Staff View: Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

Background: In Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and...

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Main Authors:	Atroosh, W.M., Al-Mekhlafi, H.M., Snounou, G., Al-Jasari, A., Sady, H., Nasr, N.A., Lau, Y.L., Surin, J.
Format:	Article
Published:	BioMed Central 2016
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/18370/ https://doi.org/10.1186/s12936-016-1344-0
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spelling	my.um.eprints.183702017-11-22T05:45:34Z http://eprints.um.edu.my/18370/ Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes Atroosh, W.M. Al-Mekhlafi, H.M. Snounou, G. Al-Jasari, A. Sady, H. Nasr, N.A. Lau, Y.L. Surin, J. R Medicine Background: In Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes. Methods: A 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification. Results: Eighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced. Conclusion: In Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria. BioMed Central 2016 Article PeerReviewed Atroosh, W.M. and Al-Mekhlafi, H.M. and Snounou, G. and Al-Jasari, A. and Sady, H. and Nasr, N.A. and Lau, Y.L. and Surin, J. (2016) Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes. Malaria Journal, 15 (1). p. 295. ISSN 1475-2875 https://doi.org/10.1186/s12936-016-1344-0 doi:10.1186/s12936-016-1344-0
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Atroosh, W.M. Al-Mekhlafi, H.M. Snounou, G. Al-Jasari, A. Sady, H. Nasr, N.A. Lau, Y.L. Surin, J. Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
description	Background: In Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes. Methods: A 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification. Results: Eighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced. Conclusion: In Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria.
format	Article
author	Atroosh, W.M. Al-Mekhlafi, H.M. Snounou, G. Al-Jasari, A. Sady, H. Nasr, N.A. Lau, Y.L. Surin, J.
author_facet	Atroosh, W.M. Al-Mekhlafi, H.M. Snounou, G. Al-Jasari, A. Sady, H. Nasr, N.A. Lau, Y.L. Surin, J.
author_sort	Atroosh, W.M.
title	Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
title_short	Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
title_full	Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
title_fullStr	Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
title_full_unstemmed	Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
title_sort	sustained efficacy of artesunate-sulfadoxine-pyrimethamine against plasmodium falciparum in yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes
publisher	BioMed Central
publishDate	2016
url	http://eprints.um.edu.my/18370/ https://doi.org/10.1186/s12936-016-1344-0
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score	13.211869

Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

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