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Plasmodium falciparum: in vitro chloroquine susceptibility and allele-specific PCR detection of Pfmdr1Asn86Tyr polymorphism in Lambarene, Gabon

Published online by Cambridge University Press:  01 March 1998

M. P. GROBUSCH ,
I. S. ADAGU ,
P. G. KREMSNER  and
D. C. WARHURST
M. P. GROBUSCH
Affiliation:
II. Medizinische Klinik, Virchow-Klinikum, Humboldt-Universität, 13353 Berlin, Germany Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Research Laboratory, Albert Schweitzer Hospital, Lambarene, Gabon
I. S. ADAGU
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
P. G. KREMSNER
Affiliation:
Research Laboratory, Albert Schweitzer Hospital, Lambarene, Gabon Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Germany
D. C. WARHURST
Affiliation:
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
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Abstract

Plasmodium falciparum resistance to chloroquine has been described in many parts of the world particularly in Africa where malaria is endemic. High levels of chloroquine resistance in our study area, Lambarene–Gabon, has led to the use of an alternative regimen for treatment and prevention of P. falciparum infection. In this study, we examined the in vitro chloroquine sensitivity of 15 isolates from this area and assessed the prevalence of a putative chloroquine resistance associated Pfmdr1 polymorphism (Asn86Tyr) using a novel allele-specific polymerase chain reaction (PCR). Only 4 of the isolates examined were chloroquine sensitive. The allele-specific PCR shows that all 15 isolates carried the variant (86Tyr) codon. Eleven of these were resistant to chloroquine suggesting a 73% agreement between chloroquine resistance phenotype and the point mutation. This molecular marker was examined in a further 73 Gabonese isolates, where 58 (79·5%) showed 86Tyr and 15 (20·5%) showed 86Asn. In all, 4 (4·5%) of the 88 isolates assessed carry both mutant and wild-type codons, suggesting mixed parasite populations. The incomplete agreement found between chloroquine resistance phenotype and Pfmdr1 (86Tyr) polymorphism would support the view that other genetic factors as well as Pfmdr1 may be involved in chloroquine resistance. While our results suggest a high prevalence of 86Tyr polymorphism in Lambarene, the Asp1246Tyr polymorphism (a point mutation which to date has only been associated with South American P. falciparum) seems to be absent in our study area.

Keywords

Plasmodium falciparumchloroquine resistanceallele specific PCRPfmdr1 polymorphismsGabon
Type
Research Article
Information
Parasitology , Volume 116 , Issue 3 , March 1998 , pp. 211 - 217
Copyright
1998 Cambridge University Press

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