Amodiaquine resistance is not related to rare findings of pfmdr1 gene amplifications in Kenya.
OBJECTIVE
Many countries are now adopting artemisinin-based combination therapy (ACT) for treatment of Plasmodium falciparum malaria. In multi-drug resistant areas in South East Asia amplifications of the pfmdr1 gene are frequent and tentatively associated with reduced susceptibility to the common quinoline partner drugs mefloquine and lumefantrine. In Africa where amodiaquine is one of the favoured quinoline partner drugs in ACT, studies on multi-drug resistance associated pfmdr1 gene amplifications are urgent. Our aim was to determine the current prevalence of pfmdr1 gene amplifications and a possible association between pfmdr1 gene copy number and amodiaquine treatment outcome in Kenya.


METHODS
Seventy-two children with Plasmodium falciparum infection in Kenya were treated with amodiaquine monotherapy and followed for 21 days. Possible amplification of the pfmdr1 gene was assessed from blood-spotted filterpaper by TaqMan probe based real-time polymerase chain reaction.


RESULTS
The recrudescent rate was 14 of 72 (19%). All children had single pfmdr1 copy infections, with the exception of one child who had an infection with two pfmdr1 copies. This child had an adequate treatment response.


CONCLUSIONS
Pfmdr1 amplifications do exist in Kenya but at a very low frequency. Yet, the substantial number of children with recrudescent infections implies that amodiaquine resistance is not related to pfmdr1 gene amplifications in Kenya.
Holmgren
Gabrielle
G
Malaria Research Unit, Division of Infectious Diseases, Department of Medicine, Karolinska Institute, Stockholm, Sweden. gabrielle.holmgren@karolinska.se
Björkman
Anders
A
Gil
José Pedro
JP
D000655:Amodiaquine / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002648:Child; D018432:Drug Resistance, Multiple; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D012008:Recurrence; D017211:Treatment Failure
D000655:Amodiaquine; D000962:Antimalarials; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum