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

Abstract

BackgroundFirst-line schizontocidal treatment for uncomplicated malaria in the Republic of the Sudan is artesunate (total dose 12 mg/kg) plus Sulphadoxine/pyrimethamine (25/1.25 mg/kg) (AS/SP). Patients with Plasmodium vivax are also treated with 14 days primaquine (total dose 3.5 mg/kg) (PQ). The aim of this study was to assess the efficacy of the national policy.MethodsPatients above 1 year, with microscopy-confirmed, Plasmodium falciparum and/or P. vivax malaria were treated with AS/SP. Patients with P. falciparum were randomized to no primaquine (Pf-noPQ) or a single 0.25 mg/kg dose of PQ (Pf-PQ1). Patients with P. vivax received 14 days unsupervised 3.5 mg/kg PQ (Pv-PQ14) on day 2 or at the end of follow up (Pv-noPQ). Primary endpoint was the risk of recurrent parasitaemia at day 42. G6PD activity was measured by spectrophotometry and the Accessbio Biosensor™.Results231 patients with P. falciparum (74.8%), 77 (24.9%) with P. vivax and 1 (0.3%) patient with mixed infection were enrolled. The PCR corrected cumulative risk of recurrent parasitaemia on day 42 was 3.8% (95% CI 1.2–11.2%) in the Pf-noPQ arm compared to 0.9% (95% CI 0.1–6.0%) in the Pf-PQ1 arm; (HR = 0.25 [95% CI 0.03–2.38], p = 0.189). The corresponding risks of recurrence were 13.4% (95% CI 5.2–31.9%) in the Pv-noPQ arm and 5.3% (95% CI 1.3–19.4%) in the Pv-PQ14 arm (HR 0.36 [95% CI 0.1–2.0], p = 0.212). Two (0.9%) patients had G6PD enzyme activity below 10%, 19 (8.9%) patients below 60% of the adjusted male median. Correlation between spectrophotometry and Biosensor™ was low (rs = 0.330, p < 0.001).ConclusionAS/SP remains effective for the treatment of P. falciparum and P. vivax. The addition of PQ reduced the risk of recurrent P. falciparum and P. vivax by day 42, although this did not reach statistical significance. The version of the Biosensor™ assessed is not suitable for routine use. Trial registration https://clinicaltrials.gov/ct2/show/NCT02592408 Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2266-9) contains supplementary material, which is available to authorized users.

Genetic polymorphism of the N-terminal region in circumsporozoite surface protein of Plasmodium falciparum field isolates from Sudan

“…This divergence in frequency which also affects the genetic diversity in the N-terminal region could be owed to environmental pressures in terms of evading host immune response or evading drugs pressures such the case on the great Mekong sub-region or the Indian subcontinent [14, 16, 25]. Also, the diversity of circulating parasite strains in a specific region such as Sudan could implicate in the process of specific dominant strain in that region, and through time this could result in maintaining a specific strain that able to overcome not only the host immune response but also drug pressure [3, 5–10, 38]. Also, the ability of a monoclonal antibody to bind to the linear epitope in the N-terminal region has effectively neutralized the infection of the sporozoites in vivo; accordingly, besides the similarity in the PfCSP N-terminal region this region could provide a potential vaccine candidate against falciparum malaria infection [45].…”

“…In Sudan, malaria continues to spread despite the efforts of the National Malaria Control Programme (NMCP). Many studies in Sudan have focused on addressing the situation of malaria treatment efficacy [3–5], while others focused on reporting the genetic diversity and the genetic makeup of the parasite itself [6–10]. RTS,S, which is the most advanced malaria vaccine to be implemented in most African countries, has shown a remarkable reduction of falciparum malaria episodes in children [11–13].…”

Novel highly-multiplexed AmpliSeq targeted assay for Plasmodium vivax genetic surveillance use cases at multiple geographical scales

“…To increase the range of geographical locations, we additionally included 31 samples collected by vivaxGEN network ( ) as part of previously described clinical and cross-sectional surveys conducted between 2006-2016 (Afghanistan, Bangladesh, Bhutan, China, Colombia, Ethiopia, Malaysia, Papua New Guinea, Sudan and Thailand) and collections from returning travelers (India and Indonesia) to the Royal Darwin Hospital, Australia ( Liu et al., 2014 ; Auburn et al., 2016 ; Hamedi et al., 2016 ; Ley et al., 2016 ; Wangchuk et al., 2016 ; Auburn et al., 2018 ; Hamid et al., 2018 ; Auburn et al., 2019 ; Taylor et al., 2019 ). In all studies, 1-5 mL venous blood samples were collected from informed, consenting patients (or a parent or guardian for individuals under 18 years of age) presenting with symptomatic, P. vivax- positive infection in clinical frameworks.…”

Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance, and genetic variants in two malaria-endemic areas in Sudan

“…vivax infection. To date, reports originating from Sudan on glucose-6-phosphate dehydrogenase deficiency (G6PDd) are limited [ 4 – 6 ]. The G6PD gene consists of 13 exons and 12 introns, which are located on the long arm of the X-chromosome at gene loci Xq28.…”