The attached graphic shows the distribution of artemesinin resistance throughout the world. “Dark Green” means that all parasites are more or less “normal” (and therefore not resistant to artemisinins), “Red” (primarily in South-East Asia) means that a very high percentage carry a mutation (so-called K13 polymorphism), which is associated with artemesinin resistance.
Credit: Image courtesy of Medical University of Vienna
Practically all currently available treatments for malaria are based in some form or other on a derivative of artemisinin, a plant substance that is found in the leaves and flowers of annual mugwort (Artemisia annua). However, more and more malaria parasites are becoming resistant to artemesinin — especially in South-East Asia. In order to provide an accurate view of the spread of resistance throughout the world, an international research group from more than 50 countries — led by the Pasteur Institute in Phnom Penh (Cambodia) — has drawn up a map of artemesinin resistance. Under the lead of Harald Noedl and Michael Ramharter, MedUni Vienna and VetMedUni Vienna (Hans-Peter Fuehrer) participated in this study, which has recently been published in the journal,New England Journal of Medicine (NEJM).
Scientists examined a total of 14,000 samples, including around 700 from the research areas of Michael Ramharter (University Department of Medicine I, Division of Infectious Diseases and Tropical Medicine) in Gabon and Harald Noedl (Institute for Specific Prophylaxis and Tropical Medicine) in Bangladesh and Ethiopia. It is one of the largest international and cross-disciplinary projects in the history of malaria research.
The central finding: “Currently artemesinin resistance is exclusively concentrated on South-East Asia; African regions are not yet affected.” With the emphasis on “Not yet,” say the MedUni Vienna researchers. However, for years now the greatest threat when it comes to malaria has been that a resistant pathogen develops in Africa and then spreads. Ramharter: “The descendants of these parasites are like clones. If one becomes resistant, they may spread and be transmitted further.”
However, there is still a high probability that resistance will spread to Africa, because it is based on a genetic mutation — as has been shown in previous studies. Little more than ten years ago, many malaria researchers did not consider the possibility of resistance developing to artemesinins, because of their new modes of action and because they are administered in combination with other drugs. Noedl: “We were way too optimistic.” In a publication that likewise appeared in the NEJM in 2008, MedUni Vienna researchers identified the existence of clinical resistance to artemesinins for the first time.
The scientists stress that the new map of artemesinin resistance will make it possible to observe further developments carefully, to identify any shifts more quickly and to optimize control of one of the humankind’s most deadly diseases.
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The most important aspect of malaria treatment continues to be strict observance of treatment protocols. However, that is still a problem — and not only in Africa. Noedl explains: If someone is meant to take the medication for three days but stops after one or two days, because the symptoms have subsided and he/she feels better, then some of the pathogens will inevitably survive. This is the context in which resistance develops.” In South-East Asia, resistance is presumably also due to the fact that there are far fewer cases of malaria so that selection pressure is greater. Ramharter: “It is much easier for one resistant parasite in 100 to survive and pass on the resistant gene than it is for one in several thousand.”
According to figures from the World Health Organization, worldwide more than 200 million people develop malaria every year. Last year around 600,000 patients died from the tropical disease, 90% of them in Africa, in most cases children under five. Malaria is caused by parasites, which are transmitted by bites from infected mosquitoes.
Source: Medical University of Vienna
Journal: The New England Journal of Medicine
Research Reference:
- Didier Menard, H. Noedl, M. Ramharter, H.P. Fuehrer et al. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N Engl J Med, June 2016 DOI: 10.1056/NEJMoa15131375
