RESUMO
BACKGROUND: As a result of the spread of parasites resistant to antimalarial drugs, Malaria treatment guidelines in Cameroon evolved from nonartemisinin monotherapy to artemisinin-based combination therapy. The aim of this study was to assess the effect of these therapy changes on the prevalence of molecular markers of resistance from 2003 to 2013 in Mutengene, Cameroon. METHODOLOGY: Dry blood samples (collected in 2003-2005 and 2009-2013) were used for parasite DNA extraction. Drug resistance genes were amplified by PCR and hybridized with oligonucleotide probes or subjected to restriction digestion. The prevalence of individual marker polymorphisms and haplotypes was compared in these two study periods using the Chi square test. RESULTS: Alleles conferring resistance to 4-aminoquinolines in the Pfcrt 76T and Pfmdr1 86Y, 184F, and 1246Y genotypes showed a significant reduction of 97.0% to 66.9%, 83.6% to 45.2%, 97.3% to 56.0%, and 3.1% to 0.0%, respectively (P < 0.05). No difference was observed in SNPs associated with antifolate drugs resistance 51I, 59R, 108N, or 540E (P > 0.05). Haplotype analysis in the Pfmdr1 gene showed a reduction in the YFD from 75.90% to 42.2%, P < 0.0001, and an increase in the NYD (2.9% to 30.1%; P < 0.0001). CONCLUSIONS: The results indicated a gradual return of the 4-aminoquinoline sensitive genotype while the antifolate resistant genotypes increased to saturation.
RESUMO
BACKGROUND: Artemether-lumefantrine and artesunate-amodiaquine are first-line treatment for uncomplicated malaria in Cameroon. No study has yet compared the efficacy of these drugs following the WHO recommended 42-day follow-up period. The goal of this study was to compare the clinical efficacy, tolerability and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and dihydroartemisinin piperaquine (DHAP) among children aged less than ten years in two malaria-endemic ecological regions of Cameroon. METHODS: A three-arm, randomized, controlled, non-inferiority trial was conducted among children of either gender aged six months (>5 kg) to ten years (n = 720) with acute uncomplicated Plasmodium falciparum infection. Parents/guardians of children provided consent prior to randomization to receive ASAQ, DHAP or AL in the ratio of 2:2:1, respectively. Treatment outcome was assessed based on standard WHO 2003 classification after 42 days of follow-up. The primary outcome was PCR-corrected day-42 cure rates. The non-inferiority, one-sided, lower limit asymptotic 97.5% confidence interval (CI) on the difference in PCR-corrected cure rates of ASAQ and DHAP when compared to AL was accepted if the lower limit of the CI was greater than -10%. Secondary outcomes were parasite and fever clearances and day 7 haemoglobin changes. RESULTS: PCR-corrected PP cure rates of 96.7, 98.1 and 96.3, respectively, for AL, ASAQ and DHAP was observed. The lower bound of the one-sided 97.5% CI calculated around the difference between day-42 cure rate point estimates in AL and ASAQ groups, AL and DHAP groups were, -6% and -4% respectively. There were no statistical significant differences in parasite or fever clearance times between treatments, although fever clearance pattern was different between ASAQ and DHAP. No statistical significant differences were observed in the occurrence of adverse events among treatment groups. CONCLUSION: ASAQ and DHAP are considered safe and tolerable and are not inferior to AL in the treatment of uncomplicated P. falciparum malaria in Cameroonian children. TRIAL REGISTRATION: NCT01845701.