Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate in comparison with chloroquine phosphate in children with acute uncomplicated Plasmodium vivax malaria: A phase III, randomised, multicentric study.

BACKGROUND & OBJECTIVES: In India, the burden of Plasmodium vivax malaria has been projected to be highest in some areas. This study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate (AM) 37.5 mg and piperaquine phosphate 187.5 mg (PQP) dispersible tablets and (not with) chloroquine in the treatment of uncomplicated vivax malaria in pediatric patients. METHODS: This multicentric, open-label trial was carried out at 12 sites in India. A total of 164 patients aged 6 months to 12 years with P. vivax malaria were randomized in a ratio of 2:1 to AM-PQP (111 patients) or chloroquine (53 patients) arms. The duration of follow up was 42 days. RESULTS: At 72 hours, the proportion of a parasitaemic and afebrile patients was 100% in both treatment arms in per protocol (PP) population, and 98.2% and 100% [95% CI: -1.8 (-6.33 to 5.08)] in AM-PQP and chloroquine arms, respectively, in intent to treat (ITT) population. The efficacy and safety of AM-PQP was found to be comparable to chloroquine in the treatment of uncomplicated P. vivax malaria in pediatric patients. Overall, the cure rate at Day 28 and 42 was >95% for both AM-PQP or CQ. The commonly reported clinical adverse event was vomiting. No patient was discontinued for any QTc abnormality. INTERPRETATION & CONCLUSION: The efficacy and safety of FDC of arterolane maleate and piperaquine phosphate was found to be comparable to chloroquine for treatment of uncomplicated P. vivax malaria in pediatric patients.

Comparison of diastolic function in children with transfusion dependent beta thalassemia major by tissue and conventional doppler imaging indices and its correlation with serum ferritin levels.

Nanjegowda CK, Kamath SP, Kamath P, Shah TD, Kulkarni V, Lashkari HP, Baliga BS. Comparison of diastolic function in children with transfusion dependent beta thalassemia major by tissue and conventional doppler imaging indices and its correlation with serum ferritin levels. Turk J Pediatr 2019; 61: 250-259. Regular blood transfusions for children with beta thalassemia major (ß- TM) results in iron overload cardiomyopathy/cardiac failure. Mortality in these children is most often because of heart failure. We compared Tissue Doppler Imaging (TDI) and conventional pulse wave Doppler (PWD) indices in evaluating diastolic function in chronically transfused ß-TM children and correlated the Doppler indices with mean serum ferritin levels. This was a prospective cross-sectional study conducted at tertiary teaching hospital. ß-TM children aged 3 to 18 years were enrolled as per inclusion criteria. PWD parameters at the mitral inflow (E, A, E/A and DT) and TDI parameters at the medial mitral annulus (E'and E/E') were used for estimation of diastolic dysfunction. Of the 66 children with thalassemia, the mean age was 10.2±3.77yrs and 60.6% were boys. The E/E' ratio estimated diastolic dysfunction (34/66, 51.5%) greater than four times that assessed by E/A ratio indices (8/66, 12.1%) in the subjects. Association of serum ferritin levels with E/E' ratio by chi square test was significant statistically (P=0.027), however was not significant with E/A ratio. By Mann Whitney test, the median serum ferritin levels (ng/ml) were higher [4034.50, (IQR-2084-5340.25) in those with diastolic dysfunction (abnormal E/E'), when compared to those with normal E/E'[2037.50(1510.75- 3572.25)], with their difference being significant (p=0.011), however serum ferritin levels were not significant with E/A ratio and DT. E/E' parameter had a sensitivity and specificity of 76.5% and 53.1% respectively at a mean serum ferritin cutoff level of 2076 ng/mL by ROC analysis. In conclusion, TDI is a more reliable modality for diagnosing early diastolic dysfunction when compared to PWD. Threshold level of serum ferritin greater than 2076 ng/mL is associated with increased incidence of diastolic dysfunction.