Abstract
Background: Plasmodium vivax malaria commonly follows treatment of falciparum malaria in regions of coendemicity. 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 5.001). 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 (t1/2<1 day), 35.3% (95% CI, 31.8%-39.0%) after treatment with intermediate half-life drugs (t1/2 1-7 days), and 19.6% (95% CI, 18.1%-21.3%) after treatment with slowly eliminated drugs (t1/2 > 7 days) (P <.001, by test for trend). Artemisinin-based combinations containing mefloquine or piperaquine, compared with the artemetherlumefantrine 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.
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 5.001). 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 (t1/2<1 day), 35.3% (95% CI, 31.8%-39.0%) after treatment with intermediate half-life drugs (t1/2 1-7 days), and 19.6% (95% CI, 18.1%-21.3%) after treatment with slowly eliminated drugs (t1/2 > 7 days) (P <.001, by test for trend). Artemisinin-based combinations containing mefloquine or piperaquine, compared with the artemetherlumefantrine 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.
| Original language | English |
|---|---|
| Pages (from-to) | 612-620 |
| Number of pages | 9 |
| Journal | Clinical Infectious Diseases |
| Volume | 52 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2011 |