Quantifying and preventing Plasmodium vivax recurrences in primaquine-untreated pregnant women: An observational and modeling study in Brazil.

Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.

Risk stratification in a Brazilian hospital-based cohort of 1220 outpatients with heart failure: role of Chagas' heart disease.

BACKGROUND: Few studies evaluated prognostic factors of outpatients with heart failure of different etiologies including Chagas' heart disease. METHODS: We studied 1220 outpatients with heart failure in functional classes III and IV (NYHA) to evaluate prognostic factors. Patients aged 13-72 years (mean 45.5, standard deviation 11); 952 men (78%) and 268 women (22%) were followed up for 25.6+/-26 months from 1991 to 2000. Heart failure was attributed to idiopathic dilated cardiomyopathy in 454 (37%) patients. Etiologies were Chagas' heart disease in 242 (20%) patients, ischemic cardiomyopathy in 212 (17%), hypertensive cardiomyopathy in 170 (14%) and others in 142 (12%). Statistical analyses were performed with Kaplan-Meier and Cox proportional hazards methods, following a strategy of noninvasive model as well as in an invasive model to identify the risk of death. RESULTS: Four hundred fifteen (34%) patients died in the follow-up period, 71 (6%) patients underwent heart transplantation and 28 (2%) underwent other surgical interventions. In the noninvasive model, Chagas' heart disease (relative risk compared with other etiologies 2.26 to 2.97), left ventricular end diastolic diameter on echocardiography (relative risk 1.13) and left ventricular ejection fraction on radionuclide angiography (relative risk 0.96) were associated with higher mortality. In the invasive model, Chagas' heart disease (relative risk compared with other etiologies 2.66 to 9.13) was the most important determinant of mortality in association with the cardiac index (relative risk 0.40). CONCLUSIONS: In this cohort of patients with heart failure of different etiologies, Chagas' heart disease was the main prognostic factor for mortality.