The impact on malaria of biannual treatment with azithromycin in children age less than 5 years: a prospective study.

BACKGROUND: The MORDOR study, a cluster randomized clinical trial, showed that single-dose azithromycin (20 mg/kg) administered biannually for 2 years to preschool children reduced mortality; a study was conducted to determine its effect on clinical symptomatic episodes of malaria as a potential mechanism for mortality benefit. METHODS: A randomized control trial (RCT) was conducted, whereby 30 randomly selected communities in Kilosa District, Tanzania were randomized to receive 6-monthly treatment of children ages 1-59 months with single-dose azithromycin (20 mg/kg) vs. placebo. A prospective cohort study was nested within the RCT: children, aged 1 to 35 months at baseline, were randomly selected in each community and evaluated at 6-monthly intervals for 2 years. At each visit, the children were assessed for recent or ongoing fever and anti-malarial treatment; a rapid diagnostic test (RDT) for malaria was performed. The two major outcomes of interest were prevalence of RDT positivity and clinical malaria. The latter was defined as RDT-positivity with fever at time of evaluation and/or reported fever in the 3 days prior to evaluation. Methods that account for correlations at community level and within individuals over time were used to evaluate associations. RESULTS: At baseline, the prevalence rates in the children in the azithromycin and placebo arms were 17.6% vs. 15.5% for RDT positivity (p = 0.76) and 6.1% vs. 4.3% (p = 0.56) for clinical malaria. There was a decline in both RDT-positivity and clinical malaria over time in both arms. The difference by treatment assignment was not significant for clinical malaria; it was significant for RDT-positivity with greater odds of decline in the placebo arm (p = 0.01). CONCLUSIONS: Lack of evidence for a significant difference in the prevalence of clinical malaria in children at any visit following treatment suggests that the effect of single-dose azithromycin on malaria is at best transient and limited in scope. Chance overrepresentation of non-seasonal transmission in the communities in the azithromycin arm may account for higher rates of RDT-positivity and less decline over time. Trial registration Clinicaltrials.gov NCT02047981.

Multimodal Assessment of Corneal Thinning Using Optical Coherence Tomography, Scheimpflug Imaging, Pachymetry, and Slit-Lamp Examination.

PURPOSE: To assess the relationship between corneal thinning measured by clinician-graded slit-lamp examination compared with ultrasound pachymetry (USP), anterior segment optical coherence tomography (AS-OCT), and the Pentacam. METHODS: Patients with corneal thinning underwent USP, AS-OCT, Pentacam measurements and standardized clinical grading by 2 cornea specialists estimating thinning on slit-lamp examination. Reproducibility of each testing modality was assessed using the intraclass correlation coefficient. Bland-Altman plots were used to determine precision and limits of agreement (LOA) between imaging modalities and clinical grading. RESULTS: We included 22 patients with corneal thinning secondary to infectious or inflammatory keratitis. Mean percent stromal thinning estimated by grader 1 was 51% (SD 31) and grader 2 was 49% (SD 33). The intraclass correlation coefficient between the masked examiners was 0.95 (95% confidence interval, 0.88-0.98). Graders were more similar to each other than to any other modality with 2% difference and 4.6% of measurements outside the LOA. When measuring the area of maximum thinning, AS-OCT measured approximately 10% thicker than human graders while the Pentacam measured approximately 10% thinner than human graders with 16.7% outside the LOA. USP measured approximately 20% thinner than human graders with 5.6% outside the LOA. CONCLUSIONS: Trained corneal specialists have a high degree of agreement in location and degree of corneal thinning when measured in a standardized fashion on the same day. Other testing modalities had acceptable reproducibility and agreement with clinical examination and each other, although Scheimpflug imaging fared worse for corneal thinning, particularly in the periphery, than the other modalities.