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

Abstract

BackgroundThe 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.MethodsThe 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.ResultsIn 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.ConclusionThe 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 RegistryTrial registration numbers 2011–2012: ACTRN12611001253998, 2013–2015: ACTRN12613000945729

Efficacy and safety of artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Sudan: a systematic review and meta-analysis

“…were also included in this review. Twenty out of the retrieved 24 studies satisfied the inclusion criteria and were included in this systematic review and meta-analysis with a total sample size of 4070 participants that ranged from 30 patients [ 19 ] to 1463 patients [ 23 ]. Treatment outcomes in all studies were assessed using clinical and parasitological criteria according to WHO guidelines [ 10 – 12 , 35 ].…”

Molecular surveillance of putative drug resistance markers of antifolate and artemisinin among importedPlasmodium falciparumin Qatar

“…Moreover, the double mutant genotype (51I/108N) was predominant from East African isolates than other areas because the majority of the isolates were from Sudan origin. The double mutation was prevalent in Sudan in 2007 [30] and still maintains the double mutant genotype with an emerging triple mutation [31]. Triple mutants (51I, 59R, 108N), which associated with highlevel pyrimethamine resistance [10,11], were almost fixed in the African population [32,33].…”

Low risk of recurrence following artesunate–Sulphadoxine–pyrimethamine plus primaquine for uncomplicated Plasmodium falciparum and Plasmodium vivax infections in the Republic of the Sudan

“…In 2006, a study in the east of the country reported a day 28 PCR corrected efficacy of 93.5% for AS/SP for P. falciparum [ 31 ]. Other clinical studies conducted between 2010 and 2015 at six sites suggest that the PCR corrected efficacy of AS/SP against P. falciparum by day 28 generally exceeds 95%, except for one site in Gedaref, in the East of the country, where the efficacy fell from 91% in 2012 to 87% in 2015 [ 32 ].…”