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

Abstract

BackgroundArtemisinin-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.MethodsA 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.ResultsFifty-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%.ConclusionDHA–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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1817-9) contains supplementary material, which is available to authorized users.

Assessment of Plasmodium falciparum drug resistance molecular markers from the Blue Nile State, Southeast Sudan

“…The other markers were not studied. The choice of DHA-PPQ as second line of treatment [17] is well supported by this evidence. PPQ enjoys the fact that it has never been used as a mono-therapy for malaria treatment [42,43].…”

“…Earlier reports in Sudan have shown that multiple mutations were highly prevalent in eastern Sudan [7,14]. Failure of combination therapy AS/SP in Sudan was ascribed to failure of the partner drug SP [23] and that combination was replaced by AL as the first-line of treatment [17]. This high resistance of SP also means that it cannot be used intermittently for the protection of pregnant women in highly endemic areas in Sudan.…”

“…The study was conducted in two health centres in Damazin, the Capital of the Blue Nile State, Southeastern Sudan (location 11.7855° N, 34.3421° E). Malaria transmission is seasonal unstable transmission following the rainy season which is July to October [17]. There is another minor peak during December to February winter months [22].…”

“…The samples of this study were dried blood spots (DBS) from uncomplicated P. falciparum malaria patients taken at day zero. Samples were part of efficacy studies for AS/ SP (n = 63) and DHA-PPQ (n = 67) performed in the Blue Nile state between November 2015 and January 2016, Sudan [17]. The total number of samples was 130 (123 were from the adequately responsive patients and 7 Keywords: P. falciparum, Molecular marker, Sudan, Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfk13, Exonuclease with late parasitological drug failure (LPF) belonging to AS/SP group).…”

“…This combination together with other control measures remarkably reduced the cases of malaria in Sudan during 10 years period [1]. Again treatment failure to this combination became a public health problem [15,17] and the combination of artemether/lumefantrine as first-line of treatment of uncomplicated malaria and dihydroartemisinin/piperaquine (DHA-PPQ) as a second-line were introduced in March 2017 [17]. Exonuclease gene mutation (415G) has been noticed to be associated with increased tolerance of piperaquine [18].…”