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A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan.

Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M - PLoS ONE (2008)

Bottom Line: Restricted analysis allowing for a post-treatment prophylactic effect confirmed that the 8-week regimen was superior to current treatment.There were no serious adverse events.The 8-week PQ course is more effective at preventing relapse than current treatment with chloroquine alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. toby.leslie@lshtm.ac.uk

ABSTRACT

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.

Methods and principal findings: 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.

Trial registration: ClinicalTrials.gov NCT00158587.

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Related in: MedlinePlus

Kaplan Meier survival analysis, by treatment group, restricted to post-treatment period (months 2–11).
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pone-0002861-g003: Kaplan Meier survival analysis, by treatment group, restricted to post-treatment period (months 2–11).

Mentions: Table 4 shows the number of episodes of malaria recorded during the observation period. In the placebo group, 5 additional episodes of malaria were recorded in one patient, whereas only single episodes were recorded in any of the PQ treated patients. Median time to first episode was, 63 days (range 36–322 days) (n = 22) in the placebo group; 285 days (n = 1) in the 14-day group and 125 days (range 113–158) (n = 4) in the 8-week group. There were too few failures for reliable statistical assessment of differences in the median time to failure. Table 5 shows the frequency of first relapse during the 2 month period of treatment and then at 3 month intervals during the follow-up period. In the 8-week placebo group 11/22 (50.0%) of failures were recorded during the first two months. Cumulative probability of treatment failure for each group over the full 11 month observation period was 35.2% (95%CI: 25.3–47.5%) in the placebo group, 3.6% (95%CI: 0.9–13.8%) in the 14-day and 13.5% (95%CI: 7.5–23.7%) in the 8-week PQ group (long-rank test for equality of survivor functions-Chi2 = 22.1, p<0.001) (Figure 2). Figure 3 shows the cumulative probability of treatment failure for the restricted analysis, which excluded all failures occurring during the period of treatment (0–8 weeks).


A randomised trial of an eight-week, once weekly primaquine regimen to prevent relapse of plasmodium vivax in Northwest Frontier Province, Pakistan.

Leslie T, Mayan I, Mohammed N, Erasmus P, Kolaczinski J, Whitty CJ, Rowland M - PLoS ONE (2008)

Kaplan Meier survival analysis, by treatment group, restricted to post-treatment period (months 2–11).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2481394&req=5

pone-0002861-g003: Kaplan Meier survival analysis, by treatment group, restricted to post-treatment period (months 2–11).
Mentions: Table 4 shows the number of episodes of malaria recorded during the observation period. In the placebo group, 5 additional episodes of malaria were recorded in one patient, whereas only single episodes were recorded in any of the PQ treated patients. Median time to first episode was, 63 days (range 36–322 days) (n = 22) in the placebo group; 285 days (n = 1) in the 14-day group and 125 days (range 113–158) (n = 4) in the 8-week group. There were too few failures for reliable statistical assessment of differences in the median time to failure. Table 5 shows the frequency of first relapse during the 2 month period of treatment and then at 3 month intervals during the follow-up period. In the 8-week placebo group 11/22 (50.0%) of failures were recorded during the first two months. Cumulative probability of treatment failure for each group over the full 11 month observation period was 35.2% (95%CI: 25.3–47.5%) in the placebo group, 3.6% (95%CI: 0.9–13.8%) in the 14-day and 13.5% (95%CI: 7.5–23.7%) in the 8-week PQ group (long-rank test for equality of survivor functions-Chi2 = 22.1, p<0.001) (Figure 2). Figure 3 shows the cumulative probability of treatment failure for the restricted analysis, which excluded all failures occurring during the period of treatment (0–8 weeks).

Bottom Line: Restricted analysis allowing for a post-treatment prophylactic effect confirmed that the 8-week regimen was superior to current treatment.There were no serious adverse events.The 8-week PQ course is more effective at preventing relapse than current treatment with chloroquine alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. toby.leslie@lshtm.ac.uk

ABSTRACT

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.

Methods and principal findings: 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.

Trial registration: ClinicalTrials.gov NCT00158587.

Show MeSH
Related in: MedlinePlus