Interferon gamma release assay post BCG among newborns and family members living in a crowded area in Jakarta, Indonesia.

INTRODUCTION: BCG vaccine is a mandatory for newborn in Indonesia, an endemic tuberculosis (TB) country that ranks second worldwide. A close contact with untreated active pulmonary TB individuals in a crowded area may result in TB disease or otherwise develop a latent TB infection (LTBI), as shown by positive result of interferon gamma release assay (IGRA). OBJECTIVE: To explore LTBI among newborns and their family members living in a crowded area in Jakarta, Indonesia. METHODOLOGY: A prospective analytical study was conducted among newborns between October 2016 and March 2017. IGRA was examined before BCG vaccination and after 12 weeks. In parallel, TB active case finding was performed among family members of the newborns. RESULTS: Out of 135 newborns, only 117 (86.7%) came for BCG vaccination. Of 346 family members screened, 8 (2.3%) were detected as untreated active pulmonary TB, confirmed by positive sputum and/or MTB culture. Family members living in the same house with active TB individuals (p = 0.011, OR 2.69) as well as being males (p = 0.025, OR 1.68) had a significant higher risk of having a positive IGRA. CONCLUSIONS: Untreated pulmonary TB infection in a crowded area infects the surrounding neighbors, resulting in latent TB infection. An active program for detecting pulmonary TB cases and preventive measures need to be taken seriously to contain the potential spread of the infection.

Extended spectrum beta-lactamase-producing Escherichia coli surveillance in the human, food chain, and environment sectors: Tricycle project (pilot) in Indonesia.

The World Health Organization (WHO) has been implementing antimicrobial surveillance with a "One Health" approach, known as the Global Surveillance ESBL E. coli Tricycle Project. We describe the implementation of the Tricycle Project (pilot) in Indonesia, focusing on its results, challenges and recommendations. The samples were 116 patients with bloodstream infections caused by ESBL E. coli, 100 rectal swabs collected from pregnant women, 240 cecums of broiler, and 119 environmental samples, using the standardized method according to the guidelines. ESBL-producing E. coli was found in 40 (40%) of the 100 pregnant women, while the proportion of ESBL-producing E. coli was 57.7% among the total E. coli-induced bloodstream infections. ESBL-producing E. coli was isolated from 161 (67.1%) out of 240 broilers. On the other hand, the average concentration of E. coli in the water samples was 2.0 × 108 CFU/100 mL, and the ratio of ESBL-producing E. coli was 12.8% of total E. coli. Unfortunately, 56.7% of questionnaires for patients were incomplete. The Tricycle Project (pilot) identified that the proportion of ESBL-producing E. coli was very high in all types of samples, and several challenges and obstacles were encountered during the implementation of the study in Indonesia. The finding of this study have implication to health/the antimicrobial resistance (AMR) surveillance. We recommend continuing this project and extending this study to other provinces to determine the AMR burden as the baseline in planning AMR control strategies in Indonesia. We also recommend improving the protocol of this study to minimize obstacles in the field.

A randomized pilot study of L-arginine infusion in severe falciparum malaria: preliminary safety, efficacy and pharmacokinetics.

BACKGROUND: Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed. METHODS: In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM. RESULTS: Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM. CONCLUSION: In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine. TRIAL REGISTRATION: ClinicalTrials.gov NCT00616304.

Pharmacokinetics of L-arginine in adults with moderately severe malaria.

Severe malaria is associated with decreased nitric oxide (NO) production and low plasma concentrations of L-arginine, the substrate for NO synthase. Supplementation with L-arginine has the potential to improve NO bioavailability and outcomes. We developed a pharmacokinetic model for L-arginine in moderately severe malaria to explore the concentration-time profile and identify important covariates. In doses of 3, 6, or 12 g,L-arginine was infused over 30 min to 30 adults with moderately severe malaria, and plasma concentrations were measured at 8 to 11 time points. Patients who had not received L-arginine were also assessed and included in the model. The data were analyzed using a population approach with NONMEM software. A two-compartment linear model with first-order elimination best described the data, with a clearance of 44 liters/h (coefficient of variation [CV] = 52%) and a volume of distribution of 24 liters (CV = 19%). The natural time course of L-arginine recovery was described empirically by a second-order polynomial with a time to half recovery of 26 h. The half-life of exogenous L-arginine was reduced in patients with malaria compared with that for healthy adults. Weight and ethnicity were significant covariates for clearance. MATLAB simulations of dosing schedules for use in future studies predicted that 12 g given over 6, 8, or 12 h will provide concentrations above the K(m) of endothelial cell CAT-1 transporters in 90%, 75%, and 60% of patients, respectively.