Genetic diversity and drug resistance surveillance of Plasmodium falciparum for malaria elimination: is there an ideal tool for resource-limited sub-Saharan Africa?

Table 2 Mode of action, targets and resistance mechanisms of drugs for P. falciparum malaria treatment and control in sSA

Drugs	Mode of action	Molecular markers of resistance	Resistance mechanism
Artemether (AM)	Not well understood, oxidative damage to proteins and lipids and/or targeting the phosphatidylinositol-3-kinase (PfPI3K)	Pfk13, Pfmdr-1, Pfmrp-1	Not clearly understood; SNPs, CNVs
Artesunate (AS)
Dihydroartemisinin (DHA)
Pyrimethamine	Inhibits folic acid synthesis	Pfdhfr	SNPs
Sulphadoxine	Inhibits folic acid synthesis	Pfdhps	SNPs
Amodiaquine (AQ), lumefantrine (LM)	Inhibits haem detoxification	Pfcrt	SNPs
Amodiaquine (AQ), lumefantrine (LM)		Pfmdr-1	SNPs
Mefloquine (MQ)		Pfmdr-1	CNVs
Mefloquine (MQ)		Pfcrt, plasmepsin 2/3	SNPs, CNVs
Quinine (QN)		Pfmdr-1, Pfcrt, Pfmrp-1, Pfnhe-1	SNPs
Piperaquine (PPQ)	Inhibits haem detoxification, inhibits one or more steps in the haemoglobin degradation
Clindamycin	Inhibits protein synthesis	Pfmdt, PftetQ	CNVs
Doxycycline	Inhibits protein synthesis	Pfmdt, PftetQ	CNVs

Recommended ACTs for treatment of malaria have artemisinin or its derivative combined with one or more drugs and include: AL, AS–AQ, AS–MQ, AS–SP and DHA–PPQ. As of 2016, most African countries use AL and AS–AQ, with some adding DHA–PPQ for uncomplicated malaria, AS, AM and QN for severe malaria and SP for IPTp (1)
CNV copy number variation, Pfmrp-1 P. falciparum multi-resistance protein 1 gene, Pfnhe-1 P. falciparum Na⁺/H⁺ exchanger-1, Pfmdt P. falciparum metabolic drug transporter, PftetQ P. falciparum tet Q GTPase

ISSN: 1475-2875