344 - Combination therapies against drug resistance in malaria
Malaria kills between one and three million people each year. The African continent suffers 90% of these deaths. The pathogen responsible is Plasmodium falciparum , a parasite transmitted to humans by Anopheles mosquitoes.
Treatments exist which in the past have proved to be effective, such as chloroquine. However, confronted by the emergence in Africa of resistant parasitic forms in the 1980s, monotherapies 1 failed. Researchers from the IRD and the Organisation de coordination pour la lutte contre les endémies en Africa centrale , working in conjunction with the Cameroon Ministry of Public Health 2, recently tested the efficacies of two-drug combination therapies based on an artemisinin 3 derivative, the latest development in antimalarial medicines. The result was a 96% success rate. The two-drug combination helps alleviate that drug’s rapid elimination by the human body and holds back the emergence of resistance to this new treatment.
Malaria is the world’s most widespread parasitic diseases, with about 600 million people affected. The pathogen responsible is a microscopic parasite of the genus Plasmodium , the species P. falciparum which causes the most serious form of this disease. It is still a major public health problem in the countries of the South, especially Africa. Since the 1980s, efforts to control the disease in Africa have come up against the parasites’ resistance to medicines, used up to then in single-drug based treatment, or monotherapy 1. In an effort to counter this problem, researchers from the IRD and the Organisation de coordination pour la lutte contre les endémies en Africa centrale (OCEAC), in collaboration with the Cameroon Ministry of Public Health 2, assessed the efficacy of seven two-drug therapeutic combinations.
Treatment failure or new attack ?
In line with the World Health Organization protocol, the research team conducted a clinical trial on 1 400 patients infected by malaria, mostly children under 5 years of age, in four sites in Cameroon. If treatment failure occurred4, they identified two possible causes. Either the same strain of the parasite reappears: in which case, the failure may be linked to the drug’s insufficient level of efficacy. Or the strain is different: here a second malaria attack is responsible, independent of the first. This second case is therefore considered as a therapeutic success. A re-infection is commonly observed in an endemic zone where malaria transmission to humans, perpetrated by mosquitoes of the genus Anopheles , is permanent and intense. In some places, every person can receive one infectious bite per night.
Artemisinin: greater efficacy proved
During the trial, the research team tested different treatment combinations comprising one of the artemisinin derivatives 3, the latest development in in antimalarials. These proved highly effective against the parasite P. falciparum , producing a cure rate of 96 % after three days of treatment (as against less than 88% for amodiaquine alone or combined with sulphadoxine-pyrimethamine) and 95% one month later. These results also show their speed of action.
In contrast with other antimalarials which can provoke severe allergies, vomiting or nausea, the artemisinin derivatives are almost devoid of serious side-effects. However, they are eliminated from the human body very rapidly. This rapid elimination can be the factor behind a resurgence of malaria if another more slowly eliminated medicine has not been given at the same time.
Artemisinin: agent against new resistance
Derivatives of artemisinin are the most recent antimalarial drugs, for which there is currently no form of resistance in Africa. Combined use of this compound is a new therapeutic strategy which improves care for patients hit by malaria and delays the emergence of resistant strains of P. falciparum . This method certainly represents a major advance for malaria control and, in some endemic areas of South-Est Asia, is the only effective means of treating against malaria caused by resistant P. falciparum . It is generally well tolerated and now strongly recommended in countries like Cameroon where the resistance level is high.
Africa currently has quite a good range of antimalarial medicines at its disposal. Assessment and comparison of their cost-effectiveness and safety-tolerance levels are essential for rational choices to be made between them. They are also imperative for devising, as far as possible, a common policy for using these powerful malaria-control weapons at the sub-regional level of Central Africa. One question remains: will these new treatments maintain-their efficacy against the resistant parasite much longer? And if this is the case, can China, the main producer, supply enough artemisinin to meet the growing demand for Africa as a whole, or even of the whole globe, at an affordable price for all malaria sufferers ?
2. Statistical analysis of data collected by the researchers of the IRD-OCEAC team was conducted in partnership with mathematicians from the Ecole Nationale Supérieure Polytechnique of the University of Yaounde I and the Centre National de la Recherche Scientifique (CNRS) – University of Paris V.
4. Therapeutic failure is defined either as the persistence of fever and the presence of the parasite in the blood, even of worsening of the clinical signs, even after 2 to 3 days’ course of treatment, or as the recurrence of symptoms, fever in particular, linked to the reappearance of parasites in the blood after their elimination by the treatment.
Rédaction DIC - Gaëlle COURCOUX
Translation - Nicholas FLAY