Food decreased absolute bioavailability and maximum concentration of isoniazid and rifampicin, but not of ethambutol or pyrazinamide, in treatment-naive TB patients. In patients prone to low drug exposure, this may further compromise treatment efficacy and increase the risk of acquired drug resistance.

Background Breath tests may diagnose tuberculosis (TB) through detecting specific volatile organic compounds produced by Mycobacterium tuberculosis or the infected host. Methods To estimate the diagnostic accuracy of breath test with electronic-nose and other devices against culture or other tests for TB, we screened multiple databases until January 6, 2019. Findings We included fourteen studies, with 1715 subjects in the analysis. The pooled sensitivity and specificity of electronic-nose were 0.93 (95% CI 0.82–0.97) and 0.93 (95% CI 0.82–0.97), respectively, and no heterogeneity was found. The sensitivity and specificity of other breath test devices ranged from 0.62 to 1.00, and 0.11 to 0.84, respectively. Interpretation The low to moderate evidence of these studies shows that breath tests can diagnose TB accurately, however, to give a real-time test result, additional development is needed. Research should also focus on sputum smear negative TB, children, and the positioning of breath testing in the diagnostic work flow. Funding The authors received no specific funding for this work.

The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approach has been widely used to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, instead of using it alone, clinicians often prefer to diagnose the coronavirus disease 2019 (COVID-19) by utilizing a combination of clinical signs and symptoms, laboratory test, imaging measurement (e.g., chest computed tomography scan), and multivariable clinical prediction models, including the electronic nose. Here, we report on the development and use of a low cost, noninvasive method to rapidly sniff out COVID-19 based on a portable electronic nose (GeNose C19) integrating an array of metal oxide semiconductor gas sensors, optimized feature extraction, and machine learning models. This approach was evaluated in profiling tests involving a total of 615 breath samples composed of 333 positive and 282 negative samples. The samples were obtained from 43 positive and 40 negative COVID-19 patients, respectively, and confirmed with RT-qPCR at two hospitals located in the Special Region of Yogyakarta, Indonesia. Four different machine learning algorithms (i.e., linear discriminant analysis, support vector machine, stacked multilayer perceptron, and deep neural network) were utilized to identify the top-performing pattern recognition methods and to obtain a high system detection accuracy (88–95%), sensitivity (86–94%), and specificity (88–95%) levels from the testing datasets. Our results suggest that GeNose C19 can be considered a highly potential breathalyzer for fast COVID-19 screening.

No abstract

The international literature shows that HIV-risk behaviour for women mostly occurs in the context of intimate relationships. Power imbalances in the social, economic and cultural spheres put women at risk. This paper addresses the roles of male partners in women's engagement in drug-use behaviour and drug-related HIV-risk behaviour in Indonesia. Data were gathered through in-depth interviews with 19 women who had injected drugs in the previous month in three sites in central Java. Most of the women had male partners who also injected drugs. Results show that male partners play a significant role in the initiation of drug use, the provision of drugs, injecting behaviour and in the constitution of women injectors' social networks. These findings suggest the need to develop couple-based interventions and to facilitate women-only groups as part of HIV prevention.

Objective To investigate the potency of a hand-held point-of-care electronic-nose to diagnose pulmonary tuberculosis (PTB) among those suspected of PTB. Methods Setting: Lung clinics and Dr. Sardjito Hospital, Yogyakarta, Indonesia. Participants: patients with suspected PTB and healthy controls. Sampling: 5 minutes exhaled breath. Sputum-smear-microscopy, culture, chest-radiography, and follow-up for 1.5–2.5 years, were used to classify patients with suspected PTB as active PTB, probably active PTB, probably no PTB, and no PTB. After building a breath model based on active PTB, no PTB, and healthy controls (Calibration phase), we validated the model in all patients with suspected PTB (Validation phase). In each variable (sex, age, Body Mass Index, co-morbidities, smoking status, consumption of alcohol, use of antibiotics, flu symptoms, stress, food and drink intake), one stratum’s Receiver Operating Characteristic (ROC)-curve indicating sensitivity and specificity of the breath test was compared with another stratum’s ROC-curve. Differences between Area-under-the-Curve between strata ( p <0.05) indicated an association between the variable and sensitivity—specificity of the breath test. Statistical analysis was performed using STATA/SE 15. Results Of 400 enrolled participants, 73 were excluded due to extra-pulmonary TB, incomplete data, previous TB, and cancer. Calibration phase involved 182 subjects, and the result was validated in 287 subjects. Sensitivity was 85% (95%CI: 75–92%) and 78% (95%CI: 70–85%), specificity was 55% (95%CI: 44–65%) and 42% (95%CI: 34–50%), in calibration and validation phases, respectively. Test sensitivity and specificity were lower in men. Conclusion The electronic-nose showed modest sensitivity and low specificity among patients with suspected PTB. To improve the sensitivity, a larger calibration group needs to be involved. With its portable form, it could be used for TB screening in remote rural areas and health care settings.

BackgroundThe 24-h area under the concentration–time curve (AUC24)/minimal inhibitory concentration ratio is the best predictive pharmacokinetic/pharmacodynamic (PK/PD) parameter of the efficacy of first-line anti-tuberculosis (TB) drugs. An optimal sampling strategy (OSS) is useful for accurately estimating AUC24; however, OSS has not been developed in the fed state or in the early phase of treatment for first-line anti-TB drugs.MethodsAn OSS for the prediction of AUC24 of isoniazid, rifampicin, ethambutol and pyrazinamide was developed for TB patients starting treatment. A prospective, randomized, crossover trial was performed during the first 3 days of treatment in which first-line anti-TB drugs were administered either intravenously or in fasting or fed conditions. The PK data were used to develop OSS with best subset selection multiple linear regression. The OSS was internally validated using a jackknife analysis and externally validated with other patients from different ethnicities and in a steady state of treatment.ResultsOSS using time points of 2, 4 and 8 h post-dose performed best. Bias was < 5% and imprecision was < 15% for all drugs except ethambutol in the fed condition. External validation showed that OSS2-4-8 cannot be used for rifampicin in steady state conditions.ConclusionOSS at 2, 4 and 8 h post-dose enabled an accurate and precise prediction of AUC24 values of first-line anti-TB drugs in this population.Trial RegistrationClinicalTrials.gov (NCT02121314).

Background Establishing a correct diagnosis is challenging. We aimed to investigate the sensitivity and specificity of routine tuberculosis (TB) diagnostic work-up in lung clinics in Indonesia, a country with the third highest TB burden and the second highest gap between notifications of TB cases and the best estimate of incident cases in the world. Methods In the lung clinics of the Province of Yogyakarta, Indonesia, we recruited all consecutive patients with symptoms suggesting TB, aged ≥18 years. Routine TB examination consisted of clinical evaluation, sputum smear microscopy, and chest radiography. For research purposes, we added sputum culture, Human Immunodeficiency Virus (HIV) testing, and follow-up for 1.5 years or 2.5 years if culture results disagreed with the initial clinical diagnosis. The initial diagnosis was considered incorrect if patients did not respond to treatment. We calculated sensitivity and specificity of the TB routine examination using culture and a composite reference standard (CRS – a combination of routine examination, culture, and follow-up) as the reference standards. All analyses were conducted with IBM SPSS Statistics 25 (IBM Corp., Armonk, NY, USA). Results Between 2013 and 2015, we included 360 participants, and 21 were excluded due to incomplete data. Among those analyzed, 115 were initially diagnosed with smear-positive TB, 12 with smear-negative TB, and 212 non-TB. In 15 study participants, the diagnosis was changed after median 45 (range: 14–870) days; 14 participants initially not diagnosed with TB were later diagnosed with TB, while one subject initially diagnosed with TB actually did not have TB. Compared with culture and CRS, TB routine examination had sensitivity of 85% (95%CI: 77–91) and 90% (95%CI: 84–94), and specificity of 86.3% (95%CI: 81–91) and 99.5% (95%CI: 97–100), respectively. Conclusions A combination of clinical evaluation with sputum microscopy and chest radiography provided high sensitivity and specificity in diagnosing TB in lung clinics; in only 4.4% the diagnosis was incorrect. There is a need to improve routine TB diagnostic work by using clinical evaluation, sputum smear microscopy, and chest radiography all together in other settings, such as in primary health centers. Trial registration NCT02219945 , clinicaltrials.gov . Registered 19 August 2014 (retrospectively registered).