Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction
Background: Combination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended treatment for Plasmodium falciparum infection in Afghanistan in 2003. Methods: A series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine...
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th-mahidol.31582023-03-30T23:07:59Z Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction Ghulam Rahim Awab Mallika Imwong Sasithon Pukrittayakamee Fazel Alim Warunee Hanpithakpong Joel Tarning Dondorp, Arjen M. Day, Nicholas P. J. White, Nicholas J. Woodrow, Charles J. Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU) Open Access article Malaria Falciparum Afghanistan Artesunate Sulphadoxine Pyrimethamine Dihydrofolate reductase Dihydropteroate synthase Piperaquine Kelch Background: Combination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended treatment for Plasmodium falciparum infection in Afghanistan in 2003. Methods: A series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine (AS + SP) against P. falciparum were undertaken in sentinel sites in Afghanistan from 2007 to 2014, accompanied by relevant molecular studies. The first study was a randomized trial of AS + SP versus dihydroartemisinin-piperaquine, while two subsequent studies were standard therapeutic efficacy studies of AS + SP. Results: Three hundred and three patients were enrolled across four provinces in the north and east of the country. Curative efficacy was high in all the trials, with an adequate clinical and parasitological response (ACPR) of more than 95 % in all groups and trial stages. Genotyping for drug-resistance alleles at dhfr indicated fixation of the S108 N mutation and a prevalence of the C59R mutation of approximately 95 % across all sites. Other mutations in dhfr and dhps remained rare or absent entirely, although five isolates from the first trial carried the dhps triple mutant SGEGA haplotype. In the last study undertaken in 2012–2014 the K13 artemisinin resistance marker was examined; only two of 60 successfully sequenced samples carried a K13-propeller mutation. Conclusions: These data confirm maintained efficacy 10 years after introduction of artesunate plus SP as combination treatment of P. falciparum in Afghanistan. The molecular data indicate that despite a substantial fall in incidence, resistance has not developed to artemisinins, or intensified to the ACT partner drug components. Trial Registration http://www.clinicaltrials.gov/ct NCT00682578, NCT01115439 and NCT01707199 2017-11-16T07:37:05Z 2017-11-16T07:37:05Z 2017-11-16 2016 Research Article Malaria Journal. Vol.15, (2016), 121 10.1186/s12936-016-1167-z https://repository.li.mahidol.ac.th/handle/123456789/3158 eng Mahidol University BioMed Central application/pdf |
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Open Access article Malaria Falciparum Afghanistan Artesunate Sulphadoxine Pyrimethamine Dihydrofolate reductase Dihydropteroate synthase Piperaquine Kelch |
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Open Access article Malaria Falciparum Afghanistan Artesunate Sulphadoxine Pyrimethamine Dihydrofolate reductase Dihydropteroate synthase Piperaquine Kelch Ghulam Rahim Awab Mallika Imwong Sasithon Pukrittayakamee Fazel Alim Warunee Hanpithakpong Joel Tarning Dondorp, Arjen M. Day, Nicholas P. J. White, Nicholas J. Woodrow, Charles J. Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
description |
Background: Combination therapy with artesunate plus sulfadoxine-pyrimethamine (SP) was adopted as recommended
treatment for Plasmodium falciparum infection in Afghanistan in 2003.
Methods: A series of prospective clinical studies examining the efficacy of artesunate plus sulfadoxine-pyrimethamine
(AS + SP) against P. falciparum were undertaken in sentinel sites in Afghanistan from 2007 to 2014, accompanied
by relevant molecular studies. The first study was a randomized trial of AS + SP versus dihydroartemisinin-piperaquine,
while two subsequent studies were standard therapeutic efficacy studies of AS + SP.
Results: Three hundred and three patients were enrolled across four provinces in the north and east of the country.
Curative efficacy was high in all the trials, with an adequate clinical and parasitological response (ACPR) of more
than 95 % in all groups and trial stages. Genotyping for drug-resistance alleles at dhfr indicated fixation of the S108 N
mutation and a prevalence of the C59R mutation of approximately 95 % across all sites. Other mutations in dhfr and
dhps remained rare or absent entirely, although five isolates from the first trial carried the dhps triple mutant SGEGA
haplotype. In the last study undertaken in 2012–2014 the K13 artemisinin resistance marker was examined; only two
of 60 successfully sequenced samples carried a K13-propeller mutation.
Conclusions: These data confirm maintained efficacy 10 years after introduction of artesunate plus SP as combination
treatment of P. falciparum in Afghanistan. The molecular data indicate that despite a substantial fall in incidence,
resistance has not developed to artemisinins, or intensified to the ACT partner drug components.
Trial Registration http://www.clinicaltrials.gov/ct NCT00682578, NCT01115439 and NCT01707199 |
author2 |
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU) |
author_facet |
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit (MORU) Ghulam Rahim Awab Mallika Imwong Sasithon Pukrittayakamee Fazel Alim Warunee Hanpithakpong Joel Tarning Dondorp, Arjen M. Day, Nicholas P. J. White, Nicholas J. Woodrow, Charles J. |
format |
Article |
author |
Ghulam Rahim Awab Mallika Imwong Sasithon Pukrittayakamee Fazel Alim Warunee Hanpithakpong Joel Tarning Dondorp, Arjen M. Day, Nicholas P. J. White, Nicholas J. Woodrow, Charles J. |
author_sort |
Ghulam Rahim Awab |
title |
Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
title_short |
Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
title_full |
Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
title_fullStr |
Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
title_full_unstemmed |
Clinical trials of artesunate plus sulfadoxine‑pyrimethamine for Plasmodium falciparum malaria in Afghanistan: maintained efficacy a decade after introduction |
title_sort |
clinical trials of artesunate plus sulfadoxine‑pyrimethamine for plasmodium falciparum malaria in afghanistan: maintained efficacy a decade after introduction |
publishDate |
2017 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/3158 |
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1763494412656050176 |