SNEAKY MUTATIONS IN THE FIGHT AGAINST MALARIA
Plasmodium falciparum — one of the parasites responsible for the transmission of malaria — is the umpteenth amazing example of how environmental constraints encourage adaptation for survival and of how inbreeding, by promoting lower genetic diversity, can cause a normally rare trait to become the norm.
Recent scientific studies have shown that the continuous occurrence of genetic mutations in this lethal pathogen keep malaria near the top of the list of threats to the health of the world’s population, and a leading concern for the international scientific community.
In fact, the World Health Organization reports that more than half a million people die annually because of malaria.
A study published in Nature Genetics in 2013 identified new strains of malaria parasites resistant to artemisinin — the most effective drug currently employed to treat this deadly disease.
Although different drugs have been successfully identified and employed in the fight against the disease over time, malaria parasites have regularly developed resistance to these drugs.
In 1957, a genetically mutated conferred parasite became resistant to the most successful drug at the time, chloroquine. The mutation spread and it is found today in most circulating parasites, which means that chloroquine is mostly ineffective.
The current frontline drug used to treat affected patients is artemisinin which, used in combination with a partner drug, offers rapid and effective treatment for falciparum malaria.
Resistance to artemisinin, known as ART-R, currently manifests itself as a slowdown in treatment rate; the drug still works, but it takes longer and it is feared that this could lead to treatment failure.
Resistant parasites found in Cambodia were found in two studies to be developing profound genetic changes. These populations of parasites live in regions of Cambodia where malaria transmission is very low, which favors low genetic diversity.
Dr. Olivo Miotto, the bioinformatic team leader of this scientific breakthrough, explained that this drug was introduced to Cambodian earlier than in other countries, so in this country the parasites have received more prolonged exposure than anywhere else.
Furthermore, in Cambodia, social and political changes over the years have had affected public health interventions as well as drug pressures.
“Paradoxically”, Miotto said, “it is perhaps the diminishing incidence of malaria, and the consequent smaller size and lower diversity of the parasite population, that might have had the greatest impact. P. falciparum parasites in Western Cambodia are few and highly inbred, subjected to high drug pressure, but not yet eliminated: possibly the worst scenario for the emergence of resistance.”
The current state of malaria in the world indicates that Africa is the most stricken continent, where there are more frequent infections and far higher death tolls than anywhere else.
However, larger populations and the genetically dynamic scenario in Africa means that people get sick more often, but parasite populations are more diverse.
The high number of malaria-related deaths in Africa is partly due to lack of resources, infrastructure and education, not just to the effectiveness of antimalarials.
“This is why it is so urgent to protect artemisinin; we owe it to millions of people at risk in Africa to preserve their most effective defense against this appalling disease,” said Miotto, who is senior informatics fellow for the Center for Genomics and Global Health based at the Mahidol-Oxford Research Unit in Bangkok, Thailand.
Until now, mutations of this gene have been observed only in parasites that have been exposed to artemisinin.
At the moment, scientists are attempting to determine if these mutations only happen within specific environmental conditions, or in parasites with specific genetic backgrounds.
The drug-resistant mutations identified so far do not occur naturally, and this could mean that survival from drug exposure has a cost: Whatever allows these parasites to survive is a handicap once you remove drug pressure.
“So far ART-R has only been reported in Cambodia, Vietnam, Thailand and Myanmar. There is no suggestion that it is present in Africa or elsewhere. Artemisinin resistance might not spread as rapidly where there are more parasites and more diversity- though we’d rather not have to test that theory,” Miotto concluded.
The history of the evolution of Plasmodium falciparum and that of mankind are profoundly intertwined.
Malaria has been shown to have caused natural selection in humans.
Analogies between human migration patterns and the diffusion of malaria as well as Miotto and his team’s studies suggest that genetic mutations in P. falciparum happen as we speak.
Human beings and malaria parasites maintain a strong genetic interplay, each side adapting and presenting genetic mutations in order to gain the upper hand.
The WHO World Malaria Report 2013 lists Indonesia as a malaria endemic country. In fact, 417,000 malaria cases were reported in 2012, as recalled by Health Minister Nafsiah Mboi at a 2013 World Malaria Day event in Jakarta.
Extensive research and greater resources in this field will help save lives and will yield valuable results for the whole scientific community.
Published on the Jakarta Post