Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Tuberculosis screening among persons with diabetes mellitus in Pune, India

Abstract Background Diabetes mellitus (DM) increases tuberculosis (TB) risk, and there is increasing concern over the public health implications of the convergence of these two epidemics. Screening for TB among people with DM is now recommended in India. Methods People with DM seeking care at a large public sector tertiary care hospital clinic in Pune, India, were screened for TB from June 2015 to May 2016. All consenting people with DM were screened for TB at each clinic visit using a five-item, WHO-recommended questionnaire and those with TB symptoms and/or risk factors were tested for active TB using sputum smear microscopty, Xpert® MTB/RIF and TB culture. Categorical data and continuous variables were summarized using descriptive statistics. The x 2 test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. Results Among 630 adults approached for screening, median age was 60 (interquartile range (IQR), 57–64) years and 350 (56%) were females. Median hemoglobin A1c (HbA1c) was 8.7% (IQR, 6.7–9.9) and 444 (70.5%) were poorly controlled DM (HbA1c > 7). Forty-four (7%) had prior history of TB but the proportion with TB risk factors at screening was low (<5%). While 18% of participants reported any TB symptoms, none of these patients were diagnosed with culture confirmed TB. Conclusions Our study failed to yield any active TB cases using a WHO-recommended questionnaire among people with DM. High TB risk populations among people with DM must be identified if TB screening is to be feasible in settings such as India where the DM epidemic continues to rise

Challenges with the use of Xpert HPV as a screening tool for oral HPV among people living with HIV (PLHIV): experiences from Pune, India

Abstract Background People living with HIV (PLHIV) are at higher risk for human papillomavirus (HPV)-related oropharyngeal cancers compared to the general population. Xpert HPV test is a polymerase chain reaction (PCR) assay capable of rapid HPV detection. Performing the assay requires minimal intervention by laboratory personnel. Its use could improve oropharyngeal cancer screening among PLHIV living in low-and middle-income countries (LMICs) with limited diagnostic capacities. However, Xpert HPV performance for oral samples has not been evaluated. Here, we describe our experience with Xpert HPV and compare its results with traditional PCR, for oral samples. Methods Oral samples from 429 PLHIV receiving care at a tertiary care hospital affiliated antiretroviral therapy center in Pune, India were used. Samples were collected either after a 30s oral rinse and gargle (n = 335) or in combination with cytobrush scraping of the oral mucosa (n = 91). Unsuccessful tests were those that generated an invalid or error result on Xpert HPV. Successful tests were those that generated a positive or negative result. Kappa statistic was used to compare concordance between Xpert HPV and traditional real-time PCR results. Results There were 29.8% (n = 127) unsuccessful tests, of which 78.7% (n = 100) were invalid and 21.3% (n = 27) were error results. Adding cytobrush scraping to oral rinse as a collection procedure did not significantly reduce the proportion of unsuccessful tests (p = 0.9). For successful tests, HPV positivity on Xpert was 0.3% (n = 1/299). Kappa statistic was 0.11, indicating poor agreement between Xpert HPV and traditional PCR results. Conclusions Presently, Xpert HPV appears to have limited use for oral HPV detection among PLHIV using oral samples. More research to improve the diagnostic capabilities of Xpert HPV for oral samples among PLHIV is needed

Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment

Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment

Additional file 1: of Tuberculosis screening among persons with diabetes mellitus in Pune, India

Supplementary file: Raw data of the TB screening in patients with diabetes study. (XLSX 497 kb

Additional file 1 of Challenges with the use of Xpert HPV as a screening tool for oral HPV among people living with HIV (PLHIV): experiences from Pune, India

Supplementary Material

Isoniazid hair concentrations in children with tuberculosis: a proof of concept study

Assessing treatment adherence and quantifying tuberculosis drug exposure among children is challenging. We undertook a “proof of concept” study to assess the drug concentrations of isoniazid in hair as a therapeutic drug monitoring tool. Children <12 years of age initiated on thrice-weekly treatment including isoniazid (10 mg/kg) for newly diagnosed tuberculosis were enrolled. Isoniazid concentrations in hair were measured using liquid chromatography-tandem mass spectrometry at 1, 2, 4 and 6 months after tuberculosis treatment initiation. We found that isoniazid hair concentrations in all children on thrice weekly isoniazid were detectable and displayed variability across a dynamic range

Plasma area-under-the curve (AUC) concentrations and hair concentrations of isoniazid (INH) among children with 100% adherence to tuberculosis (TB) treatment compared to females (1.64 (1.21–13.2) vs. 0.66 (0.47–1.08), p = 0.05); INH hair levels were lower in older children (correlation = -0.42; p = 0.11) and among children who were heavier (-0.43; p = 0.10).

<p>Plasma area-under-the curve (AUC) concentrations and hair concentrations of isoniazid (INH) among children with 100% adherence to tuberculosis (TB) treatment compared to females (1.64 (1.21–13.2) vs. 0.66 (0.47–1.08), p = 0.05); INH hair levels were lower in older children (correlation = -0.42; p = 0.11) and among children who were heavier (-0.43; p = 0.10).</p