Malaria, a parasite vector-borne disease, is one of the most significant health threats in tropical regions, despite the availability of individual chemoprophylaxis. Malaria chemoprophylaxis and chemotherapy remain a major area of research, and new drug molecules are constantly being developed before drug-resistant parasites strains emerge. The use of anti-malarial drugs is challenged by contra-indications, the level of resistance of Plasmodium falciparum in endemic areas, clinical tolerance and financial cost. New therapeutic approaches are currently needed to fight against this disease. Some antibiotics that have shown potential effects on malaria parasite have been recently studied in vitro or in vivo intensively. Two families, tetracyclines and macrolides and their derivatives have been particularly studied in recent years. However, other less well-known have been tested or are being used for malaria treatment. Some of these belong to older families, such as quinolones, co-trimoxazole or fusidic acid, while others are new drug molecules such as tigecycline. These emerging antibiotics could be used to prevent malaria in the future. In this review, the authors overview the use of antibiotics for malaria treatment.
Resistance to piperaquine has been associated with the amplification of the plasmepsin II gene in Cambodia. None of the 175 African isolates that we analyzed had plasmepsin II gene amplification (piperaquine 50% inhibitory concentration ranged from 0.94 to 137.5 nM), suggesting there is a low prevalence of piperaquine reduced susceptibility in Africa. Additionally, the few isolates with reduced susceptibility to piperaquine did not harbor amplification of the plasmepsin II gene.
Dihydroartemisinin-piperaquine, which was registered in 2017 in Senegal, is not currently used as the first-line treatment against uncomplicated malaria. A total of 6.6% to 17.1% of P. falciparum isolates collected in Dakar in 2013 to 2015 showed ex vivo-reduced susceptibility to piperaquine. Neither the exonuclease E415G mutation nor the copy number variation of the plasmepsin II gene (Pfpm2), associated with piperaquine resistance in Cambodia, was detected in Senegalese parasites.
Mutations in the propeller domain of
Plasmodium falciparum kelch 13
(
Pfk13
) gene are associated with artemisinin resistance in Southeast Asia. Artemisinin resistance is defined by increased ring survival rate and delayed parasite clearance half-life in patients. Additionally, an amplification of the
Plasmodium falciparum plasmepsin II
gene (
pfpm2
), encoding a protease involved in hemoglobin degradation, has been found to be associated with reduced in vitro susceptibility to piperaquine in Cambodian
P. falciparum
parasites and with dihydroartemisinin–piperaquine failures in Cambodia. The World Health Organization (WHO) has recommended the use of these two genes to track the emergence and the spread of the resistance to dihydroartemisinin–piperaquine in malaria endemic areas. Although the resistance to dihydroartemisinin–piperaquine has not yet emerged in Africa, few reports on clinical failures suggest that
k13
and
pfpm2
would not be the only genes involved in artemisinin and piperaquine resistance. It is imperative to identify molecular markers or drug resistance genes that associate with artemisinin and piperaquine in Africa.
K13
polymorphisms and
Pfpm2
copy number variation analysis may not be sufficient for monitoring the emergence of dihydroartemisinin–piperaquine resistance in Africa. But, these markers should not be ruled out for tracking the emergence of resistance.
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