IntroductionChagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Patients and MethodsProspective population pharmacokinetic (PK) cohort study in children 2–12 years old with Chagas disease treated with oral benznidazole 5–8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387).ResultsForty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs).DiscussionObserved benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.Trial RegistrationClinicalTrails.gov NCT00699387

BackgroundChildhood pneumonia is a major cause of childhood illness and the second leading cause of child death globally. Understanding the costs associated with the management of childhood pneumonia is essential for resource allocation and priority setting for child health.MethodsWe conducted a systematic review to identify studies reporting data on the cost of management of pneumonia in children younger than 5 years old. We collected unpublished cost data on non–severe, severe and very severe pneumonia through collaboration with an international working group. We extracted data on cost per episode, duration of hospital stay and unit cost of interventions for the management of pneumonia. The mean (95% confidence interval, CI) and median (interquartile range, IQR) treatment costs were estimated and reported where appropriate.ResultsWe identified 24 published studies eligible for inclusion and supplemented these with data from 10 unpublished studies. The 34 studies included in the cost analysis contained data on more than 95 000 children with pneumonia from both low– and–middle income countries (LMIC) and high–income countries (HIC) covering all 6 WHO regions. The total cost (per episode) for management of severe pneumonia was US$ 4.3 (95% CI 1.5–8.7), US$ 51.7 (95% CI 17.4–91.0) and US$ 242.7 (95% CI 153.6–341.4)–559.4 (95% CI 268.9–886.3) in community, out–patient facilities and different levels of hospital in–patient settings in LMIC. Direct medical cost for severe pneumonia in hospital inpatient settings was estimated to be 26.6%–115.8% of patients’ monthly household income in LMIC. The mean direct non–medical cost and indirect cost for severe pneumonia management accounted for 0.5–31% of weekly household income. The mean length of stay (LOS) in hospital for children with severe pneumonia was 5.8 (IQR 5.3–6.4) and 7.7 (IQR 5.5–9.9) days in LMIC and HIC respectively for these children.ConclusionThis is the most comprehensive review to date of cost data from studies on the management of childhood pneumonia and these data should be helpful for health services planning and priority setting by national programmes and international agencies.

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Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study.

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Objective We conducted a population-based pharmacokinetic study to assess blood levels and elimination of mercury following vaccination of premature infants born at ≥ 32 and < 37 weeks of gestation and with birth weight ≥ 2000 but < 3000 grams. Study design Blood, stool, and urine samples were obtained pre-vaccination and 12 hours to 30 days post-vaccination from 72 premature newborns. Total mercury levels were measured by atomic absorption. Results The mean ± standard deviation (SD) birth weight was 2.4 ±0.3 Kg for the study population. Maximal mean ± SD blood mercury levels was 3.6 ± 2.1 ng/mL occurring at 1 day after vaccination, maximal mean ± SD stool mercury levels were 35.4 ± 38.0 ng/g, occurring on day 5 after vaccination, and urine mercury levels were mostly non-detectable. The blood mercury half-life was calculated to be 6.3 (95% CI:3.85-8.77) days and mercury levels returned to pre-vaccination levels by day 30. Conclusions The blood half-life of intramuscular ethyl mercury from thimerosal in vaccines given to premature infants is substantially shorter than that of oral methyl mercury in adults. Because of the differing pharmacokinetics, exposure guidelines based on oral methyl mercury in adults may not be accurate for children who receive thimerosal-containing vaccines.

The clinical burden of varicella in Argentina was associated with utilization of significant amounts of healthcare resources, resulting in substantial economic costs. These costs should be reduced with the recent implementation of routine vaccination of children.

Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.