Antimalarial resistance and DHFR/DHPS genotypes of Plasmodium falciparum three years after introduction of sulfadoxine-pyrimethamine and amodiaquine in rural Tanzania.

We assessed the efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania, 3 years after their introduction as first- and second-line treatments for uncomplicated malaria, respectively. Under five children with uncomplicated malaria were given standard treatments of either SP (n=66) or AQ (n=30) and treatment outcomes after 14 and 28 days were determined. Total treatment failure of 18 and 42.5% was observed for SP on days 14 and 28, respectively. For AQ, total treatment failure of 27 and 53% was found on day 14 and 28, respectively. On day 14, significantly lower SP total treatment failures were observed in 2004 compared with results from a study conducted in 1999 in the same location. No relationship was detected between clinical outcome and DHFR/DHPS genotypes, but the point mutation prevalence in parasites was higher than in 1999. Pre-treatment blood levels of SP were detected in a quarter of the study children: less than expected. We report unacceptably high levels of total treatment failures, both for first- and second-line treatments for uncomplicated malaria in Tanzania 3 years after their introduction, supporting the decision to replace them with artemisinin-based combination therapy.

Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine.