Monitoring the efficacy and safety of three artemisinin based-combinations therapies in Senegal: results from two years surveillance

Abstract

BackgroundMalaria remains a major public health problem in developing countries. Then in these countries prompt access to effective antimalarial treatment such as Artemisinin based-Combination Therapies (ACT) proves to be an essential tool for controlling the disease. In Senegal, since 2006 a nationwide scaling up program of ACT is being implemented. In this context it has become relevant to monitor ACT efficacy and provide recommendations for the Senegalese national malaria control program.MethodsAn open randomized trial was conducted during two malaria transmission seasons (2011 and 2012) to assess the efficacy and safety of three combinations: dihydro-artemisinin-piperaquine (DHAPQ), artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ). The primary end point of the study was represented by a PCR adjusted adequate clinical and parasitological response (ACPR) at day 28. Secondary end points included: (i) a ACPR at days 35 and 42, (ii) a parasite and fever clearance time, (iii) ACTs safety and tolerability. The 2003 WHO’s protocol for antimalarial drug evaluation was used to assess each outcome.ResultsOverall, 534 patients were randomized selected to receive, either ASAQ (n = 180), AL (n = 178) or DHAPQ (n = 176). The PCR adjusted ACPR at day 28 was 99.41% for the group ASAQ, while that was 100% in the AL and DHAPQ groups (p = 0.37). The therapeutic efficacy was evaluated at 99.37% in the ASAQ arm versus 100% in AL and DHAPQ arm at day 35 (p = 0.37). At day 42, the ACPR was 99.27% in the ASAQ group versus 100% for both AL and DHAPQ groups, (p = 0.36). No serious adverse event was noted during the study period. Also a similar safety profile was noted in the 3 study groups.ConclusionIn the context of scaling up of ACTs in Senegal, ASAQ, AL and DHAPQ are highly effective and safe antimalarial drugs. However, it’s remains important to continue to monitor their efficacy.Trial registrationPACTR 201305000552290.

Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013

“…Further studies are needed to better characterize these variations. However, the absence of putative P. falciparum artemisinin resistance mutations in Senegal is consistent with the efficacy of ACT in Senegal [22, 23]. …”

“…The polymorphisms associated with artemisinin resistance in Southeast Asia were not detected in other countries in Africa with the exception of the P553L which was detected in one isolate in Mali [12, 23, 24]. In Uganda, the prevalence of k13 -propeller polymorphisms was not associated with the persistence of parasites after two days following treatment with artemether-lumefantrine [21].…”

“…The V520A mutation that was identified in 13 of 14 parasites populations from West Africa (Gambia, Mali, Ghana, Burkina Faso), Central Africa (Democratic Republic of Congo) and East Africa (Kenya, Tanzania, Malawi) was not detected in Dakar [23]. This mutation was not found in Uganda [24].…”

Molecular Epidemiology of Plasmodium falciparum kelch13 Mutations in Senegal Determined by Using Targeted Amplicon Deep Sequencing

“…Monitoring the changes in Pfk13 allele frequencies over time will be critical for guiding both treatment policy and elimination campaigns. To date, only a limited number of Pfk13 polymorphisms have been reported in Senegal (23,25,26), and overall ACT efficacy remains high (21)(22)(23).…”

“…Artemisinin combination therapy (ACT) was first implemented in Senegal in 2006, and reports indicate that artemisinin-based therapies remain efficacious in the country (21)(22)(23). In addition, no evidence of the confirmed Pfk13 alleles associated with artemisinin resistance have been reported in Senegal.…”