scholarly journals Susceptibility of Plasmodium falciparum isolates to antimalarial drugs in a highly seasonal malaria endemic village in Mali

2019 ◽  
Author(s):  
Karim Traoré ◽  
Seidina AS Diakité ◽  
Sekou Bah ◽  
Drissa S Konaté ◽  
Djeneba Dabitao ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Ex Vivo ◽  
Control Program ◽  
Antimalarial Drugs ◽  
Sensitivity Testing ◽  
Artemisinin Derivatives ◽  
Malaria Control Program ◽  
National Malaria Control Program ◽  
Antimalarial Resistance ◽  
Ic50 Values

Abstract Background: In 2006, the National Malaria Control Program (NMCP) in Mali recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. Since the introduction of ACT, few reports are available on the level of resistance of Plasmodium falciparum (P. falciparum) to antimalarial drugs in Mali. Dihydroartermisinin is the active metabolite of artemisinin derivatives. Here, we conducted an ex-vivo drug sensitivity testing in a rural area of southern Mali, namely the Kéniéroba village from 2016 to 2017. Methods: Seventy-five (75) isolates of P. falciparum were successfully evaluated for ex-vivo sensitivity to key anti-malarial drugs, namely chloroquine (CQ), quinine (QN), amodiaquine (AQ), mefloquine (MQ), lumefantrine (LUM), dihydroartermisinin (DHA) , and piperaquine (PPQ). P. falciparum sensitivity to these drugs was assessed using the World Wide Antimalarial Resistance Network (WWARN) SYBR-GREEN method of inhibitory concentration of 50% (IC50) determination. Reduced sensitivity to antimalarial drugs was defined as IC50 less than the WWARN standard IC50. Results: The proportion of resistant P. falciparum isolates was 20.2% for CQ, 40.5% for QN, 6.8% for AQ, and 1.3% for MQ. All tested P. falciparum isolates were sensitive to LUM, DHA, and PPQ. A statistically significant correlation was found between QN and AQ IC50 values (r = 0.80; r2 = 0.64, P<0.0001). Conclusions: P. falciparum isolates were sensitive to all ACT derivates tested in Kenieroba in Mali. In contrast, P. falciparum isolates were resistant to, CQ, QN, and AQ as evidenced by high IC50 to these drugs.

scholarly journals Therapeutic efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali, 2015–2016

2020 ◽  
Author(s):  
Youssouf Diarra ◽  
Oumar Koné ◽  
Lansana Sangaré ◽  
Lassina Doumbia ◽  
Dade Bouye Ben Haidara ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Uncomplicated Malaria ◽  
Artemisinin Resistance ◽  
Control Program ◽  
Plasmodium Falciparum Malaria ◽  
Malaria Control Program ◽  
National Malaria Control Program ◽  
Pre Treatment ◽  
Better Than

Abstract Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Program in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015–2016, we conducted an in vivo study to assess the clinical and parasitological responses to AL and ASAQ in Sélingué, Mali. Methods Children between 6 and 59 months of age with uncomplicated Plasmodium falciparum infection and 2,000–200,000 asexual parasites/µL of blood were enrolled, randomly assigned to either AL or ASAQ, and followed up for 42 days. Uncorrected and PCR-corrected efficacy results at days 28 and 42 were calculated. Known markers of resistance in the Pfk13, Pfmdr1, and Pfcrt genes were assessed using Sanger sequencing. Results A total of 449 patients were enrolled: 225 in the AL group and 224 in the ASAQ group. Uncorrected efficacy at day 28 was 83.4% (95% CI: 78.5–88.4%) in the AL arm and 93.1% (95% CI: 89.7–96.5%) in the ASAQ arm. The per protocol PCR-corrected efficacy at day 28 was 91.0% (86.0–95.9%) in the AL arm and 97.1% (93.6–100%) in the ASAQ arm. ASAQ was significantly (p < 0.05) better than AL for each of the aforementioned efficacy outcomes. No mutations associated with artemisinin resistance were identified in the Pfk13 gene. Overall, for Pfmdr1, the N86 allele and the NFD haplotype were the most common. The NFD haplotype was significantly more prevalent in the post-treatment than in the pre-treatment isolates in the AL arm (p < 0.01) but not in the ASAQ arm. For Pfcrt, the CVIET haplotype was the most common. Conclusions Our findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

scholarly journals Molecular Surveillance of Antimalarial Resistance Pfcrt, Pfmdr1 and Pfk13 Polymorphisms in African Plasmodium Falciparum Imported Parasites to Wuhan, China

2020 ◽  
Author(s):  
Cheng Weijia ◽  
Xiaonan Song ◽  
Huabing Tan ◽  
Kai Wu ◽  
Jian Li
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Mixed Type ◽  
Antimalarial Drugs ◽  
Wild Type ◽  
Mutant Type ◽  
Molecular Surveillance ◽  
Severe Problem ◽  
Antimalarial Resistance ◽  
Effective Drugs

Abstract Background: The development of drug resistance in Plasmodium falciparum becomes a severe problem for malaria control globally. Before finding a practical solution, monitoring the susceptibility of P. falciparum resistance-related genes is crucial. It will offer valuable information on the drug resistance in malaria-endemic areas and guides the rational clinical use of antimalarial drugs.Methods：Filter paper blood was taken from patients with positive P. falciparum during 2017-2019 in Wuhan, China. The target fragments from pfcrt, pfmdr1, and k13 propeller (pfk13) genes of P. falciparum were amplified and sequenced. Subsequently, the polymorphisms of pfcrt, pfmdr1, and pfk13 and the haplotypes of Pfcrt and Pfmdr1 were analyzed.Results: Totally, 106 samples were collected. Subsequently, 98.11% (104/106), 100% (106/106), and 86.79% (92/106) of these samples were successfully amplified and sequenced for the pfcrt, pfmdr1, and pfk13 genes, respectively. The prevalence of Pfcrt K76T, Pfmdr1 N86Y, and Pfmdr1 Y184F mutation were 9.62%, 4.72%, and 47.17%, respectively. At codons 72-76 of pfcrt gene locus were showed three haplotypes, including CVMNK (wild-type), CVIET (mutation type), CV M/I N/E K/T (mixed type), with 87.50%, 9.62%, and 2.88% prevalence, respectively. For the pfmdr1 gene, including NY (wild type), NF and YF (mutant type), N Y/F, Y Y/F, and N/Y Y/F (mixed type), accounted for 34.91%, 43.40%, 3.77%, 15.09%, 0.94%, and 1.89%, respectively. A total of eleven Pfcrt/Pfmdr1 combined haplotypes, including six types of combined haplotypes, and five combined haplotypes with mixed-type, For pfk13, no mutation was detected. Conclusions: The wild-type SNPs and haplotypes for the pfcrt, and pfmdr1 genes become predominant in the current study. It indicates these isolates entirely or partly recovery their susceptibility to antimalarial drugs, including chloroquine, amodiaquine, and mefloquine. Moreover, it demonstrates these drugs can continue to be effective drugs for P. falciparum malaria cases treatment in Africa. Although no mutation is detected in pfk13, continuous molecular surveillance is still urgently necessary.

scholarly journals Performance of pirimiphos-methyl based Indoor Residual Spraying on entomological parameters of malaria transmission in the pyrethroid resistance region of Koulikoro, Mali.

2020 ◽  
Author(s):  
Moussa KEITA ◽  
Nafomon SOGOBA ◽  
Boïssé Traoré ◽  
Fousseyni Kané ◽  
Boubacar Coulibaly ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Pyrethroid Resistance ◽  
Control Strategies ◽  
Indoor Residual Spraying ◽  
Control Program ◽  
Mosquito Vector ◽  
Monthly Basis ◽  
Malaria Control Program ◽  
National Malaria Control Program ◽  
Pirimiphos Methyl

Abstract Background:Vector control relies heavily on Long-lasting insecticidal nets ( (LLINs) and Indoor Residual Spraying (IRS) in selected districts in Mali including Koulikoro district. As part of strengthening vector control strategies in the district, IRS was initiated by the National Malaria Control Program (NMCP) with the support of the US President's Malaria Initiative (PMI) since 2008. LLINs coverage was 93.3% and 98.2% for IRS in Koulikoro, the only district of the region where IRS was supported by PMI. Following mosquito vector resistance to both pyrethroid and carbamates, organophosphate (pirimiphos-methyl) was used for the IRS campaigns of 2015 and 2016 in the district of Koulikoro. In this study, we assessed the effect of IRS on malaria transmission by comparing entomological indices in of the district of Koulikoro, where IRS was implemented and its neighbored district of Banamba, where IRS had never been implemented. Methods:The study was conducted in two villages of each district (Koulikoro and Banamba). Pyrethrum spray catches and entry window trapping were used to collect mosquitoes on a monthly basis. WHO tube tests were carried out to assess mosquito susceptibility to insecticides. Mosquitoes were identified to species level by PCR and their infection to P. falciparum was detected by ELISA.Results:Of the 527 specimens identified, An. coluzzii was the most frequent species (95%) followed by An. gambiae (4%) and An. arabiensis (1%). Its density was rainfall dependent in the no-IRS area, and almost independent in the IRS area. The infection rate (IR) in the no-IRS area was 0.96%, while it was null in the IRS area. In the no-IRS area, the entomological inoculation rates (EIR) was 0.21 infective bites /person month with a peak in September. High resistance to pyrethroids and carbamates and susceptibility to organophosphates was observed at all sites.Conclusion:The introduction of pirimiphos-methyl based IRS in the area resulted in a significant decrease in malaria transmission. An.gambiae s.l., the main malaria vector of the area, was resistant to pyrethroids and carbamates, and remained susceptible to the organophosphates.

scholarly journals The Mu Subunit of Plasmodium falciparum Clathrin-Associated Adaptor Protein 2 ModulatesIn VitroParasite Response to Artemisinin and Quinine

2015 ◽  
Vol 59 (5) ◽  
pp. 2540-2547 ◽  
Author(s):  
Gisela Henriques ◽  
Donelly A. van Schalkwyk ◽  
Rebekah Burrow ◽  
David C. Warhurst ◽  
Eloise Thompson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adaptor Protein ◽  
Content Type ◽  
Artemisinin Derivatives ◽  
Combination Treatments ◽  
Antimalarial Resistance ◽  
Transgenic Parasites ◽  
Multiple Drugs

ABSTRACTThe emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance,ap2-mu(encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasitePlasmodium chabaudi(pcap2-mu). Furthermore, analysis in Kenyan malaria patients of polymorphisms in thePlasmodium falciparumap2-muhomologue,pfap2-mu, found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survivalin vivofollowing combination treatments which included artemisinin derivatives. Here, we characterize the role ofpfap2-muin mediating thein vitroantimalarial drug response ofP. falciparumby generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form ofpfap2-mu. Transgenic parasites carrying thepfap2-mu160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-hin vitrotest, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence thatpfap2-muvariants can modulate parasite sensitivity to quinine. No evidence was found thatpfap2-muvariants contribute to the slow-clearance phenotype exhibited byP. falciparumin Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence thatpfap2-mucan modulateP. falciparumresponses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance.

scholarly journals Implementation Fidelity of the National Malaria Control Program in Burkina Faso

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69865 ◽  
Author(s):  
Valéry Ridde ◽  
Thomas Druetz ◽  
Serge Poppy ◽  
Seni Kouanda ◽  
Slim Haddad
Keyword(s):  
Burkina Faso ◽  
Malaria Control ◽  
Implementation Fidelity ◽  
Control Program ◽  
Malaria Control Program ◽  
National Malaria Control Program

scholarly journals A rapid, low-cost methodology for longitudinal evaluation of insecticide treated bednet distributions: a pilot survey coupling bednet usage with malaria prevalence at the household level

2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Karen B. Jacobson ◽  
Dennis Danforth ◽  
James Lin ◽  
Steven Merjavy ◽  
Brendan Milliner ◽  
...  
Keyword(s):  
Low Cost ◽  
Control Program ◽  
Malaria Prevalence ◽  
Bed Nets ◽  
Distribution Data ◽  
Household Level ◽  
Malaria Control Program ◽  
National Malaria Control Program ◽  
Individual Use ◽  
Distribution Campaign

Tanzania’s National Malaria Control Program distributed 23.3 million insecticidetreated bed nets (ITNs) between 2009 and 2011. Annual randomized household surveys were conducted from 2009 to 2011 to assess the incremental effects of the distribution campaign on malaria prevalence and bednet usage in Kijumbura village in Kagera, Tanzania. Data was collected about household ITN ownership and individual use, and each household member was given a rapid malaria diagnostic test (RDT). In total, 1247 individuals from 285 households participated. From 2009 to 2011, household ITN ownership increased from 50.6 to 95.3% and individual usage increased from 9.7 to 55.3% in 2011. Malaria point prevalence decreased from 15.8% in 2009 to 6.5% in 2010, and increased from 6.5% in 2010 to 10.7% in 2011. The survey cost in 2011 was 23.50 USD per household; major expenses were transportation, personnel payment, and the purchase of the RDTs. Evaluations of bednet distribution programs generally rely on distribution data and selfreported net ownership, but it is important to also assess the goal endpoint of reduction in malaria prevalence. We show that this can be achieved quickly and cost-effectively through randomized surveys measuring bednet usage coupled with malaria prevalence at the household level.

scholarly journals Modulation of PF10_0355 (MSPDBL2) Alters Plasmodium falciparum Response to Antimalarial Drugs

2013 ◽  
Vol 57 (7) ◽  
pp. 2937-2941 ◽  
Author(s):  
Daria Van Tyne ◽  
Alessandro D. Uboldi ◽  
Julie Healer ◽  
Alan F. Cowman ◽  
Dyann F. Wirth
Keyword(s):  
Plasmodium Falciparum ◽  
Copy Number ◽  
Specific Effect ◽  
Antimalarial Drugs ◽  
New Drugs ◽  
Resistance Locus ◽  
Specific Class ◽  
Drug Pressure ◽  
Content Type ◽  
Antimalarial Resistance

ABSTRACTMalaria's ability to rapidly adapt to new drugs has allowed it to remain one of the most devastating infectious diseases of humans. Understanding and tracking the genetic basis of these adaptations are critical to the success of treatment and intervention strategies. The novel antimalarial resistance locusPF10_0355(Pfmspdbl2) was previously associated with the parasite response to halofantrine, and functional validation confirmed that overexpression of this gene lowered parasite sensitivity to both halofantrine and the structurally related antimalarials mefloquine and lumefantrine, predominantly through copy number variation. Here we further characterize the role ofPfmspdbl2in mediating the antimalarial drug response ofPlasmodium falciparum. Knockout ofPfmspdbl2increased parasite sensitivity to halofantrine, mefloquine, and lumefantrine but not to unrelated antimalarials, further suggesting that this gene mediates the parasite response to a specific class of antimalarial drugs. A single nucleotide polymorphism encoding a C591S mutation withinPfmspdbl2had the strongest association with halofantrine sensitivity and showed a high derived allele frequency among Senegalese parasites. Transgenic parasites expressing the ancestralPfmspdbl2allele were more sensitive to halofantrine and structurally related antimalarials than were parasites expressing the derived allele, revealing an allele-specific effect on drug sensitivity in the absence of copy number effects. Finally, growth competition experiments showed that under drug pressure, parasites expressing the derived allele ofPfmspdbl2outcompeted parasites expressing the ancestral allele within a few generations. Together, these experiments demonstrate that modulation ofPfmspdbl2affects malaria parasite responses to antimalarial drugs.

scholarly journals Quadruple Mutations in Dihydrofolate Reductase of Plasmodium falciparum Isolates from Car Nicobar Island, India

2006 ◽  
Vol 50 (4) ◽  
pp. 1546-1549 ◽  
Author(s):  
Anwar Ahmed ◽  
Manoj K. Das ◽  
Vas Dev ◽  
Muheet A. Saifi ◽  
Wajihullah ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Malaria Control ◽  
Control Program ◽  
Nicobar Island ◽  
Drug Pressure ◽  
Malaria Control Program ◽  
Very High

ABSTRACT Quadruple mutations in the Plasmodium falciparum dihydrofolate reductase (PFDHFR) enzyme give rise to the highest level of pyrimethamine resistance leading to treatment failures. We describe here the presence of these quadruple mutations in a majority of P. falciparum isolates from Car Nicobar (Andaman and Nicobar) Island, India. Isolates from the mainland, however, continue to show a prevalence of double PFDHFR mutations and some with triple but none with quadruple mutations. In conclusion, the antifolate drug pressure is very high in the island, which should be a cause of concern for the malaria control program in the country.

scholarly journals In VitroActivity of Proveblue (Methylene Blue) on Plasmodium falciparum Strains Resistant to Standard Antimalarial Drugs

2011 ◽  
Vol 55 (5) ◽  
pp. 2472-2474 ◽  
Author(s):  
Aurélie Pascual ◽  
Maud Henry ◽  
Sébastien Briolant ◽  
Serge Charras ◽  
Eric Baret ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Plasmodium Falciparum ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Antimalarial Drugs ◽  
European Pharmacopoeia ◽  
Content Type ◽  
Copy Numbers ◽  
Antimalarial Resistance

ABSTRACTThe geometric mean 50% inhibitory concentration (IC50) for Proveblue, a methylene blue complying with the European Pharmacopoeia, was more active on 23P. falciparumstrains than chloroquine, quinine, mefloquine, monodesethylamodiaquine, and lumefantrine. We did not find significant associations between the Proveblue IC50and polymorphisms in thepfcrt,pfmdr1,pfmdr2,pfmrp, andpfnhe-1genes or the copy numbers of thepfmdr1andpfmdr2genes, all of which are involved in antimalarial resistance.

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