pfmdr1 mutations in imported African Plasmodium falciparum isolates

Area of Science:

• Malariology
• Molecular Epidemiology
• Parasitic Diseases

Background:

• Amodiaquine/artesunate and artemether/lumefantrine are key antimalarials in Africa.
• The Plasmodium falciparum multidrug resistance gene 1 (pfmdr1) is implicated in reduced drug sensitivity.

Purpose of the Study:

• To assess the prevalence of specific pfmdr1 alleles associated with reduced sensitivity to amodiaquine/artesunate and artemether/lumefantrine.
• To investigate geographical variations in these alleles between West and East African Plasmodium falciparum isolates.

Main Methods:

• Analysis of 111 Plasmodium falciparum isolates imported to Germany (1997-2005).
• Genotyping of pfmdr1 alleles, specifically focusing on mutations at positions 86, 184, and 1246.
• Correlation of allele frequencies with geographical origin (West vs. East Africa) and antimalarial drug policy.

Main Results:

• The 86Y-184Y-1246Y pfmdr1 genotype, linked to amodiaquine/artesunate resistance, was significantly more common in East African isolates (45.8%) than West African isolates (2.5%).
• This genotype was also more frequent in isolates from countries with an artemether/lumefantrine policy (20.8%) compared to those with an amodiaquine/artesunate policy (5.7%).
• The 184F mutation showed an inverse geographical distribution.

Conclusions:

• Significant geographical differences in pfmdr1 allele frequencies exist between West and East Africa.
• These genetic variations support the current regional implementation strategies for first-line antimalarial treatments in Africa.