Outcomes of TB contact tracing and predictors of success: a 10-year retrospective cohort analysis in Birmingham, UK.

BACKGROUND: Contacts of TB cases in Birmingham and Solihull, UK, are offered screening for TB infection. Between 1990 and 2010, only 59.1% of contacts completed screening. The service has since increased screening staff numbers, changed screening locations and increased screening follow-up. Our primary aim was to identify whether screening completion rates have improved. Our secondary aim was to identify predictors of screening completion.METHODS: This was a retrospective analysis of all contacts of TB patients in Birmingham and Solihull between 1 January 2011 and 31 December 2020, stratified by pulmonary and extrapulmonary TB (PTB or EPTB) index infection. Multiple logistic regression analysis for predictors of screening completion was performed.RESULTS: A total of 3,255 index cases and 27,820 contacts were identified. TB incidence has declined, in keeping with national trends. Screening completion has improved from 59.1% of contacts to 74.9% overall since service improvements were made, with improvement in screening completion for contacts of both PTB and EPTB index cases (OR 1.087, 95% CI 1.074-1.101; P < 0.001) and (OR 1.048, 95% CI 1.019-1.078; P = 0.001), respectively.CONCLUSIONS: Changes made to the TB service have improved screening outcomes over the last decade. Significant predictors of screening completion have been identified, highlighting areas for targeted resource allocation.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

Management of patients with multidrug-resistant tuberculosis.

The emergence of multidrug-resistant tuberculosis (MDR-TB; defined as resistance to at least rifampicin and isoniazid) represents a growing threat to public health and economic growth. Never before in the history of mankind have more patients been affected by MDR-TB than is the case today. The World Health Organization reports that MDR-TB outcomes are poor despite staggeringly high management costs. Moreover, treatment is prolonged, adverse events are common, and the majority of affected patients do not receive adequate treatment. As MDR-TB strains are often resistant to one or more second-line anti-TB drugs, in-depth genotypic and phenotypic drug susceptibility testing is needed to construct personalised treatment regimens to improve treatment outcomes. For the first time in decades, the availability of novel drugs such as bedaquiline allow us to design potent and well-tolerated personalised MDR-TB treatment regimens based solely on oral drugs. In this article, we present management guidance to optimise the diagnosis, algorithm-based treatment, drug dosing and therapeutic drug monitoring, and the management of adverse events and comorbidities, associated with MDR-TB. We also discuss the role of surgery, physiotherapy, rehabilitation, palliative care and smoking cessation in patients with MDR-TB. We hope that incorporating these recommendations into patient care will be helpful in optimising treatment outcomes, and lead to more MDR-TB patients achieving a relapse-free cure.

Risk factors associated with the development of active tuberculosis among patients with advanced chronic kidney disease.

OBJECTIVES: The risk of developing active TB is greater in those receiving haemodialysis. This study aimed to describe the incidence of active tuberculosis among patients referred for management of kidney disease and dialysis in a high incidence UK city, with the purpose of informing latent TB testing and treatment practice. METHODS: Information from the tuberculosis register was cross-referenced with the Department of Renal Medicine patient information system. All patients seen between 1st January 2005 and 1st October 2016 were included in the analyses with the exception of those with prior TB. RESULTS: 68 cases of active TB were identified, an incidence of 126/100,000 patient-years (95% CI 97-169). Incidence was lowest in those with CKD 1 or 2 and rose as high as 256/100,000 patient-years (95% CI 183-374) in those receiving renal replacement therapy. 48% of cases were pulmonary and 87% of TB patients gave their ethnicity as either black/black British or Asian/Asian British, significantly more than in the non-TB renal group. Cases occurred steadily over the time period in which patients were in the cohort. CONCLUSION: TB incidence was very high among those receiving renal replacement therapy or CKD 4 or 5. Most cases occurred in those of an Asian/Asian British or black/black British background. Testing and treating such patients for latent TB is justified and should include those who have been receiving renal replacement therapy for some years.

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases.

OBJECTIVES: Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. METHODS: Case note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. RESULTS: Thirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20-39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival. CONCLUSIONS: Mycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

Acceptability of latent tuberculosis testing of migrants in a college environment in England.

OBJECTIVES: The majority of tuberculosis (TB) cases in England occur from reactivation of latent tuberculosis infection (LTBI) in the settled migrant population. The National Institute for Health and Clinical Excellence recommends that new entrants from high-incidence countries are screened to detect LTBI. This article seeks to describe an outreach programme and testing for LTBI in an innovative setting-ESOL (English for Speakers of Other Languages) classes at a community college (CC) with evaluation of acceptability. STUDY DESIGN: Partnership working with mixed methods used for evaluation of acceptability. METHODS: A pre-existing network from the local TB partnership designed an outreach intervention and screening for LTBI among students from an ESOL programme at a CC. Screening for LTBI with interferon gamma release assay was the culmination of a programme of health improvement activities across the college. Any student on the ESOL programme younger than the age of 35 years and resident in the UK for less than 5 years was eligible for testing. LTBI testing was carried out on-site, and the experience was evaluated by questionnaires to staff, students and partners. A facilitated debrief among the partners gave further data. RESULTS: A total of 440 eligible students were tested. One hundred and seventy-two student feedback questionnaires were completed, and 36 partner questionnaires were received with 18 CC staff responding. Students, tutors and healthcare professionals found the setting acceptable with some concerns about insufficient resource for timely follow-up. CONCLUSIONS: Students, tutors, community organisations and health professionals found the exercise worthwhile and the method and setting acceptable. There were resource issues for the clinical team in follow-up of students with positive results for such a large screening event. Unexpected barriers were found by the CC as this kind of activity was not recognised for external quality review purposes. There were concerns about reputational loss and stigma of being involved in a TB project. As current initiatives aim to divert workload from stretched general practice surgeries, this may be an important addition to primary care screening.

Latent tuberculous screening of recent migrants attending language classes: a cohort study and cost analysis.

SETTING: England's national tuberculosis (TB) strategy recommends testing for and treatment of latent tuberculous infection (LTBI) among new migrants. Programmatic testing occurs in primary care, which may be inaccessible for some individuals. Current strategies could therefore be complemented by screening in other settings. OBJECTIVE: To investigate the feasibility and effectiveness of LTBI screening in a community college. DESIGN: A cohort study using observational data collected during the pilot study. Eligible students from high-incidence countries provided consent and were tested with a single-step interferon-gamma release assay (IGRA) and enrolled. We used single and multivariable analyses to estimate screening effectiveness and to explore different subgroups. We included costs from a UK National Health Service perspective. RESULTS: Screening uptake was 75% and treatment completion was 85%. Of 440 students, 71 (16%) were LTBI-positive; two had active TB. There was an association of positivity with age and incidence in the country of origin. Three incidence thresholds met our criteria for screening: countries with >40, >100 and >200 cases per 100 000 population, plus students from sub-Saharan Africa. CONCLUSION: We found that LTBI screening can be offered effectively in a community college, and could be a complement to primary care-based programmes in low-incidence countries.

Programmatic utility of tuberculosis cluster investigation using a social network approach in Birmingham, United Kingdom.

SETTING: Birmingham, United Kingdom, 2010-2014. OBJECTIVE: To investigate predictors for clustering of tuberculosis (TB) cases and cluster size and to evaluate the impact of cluster investigation using social network data. DESIGN: Retrospective observational cohort study. Prioritised cases linked using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were interviewed using a social network approach to find epidemiological links. RESULTS: Of 2055 TB cases notified, 56% could be typed. Clustering was associated with younger age, UK birth, Black Caribbean ethnicity, social risk factors, pulmonary TB and negative human immunodeficiency virus status. Only UK birth and presence of more than one social risk factor were associated with larger cluster size, while drug resistance was associated with smaller cluster size. Social network data from 139/431 clustered cases found new epidemiological links in 11/19 clusters with ⩾5 members (undirected median network density 0.09, interquartile range 0.05-0.4). Ninety-eight additional contacts were assessed, with one case of active TB and 24 with latent tuberculous infection diagnosed. CONCLUSION: A social network approach increased knowledge of likely transmission events, but few additional TB cases were diagnosed. Obtaining social network data for all typed and untyped TB cases may improve contact tracing and reduce unexpected transmission detected from molecular data.

Testing for latent tuberculosis infection using interferon gamma release assays in commercial sex workers at an outreach clinic in Birmingham.

This report demonstrates that using interferon gamma release assays to screen for latent tuberculosis infection in female commercial sex workers in an outreach sexual health clinic is feasible and acceptable. Routine interferon gamma release assay use successfully identified high numbers of latent tuberculosis infection. Innovative approaches to treatment and follow up were required to improve treatment adherence in this group. Direct observation of therapy within the sexual health clinic was also feasible. Successful follow up was dependent on the support of outreach workers, interpreters and tuberculosis nurses.

Beyond multidrug-resistant tuberculosis in Europe: a TBNET study.

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).

Isoniazid-resistant tuberculosis in Birmingham, United Kingdom, 1999-2010.

BACKGROUND: There have been few studies on risk factors and treatment outcomes of isoniazid (H)-resistant tuberculosis (TB), and optimal treatment regimens are debated. AIM: : To identify risk factors for H-resistant TB, describe treatment regimens and compare these to national guidelines and describe short-term outcomes of H-resistant TB in Birmingham, UK. DESIGN: Retrospective case series. METHODS: Cases of H-resistant tuberculosis in Birmingham between January 1999 and December 2010 (n = 89) were compared with drug-susceptible cases (n = 2497). Treatment regimens and outcomes at 12 months from diagnosis were evaluated by case note review. RESULTS: No independent predictors for H-resistant TB were found. For 76/89 (85%) patients with full treatment details available, median treatment duration was 11 months (interquartile range 9-12 months). Only 27/72 (38%) patients with H-monoresistance were treated in line with national guidelines. A further 14/72 (19%) were treated according to other recognized guidelines. Overall treatment success was 75/89 (84%). Treatment failure occurred in 6/89 (7%) patients, all developed multi-drug resistance. Poor adherence was documented in these patients and use of a non-standard regimen in one patient was not thought to have contributed to treatment failure. CONCLUSIONS: No discriminating risk factors for early detection of H-resistant TB were found. Treatment regimens in clinical practice were highly varied. H-resistance can drive MDR-TB when there is evidence or suspicion of poor adherence. A low threshold for enhanced case management with directly observed therapy is warranted in this group.

Predictors of contact tracing completion and outcomes in tuberculosis: a 21-year retrospective cohort study.

SETTING: Birmingham, UK, 1990-2010. OBJECTIVE: To identify predictors in contacts for completion of screening and of a positive screening outcome, i.e., a diagnosis of latent tuberculous infection (LTBI) or active tuberculosis (TB). DESIGN: A retrospective cohort study of TB notifications for a European city. RESULTS: A total of 46,158 contacts were identified from 7365 index cases. Over the study period 17,471 (40.9%) failed to complete screening. Active TB or LTBI was diagnosed in 2220 (7.0%) contacts of cases of pulmonary TB (PTB) and in 222 (2.7%) contacts of cases of extra-pulmonary TB (EPTB). The proportion of contacts offered LTBI treatment increased (P < 0.001) over the study period. Age, ethnicity, sex and use of interferon-gamma release assays (IGRA) were the most important predictors of screening completion, with working age adult males who were Black or from the Indian subcontinent least likely to complete. Age, smear positivity status of the index case and IGRA usage were the most important predictors of a positive screening outcome (active TB or LTBI diagnosed). CONCLUSION: Contact tracing of both PTB and EPTB index cases is useful for active case finding. The findings of this study can be used to target screening and improve the effectiveness and efficiency of local contact tracing programmes.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Long-term glycaemic outcome of structured nurse-led diabetes care in rural Africa.

BACKGROUND: Diabetes care delivery in rural Africa is difficult. Problems include lack of dedicated personnel, monitoring systems, laboratory support and drugs. Few structured intervention projects have been undertaken, none with long-term follow-up. AIM: To determine the long-term (4 years) glycaemic outcome of a structured nurse-led intervention programme for type 2 diabetic patients in rural Africa. DESIGN: Single-centre, observational cohort study. METHODS: The programme was delivered in the scattered primary health clinics of Hlabisa District, in northern Kwazulu Natal, South Africa. Monthly diabetic clinics were held at which empowerment-based education was delivered and regularly reinforced. Oral hypoglycaemic agents (OHAs) were titrated according to a previously validated clinical algorithm. Outcome was measured by glycated haemoglobin (HbA(1)c), as well as body mass index (BMI). Data were collected at baseline, and then 6, 18, 24 and 48 month's post-intervention. RESULTS: Eighty patients had data available at all time collection points. They were of mean ± SD, age 56 ± 11 years, 70% were female, BMI 31.5 ± 7.2 kg/m(2) and HbA(1)c 10.8 ± 4.2%. HbA(1)c fell significantly to 8.1 ± 2.2% at 6 months and 7.5 ± 2.0% at 18 months. By 24 months, it had risen (8.4 ± 2.3%), and at 4 years post-intervention it was 9.7 ± 4.0% (still significantly lower than baseline, P = 0.015). BMI rose significantly at 6 and 18 months, but by 48 months was not significantly different from baseline. CONCLUSION: We conclude that the intervention led to marked HbA(1)c improvements up to 18 months follow-up, but thereafter there was 'glycaemic slippage'. This may be not only due to educational 'wear-off', noted in other education-intervention programmes, but also to the expected glycaemic deterioration with time known to occur in type 2 diabetes. Nevertheless, 4-year HbA(1)c levels were still significantly lower than at baseline. The programme was also well received by staff and patients, and we believe is an appropriate and effective diabetes intervention system in rural Africa.