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The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial

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Sutanto, I, Suprijanto, S, Kosasih, A, Dahlan, M. S, Syafruddin, D, Kusriastuti, R, Hawley, W. A, Lobo, N. F and terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617 (2013) 'The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin-piperaquine in South sumatra, Western indonesia: an open-label, randomized, controlled trial'. Clinical Infectious Diseases, Vol 56, Issue 5, pp. 685-693.

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Abstract

BACKGROUND:
Artemisinin-based combination therapy is very effective in clearing asexual stages of malaria and reduces gametocytemia, but may not affect mature gametocytes. Primaquine is the only commercially available drug that eliminates mature gametocytes.

METHODS:
We conducted a 2-arm, open-label, randomized, controlled trial to evaluate the efficacy of single-dose primaquine (0.75 mg/kg) following treatment with dihydroartemisinin-piperaquine (DHP) on Plasmodium falciparum gametocytemia, in Indonesia. Patients aged ≥5 years with uncomplicated falciparum malaria, normal glucose-6-phosphate dehydrogenase enzyme levels, and hemoglobin levels ≥8 g/dL were assigned by computerized-generating sequence to a standard 3-day course of DHP alone (n = 178) or DHP combined with a single dose of primaquine on day 3 (n = 171). Patients were seen on days 1, 2, 3, and 7 and then weekly for 42 days to assess the presence of gametocytes and asexual parasites by microscopy. Survival analysis was stratified by the presence of gametocytes on day 3.

RESULTS:
DHP prevented development of gametocytes in 277 patients without gametocytes on day 3. In the gametocytemic patients (n = 72), primaquine was associated with faster gametocyte clearance (hazard ratio = 2.42 [95% confidence interval, 1.39-4.19], P = .002) and reduced gametocyte densities (P = .018). The day 42 cure rate of asexual stages in the DHP + primaquine and DHP-only arms were: polymerase chain reaction (PCR) unadjusted, 98.7% vs 99.4%, respectively; PCR adjusted, 100% for both. Primaquine was well tolerated.

CONCLUSIONS:
Addition of single-dose 0.75 mg/kg primaquine shortens the infectivity period of DHP-treated patients and should be considered in low-transmission regions that aim to control and ultimately eliminate falciparum malaria.

Item Type: Article
Additional Information: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The definitive publisher-authenticated version, Inge Sutanto, Sri Suprijanto, Ayleen Kosasih, Muhamad S. Dahlan, Din Syafruddin, Rita Kusriastuti, William A. Hawley, Neil F. Lobo, and Feiko O. ter Kuile The Effect of Primaquine on Gametocyte Development and Clearance in the Treatment of Uncomplicated Falciparum Malaria With Dihydroartemisinin-Piperaquine in South Sumatra, Western Indonesia: An Open-Label, Randomized, Controlled Trial Clin Infect Dis. (2013) 56 (5): 685-693 first published online November 21, 2012 doi:10.1093/cid/cis959 is available online at: http://cid.oxfordjournals.org/content/56/5/685.full
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 258 Primaquine. Quinacrine
QX Parasitology > Protozoa > QX 135 Plasmodia
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/cid/cis959
Depositing User: Users 27 not found.
Date Deposited: 26 Jul 2013 11:26
Last Modified: 15 Jun 2018 14:53
URI: http://archive.lstmed.ac.uk/id/eprint/3451

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