scholarly journals Efficacy of Artesunate-Amodiaquine and Artemether-Lumefantrine for Uncomplicated Plasmodium Falciparum Malaria in Madagascar, 2018

2021 ◽  
Author(s):  
Catherine M. Dentinger ◽  
Tovonahary Angelo Rakotomanga ◽  
Antsa Rakotondrandriana ◽  
Arinomenjanahary Rakotoarisoa ◽  
Marie Ange Rason ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Outcome Data ◽  
World Health ◽  
Antimalarial Resistance ◽  
Health Organization ◽  
Uncomplicated Plasmodium Falciparum Malaria

Abstract Background: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated Plasmodium falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of antimalarial resistance.Methods: Children aged six months through 14 years with uncomplicated P. falciparum malaria and a parasitemia of 1,000—100,000 parasites/µl determined by microscopy were enrolled from May—September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring antimalarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt, and pfmdr1 genes were conducted.Results: Of 344 patients enrolled, 164/170 (96%) receiving ASAQ and 170/174 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100–100) and 95% (95% CI 91–100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97–100) in Ankazomborona and 84% (95% CI 76–92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100–100) and 97% (95% CI 94–100%) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99–100) in Ankazomborona and 96% (95% CI 91–100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutations associated with artemisinin resistance were observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184, and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72–76. Conclusion: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. We did not observe any genetic evidence of resistance to artemisinin, consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.

scholarly journals Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium falciparum Malaria in Bohicon and Kandi, Republic of Benin, 2018–2019

2021 ◽  
Author(s):  
Augustin Kpemasse ◽  
Fortune Dagnon ◽  
Ramani Saliou ◽  
Alexis Sacca Yarou Maye ◽  
Cyriaque Dossou Affoukou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Falciparum Malaria ◽  
World Health ◽  
Antimalarial Resistance ◽  
Resistance Markers ◽  
Republic Of Benin ◽  
Health Organization ◽  
Treatment Policies ◽  
Parasitological Response ◽  
C580y Mutation

In 2005, artemether-lumefantrine (AL), an artemisinin-based combination therapy, was introduced as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Benin. Per World Health Organization recommendations to monitor the efficacy of antimalarial treatment, we conducted a therapeutic efficacy study with AL for uncomplicated P. falciparum malaria in Bohicon and Kandi, Benin, from 2018 to 2019. Febrile patients aged 6 to 59 months with confirmed P. falciparum monoinfection received supervised doses of AL for 3 days. We monitored patients clinically and parasitologically on days 1, 2, 3, 7, 14, 21, and 28. A molecular analysis to detect mutations in the P. falciparum Kelch propeller gene (Pfk13) gene was carried out on day 0 samples. A total of 205 patients were included in the study. In Bohicon, the uncorrected adequate clinical and parasitological response (ACPR) proportion was 91.3% (95% confidence interval [CI]: 84.6–95.8%), whereas in Kandi this proportion was 96.7% (95% CI: 90.6–99.3%). Genotype-corrected ACPR proportions were 96.3% (95% CI: 90.9–99.0%) and 96.7% (95% CI: 90.6–99.3%) in Bohicon and Kandi, respectively. On day 3, 100% of patients in Bohicon and 98.9% of patients in Kandi had undetectable parasitemia. The C580Y mutation in the Pfk13 gene was not observed. AL remains effective for P. falciparum malaria in these two sites in Benin. Monitoring antimalarial efficacy and prevalence of molecular-resistance markers in Benin should be continued to allow for early detection of antimalarial resistance and to guide treatment policies.

Chloroquine-Resistant Plasmodium Falciparum Among Children in Calabar, South Eastern Nigeria

1997 ◽  
Vol 27 (3) ◽  
pp. 146-149 ◽  
Author(s):  
O E Antia-Obong ◽  
A A A Alaribe ◽  
M U Young ◽  
A Bassy ◽  
B V Etim
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Falciparum Malaria ◽  
Chloroquine Resistance ◽  
World Health ◽  
Response To Treatment ◽  
Treatment Groups ◽  
The World ◽  
Health Organization ◽  
The University

Sixty-nine children aged between 6 and 60 months with parasitologically proven Plasmodium falciparum malaria were treated with chloroquine (2.5 mg/kg) in the Children's Emergency Room of the University of Calabar Teaching Hospital (UCTH) in 1993. Thirty subjects (mean age 27.8 months) and 39 (mean age 29.5 months) received chloroquine phosphate suppository (Pharma Deko) and chloroquine sulphate syrup (May & Baker), respectively. The World Health Organization (WHO) 14-day in vivo field test was used in evaluating the response to treatment. In both treatment groups the responses were similar. Overall, parasitological cure occurred in 24 subjects (34.8%) and in the remaining 45 subjects (65.2%) treatment failed (chloroquine resistance). This level of chloroquine resistant Plasmodium falciparum (CRPF) is higher than 53.6% reported in this centre in 1989. Furthermore, in the present study the proportion of RII (46.4%) is significantly higher than 21.4% ( P < 0.02) obtained in 1989. Our findings show a worsening of CRPF in Calabar with RII being the main contributor. This observation indicates the need for continued surveillance of the response of P. falciparum to chloroquine and alternative antimalarials as a means of evolving an effective treatment policy for malaria.

scholarly journals Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial

2012 ◽  
Vol 45 (6) ◽  
pp. 732-738 ◽  
Author(s):  
Fernando De la Hoz Restrepo ◽  
Alexandra Porras Ramírez ◽  
Alejandro Rico Mendoza ◽  
Freddy Córdoba ◽  
Diana Patricia Rojas
Keyword(s):  
Plasmodium Falciparum ◽  
World Health Organization ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
World Health ◽  
Open Label ◽  
Fever Clearance Time ◽  
Health Organization ◽  
Parasitological Response ◽  
Uncomplicated Plasmodium Falciparum Malaria

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

scholarly journals Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia

2016 ◽  
Vol 60 (7) ◽  
pp. 3884-3890 ◽  
Author(s):  
Rithea Leang ◽  
Sara E. Canavati ◽  
Nimol Khim ◽  
Lasse S. Vestergaard ◽  
Isabelle Borghini Fuhrer ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Parasite Clearance ◽  
World Health ◽  
Rank Test ◽  
Content Type ◽  
Kaplan Meier ◽  
Registration Number ◽  
Health Organization

ABSTRACTPyronaridine-artesunate efficacy for the treatment of uncomplicatedPlasmodium falciparummalaria was assessed in an area of artemisinin resistance in western Cambodia. This nonrandomized, single-arm, observational study was conducted between 2014 and 2015. Eligible patients were adults or children with microscopically confirmedP. falciparuminfection and fever. Patients received pyronaridine-artesunate once daily for 3 days, dosed according to body weight. The primary outcome was an adequate clinical and parasitological response (ACPR) on day 42, estimated by using Kaplan-Meier analysis, PCR adjusted to exclude reinfection. One hundred twenty-three patients were enrolled. Day 42 PCR-crude ACPRs were 87.2% (95% confidence interval [CI], 79.7 to 92.6%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 82.1% (95% CI, 68.4 to 90.2%) for Pailin. Day 42 PCR-adjusted ACPRs were 87.9% (95% CI, 80.6 to 93.2%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 84.0% (95% CI, 70.6 to 91.7%) for Pailin (P= 0.353 by a log rank test). Day 28 PCR-crude and -adjusted ACPRs were 93.2% (95% CI, 82.9 to 97.4%) and 88.1% (95% CI, 75.3 to 94.5%) for Pursat and Pailin, respectively. A significantly lower proportion of patients achieved day 3 parasite clearance in Pailin (56.4% [95% CI, 43.9 to 69.6%]) than in Pursat (86.7% [95% CI, 76.8 to 93.8%];P= 0.0019). Fever clearance was also extended at Pailin versus Pursat (P< 0.0001). Most patients (95.9% [116/121]) harboredP. falciparumkelch13C580Y mutant parasites. Pyronaridine-artesunate was well tolerated; mild increases in hepatic transaminase levels were consistent with data from previous reports. Pyronaridine-artesunate efficacy was below the World Health Organization-recommended threshold at day 42 for medicines with a long half-life (90%) for first-line treatment ofP. falciparummalaria in western Cambodia despite high efficacy elsewhere in Asia and Africa. (This study has been registered at ClinicalTrials.gov under registration number NCT02389439.)

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

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Youssouf Diarra ◽  
Oumar Koné ◽  
Lansana Sangaré ◽  
Lassina Doumbia ◽  
Dade Bouye Ben Haidara ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Uncomplicated Malaria ◽  
Artemisinin Resistance ◽  
National Malaria Control Programme ◽  
Plasmodium Falciparum Malaria ◽  
Control Programme ◽  
Malaria Control Programme ◽  
Pre Treatment ◽  
Better Than

Abstract Background The current first-line treatments for uncomplicated malaria recommended by the National Malaria Control Programme in Mali are artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ). From 2015 to 2016, an in vivo study was carried out 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 2000–200,000 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 The findings indicate that both AL and ASAQ remain effective for the treatment of uncomplicated malaria in Sélingué, Mali.

BLOOD FOLATE CONCENTRATIONS AND IN VIVO SULFADOXINE-PYRIMETHAMINE FAILURE IN MALAWIAN CHILDREN WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA

2005 ◽  
Vol 72 (3) ◽  
pp. 267-272 ◽  
Author(s):  
FRACTION K. DZINJALAMALA ◽  
KAREN I. BARNES ◽  
CHRISTOPHER V. PLOWE ◽  
TERRIE E. TAYLOR ◽  
MALCOM E. MOLYNEUX ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Uncomplicated Plasmodium Falciparum Malaria

scholarly journals Clinical and in vitro resistance of Plasmodium falciparum to artesunate-amodiaquine in Cambodia

2020 ◽  
Author(s):  
Melissa Mairet-Khedim ◽  
Rithea Leang ◽  
Camille Marmai ◽  
Nimol Khim ◽  
Saorin Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Markers ◽  
Falciparum Malaria ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Open Label ◽  
Parasite Survival ◽  
Adults And Children

Abstract Background Artesunate-amodiaquine is a potential therapy for uncomplicated malaria in Cambodia. Methods Between September 2016 and January 2017, artesunate-amodiaquine efficacy and safety were evaluated in a prospective, open-label, single-arm observational study at health centers in Mondulkiri, Pursat and Siem Reap Provinces, Cambodia. Adults and children with microscopically-confirmed Plasmodium falciparum malaria received oral artesunate-amodiaquine once daily for three days plus single-dose primaquine, with follow-up on Days 7, 14, 21 and 28. The primary outcome was Day-28 PCR-adjusted adequate clinical and parasitological response (ACPR). An amodiaquine parasite survival assay (AQSA) was developed and applied to whole genome sequencing results to evaluate potential amodiaquine resistance molecular markers. Results In 63 patients, Day-28 PCR-adjusted ACPR was 81.0% (95% confidence interval [CI], 68.9–88.7). Day 3 parasite positivity rate was 44.4% (28/63; 95%CI, 31.9–57.5). All 63 isolates had the K13(C580Y) marker for artemisinin resistance; 79.4% (50/63) had Pfpm2 amplification. The AQSA resistance phenotype (≥45% parasite survival) was expressed in 36.5% (23/63) of isolates and was significantly associated with treatment failure (P = 0.0020). Pfmdr1 mutant haplotypes were N86/184F/D1246 and Pfcrt was CVIET or CVIDT at positions 72–76. Additional Pfcrt mutations were not associated with amodiaquine resistance, but the G353V mutant allele was associated with ACPR compared to Pfmdr1 haplotypes harboring F1068L or S784L/R945P mutations (P = 0.030 and P = 0.0004, respectively). Conclusions For uncomplicated falciparum malaria in Cambodia, artesunate-amodiaquine had inadequate efficacy owing to amodiaquine-resistant P. falciparum. Amodiaquine resistance was not associated with previously identified molecular markers.

scholarly journals Tailoring a Pediatric Formulation of Artemether-Lumefantrine for Treatment of Plasmodium falciparum Malaria

2015 ◽  
Vol 59 (8) ◽  
pp. 4366-4374 ◽  
Author(s):  
Quique Bassat ◽  
Bernhards Ogutu ◽  
Abdoulaye Djimde ◽  
Kirstin Stricker ◽  
Kamal Hamed
Keyword(s):  
Plasmodium Falciparum ◽  
Plasma Concentrations ◽  
Plasmodium Falciparum Malaria ◽  
Pharmacokinetic Profile ◽  
World Health ◽  
Maximum Plasma ◽  
Comprehensive Overview ◽  
Content Type ◽  
Pediatric Formulation ◽  
Health Organization

ABSTRACTSpecially created pediatric formulations have the potential to improve the acceptability, effectiveness, and accuracy of dosing of artemisinin-based combination therapy (ACT) in young children, a patient group that is inherently vulnerable to malaria. Artemether-lumefantrine (AL) Dispersible is a pediatric formulation of AL that is specifically tailored for the treatment of children with uncomplicatedPlasmodium falciparummalaria, offering benefits relating to efficacy, convenience and acceptance, accuracy of dosing, safety, sterility, stability, and a pharmacokinetic profile and bioequivalence similar to those of crushed and intact AL tablets. However, despite being the first pediatric antimalarial to meet World Health Organization (WHO) specifications for use in infants and children who are ≥5 kg in body weight and its inclusion in WHO Guidelines, there are few publications that focus on AL Dispersible. Based on a systematic review of the recent literature, this paper provides a comprehensive overview of the clinical experience with AL Dispersible to date. A randomized, phase 3 study that compared the efficacy and safety of AL Dispersible to those of crushed AL tablets in 899 African children reported high PCR-corrected cure rates at day 28 (97.8% and 98.5% for AL Dispersible and crushed tablets, respectively), and the results of several subanalyses of these data indicate that this activity is observed regardless of patient weight, food intake, and maximum plasma concentrations of artemether or its active metabolite, dihydroartemisinin. These and other clinical data support the continued use of pediatric antimalarial formulations in all children <5 years of age with uncomplicated malaria when accompanied by continued monitoring for the emergence of resistance.

Sign in / Sign up

Export Citation Format

Share Document