Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

Collapse dynamics of spherical cavities in a solid under shock loading.

Extraordinary states of highly localised pressure and temperature can be generated upon the collapse of impulsively driven cavities. Direct observation of this phenomenon in solids has proved challenging, but recent advances in high-speed synchrotron radiography now permit the study of highly transient, subsurface events in real time. We present a study on the shock-induced collapse of spherical cavities in a solid polymethyl methacrylate medium, driven to shock states between 0.49 and 16.60 GPa. Utilising multi-MHz phase contrast radiography, extended sequences of the collapse process have been captured, revealing new details of interface motion, material failure and jet instability formation. Results reveal a rich array of collapse characteristics dominated by strength effects at low shock pressures and leading to a hydrodynamic response at the highest loading conditions.

Ultrafast Imaging of Laser Driven Shock Waves using Betatron X-rays from a Laser Wakefield Accelerator.

Betatron radiation from laser wakefield accelerators is an ultrashort pulsed source of hard, synchrotron-like x-ray radiation. It emanates from a centimetre scale plasma accelerator producing GeV level electron beams. In recent years betatron radiation has been developed as a unique source capable of producing high resolution x-ray images in compact geometries. However, until now, the short pulse nature of this radiation has not been exploited. This report details the first experiment to utilize betatron radiation to image a rapidly evolving phenomenon by using it to radiograph a laser driven shock wave in a silicon target. The spatial resolution of the image is comparable to what has been achieved in similar experiments at conventional synchrotron light sources. The intrinsic temporal resolution of betatron radiation is below 100 fs, indicating that significantly faster processes could be probed in future without compromising spatial resolution. Quantitative measurements of the shock velocity and material density were made from the radiographs recorded during shock compression and were consistent with the established shock response of silicon, as determined with traditional velocimetry approaches. This suggests that future compact betatron imaging beamlines could be useful in the imaging and diagnosis of high-energy-density physics experiments.

Risk factors for treatment default among adult tuberculosis patients in Indonesia.

SETTING: Defaulting from anti-tuberculosis treatment hinders tuberculosis (TB) control. OBJECTIVE: To identify potential defaulters. DESIGN: We conducted a cohort study in newly diagnosed Indonesian TB patients. We administered a questionnaire, prospectively identified defaulters (discontinued treatment ≥ 2 weeks) and assessed risk factors using Cox's regression. RESULTS: Of 249 patients, 39 (16%) defaulted, 61% in the first 2 months. Default was associated with liver disease (HR 3.40, 95%CI 1.02-11.78), chest pain (HR 2.25, 95%CI 1.06-4.77), night sweats (HR 1.98, 95%CI 1.03-3.79), characteristics of the head of the household (self-employed, HR 2.47, 95%CI 1.15-5.34; patient's mother, HR 7.72, 95%CI 1.66-35.88), household wealth (HR 4.24, 95%CI 1.12-16.09), walking to clinic (HR 4.53, 95%CI 1.39-14.71), being unaccompanied at diagnosis (HR 30.49, 95%CI 7.55-123.07) or when collecting medication (HR 3.34, 95%CI 1.24-8.98) and low level of satisfaction with the clinic (HR 3.85, 95%CI 1.17-12.62) or doctors (HR 2.45, 95%CI 1.18-5.10). Health insurance (HR 0.24, 95%CI 0.07-0.74) and paying for diagnosis (HR 0.14, 95%CI 0.04-0.48) were protective. CONCLUSION: Defaulting is common and occurs early. Interventions that improve clinic services, strengthen patient support and increase insurance coverage may reduce default in Indonesia.

Risk factors for Mycobacterium tuberculosis infection in Indonesian children living with a sputum smear-positive case.

SETTING AND OBJECTIVES: Young children living with infectious tuberculosis (TB) cases are at high risk of infection and disease, and screening is recommended. This is rarely conducted in resource-limited settings. Identifying children most at risk of infection may be useful for setting practical screening policies. DESIGN: Child contacts of smear-positive adult TB patients were invited for Mycobacterium tuberculosis infection and disease screening by symptoms, tuberculin skin test (TST), QuantiFERON-TB Gold In-Tube assay (QFT-GIT) and chest X-ray. Risk factors for infection were collected using a questionnaire and were calculated separately for TST, for QFT-GIT and for both tests combined. RESULTS: Of 304 screened children 145/302 (48%) were positive using TST, 152/299 (51%) by QFT-GIT and 180/304 (59%) were positive using either or both tests. Positivity for both tests was associated with index case infectivity (acid-fast bacilli [AFB] 3+ vs. AFB 1+: TST OR 2.93, 95%CI 1.59-5.39; QFT-GIT OR 2.28, 95%CI 1.06-4.90) and exposure (child contact's parent is the index case: TST OR 7.04, 95%CI 2.23-22.28; QFT-GIT OR 4.30, 95%CI 1.48-12.45). CONCLUSION: M. tuberculosis infection according to either test was high, supporting screening and preventive treatment. Children of smear-positive TB cases who accompany their parents to the clinic should be prioritised for immediate screening.

QuantiFERON®-TB Gold In-Tube assay vs. tuberculin skin test in Indonesian children living with a tuberculosis case.

SETTING AND OBJECTIVES: The tuberculin skin test (TST) has limitations in diagnosing latent tuberculosis (TB) infection (LTBI). Interferon-gamma release assays may improve diagnostic accuracy. We compared QuantiFERON®-TB Gold In-Tube (QFT-GIT) and TST in Indonesian children. DESIGN: Children aged from 6 months to 9 years exposed to a TB case at household and neighbourhood levels were recruited. The children underwent QFT-GIT and TST. Test responsiveness was assessed according to an exposure gradient. RESULTS: A total of 299 household-exposed and 72 neighbourhood-exposed children were analysed. Overall, respectively 46% and 41% were positive using QFT-GIT and the TST. Test positivity increased with exposure (QFT-GIT P value for trend <0.001, and TST P < 0.001); however, only QFT-GIT responded significantly to a 'within-household' gradient. The TST was less likely to be positive than the QFT-GIT in neighbourhood-exposed children (P = 0.05). BCG-vaccinated children were less likely to be QFT-GIT-positive, while older children were more likely to be QFT-GIT-positive. Both tests had increasing positivity with increasing smear grade. CONCLUSION: QFT-GIT performed similarly to the TST in Indonesian children living with an infectious TB case. Test accuracy was not compromised by young age or BCG vaccination. Our findings suggest that QFT-GIT offers little advantage over the TST in this population. High rates of LTBI diagnosed in household-exposed children by both tests support preventive therapy.