TY - JOUR
T1 - The effect of primaquine on gametocyte development and clearance in the treatment of uncomplicated falciparum malaria with dihydroartemisinin- piperaquine in South Sumatra, Western Indonesia
T2 - An open-label, randomized, controlled trial
AU - Sutanto, Inge
AU - Suprijanto, Sri
AU - Kosasih, Ayleen
AU - Dahlan, Muhamad S.
AU - Syafruddin, Din
AU - Kusriastuti, Rita
AU - Hawley, William A.
AU - Lobo, Neil F.
AU - Ter Kuile, Feiko O.
N1 - Funding Information:
Financial support. This work was supported by the Bill & Melinda Gates Foundation through grant 45114 to the Malaria Transmission Consortium. Potential conflicts of interest. All authors: No reported conflicts.
PY - 2013
Y1 - 2013
N2 - 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.Clinical Trials Registration. NCT01392014.
AB - 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.Clinical Trials Registration. NCT01392014.
KW - Indonesia
KW - dihydroartemisinin-piperaquine
KW - gametocyte P. falciparum
KW - primaquine
UR - http://www.scopus.com/inward/record.url?scp=84873633438&partnerID=8YFLogxK
U2 - 10.1093/cid/cis959
DO - 10.1093/cid/cis959
M3 - Article
C2 - 23175563
AN - SCOPUS:84873633438
SN - 1058-4838
VL - 56
SP - 685
EP - 693
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
ER -
