Efficacies of DHA-PPQ and AS/SP in patients with uncomplicated Plasmodium falciparum malaria in an area of an unstable seasonal transmission in Sudan.

BACKGROUND: Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015-16. METHODS: A total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards. RESULTS: Fifty-five patients completed the DHA-PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%. CONCLUSION: DHA-PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.

High efficacy of artemether-lumefantrine and declining efficacy of artesunate + sulfadoxine-pyrimethamine against Plasmodium falciparum in Sudan (2010-2015): evidence from in vivo and molecular marker studies.

BACKGROUND: The present paper reports on studies that evaluated artesunate + sulfadoxine-pyrimethamine (AS + SP) which is the first-line drug and artemether-lumefantrine (AL) which is a second-line drug against uncomplicated falciparum malaria in Sudan. This evaluation was performed in twenty studies covering six sentinel sites during five successive annual malaria transmission seasons from 2010 to 2015. METHODS: The standard World Health Organization protocol was used for a follow-up period of 28 days. The frequency distribution of molecular markers for antifolate resistance in dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes was studied in pre-treatment samples in four sites in 2011. RESULTS: In the nine studies of AL conducted at five sites (n = 595), high PCR-corrected cure rates were found, ranging from 96.8 to 100 %. Among the eleven studies of AS + SP (n = 1013), a decline in the PCR-corrected cure rates was observed in Gedaref in Eastern Sudan: 91.0 % in the 2011-12 season and 86.5 % in the 2014-15 season. In the remaining sites, the AS + SP cure rates ranged between 95.6 and 100 %. The rate of clearance of microscopic gametocytaemia after treatment was not significantly different with AL or AS + SP on days 7, 14, 21 and 28 of follow-up. A total of 371 pre-treatment samples were analysed for molecular markers of SP resistance. The temporal changes and geographical differences in the frequency distribution of SP-resistance genotypes showed evidence of regional differentiation and selection of resistant strains. CONCLUSION: The findings of this study call for a need to review the Sudan malaria treatment policy. Epidemiological factors could play a major role in the emergence of drug-resistant malaria in eastern Sudan. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: Trial registration numbers 2011-2012: ACTRN12611001253998, 2013-2015: ACTRN12613000945729.