Background: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon.
Methods: We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method.
Findings: Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis.
Interpretation: The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0140-6736(02)08348-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In vitro antiplasmodial activity and chemical composition of Combretum aculeatum, a medicinal plant from Niger.
Chem Biodivers
January 2025
Universite de Strasbourg, UMR 7200 Laboratoire d'Innovation Thérapeutique, 74 route du Rhin - CS 60024 - 67401 Illkirch Cédex - France, 67400, Illkirch-Graffenstaden, BELGIUM.
Malaria remains a significant public health challenge in Niger, accounting for 5.6% of global malaria-related deaths. Local medicinal plants are frequently used as traditional treatments for malaria, although their efficacy and safety are often insufficiently investigated.
View Article and Find Full Text PDFDevelopment and experimental validation of a machine learning model for the prediction of new antimalarials.
BMC Chem
January 2025
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan, 333 031, India.
A large set of antimalarial molecules (N ~ 15k) was employed from ChEMBL to build a robust random forest (RF) model for the prediction of antiplasmodial activity. Rather than depending on high throughput screening (HTS) data, molecules tested at multiple doses against blood stages of Plasmodium falciparum were used for model development. The open-access and code-free KNIME platform was used to develop a workflow to train the model on 80% of data (N ~ 12k).
View Article and Find Full Text PDFQuantifying the potential value of entomological data collection for programmatic decision-making on malaria control in sub-Saharan African settings.
Malar J
January 2025
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, UK.
Background: The availability of many tools for malaria control leads to complex decisions regarding the most cost-effective intervention package based on local epidemiology. Mosquito characteristics influence the impact of vector control, but entomological surveillance is often limited due to a lack of resources in national malaria programmes.
Methods: This study quantified the monetary value of information provided by entomological data collection for programmatic decision-making using a mathematical model of Plasmodium falciparum transmission.
Accurate malaria diagnosis with precise identification of Plasmodium species is crucial for an effective treatment. While microscopy is still the gold standard in malaria diagnosis, it relies heavily on trained personnel. Artificial intelligence (AI) advances, particularly convolutional neural networks (CNNs), have significantly improved diagnostic capabilities and accuracy by enabling the automated analysis of medical images.
View Article and Find Full Text PDFStudy of antiplasmodial activity, toxicity, pharmacokinetic profiles of n-methyl-isatin (CHISACN) derivative.
Exp Parasitol
January 2025
Post-graduate Program in Studies in Natural Products and Synthetic Bioactive, Federal University of Paraíba, João Pessoa, PB, Brazil; Laboratory of Toxicological Tests, Federal University of Paraíba, João Pessoa, PB, Brazil; Post-graduate Program in Studies in Development and Technological Innovation in Medicines, Federal University of Paraíba, João Pessoa, PB, Brazil.
One of the main factors that have made it difficult to control malaria is the large number of parasites that are resistant to the usual antimalarial drugs. Therefore, the development of new drugs that are more effective and with low toxicity for humans is necessary. In this work, we evaluated the adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-yl) acrylonitrile, also called CHISACN, as a potential antimalarial through in vitro studies, and evaluated its effects in silico and in vivo toxicology.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!