Publications

BACKGROUND

Artemisinin-based combination regimens are widely advocated for malarial treatment, but other effective regimens might be cheaper and more readily available. Our aim was to compare the risk of recurrent parasitaemia in patients given artemether-lumefantrine with that in those given amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated malaria.

METHODS

We enrolled 521 patients aged 6 months or older with uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina Faso. Patients were randomly assigned to receive standard doses of either artemether-lumefantrine (261) or amodiaquine plus sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. The study is registered at controlled-trials.gov with the identifier ISRCTN54261005.

FINDINGS

Of enrolled patients, 478 (92%) completed the 28-day study. The risk of recurrent symptomatic malaria was lowest in the group given amodiaquine plus sulfadoxine-pyrimethamine (1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were due to new infections. Recrudescences were four late treatment failures with artemether-lumefantrine and one early treatment failure with amodiaquine plus sulfadoxine-pyrimethamine. Both regimens were safe and well tolerated, with pruritus more common with amodiaquine plus sulfadoxine-pyrimethamine than with artemether-lumefantrine. Each regimen selected for new isolates with mutations that have been associated with decreased drug susceptibility.

INTERPRETATION

Amodiaquine plus sulfadoxine-pyrimethamine was more effective than was artemether-lumefantrine for the treatment of uncomplicated malaria. For regions of Africa where amodiaquine plus sulfadoxine-pyrimethamine continues to be effective, this less expensive and more available regimen should be considered as an alternative to blanket recommendations for artemisinin-based combination treatment for malaria.

OBJECTIVES

We sought to determine whether right ventricular (RV) function late after myocardial infarction (MI) impacts long-term prognosis.

BACKGROUND

Right ventricular failure predicts early mortality in patients with acute MI. The prognostic impact of RV function late after MI is not well defined. Accordingly, we determined whether RV dysfunction late after MI influences survival beyond traditional risk predictors, including patient age, left ventricular ejection fraction (LVEF), and infarct size.

METHODS

We studied 147 consecutive patients >30 days after MI (mean age of infarct 6.7 +/- 8.2 years) who were referred for contrast-enhanced cardiovascular magnetic resonance imaging. We assessed hazard ratios for death by RV ejection fraction (RVEF). The association of RVEF with mortality adjusted to traditional risk predictors was examined by using multivariable Cox proportional hazards regression models.

RESULTS

A total of 26 deaths occurred during a median follow-up of 17 months (range 6 to 53 months). By univariable analysis, RVEF <40% was strongly associated with mortality (unadjusted hazard ratio 4.02; p = 0.0007). By multivariable analysis that adjusted for patient age, left ventricular (LV) infarct size, and LVEF, RVEF <40% remained a significant independent predictor of mortality (adjusted hazard ratio 2.86; p = 0.03).

CONCLUSIONS

Right ventricular ejection fraction quantified late after MI is an important predictor of prognosis adjusted for patient age, LV infarct size, and LVEF. Accordingly, evaluation of RVEF using cardiovascular magnetic resonance imaging can improve risk-stratification and potentially refine patient management after MI.