Interventions to improve latent and active tuberculosis treatment completion rates in underserved groups in low incidence countries: a scoping review.

BACKGROUND: People in underserved groups have higher rates of tuberculosis (TB) and poorer treatment outcomes compared with people with no social risk factors. OBJECTIVES: This scoping review aimed to identify interventions that improve TB treatment adherence or completion rates. ELIGIBILITY CRITERIA: Studies of any design focusing on interventions to improve adherence or completion of TB treatment in underserved populations in low incidence countries. SOURCES OF EVIDENCE: MEDLINE, Embase and Cochrane CENTRAL were searched (January 2015 to December 2023). CHARTING METHODS: Piloted data extraction forms were used. Findings were tabulated and reported narratively. Formal risk of bias assessment or synthesis was not undertaken. RESULTS: 47 studies were identified. There was substantial heterogeneity in study design, population, intervention components, usual care and definition of completion rates. Most studies were in migrants or refugees, with fewer in populations with other risk factors (eg, homelessness, imprisonment or substance abuse). Based on controlled studies, there was limited evidence to suggest that shorter treatment regimens, video-observed therapy (compared with directly observed therapy), directly observed therapy (compared with self-administered treatment) and approaches that include tailored health or social support beyond TB treatment may lead to improved outcomes. This evidence is mostly observational and subject to confounding. There were no studies in Gypsy, Roma and Traveller populations, or individuals with mental health disorders and only one in sex workers. Barriers to treatment adherence included a lack of knowledge around TB, lack of general health or social support and side effects. Facilitators included health education, trusted relationships between patients and healthcare staff, social support and reduced treatment duration. CONCLUSIONS: The evidence base is limited, and few controlled studies exist. Further high-quality research in well-defined underserved populations is needed to confirm the limited findings and inform policy and practice in TB management. Further qualitative research should include more people from underserved groups.

A Persistent Tuberculosis Outbreak in the UK Is Characterized by Hydrophobic fadB4-Deficient Mycobacterium tuberculosis That Replicates Rapidly in Macrophages.

The genetic diversity of Mycobacterium tuberculosis can influence disease severity and transmissibility. To better understand how this diversity influences individuals and communities, we phenotyped M. tuberculosis that was causing a persistent outbreak in the East Midlands, United Kingdom. Compared to nonoutbreak isolates, bacilli had higher lipid contents and more hydrophobic cell surfaces. In macrophage infection models, the bacteria increased more rapidly, provoked the enhanced accumulation of macrophage lipid droplets and enhanced the secretion of IL-1ß. Natural deletions in fadB4, nrdB, and plcC distinguished the outbreak isolates from other lineage 3 isolates in the region. fadB4 is annotated with a putative role in cell envelope biosynthesis, so the loss of this gene has the potential to alter the interactions of bacteria with immune cells. Reintroduction of fadB4 to the outbreak strain led to a phenotype that more closely resembled those of nonoutbreak strains. The improved understanding of the microbiological characteristics and the corresponding genetic polymorphisms that associate with outbreaks have the potential to inform tuberculosis control. IMPORTANCE Tuberculosis (TB) killed 1.5 million people in 2020 and affects every country. The extent to which the natural genetic diversity of Mycobacterium tuberculosis influences disease manifestation at both the individual and epidemiological levels remains poorly understood. Insights into how pathogen polymorphisms affect patterns of TB have the potential to translate into clinical and public health practice. Two distinct lineage 3 strains isolated from local TB outbreaks, one of which (CH) was rapidly terminated and the other of which (Lro) persistently transmitted for over a decade, provided us with an opportunity to study these issues. We compared genome sequences, microbiological characteristics, and early immune responses that were evoked upon infection. Our results indicate that the natural lack of fadB4 in the Lro strain contributes to its unique features.

Cannabis use and the risk of tuberculosis: a systematic review.

BACKGROUND: Cannabis has been identified as a possible risk factor in some tuberculosis (TB) outbreaks. As the most widely used (largely) illegal substance in Western countries this may be an important public health concern. We aim to systematically review the evidence on the association between cannabis use and TB (latent infection and active disease) to inform ongoing and future TB prevention and control strategies. METHODS: We conducted a systematic review. We searched Ovid Medline, Embase and PsycInfo, together with the World Health Organization website and Google Scholar, for all years to January 2018. Reference lists and conference abstracts were hand-searched, a forward citation search was conducted on the Web of Science, and experts were contacted. Two authors independently screened studies for inclusion, extracted data and assessed risk of bias using an adapted version of ROBINS-I ("Risk of Bias in Non-randomised Studies - of Interventions"). Data were narratively synthesised. RESULTS: Of 377 records identified, 11 studies were eligible. Study designs were heterogeneous. Six studies utilised a relevant comparator group. Four of these investigated the association between cannabis use and latent TB infection; all provided some evidence of an association, although only two of these had adjusted for confounders. The remaining two comparator studies investigated the association between cannabis use and active TB disease; neither found evidence of an association after adjusting for confounding. All six studies were at "Serious" risk of bias. The five studies which did not utilise a relevant comparator group were all indicative of TB outbreaks occurring among cannabis users, but the quality of the evidence was very weak. CONCLUSIONS: Evidence for an association between cannabis use and TB acquisition is weak. The topic warrants further robust primary research including the collection of consistent and accurate exposure information, including cannabis use practices, dose and frequency, and adjustment for confounders.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Bed occupancy rates and hospital-acquired Clostridium difficile infection: a cohort study.

BACKGROUND: An emergent strain (ribotype 027) of Clostridium difficile infection (CDI) has been implicated in epidemics worldwide. Organizational factors such as bed occupancy have been associated with an increased incidence of CDI; however, the data are sparse, and the association has not been widely demonstrated. We investigated the association of bed occupancy and CDI within a large hospital organization in the United Kingdom. OBJECTIVE: To establish whether bed occupancy rates are a significant risk factor for CDI in the general ward setting. METHODS: A retrospective cohort study was carried out on data from 2006 to 2008. Univariate and multivariate Cox regression modeling was used to examine the strength and significance of the associations. Variables included patient characteristics, antibiotic policy exposure, case mix, and bed occupancy rates. RESULTS: A total of 1,589 cases of hospital-acquired CDI were diagnosed (1.7% of admissions), with an overall infection rate of 2.16 per 1,000 patient-days. Median bed occupancy was 93.3% (interquartile range, 83.3%-100%) Univariate and multivariate analyses showed positive and statistically significant associations. In the adjusted model, patients on wards with occupancy rates of 80%-89.9% had rates of CDI that were 56% higher (hazard ratio, 1.56 [95% confidence interval, 1.18-2.04]; P < .001) compared with baseline (0%-69.9% occupancy). CDI rates were 55% higher for patients on wards with maximal bed occupancy (100%). CONCLUSIONS: There is strong evidence of an association between high bed occupancy and CDI. Without effective interventions at high levels of bed occupancy, the economic benefits sought from reducing bed numbers may be negated by the increased risk of CDI.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

BACKGROUND: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. CONCLUSIONS/SIGNIFICANCE: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.