Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.)

Elizabethkingia anophelis and Association with Tap Water and Handwashing, Singapore

We report an Elizabethkingia anophelis case cluster associated with contaminated aerators and tap water in a children’s intensive care unit in Singapore in 2017. We demonstrate a likely transmission route for E. anophelis to patients through acquisition of the bacteria on hands of healthcare workers via handwashing

Is breastfeeding associated with later child eating behaviours?

Individual differences in children's eating behaviours emerge early. We examined the relationship between breastfeeding exposure and subsequent eating behaviours among children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Children (n = 970) were grouped according to their breastfeeding exposure: high (full breastfeeding ≥ 4 months with continued breastfeeding ≥ 6 months), low (any breastfeeding < 3 months or no breastfeeding) and intermediate (between low and high breastfeeding categories). Aspects of eating behaviour from ages 15 months to 6 years were captured using a combination of maternal reports (Child Eating Behaviour Questionnaire; Infant Feeding Questionnaire; Preschooler Feeding Questionnaire) and laboratory-based measures of meal size, oral processing behaviours (e.g. average eating speed and bite size) and tendency to eat in the absence of hunger. Most children had low (44%) or intermediate (44%) breastfeeding exposure; only 12% had high exposure. After adjusting for confounders, multivariable linear regression analyses indicated the high (but not intermediate) breastfeeding group was associated with significantly lower reported food fussiness at 3 years compared to low breastfeeding group (−0.38 [-0.70, −0.06]), with similar but non-significant trends observed at 6 years (−0.27 [-0.66, 0.11]). At 3 years, mothers in the high breastfeeding group also reported the least difficulty in child feeding compared to low breastfeeding group (−0.22 [-0.43, −0.01]). However, high breastfeeding was not associated with any other maternal-reports of child feeding or eating behaviours, and no significant associations were observed between breastfeeding exposure and any of the laboratory measures of eating behaviour at any of the time points. These results do not strongly support the view that increased breastfeeding exposure alone has lasting and consistent associations with eating behaviours in early childhood

THE HUMIRA IN OCULAR INFLAMMATIONS TAPER (HOT) STUDY.

PURPOSE To assess factors that impact the risk of relapse in patients with non-infectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN Retrospective study. METHODS - Setting: Multicenter study. - Study Population: Patients with NIU treated with adalimumab and subsequently tapered. - Observation Procedure: Patient demographics, type of NIU, onset and duration of disease, period of inactivity before tapering adalimumab and tapering schedule were collected. - Main Outcome Measures: Independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS 328 patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2±70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8±69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7±61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs. 37.5 years, p=0.0005) and the rate of recurrence was significantly higher in younger subjects (HR=0.88 per decade of increasing age, p=0.01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR=1.23 per unit increase in speed, p<0.0005). Conversely, a more extended period of remission prior to tapering was associated with a lower rate of recurrence (HR=0.97 per 10-weeks longer period of inactivity, p=0.04). CONCLUSIONS When tapering adalimumab, factors that should be considered include patient's age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable