Molecular surveillance of drug-resistance associated mutations of Plasmodium falciparum in south-west Tanzania

Background: In Tanzania, drug-resistant malaria parasites are an
increasing public health concern. Because of widespread chloroquine
(CQ) resistance Tanzania changed its first line treatment
recommendations for uncomplicated malaria from CQ to
sulfadoxine-pyrimethamine (SP) in 2001. Loss of SP sensitivity is
progressing rapidly. SP resistance is associated with mutations in
the dihydrofolate reductase (pfdhfr) and dihydropteroate synthase
(pfdhps) genes. Methods: In samples from 86 patients with
uncomplicated Plasmodium falciparum malaria from Mbeya and Matema,
Mbeya region, south-western Tanzania, the occurrence of mutations
was investigated in the pfcrt and pfmdrl genes which are associated
with CQ resistance and in pfdhfr and pfdhps, conferring SP
resistance, as well in cytb which is linked to resistance to
atovaquone. Results: Pfcrt T76 occurs in 50% and pfmdrl Y86 in
51.7%. Pfdhfr triple mutations coexisting with pfdhps double
mutations were detected in 64.3% of the P. falciparum isolates.
This quintuple mutation is seen as a possible predictive molecular
marker for SP treatment failure. Mutations of the cytb gene were
not detected. Conclusion: These findings of a high prevalence of
mutations conferring SP resistance correspond to data of in vivo SP
efficacy studies in other regions of Tanzania and underline the
recommendation of changing first-line treatment to
artemisinin-based combination therapy.