A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan.
BACKGROUND
Vivax malaria remains a major cause of morbidity in the subtropics. To undermine the stability of the disease, drugs are required that prevent relapse and provide reservoir reduction. A 14-day course of primaquine (PQ) is effective but cannot safely be used in routine practice because of its interaction with glucose-6-phosphate dehydrogenase (G6PD) deficiency for which testing is seldom available. Safe and effective use of PQ without the need for G6PD testing would be ideal. The efficacy and safety of an 8-week, once weekly PQ regimen was compared with current standard treatment (chloroquine alone) and a 14-day PQ regimen.


RESULTS
200 microscopically confirmed Plasmodium vivax patients were randomly assigned to either once weekly 8-week PQ (0.75 mg/kg/week), once weekly 8-week placebo, or 14-day PQ (0.5mg/kg/day) in North West Frontier Province, Pakistan. All patients were treated with a standard chloroquine dose and tested for G6PD deficiency. Deficient patients were assigned to the 8-week PQ group. Failure was defined as any subsequent episode of vivax malaria over 11 months of observation. There were 22/71 (31.0%) failures in the placebo group and 1/55 (1.8%) and 4/75 (5.1%) failures in the 14-day and 8-week PQ groups, respectively. Adjusted odds ratios were: for 8-week PQ vs. placebo-0.05 (95%CI: 0.01-0.2, p<0.001) and for 14-day PQ vs. placebo-0.01 (95%CI: 0.002-0.1, p<0.001). Restricted analysis allowing for a post-treatment prophylactic effect confirmed that the 8-week regimen was superior to current treatment. Only one G6PD deficient patient presented. There were no serious adverse events.


CONCLUSIONS
A practical radical treatment for vivax malaria is essential for control and elimination of the disease. The 8-week PQ course is more effective at preventing relapse than current treatment with chloroquine alone. Widespread use of the 8-week regimen could make an important contribution to reservoir reduction or regional elimination where G6PD testing is not available.


BACKGROUND
ClinicalTrials.gov NCT00158587.
Leslie
Toby
T
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. toby.leslie@lshtm.ac.uk
Mayan
Ismail
I
Mohammed
Nasir
N
Erasmus
Panna
P
Kolaczinski
Jan
J
Whitty
Christopher J M
CJ
Rowland
Mark
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000453:epidemiology; D000962:Antimalarials / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D016780:Malaria, Vivax / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D010154:Pakistan; D010919:Placebos; D011319:Primaquine / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012449:Safety
D000962:Antimalarials; D006454:Hemoglobins; D010919:Placebos; D011319:Primaquine