The world's best drug for treating malaria, a medicine that is key to saving millions of lives in Africa and beyond, is losing its efficacy in a much larger swath of territory than was previously known, a recent study has found. Business Day reports that the research raises the troubling prospect that resistance to the drug, artemisinin, might one day severely hamper treatment of a disease that kills hundreds of thousands of people every year.
"This should focus minds," says Charles Woodrow, one of the authors of the study. "We have to eliminate these very resistant parasites. The fear is that if we don’t, we would reverse all the gains that have been made."
For several decades, artemisinin has been considered an anti-malaria wonder drug, rapidly ridding the body of the parasite that is introduced into the body by a mosquito and infects the blood. Early signs of trouble with the drug were cited a decade ago by scientists in western Cambodia. Falciparum malaria, the deadliest, was increasingly resistant to treatment with artemisinin, which is derived from a plant used in traditional Chinese medicine and is often used in conjunction with other drugs.
The new study shows that resistance to the drug extends more than 2,000km away from Cambodia, along the border between Myanmar and India. It is not known whether resistance had spread overland or whether new diagnostic tools were revealing a situation that had previously gone undetected.
There is no immediate replacement for artemisinin, which has helped contribute to steep declines in mortality rates from the disease. Scientists say any possible substitute is years if not decades away. Scientists are particularly concerned about the declining efficacy of artemisinin because it appears to follow a pattern seen in previously used malaria drugs, such as chloroquine. Such drugs were, in their time, mainstays of malaria treatment but are no longer considered useful because the parasite became resistant.
Other malaria research by a team of Scandinavian scientists explains the mechanisms behind the protection that blood type O provides those with malaria, and suggest that the selective pressure imposed by malaria may contribute to the variable global distribution of ABO blood groups in the human population.
Malaria, which is most endemic in sub-Saharan Africa, is caused by different kinds of parasites from the plasmodium family, and effectively all cases of severe or fatal malaria come from the species known as Plasmodium falciparum. In severe cases of the disease, the infected red blood cells adhere excessively in the microvasculature and block the blood flow, causing oxygen deficiency and tissue damage that can lead to coma, brain damage and, eventually death. Scientists have therefore been keen to learn more about how this species of parasite makes the infected red blood cells so sticky.
It has long been known that people with blood type O are protected against severe malaria, while those with other types, such as A, often fall into a coma and die. Unpacking the mechanisms behind this has been one of the main goals of malaria research.
A team of scientists led from Karolinska Institutet in Sweden have now identified a new and important piece of the puzzle by describing the key part played by the RIFIN protein. Using data from different kinds of experiment on cell cultures and animals, they show how the Plasmodium falciparum parasite secretes RIFIN, and how the protein makes its way to the surface of the blood cell, where it acts like glue. The team also demonstrates how it bonds strongly with the surface of type A blood cells, but only weakly to type O.
Principal investigator Mats Wahlgre, a professor at Karolinska Institutet's department of microbiology, tumour and cell biology, describes the finding as "conceptually simple". However, since RIFIN is found in many different variants, it has taken the research team a lot of time to isolate exactly which variant is responsible for this mechanism. "Our study ties together previous findings", said Wahlgren. "We can explain the mechanism behind the protection that blood group O provides against severe malaria, which can, in turn, explain why the blood type is so common in the areas where malaria is common. In Nigeria, for instance, more than half of the population belongs to blood group O, which protects against malaria."
[link url="http://www.bdlive.co.za/life/health/2015/03/12/fears-of-growing-resistance-to-malaria-wonder-drug"]Full Business Day report[/link]
[link url="http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)70032-0/abstract"]The Lancet Infectious Diseases article summary[/link]
[link url="http://ki.se/en/news/how-blood-group-o-protects-against-malaria"]Karolinska Institutet[/link]
[link url="http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3812.html"]Nature Medicine abstract[/link]