Improved treatment completion for tuberculosis patients: The case for a dedicated social care team

OBJECTIVES: The increasing social needs of people with Tuberculosis (TB), and the poor adherence to anti-TB therapy (ATT) associated with homelessness, drug or alcohol abuse, and prison history, led us to introduce a social care team (SCT) to support patient engagement with care within this low TB incidence setting. METHODS: Using a risk assessment, patients with social risk factors (SRF) for non-adherence to ATT are identified and a referral made to the SCT, who then provide intensive casework support for areas including homelessness, housing, benefits, debt and immigration. Retrospective data analysis of the social care database from 2017 to 2019 was conducted. Patients who were (n = 170) and were not referred to the SCT (n = 734) were compared. RESULTS: Patients referred were significantly more likely to complete treatment for TB than those not (88.2% versus 77.7% respectively, p = 0.0025), irrespective of receipt of Directly/Video Observed Therapy and adjusting for confounders. CONCLUSIONS: This paper demonstrates important evidence for the positive impact of a dedicated SCT within a TB service, and these improved treatment outcomes provide a strong argument for development of similar SCTs within UK TB services and similar healthcare settings

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Evaluation of QuantiFERON-TB Gold Plus for Predicting Incident Tuberculosis among Recent Contacts: A Prospective Cohort Study.

Screening for latent tuberculosis infection (LTBI) among recent tuberculosis (TB) contacts is an important component of TB control, particularly in settings with low TB incidence aiming towards pre-elimination(1). However, currently available LTBI diagnostics lack sensitivity, and have poor predictive value for incident TB(2–8) Consequently, prevention of one incident TB case requires treatment of many for LTBI. This is true for both interferon gamma release assays (IGRAs) and the tuberculin skin test (TST); a recent evaluation found that QuantiFERON Gold-InTube (QFT-GIT; Qiagen, Hilden, Germany) and T-SPOT.TB (Oxford Immunotec, UK) perform similarly to the TST when a BCG-stratified TST cut-off is used(8). A newer generation QuantiFERON (QuantiFERON-TB Gold Plus; QFT-Plus) was recently launched, adding a second TB antigen tube (TB2) that incorporates short peptides designed to stimulate a CD8+ T-cell response, in addition to the CD4+ -response tube (TB1) included in previous versions. The proposed rationale for this is that CD8+ -responses have been associated with mycobacterial load and recent TB exposure(9, 10). Initial independent evaluations have suggested QFT-Plus may have improved test sensitivity in active TB compared to QFT-GIT(11), and that the CD8+ -targeted antigen tube response may be associated with proxy measures of degree of TB exposure among contacts(12). However, no studies have examined the prognostic value of QFT-Plus for predicting incident TB. We aimed to address this key knowledge gap in a prospective cohort of UK TB contacts

Direct Whole-Genome Sequencing of Sputum Accurately Identifies Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing

This work was funded by the UCLH/UCL NIHR Biomedical Resource Centre (grant number BRC/176/III/JB/101350) and the PATHSEEK European Union's Seventh Programme for research, technological development and demonstration (grant number 304875)

Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer

Patient and health service delays in initiating treatment for patients with pulmonary tuberculosis: retrospective cohort study.

SETTING: Catchment population of the North Middlesex University Hospital (NMUH), London, UK. OBJECTIVE: To measure patient and health care delays in treatment of pulmonary tuberculosis. DESIGN: Retrospective cohort study of patients notified with pulmonary tuberculosis between 1 April 2001 and 1 March 2002. RESULTS: The median case finding delays were between 78 and 99 days. Median patient-related delay was between 34.5 and 54 days. Median health care-related delay was 29.5 days. Shorter case finding delays were found in patients born in a high prevalence country, patients presenting first to Accident and Emergency department (A&E), younger patients, and those with sputum smear-positive disease. In those presenting first to A&E, those born in a high prevalence country, and those with sputum-positive disease, this effect was predominantly due to shorter health care delays. Limitations of TB service capacity and organisational factors appeared responsible for up to half of the difference in delay between those presenting to A&E or general practitioners (GPs). CONCLUSION: Patient and health service delays contribute substantially to delays in patients accessing treatment. Considerable reduction in case finding delays may be achieved through changes in the capacity of tuberculosis services, and coordination of associated health services