Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.
Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (HRP2) and HRP3 are widely used throughout sub-Saharan Africa (SSA) to diagnose Plasmodium falciparum malaria. However, multiple SSA countries have reported pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions. Blood samples (n = 1109) collected from patients with P. falciparum infection from six health facilities throughout the Democratic Republic of the Congo (DRC) from March 2017 to January 2018 were evaluated for pfhrp2/3 deletions. Samples were assayed for HRP2, pan-Plasmodium LDH (pLDH) and aldolase (pAldolase) antigens by bead-based multiplex antigen assay. Samples with low HRP2 concentration compared to pLDH and pAldolase antigens were selected for further pfhrp2/3 genotyping PCRs. The majority of blood samples (93.3%, 1035/1109) had high concentrations of the HRP2 antigen. Single deletions of pfhrp2 were identified in 0.27% (3/1109) of screened samples, with one sample from each of the Kapolowe, Mikalayi, and Rutshuru study sites. A pfhrp3 single deletion (0.09%, 1/1109) was found in the Kapolowe site. Dual pfhrp2 and pfhrp3 deletions were not observed. Due to, the low numbers of pfhrp2 deletions and the sporadic locations of these deletions, the use of HRP2-based RDTs appears to still be appropriate for these locations in DRC.
M alaria remains a serious global health concern, causing ≈405,000 deaths annually, mainly in young children in Africa (1). Although substantial progress has been made over the past decade to reduce the global burden of malaria, several factors threaten these gains, including the emergence and spread of antimalarial drug resistance (1). Artemisinin-based combination therapies (ACTs) are the fi rst-line treatment for uncomplicated malaria caused by Plasmodium falciparum parasites, as recommended by the World Health Organization (WHO) (2). Unfortunately, resistance to ACTs (i.e., delayed parasite clearance and clinical treatment failures) has emerged in the Greater Mekong Subregion of Southeast Asia, posing a considerable risk to malaria control in the region (3). Even though clinical resistance to ACTs has not been reported in Africa (1), the threat of its emergence remains.
Alstonia boonei De Wild is very cited in ethnobotanical surveys and in literature as an antimalarial plant. In the Republic of Congo, traditional therapists use the decoction of A. boonei stem bark to treat Malaria. To verify this information obtained from the traditional therapists, we conducted a phytochemical study, evaluated the antiplasmodial activity and the acute toxicity of the decoction of its stem bark. The phytochemical study revealed the presence of alkaloids, tannins, flavonoids and saponins. It also allowed the extraction of total alkaloids with a yield of 6.33 ± 0.02%. The antiplasmodial activity evaluated on the strain isolated from patients infected with Plasmodium falciparum was comparable between the decoction (IC50 = 111.2 μg.ml -1 ) and the total alkaloids (IC50 = 116.4 μg.ml -1 ). This activity is therefore due to alkaloids. The lethal dose 50% (LD50) is greater than 5000 mg.kg -1 , the plant is not toxic.
CONTEXT AND OBJECTIVES The fight against malaria is threatened by the emergence and expansion of Plasmodium falciparum resistance to antimalarial drugs, to the point of questioning treatment patterns drawn by control programs. The objective of this work was to do a critical appraisal of the national guidelines for the treatment of malaria in the Democratic Republic of the Congo. METHODS To estimate the selective pressure that leads to the emergence of P. falciparum resistance to antimalarials, a cross-sectional survey was conducted on antimalarials in circulation in pharmacies in Kinshasa. An ex vivo evaluation of the P. falciparum resistance to antimalarial drugs and the analysis of molecular markers of Sulfadoxine-pyrimethamine resistance were conducted in the provinces of Kinshasa and Kongo Central during 2014 and 2015. RESULTS. The following antimalarial drugs were found in 404 pharmacies: Artemisinin-based combination therapies 88.1%, quinine 80.9%, Sulfadoxine-Pyrimethamine 56.4%, oral artemisinin-based monotherapies 23.0% and traditional medicine 30.2%. Artemether-lumefantrine combinations were the most frequently dispensed drugs (93% of pharmacies). The decrease in the susceptibility of P. falciparum isolates to antimalarials was as follows: chloroquine 65.7%, quinine 52.6%, monodesethylamodiaquine 25%, mefloquine ~ 45%, dihydroartemisinin 1.3%, piperaquine 1.6%, and doxycycline 4.3%. No isolates were found to be lumefantrine-resistant. The prevalence of mutations was high in pfdhfr (N51I: 98.5%, C59R: 88.2%, and S108N: 99.4%) and pfdhps (A437G: 97.8%). The pfdhps A581G, pfdhps K540E, pfdhfr I164L, and pfdhps A613S mutations were 14%, 17.5%, 0.1%, and 0.6%, respectively. CONCLUSION These findings show a high ex vivo resistance of P. falciparum to quinine, the antimalarial that plays an important role in the fight against malaria in the DRC. The present work highlights the complexity of the inappropriate antimalarials distribution. This shows the lack of regulation in the distribution system, potentially affecting the dynamics of resistance.
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