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. 2011 Mar 1;52(5):612-20.
doi: 10.1093/cid/ciq249.

Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics

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Plasmodium vivax recurrence following falciparum and mixed species malaria: risk factors and effect of antimalarial kinetics

Nicholas M Douglas et al. Clin Infect Dis. .

Abstract

Background: Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of co-endemicity. This is an important cause of preventable morbidity.

Methods: We examined the factors contributing to the risk of recurrence of P. vivax infection after treatment of acute falciparum malaria in a series of clinical trials conducted on the Thai-Myanmar border from 1991 through 2005.

Results: Overall, 10,549 patients (4960 children aged <15 years and 5589 adults) were treated for falciparum malaria; of these patients, 9385 (89.0%) had Plasmodium falciparum monoinfection and 1164 (11.0%) had mixed P. falciparum/P. vivax infections according to microscopic examinations performed at screening. The cumulative proportion of patients with P. falciparum infection recurrence by day 63 was 21.5% (95% confidence interval [CI], 20.3%-22.8%), and the cumulative proportion with P. vivax infection recurrence was 31.5% (95% CI, 30.1%-33.0%). Significant risk factors for P. vivax infection recurrence were mixed infection at enrollment, male sex, younger age, lower hematocrit, higher asexual P. falciparum parasite density (P < .001 for all factors), and P. falciparum gametocytemia at enrollment (P = .001). By day 63, the cumulative risk of vivax malaria after P. falciparum monoinfection was 51.1% (95% CI, 46.1%-56.2%) after treatment with rapidly eliminated drugs (t(1/2) <1 day), 35.3% (95% CI, 31.8%-39.0%) after treatment with intermediate half-life drugs (t(1/2) 1-7 days), and 19.6% (95% CI, 18.1%-21.3%) after treatment with slowly eliminated drugs (t(1/2) > 7 days) (P < .001, by test for trend). Artemisinin-based combinations containing mefloquine or piperaquine, compared with the artemether-lumefantrine and artesunate-atovaquone-proguanil combinations, were associated with a 3.6-fold to 4.2-fold lower adjusted hazard ratio for P. vivax infection recurrence within 63 days after pure or mixed P. falciparum infections (P < .001, for comparisons with artesunate-mefloquine).

Conclusions: On the Thai-Myanmar border, P. vivax is the most common cause of parasitological failure after treatment for falciparum malaria. Slowly eliminated antimalarials reduce the risk of early P. vivax infection recurrence.

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Figures

Figure 1.
Figure 1.
Risk of Plasmodium vivax recurrence after Plasmodium falciparum monoinfection or mixed P. vivax/P. falciparum malaria by week of follow-up and antimalarial half-life.
Figure 2.
Figure 2.
Kaplan–Meier failure estimates for the cumulative risk of Plasmodium vivax recurrence after Plasmodium falciparum infection (A) and following mixed P. falciparum/P. vivax infection (B) by antimalarial half-life.
Figure 3.
Figure 3.
Kaplan–Meier failure estimates for the cumulative risk of Plasmodium vivax recurrence after Plasmodium falciparum infection (A) and following mixed P. falciparum/P. vivax infection (B) for artemisinin combination therapies. AS+MQ, artesunate plus mefloquine; DHA + PIP, dihydroartemisinin plus piperaquine; AM+MQ, artemether plus mefloquine; AM+LUM, artemether plus lumefantrine; AS+AV+PG, artesunate plus atovaquone plus proguanil.

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