before clinical trials begin.

In the same issue of Nature, researchers at GlaxoSmithKline conducted a similar study using in-house chemicals yielding 13,500 compounds inhibiting the parasite. In addition to searching for novel therapeutics, GSK has committed over two decades to developing a successful vaccine.  Currently in phase III of clinical trials, data shows that the vaccine provides protection from malaria in African children under the age of two. According to Dr. Joe Cohen, one of the inventors of the vaccine, implementing the RTS,S malaria vaccine is an essential component in the arsenal of weapons against malaria.

The emerging drug-resistant malaria cases suggest that the current prevention measures and treatment are not enough to combat the disease. Clearly academia and pharmaceutical companies need to collaborate and develop new treatments with long-term effects. The looming threat of drug-resistant malaria spreading  further necessitates the exploration of other drugs and implementation of vaccines to combat the deadly disease now.

Nicole Germino is an MPH candidate concentrating in Epidemiology with special interests in infectious and tropical diseases and health policy.