High prevalence of Plasmodium falciparum antimalarial drug resistance markers in isolates from asymptomatic patients from the Republic of the Congo between 2010 and 2015

Voumbo-Matoumona, Dominique Fatima; Akiana, Jean; Madamet, Marylin; Kouna, Lady Charlene; Lékana-Douki, Jean Bernard; Pradines, Bruno

doi:10.1016/j.jgar.2018.08.003

Cited by 7 publications

(4 citation statements)

References 59 publications

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“…Similar patterns involving high triple mutant prevalence were observed in the population of other African countries, such as Cameroon, Congo, Equatorial Guinea, Senegal, and Tanzania [ 23 , 44 , 48 – 50 ]. On comparing with the high multiple mutations sets documented in Nigeria [ 51 ] and Kenya [ 52 ], where various SNPs increased the double, triple, and quadruple mutation sets in Pfdhfr , likewise NRNL, IRSI, ICNI, and ICNL multiple mutation sets were expressed among the current studied population.…”

Section: Discussionsupporting

confidence: 70%

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

Dinzouna-Boutamba

Iroungou

Akombi

et al. 2023

Malar J

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Background Gabon is a malaria-threatened country with a stable and hyperendemic transmission of Plasmodium falciparum monoinfection. Malaria drug resistance is widely spread in many endemic countries around the world, including Gabon. The molecular surveillance of drug resistance to antifolates and artemisinin-based combination therapy (ACT) is one of the strategies for combating malaria. As Plasmodium parasites continue to develop resistance to currently available anti-malarial drugs, this study evaluated the frequency of the polymorphisms and genetic diversity associated with this phenomenon among the parasites isolates in Gabon. Methods To assess the spread of resistant haplotypes among the malaria-infected population of Libreville, single nucleotide polymorphisms linked to sulfadoxine–pyrimethamine (SP) and artemisinin drugs resistance were screened for P. falciparum dihydrofolate reductase (Pfdhfr), P. falciparum dihydropteroate synthase (Pfdhps), and P. falciparum kelch 13-propeller domain (Pfk13) point mutations. Results The analysis of 70 malaria-positive patient samples screened for polymorphism showed 92.65% (n = 63) mutants vs. 7.35% (n = 5) wild parasite population in Pfdhfr, with high prevalence mutations at S108N(88.24%, n = 60), N51I(85.29%, n = 58), C59R(79.41%, n = 54); however, I164L(2.94%, n = 2) showed low frequency mutation. No wild haplotype existed for Pfdhps, and there were no mutations at the K540E, A581G, and A613T/S positions. However, the mutation rate at A437G(93.38%, n = 62) was the highest, followed by S436A/F(15.38%, n = 10). A higher frequency of quadruple IRNI–SGKAA (69.84%) than quintuple IRNI–(A/F)GKAA (7.94%) mutations was observed in the Pfdhfr–Pfdhps combination. Furthermore, none of the mutations associated with ACT resistance, especially those commonly found in Africa, were observed in Pfk13. Conclusions High polymorphism frequencies of Pfdhfr and Pfdhps genes were observed, with alternative alanine/phenylalanine mutation at S436A/F (7.69%, n = 5) for the first time. Similar to that of other areas of the country, the patterns of multiple polymorphisms were consistent with selection owing to drug pressure. Although there was no evidence of a medication failure haplotype in the studied population, ACT drug efficacy should be regularly monitored in Libreville, Gabon.

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Section: Discussionsupporting

confidence: 70%

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

Dinzouna-Boutamba

Iroungou

Akombi

et al. 2023

Malar J

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“…We extracted DNA from the samples and confirmed diagnosis using PCR. We sequenced the antimalarial drug resistance molecular markers Pfdhfr , Pfmdr1 , Pfcrt , and the propeller domain of PfK13 as described elsewhere ( 7 ). We treated patients with a 3-day regimen of dihydroartemisinin/piperaquine and measured levels of parasitemia on days 0 and 3; this treatment failed in 1 patient with malaria caused by P. falciparum .…”

Section: The Studymentioning

confidence: 99%

Role of Anopheles stephensi Mosquitoes in Malaria Outbreak, Djibouti, 2019

Santi¹,

Khaireh²,

Chiniard³

et al. 2021

Emerg. Infect. Dis.

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T he Republic of Djibouti, bordered by Eritrea, Ethiopia, and Somalia, is a semiarid country in the Horn of Africa. The population comprises <900,000 persons, 70% of whom live in Djibouti, the capital city. Before 2013, malaria was hypoendemic to the country, with low levels of transmission in periruban and rural areas during December-May. Localized outbreaks occurred regularly, possibly caused by migration from surrounding countries. Most cases were caused by infection with Plasmodium falciparum (>80%) or P. vivax. Before 2013, researchers considered the Anopheles arabiensis mosquito to be the primary vector (1).The incidence of malaria had drastically decreased in the country since 2008; by 2012, this transmission level was compatible with preelimination goals (2,3). In 2013, an autochthonous outbreak of malaria occurred in Djibouti; fi eld entomologic investigations identifi ed An. stephensi mosquitoes as a new malaria vector (4). This species, a known vector of urban malaria in India and the Arabian Peninsula, has changed the epidemiologic profi le of malaria in Djibouti (5). In 2018, malaria incidence increased to 25,319 confi rmed cases (64% caused by P. falciparum and 36% by P. vivax) and >100,000 suspected cases (Appendix Figure 1, https://wwwnc.cdc.gov/EID/ article/27/6/20-4557-App1.pdf).The French Armed Forces (FAF) have served in Djibouti for decades. Service members and their families (≈2,700 persons) live in the capital. Despite malaria prevention and treatment measures described elsewhere (6), an outbreak among French military personnel occurred in February 2019; failure of early artemisinin combined therapy was documented in 1 patient. The StudyWe collated FAF epidemiologic surveillance data on malaria cases among service members in Djibouti during 1993Djibouti during -2019; the 2019 data included cases among family members. We defi ned a malaria case as an illness resulting in a positive result on a rapid diagnostic test or thin blood smear.We conducted the fi eld investigation in the capital during February 28-March 22, 2019. We obtained a dried blood spot on fi lter paper from each patient and stored the samples in a sealed plastic pouch until processing. We extracted DNA from the samples and

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“…In that study, amodiaquine, dihydroartemisinin, and lumefantrine were highly active in vitro against multidrug-resistant P. falciparum . More recent analysis of P. falciparum kelch 13 propeller gene, a molecular marker of resistance to artemisinins [ 55 ], did not detect any mutation associated with resistance in isolates in Brazzaville, Pointe-Noire, and in northern region of the country [ 32 , 34 , 56 ]. Available data from in vitro drug sensitivity assays, molecular analysis of drug resistance markers, and therapeutic efficacy studies on AL and ASAQ indicate that at present these two artemisinin-based combinations are reliable first-line drugs to treat uncomplicated malaria in the Republic of the Congo.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of malaria among febrile patients and assessment of efficacy of artemether-lumefantrine and artesunate-amodiaquine for uncomplicated malaria in Dolisie, Republic of the Congo

Singana

Casimiro²,

Diassivi³

et al. 2022

Malar J

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Background In the Republic of the Congo, malaria represents a major public health problem affecting all age groups. A regular surveillance of the current efficacy of first-line anti-malarial drugs is required in the face of possible emergence and spread of artemisinin-resistant Plasmodium falciparum strains in Africa. The purpose of this study was to determine the prevalence of malaria among febrile patients of all ages and assess the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) in Congolese children. Methods Febrile patients of all ages were initially screened for malaria by both rapid diagnostic test (RDT) and microscopy. Patients less than 12 years of age, with parasitaemia ≥ 1000 asexual parasites of P. falciparum/µL of blood, without any signs of severity, were enrolled in a therapeutic efficacy study and treated after obtaining their parents' (or legal guardian’s) informed consent in two health centres in Dolisie. The patients were followed for 28 days in accordance with the 2009 World Health Organization standard protocol. If parasitaemia reappeared on or after day 7, the genetic profiles (genes expressing merozoite surface protein-1 [msp1], merozoite surface protein-2 [msp2], and glutamine-rich protein [glurp]) of pre-treatment and post-treatment isolates were compared by nested polymerase chain reaction (PCR) followed by capillary electrophoresis to make a distinction between recrudescence and re-infection. The clinical and parasitological outcome was analysed by the per-protocol method and Kaplan–Meier survival curves. Results A total of 994 febrile patients of all ages were screened by RDT and microscopy. Of 994 patients, 323 (32.5%) presented a positive RDT, and 266 (26.8%) were microscopy-positive. Based on microscopy as the reference diagnostic method, the sensitivity and the specificity of the RDT were 98.9 and 91.8%, respectively. The Cohen’s kappa coefficient was 0.86. A total of 121 children aged less than 12 years (61 in AL treatment group and 60 in ASAQ treatment group) were included in therapeutic efficacy study. Before PCR correction, the proportions of adequate clinical and parasitological response were 96.6% for AL and 86.0% for ASAQ in the per-protocol population (P < 0.05). The PCR-corrected efficacy rates were 98.2% and 94.2% for AL and ASAQ, respectively (P > 0.05). Both treatments were well tolerated. Conclusions AL and ASAQ remain highly effective for the first-line treatment of uncomplicated P. falciparum malaria in Dolisie. Despite high efficacy of first- and second-line treatment, there is a continuing need to scale up effective malaria preventive interventions and vector control strategies in the country. Trial Registration Number: ACTRN12616001422415.

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High prevalence of Plasmodium falciparum antimalarial drug resistance markers in isolates from asymptomatic patients from the Republic of the Congo between 2010 and 2015

Cited by 7 publications

References 59 publications

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

Assessment of genetic polymorphisms associated with malaria antifolate resistance among the population of Libreville, Gabon

Role of Anopheles stephensi Mosquitoes in Malaria Outbreak, Djibouti, 2019

Prevalence of malaria among febrile patients and assessment of efficacy of artemether-lumefantrine and artesunate-amodiaquine for uncomplicated malaria in Dolisie, Republic of the Congo

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