Premium
Treatment of uncomplicated malaria with artesunate plus sulfadoxine–pyrimethamine is failing in Somalia: evidence from therapeutic efficacy studies and Pfdhfr and Pfdhps mutant alleles
Author(s) -
Warsame Marian,
Hassan Abdillahi Mohamed,
Barrette Amy,
Jibril Ali Mohamed,
Elmi Husein Haji,
Arale Abdulkadir Mohamed,
Mohammady Hanan El,
Nada Rania A.,
Amran Jamal Ghilan Hefzullah,
Muse Abdikarim,
Yusuf Fahmi Essa,
Omar Abdiqani Sheikh
Publication year - 2015
Publication title -
tropical medicine and international health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.056
H-Index - 114
eISSN - 1365-3156
pISSN - 1360-2276
DOI - 10.1111/tmi.12458
Subject(s) - dihydropteroate synthase , dhps , sulfadoxine/pyrimethamine , sulfadoxine , artesunate , malaria , plasmodium falciparum , pyrimethamine , drug resistance , medicine , mefloquine , dihydrofolate reductase , biology , virology , immunology , genetics , methotrexate
Objective Artesunate plus sulfadoxine–pyrimethamine (AS + SP) has been Somalia's national treatment policy since 2006. Routine monitoring of first‐line malaria treatment is needed to ensure appropriate national malaria treatment policy and early detection of drug resistance. For this purpose, we conducted therapeutic efficacy studies of AS + SP for the treatment of uncomplicated malaria in Somalia in 2011. Methods Studies were conducted in three sentinel sites. Eligible patients were evaluated for clinical and parasitological outcomes according to the WHO standard protocol. Molecular surveillance was conducted on resistance conferring mutations in the P.falciparum dihydrofolate reductase ( dfhr ) and dihydropteroate synthase ( dhps ) genes. Results The proportion of PCR‐corrected treatment failures was high in Jamame (22%, 95% CI: 13.7–32.8%) and low (<5%) in Janale and Jowhar. All patients cleared parasites by day 3. Molecular markers associated with SP resistance were detected in all three sites. Treatment failure was associated with the presence of the double mutant dhps A437G/K540E (OR = 22.4, 95% CI: 5.1–98.1), quadruple mutant dhfr N51I/S108N+ dhps A437G/K540E (OR = 5.5, 95% CI: 2.3–13.6), quintuple mutant dhfr N51I/C59R/S108N+ dhps A437G/K540E (OR = 3.5, 95% CI: 1.4–8.8) and younger age (OR=0.86, 95% CI: 0.76–0.96). Conclusions The high treatment failure rate observed in Jamame, together with the presence of molecular mutations associated with SP resistance, indicates P. falciparum resistance to SP. In Jowhar, high treatment failure rates were absent despite the presence of molecular mutations; signs of resistance in vivo may have been masked by the stronger immunity of the older study population. The study underscores the need to update Somalia's national malaria treatment policy.