scholarly journals In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Abel Nhama ◽  
Lídia Nhamússua ◽  
Eusébio Macete ◽  
Quique Bassat ◽  
Crizolgo Salvador ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Therapeutic Efficacy ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Testing ◽  
Routine Monitoring ◽  
First Choice ◽  
Transmission Area ◽  
Recurrent Malaria ◽  
Lost To Follow Up

Abstract Background Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov: NCT04370977

scholarly journals In vivo Efficacy and Safety of Artemether-Lumefantrine and Amodiaquine-Artesunate for Uncomplicated Plasmodium Falciparum Malaria in Mozambique, 2018

2021 ◽  
Author(s):  
Abel Nhama ◽  
Lidia Nhamussua ◽  
Eusébio Macete ◽  
Quique Bassat ◽  
Crizolgo Salvador ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Combination Therapy ◽  
Falciparum Malaria ◽  
Therapeutic Efficacy ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Testing ◽  
Recommended Treatment ◽  
Recurrent Malaria ◽  
Uncomplicated Plasmodium Falciparum Malaria

Abstract Background : Artemisinin-based combination therapy has been the recommended treatment for uncomplicated malaria in Mozambique since 2006, with artemether-lumefantrine (AL) and amodiaquine-artesunate (AS-AQ) as first-line treatments. To assess efficacy of currently used artemisinin-based combination therapy, an in vivo therapeutic efficacy study was conducted. Methods : The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 to 59 months old with uncomplicated Plasmodium falciparum malaria (2,000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS-AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results : Totals of 368 and 273 patients were enrolled in the AL and AS-AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS-AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS-AQ arms, respectively. The day 28 uncorrected efficacy was 85.3% (95% CI: 81.1–88.9%) for AL and 98.8% (95% CI: 96.7–99.8%) for AS-AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI: 95.6–99.2%) for AL and 99.6 % (95% CI: 97.9–100%) for AS-AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS-AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion : Both AL and AS-AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration: Clinicaltrials.gov: NCT04370977

scholarly journals A randomized clinical trial with high dose of chloroquine for treatment of Plasmodium falciparum malaria in Brazil

1992 ◽  
Vol 34 (5) ◽  
pp. 467-473 ◽  
Author(s):  
João Guimarães de Andrade ◽  
Ana Lúcia Sampaio Sgambatti de Andrade ◽  
Elisabeth S. O. Araujo ◽  
Renato Maurício Oliveira ◽  
Simonne Almeida Silva ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Side Effects ◽  
Falciparum Malaria ◽  
Amazon Basin ◽  
Geometric Mean ◽  
Plasmodium Falciparum Malaria ◽  
High Dose ◽  
First Choice

This clinical trial compared parasitological efficacy, levels of in vivo resistance and side effects of oral chloroquine 25 mg/Kg and 50 mg/Kg in 3 days treatment in Plasmodium falciparum malaria with an extended followed-up of 30 days. The study enroled 58 patients in the 25 mg/Kg group and 66 in the 50 mg/Kg group. All eligible subjects were over 14 years of age and came from Amazon Basin and Central Brazil during the period of August 1989 to April 1991. The cure rate in the 50 mg/Kg group was 89.4% on day 7 and 71.2% on day 14 compared to 44.8% and 24.1% in the 25 mg/Kg group. 74.1% of the patients in the 25 mg/Kg group and 48.4% of the patients in the 50 mg/Kg group had detectable parasitaemia at the day 30. However, there was a decrease of the geometric mean parasite density in both groups specially in the 50 mg/Kg group. There was 24.1% of RIII and 13.8% of RH in the 25 mg/Kg group. Side effects were found to be minimum in both groups. The present data support that there was a high level resistance to chloroquine in both groups, and the high dose regimen only delayed the development of resistance and its administration should not be recommended as first choice in malaria P. falciparum therapy in Brazil.

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.

scholarly journals Metabolic Signature Profiling as a Diagnostic and Prognostic Tool in Pediatric Plasmodium falciparum Malaria

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Izabella Surowiec ◽  
Judy Orikiiriza ◽  
Elisabeth Karlsson ◽  
Maria Nelson ◽  
Mari Bonde ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Principal Component ◽  
Malaria Diagnosis ◽  
Plasmodium Falciparum Malaria ◽  
Metabolite Profile ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
In Vivo Model ◽  
Spectrometry Analysis

Abstract Background.  Accuracy in malaria diagnosis and staging is vital to reduce mortality and post infectious sequelae. In this study, we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children. Methods.  A group of 421 patients between 6 months and 6 years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192, and 122, individuals, respectively. A multivariate design was used as basis for representative selection of 20 patients in each category. Patient plasma was subjected to gas chromatography-mass spectrometry analysis, and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in vivo model where metabolic profiles were discernible over time of infection. Results.  A 2-component principal component analysis revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, 2 subgroups could be ide.jpegied in the mild malaria cohort who we believe represent patients with divergent prognoses. Conclusions.  Metabolite signature profiling could be used both for decision support in disease staging and prognostication.

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