f Radical cure of Plasmodium vivax infection applies blood schizontocidal therapy against the acute attack and hypnozoitocidal therapy against later relapse. Chloroquine and primaquine have been used for 60 years in this manner. Resistance to chloroquine by the parasite now requires partnering other blood schizontocides with primaquine. However, the safety and efficacy of primaquine against relapse when combined with other drugs have not been demonstrated. This randomized, open-label, and relapse-controlled trial estimated the efficacy of primaquine against relapse when administered with quinine or dihydroartemisinin-piperaquine for treatment of the acute infection. Among 650 soldiers who had returned to their malaria-free base in Java, Indonesia, after 12 months in malarious Papua, Indonesia, 143 with acute P. vivax malaria were eligible for study. One hundred sixteen enrolled subjects were randomized to these treatments: artesunate (200-mg dose followed by 100 mg/day for 6 days), quinine (1.8 g/day for 7 days) plus concurrent primaquine (30 mg/day for 14 days), or dihydroartemisinin (120 mg) plus piperaquine (960 mg) daily for 3 days followed 25 days later by primaquine (30 mg/day for 14 days). Follow-up was for 12 months. One hundred thirteen subjects were analyzable. Relapse occurred in 32 of 41 (78%) subjects administered artesunate alone (2.71 attacks/person-year), 7 of 36 (19%) administered quinine plus primaquine (0.23 attack/person-year), and 2 of 36 (6%) administered dihydroartemisinin-piperaquine plus primaquine (0.06 attack/personyear). The efficacy of primaquine against relapse was 92% (95% confidence interval [CI] ‫؍‬ 81% to 96%) for quinine plus primaquine and 98% (95% CI ‫؍‬ 91% to 99%) for dihydroartemisinin-piperaquine plus primaquine. Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua, Indonesia. M alaria caused by Plasmodium vivax threatens severe illness in travelers and the several billion people living at risk in zones of endemicity (1-4). Despite the long-standing dogma of benign identity for this parasite, it is pernicious and often provokes lifethreatening illness (5). Unlike the other important cause of malaria, Plasmodium falciparum, this parasite places dormant forms in the liver (hypnozoites) that cause repeated attacks called relapses (6). The only licensed therapy against relapse is primaquine (PQ) used in combination with chloroquine (CQ) for the primary attack, together called radical cure. Worsening CQ resistance threatens this 60-year-old treatment (7), and PQ efficacy against relapse has only rarely been estimated since its development in experimental challenge of American prisoner volunteers. The failing efficacy of CQ and the uncertain efficacy of PQ raise doubts regarding successful chemotherapeutic management of this dangerous infection.Emerging CQ-resistant P. vivax compels consideration of dihydroartemisinin (DHA) plus p...

Severe underweight was associated with longer time to initial sputum culture conversion among MDR-TB patients.

Rationale Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7–11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results The 1,468 eligible individuals received a median of 4 (interquartile range, 4–5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81–0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73–0.81) for 7–11 months, and 0.86 (95% CI, 0.83–0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85–0.96) for 7–11 months and 1.01 (95% CI, 0.96–1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05–1.14]). Conclusions BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person–time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens.

Abstract Delamanid should be effective against highly resistant strains of Mycobacteriumtuberculosis, but uptake has been slow globally. In the endTB (expand new drug markets for TB) Observational Study, which enrolled a large, heterogeneous cohorts of patients receiving delamanid as part of a multidrug regimen, 80% of participants experienced sputum culture conversion within 6 months. Clinical Trials Registration. NCT02754765.