Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review
Abstract Background Anti-malarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated falciparum malaria was evaluated in Oddar Meanchey province in Northern Cambodia from 2009 to 2011. Methods In this randomized, open-label, pa...
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ftdoajarticles:oai:doaj.org/article:e2910843bfe04e7b95aafa4cbbf51a08 2023-05-15T15:18:34+02:00 Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review Dysoley Lek Agus Rachmat Dustin Harrison Geoffrey Chin Suwanna Chaoratanakawee David Saunders Didier Menard William O. Rogers 2022-09-01T00:00:00Z https://doi.org/10.1186/s12936-022-04279-3 https://doaj.org/article/e2910843bfe04e7b95aafa4cbbf51a08 EN eng BMC https://doi.org/10.1186/s12936-022-04279-3 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04279-3 1475-2875 https://doaj.org/article/e2910843bfe04e7b95aafa4cbbf51a08 Malaria Journal, Vol 21, Iss 1, Pp 1-17 (2022) Uncomplicated falciparum malaria Cambodia Antimalarial resistance Randomized clinical trial Therapeutic efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2022 ftdoajarticles https://doi.org/10.1186/s12936-022-04279-3 2022-12-30T22:05:26Z Abstract Background Anti-malarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated falciparum malaria was evaluated in Oddar Meanchey province in Northern Cambodia from 2009 to 2011. Methods In this randomized, open-label, parallel group-controlled trial, 211 subjects at least 5 years old with uncomplicated falciparum malaria were treated with 3 days of directly observed therapy: 63 received artesunate–mefloquine (AS/MQ), 77 received dihydroartemisinin–piperaquine (DHA/PPQ), and 71 received atovaquone–proguanil (ATQ/PG). The subjects were followed for 42 days or until recurrent parasitaemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) were measured in vitro by 48-h isotopic hypoxanthine incorporation assay. Results The per-protocol PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8–90.5%) for AS/MQ, 97.2% (93.3–100%) for DHA/PPQ, and 92.9% (86.1–99.6%) for ATQ/PG. On day 3, 57.9% remained parasitaemic in the AS/MQ and DHA/PPQ arms. At baseline, 46.9% had microscopic Plasmodium falciparum gametocytaemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy. Conclusions This study was conducted at the epicentre of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Oddar ENVELOPE(-18.131,-18.131,63.566,63.566) Malaria Journal 21 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Uncomplicated falciparum malaria Cambodia Antimalarial resistance Randomized clinical trial Therapeutic efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Uncomplicated falciparum malaria Cambodia Antimalarial resistance Randomized clinical trial Therapeutic efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Dysoley Lek Agus Rachmat Dustin Harrison Geoffrey Chin Suwanna Chaoratanakawee David Saunders Didier Menard William O. Rogers Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
topic_facet |
Uncomplicated falciparum malaria Cambodia Antimalarial resistance Randomized clinical trial Therapeutic efficacy Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Anti-malarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated falciparum malaria was evaluated in Oddar Meanchey province in Northern Cambodia from 2009 to 2011. Methods In this randomized, open-label, parallel group-controlled trial, 211 subjects at least 5 years old with uncomplicated falciparum malaria were treated with 3 days of directly observed therapy: 63 received artesunate–mefloquine (AS/MQ), 77 received dihydroartemisinin–piperaquine (DHA/PPQ), and 71 received atovaquone–proguanil (ATQ/PG). The subjects were followed for 42 days or until recurrent parasitaemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) were measured in vitro by 48-h isotopic hypoxanthine incorporation assay. Results The per-protocol PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8–90.5%) for AS/MQ, 97.2% (93.3–100%) for DHA/PPQ, and 92.9% (86.1–99.6%) for ATQ/PG. On day 3, 57.9% remained parasitaemic in the AS/MQ and DHA/PPQ arms. At baseline, 46.9% had microscopic Plasmodium falciparum gametocytaemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy. Conclusions This study was conducted at the epicentre of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern ... |
format |
Article in Journal/Newspaper |
author |
Dysoley Lek Agus Rachmat Dustin Harrison Geoffrey Chin Suwanna Chaoratanakawee David Saunders Didier Menard William O. Rogers |
author_facet |
Dysoley Lek Agus Rachmat Dustin Harrison Geoffrey Chin Suwanna Chaoratanakawee David Saunders Didier Menard William O. Rogers |
author_sort |
Dysoley Lek |
title |
Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
title_short |
Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
title_full |
Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
title_fullStr |
Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
title_full_unstemmed |
Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review |
title_sort |
efficacy of three anti-malarial regimens for uncomplicated plasmodium falciparum malaria in cambodia, 2009–2011: a randomized controlled trial and brief review |
publisher |
BMC |
publishDate |
2022 |
url |
https://doi.org/10.1186/s12936-022-04279-3 https://doaj.org/article/e2910843bfe04e7b95aafa4cbbf51a08 |
long_lat |
ENVELOPE(-18.131,-18.131,63.566,63.566) |
geographic |
Arctic Oddar |
geographic_facet |
Arctic Oddar |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 21, Iss 1, Pp 1-17 (2022) |
op_relation |
https://doi.org/10.1186/s12936-022-04279-3 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-022-04279-3 1475-2875 https://doaj.org/article/e2910843bfe04e7b95aafa4cbbf51a08 |
op_doi |
https://doi.org/10.1186/s12936-022-04279-3 |
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Malaria Journal |
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21 |
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1 |
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1766348766803132416 |