Trial reportThe Journal of infectious diseases2009
Decreasing efficacy of antimalarial combination therapy in Uganda is explained by decreasing host immunity rather than increasing drug resistance.
Trial report in The Journal of infectious diseases, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00123552 (Longitudinal Comparison of Combination Antimalarial Therapies in Ugandan Children), which is not on this map. Cited by 27 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Longitudinal Comparison of Combination Antimalarial Therapies in Ugandan Children: Evaluation of Safety, Tolerability, and Efficacy
Who cites it
27 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Immunity as a predictor of anti-malarial treatment failure: a systematic review.Malaria journal · 2017Pooled it
- Pooled it
- Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data.Malaria journal · 2011Pooled it
- Interplay among malnutrition, chemoprevention, and the risk of malaria in young Ugandan children: Longitudinal pharmacodynamic and growth analysis.CPT: pharmacometrics & systems pharmacology · 2023Trial
- Trial
- Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children.PloS one · 2010Trial
- Therapeutic efficacy and safety of artemether-lumefantrine combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria at Teda Health Centre, Northwest Ethiopia, 2022/23.Malaria journal · 2024Observational
- Safety and therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria at Shecha health centre, Arba Minch, Ethiopia.Malaria journal · 2023Article
- Malaria PK/PD and the Role Pharmacometrics Can Play in the Global Health Arena: Malaria Treatment Regimens for Vulnerable Populations.Clinical pharmacology and therapeutics · 2021Review
- Imported Malaria in Portugal: Prevalence of Polymorphisms in the Anti-Malarial Drug Resistance GenesMicroorganisms · 2021Article
- Discrete Survival Model Analysis ofPathogens (Basel, Switzerland) · 2021Article
- Molecular surveillance of anti-malarial resistance Pfdhfr and Pfdhps polymorphisms in African and Southeast Asia Plasmodium falciparum imported parasites to Wuhan, China.Malaria journal · 2020Article
- Deployment and utilization of next-generation sequencing of Plasmodium falciparum to guide anti-malarial drug policy decisions in sub-Saharan Africa: opportunities and challenges.Malaria journal · 2019Review
- SustainedAntimicrobial agents and chemotherapy · 2017Article
- Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study.Infectious diseases of poverty · 2017Article
- How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?Antimicrobial agents and chemotherapy · 2015Article
- Genetics of chloroquine-resistant malaria: a haplotypic view.Memorias do Instituto Oswaldo Cruz · 2013Review
- Spatiotemporal mathematical modelling of mutations of the dhps gene in African Plasmodium falciparum.Malaria journal · 2013Article
- Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites.The Journal of infectious diseases · 2013Article
- Epidemiology of subpatent Plasmodium falciparum infection: implications for detection of hotspots with imperfect diagnostics.Malaria journal · 2013Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundImproved control efforts are reducing the burden of malaria in Africa but may result in decreased antimalarial immunity.
methodsA cohort of 129 children aged 1-10 years in Kampala, Uganda, were treated with amodiaquine plus sulfadoxine-pyrimethamine for 396 episodes of uncomplicated malaria over a 29-month period as part of a longitudinal clinical trial.
resultsThe risk of treatment failure increased over the course of the study from 5% to 21% (hazard ratio [HR], 2.4 per year [95% confidence interval {CI}, 1.3-4.3]). Parasite genetic polymorphisms were associated with an increased risk of failure, but their prevalence did not change over time. Three markers of antimalarial immunity were associated with a decreased risk of treatment failure: increased age (HR, 0.5 per 5-year increase [95% CI, 0.2-1.2]), living in an area of higher malaria incidence (HR, 0.26 [95% CI, 0.11-0.64]), and recent asymptomatic parasitemia (HR, 0.06 [95% CI, 0.01-0.36]). In multivariate analysis, adjustment for recent asymptomatic parasitemia, but not parasite polymorphisms, removed the association between calendar time and the risk of treatment failure (HR, 1.5 per year [95% CI, 0.7-3.4]), suggesting that worsening treatment efficacy was best explained by decreasing host immunity.
conclusionDeclining immunity in our study population appeared to be the primary factor underlying decreased efficacy of amodiaquine plus sulfadoxine-pyrimethamine. With improved malaria-control efforts, decreasing immunity may unmask resistance to partially efficacious drugs.
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