Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis
Abstract Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatm...
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ftdoajarticles:oai:doaj.org/article:98918cc9f50f4fdca2755887ede57934 2023-05-15T15:17:59+02:00 Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis The WorldWide Antimalarial Resistance Network Methodology Study Group 2022-03-01T00:00:00Z https://doi.org/10.1186/s12936-021-03980-z https://doaj.org/article/98918cc9f50f4fdca2755887ede57934 EN eng BMC https://doi.org/10.1186/s12936-021-03980-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03980-z 1475-2875 https://doaj.org/article/98918cc9f50f4fdca2755887ede57934 Malaria Journal, Vol 21, Iss 1, Pp 1-13 (2022) Malaria Plasmodium falciparum Efficacy Follow-up Recrudescence Distribution Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2022 ftdoajarticles https://doi.org/10.1186/s12936-021-03980-z 2022-12-31T08:22:12Z Abstract Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47–74%] of recrudescences in African children and 32% [95% CI 15–45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19–90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0–22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 21 1 |
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Malaria Plasmodium falciparum Efficacy Follow-up Recrudescence Distribution Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Malaria Plasmodium falciparum Efficacy Follow-up Recrudescence Distribution Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 The WorldWide Antimalarial Resistance Network Methodology Study Group Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
topic_facet |
Malaria Plasmodium falciparum Efficacy Follow-up Recrudescence Distribution Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47–74%] of recrudescences in African children and 32% [95% CI 15–45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19–90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0–22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the ... |
format |
Article in Journal/Newspaper |
author |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
author_facet |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
author_sort |
The WorldWide Antimalarial Resistance Network Methodology Study Group |
title |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
title_short |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
title_full |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
title_fullStr |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
title_full_unstemmed |
Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
title_sort |
temporal distribution of plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis |
publisher |
BMC |
publishDate |
2022 |
url |
https://doi.org/10.1186/s12936-021-03980-z https://doaj.org/article/98918cc9f50f4fdca2755887ede57934 |
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Arctic |
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Arctic |
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Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 21, Iss 1, Pp 1-13 (2022) |
op_relation |
https://doi.org/10.1186/s12936-021-03980-z https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-03980-z 1475-2875 https://doaj.org/article/98918cc9f50f4fdca2755887ede57934 |
op_doi |
https://doi.org/10.1186/s12936-021-03980-z |
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Malaria Journal |
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21 |
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1766348230622183424 |