Publication: Defining Plasmodium falciparum treatment in South West Asia: A randomized trial comparing artesunate or primaquine combined with chloroquine or SP
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Issued Date
2012-01-31
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ISSN
19326203
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2-s2.0-84856442932
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS ONE. Vol.7, No.1 (2012)
Suggested Citation
Kate Kolaczinski, Toby Leslie, Iftikhar Ali, Naeem Durrani, Sue Lee, Marion Barends, Khalid Beshir, Rosalynn Ord, Rachel Hallett, Mark Rowland Defining Plasmodium falciparum treatment in South West Asia: A randomized trial comparing artesunate or primaquine combined with chloroquine or SP. PLoS ONE. Vol.7, No.1 (2012). doi:10.1371/journal.pone.0028957 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/13504
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Title
Defining Plasmodium falciparum treatment in South West Asia: A randomized trial comparing artesunate or primaquine combined with chloroquine or SP
Abstract
Introduction: Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. Methods: A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. Findings: A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. Conclusions: CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage. © 2012 Kolaczinski et al.