Reducing the burden of TB among migrants to low TB incidence countries.

BACKGROUND: International migrants to low TB incidence countries are disproportionately affected by TB compared to the native population: migrants are at increased risk for TB transmission and TB disease due to a variety of personal, environmental and socio-economic determinants experienced during the four phases of migration (pre-departure, transit, arrival and early settlement, return travel).OBJECTIVE: To provide an up-to-date overview of the determinants that drive the TB burden among migrants, as well as effective and feasible interventions to address this for each migration phase.METHODS: We conducted a literature review by searching PubMed and the grey literature for articles and reports on determinants and interventions addressing migrant health and TB.RESULTS: Lowering the risk of TB transmission and TB disease among migrants would be most effective by improving the socio-economic position of migrants pre-, during and after migration, ensuring universal health coverage, and providing tailored and migrant-sensitive care and prevention activities.CONCLUSION: In addition to migrant-sensitive health services and cross-border collaboration between low TB incidence countries, there is a need for international financial and technical support for endemic countries.

'One Health´ approach to end zoonotic TB.

Mycobacterium bovis has a wide host range causing TB in animals, both in wildlife and cattle (bovine TB bTB), and in humans (zoonotic TB zTB). The real burden of bovine and zoonotic TB (b/zTB) remains unknown due to diagnostic challenges. Although progress has been made to reduce the burden of TB, b/zTB has been neglected in low- and middle-income countries (LMICs) with little improvement in prevention, diagnosis or treatment. Using Tanzania as a case study, because of its high TB burden, large wildlife diversity and wide reliance on livestock, we developed an approach to comprehensively estimate the burden and implement multidisciplinary actions against b/zTB. We performed a review of the literature on b/zTB, but there is a lack of available data on the b/zTB burden in Tanzania and, notably, on epidemiological indicators other than incidence. We propose a five-action programme to address b/zTB in Tanzania, and we believe our proposed approach could benefit other LMICs as it operates by implementing and strengthening surveillance and health delivery. The resulting knowledge and system organisation could further prevent and mitigate the effects of such conditions on human and animal health, livestock production, population livelihood and the economy.

No universal access to drug-resistant tuberculosis care without engaging all health care providers.

Should the engagement of all health care providers in all aspects of programmatic management of drug-resistant tuberculosis (PMDT) become a priority in the national strategic plans for tuberculosis (TB), progress towards universal access to diagnosis, treatment and care of drug-resistant tuberculosis (DR-TB) would accelerate. This would be especially crucial in countries where the private sector is a significant provider of health services. Proven successful interventions to engage all health care providers and partners in the cascade of prevention, diagnosis, treatment and care of DR-TB patients need to be urgently scaled up. Such engagement should not be limited to the diagnosis and treatment of DR-TB, but extended also to all the aspects of PMDT, including approaches ensuring that patient-centred care, social support, pharmacovigilance and surveillance. Integral to the End TB Strategy, PMDT should be embedded in all public-private mix initiatives for TB and vice versa.

Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

Global tuberculosis targets and milestones set for 2016-2035: definition and rationale.

BACKGROUND: Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016-2035) and the Sustainable Development Goals (2016-2030). OBJECTIVE: To define and explain the rationale for these targets. DESIGN: Scenarios for plausible reductions in TB deaths and cases were developed using empirical evidence from best-performing countries and modelling of the scale-up of under-used interventions and hypothetical TB vaccines. Results were discussed at consultations in 2012 and 2013. A final proposal was presented to the World Health Assembly in 2014 and unanimously endorsed by all Member States. RESULTS: The 2030 targets are a 90% reduction in TB deaths and 80% reduction in TB incidence compared with 2015 levels. The 2035 targets are for reductions of 95% and 90%, respectively. A third target-that no TB-affected households experience catastrophic costs due to the disease by 2020-was also agreed. CONCLUSION: The global TB targets and milestones set for the period 2016-2035 are ambitious. Achieving them requires concerted action on several fronts, but two things are fundamental: 1) progress towards universal health coverage to ensure that everyone with TB can access high-quality treatment; and 2) substantial investment in research and development for new tools to prevent TB disease among the approximately 1.7 billion people infected.

Isoniazid preventive treatment: predictors of adverse events and treatment completion.

SETTING: Villa Marelli Institute (VMI), Niguarda Ca'Granda Hospital, Milan, Italy. BACKGROUND: A recent report on the fatal side effects of isoniazid preventive therapy (IPT) from the United States has re-ignited discussion on the safety of this intervention. OBJECTIVE: To evaluate IPT feasibility, treatment completion and adverse events (AE) and their determinants under field conditions. METHODS: Data from consecutive subjects undergoing IPT at the VMI were recorded in an electronic database from 1992 to 2009. Logistic regression analysis was performed to detect completion and AE determinants. RESULTS: A total of 11,963 patients were included in the study. AE (odds ratio [OR] 2.70, 95%CI 2.22-3.28) and human immunodeficiency virus positive status (OR 5.20, 95%CI 2.10-12.93) were the main determinants of treatment interruption among Italians, while social weakness (no housing/job; OR 2.88, 95%CI 2.43-3.42), AEs (OR 1.33, 95%CI 1.15-1.53, 2.22-3.28) and screening in undocumented subjects (OR 1.20, 95%CI 1.01-1.44) prevailed among foreigners. Age was the main determinant of transaminase increase (OR 1.03, 95%CI 1.03-1.04), as were AEs of the gastrointestinal (OR 1.02, 95%CI 1.02-1.03), central nervous (OR 1.02, 95%CI 1.02-1.05) and peripheral nervous systems (OR 1.04, 95%CI 1.02-1.05). CONCLUSION: This analysis demonstrates the feasibility and safety of IPT, with determinants of interruption and AEs being predictable and addressable.

Systematic screening for active tuberculosis: rationale, definitions and key considerations.

The impact of current interventions to improve early detection of tuberculosis (TB) seems to have been saturated. Case detection trends have stagnated. TB incidence is falling in most settings worldwide, but the rate of decline is far lower than expected. There is growing evidence from national TB prevalence surveys and other research of a large pool of undetected TB in the community. Intensified efforts to further break down access barriers and scale up new and rapid diagnostic tools are likely to improve the situation. However, will these be enough? Or do we also need to reach out more towards people who do not actively seek care with well-recognisable TB symptoms? There have recently been calls to revisit TB screening, particularly in high-risk groups. The World Health Organization (WHO) recommends screening for TB in people with human immunodeficiency virus infection and in close TB contacts. Should other risk groups also be screened systematically? Could mass, community-wide screening, which the WHO has discouraged over the past four decades, be of benefit in some situations? If so, what screening tools and approaches should be used? The WHO is in the process of seeking answers to these questions and developing guidelines on systematic screening for active TB. In this article, we present the rationale, definitions and key considerations underpinning this process.

European union standards for tuberculosis care.

The European Centre for Disease Prevention and Control (ECDC) and the European Respiratory Society (ERS) jointly developed European Union Standards for Tuberculosis Care (ESTC) aimed at providing European Union (EU)-tailored standards for the diagnosis, treatment and prevention of tuberculosis (TB). The International Standards for TB Care (ISTC) were developed in the global context and are not always adapted to the EU setting and practices. The majority of EU countries have the resources and capacity to implement higher standards to further secure quality TB diagnosis, treatment and prevention. On this basis, the ESTC were developed as standards specifically tailored to the EU setting. A panel of 30 international experts, led by a writing group and the ERS and ECDC, identified and developed the 21 ESTC in the areas of diagnosis, treatment, HIV and comorbid conditions, and public health and prevention. The ISTCs formed the basis for the 21 standards, upon which additional EU adaptations and supplements were developed. These patient-centred standards are targeted to clinicians and public health workers, providing an easy-to-use resource, guiding through all required activities to ensure optimal diagnosis, treatment and prevention of TB. These will support EU health programmes to identify and develop optimal procedures for TB care, control and elimination.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Tuberculosis and noncommunicable diseases: neglected links and missed opportunities.

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

Harmonisation of TB control in the WHO European region: the history of the Wolfheze Workshops.

In 1990 a workshop was organised in the village of Wolfheze (the Netherlands), where experts discussed the critical interventions that would foster elimination of TB in Europe. This event has been followed by several more over the following two decades to become known as the "Wolfheze Workshops". This article provides a brief overview of the history and the impact the Wolfheze Workshops have had on the commitment of European governments to standardise definitions, recording and reporting systems and, thus, permitted comparison of interventions and improving TB control across borders. The Wolfheze Workshops have been and still are an essential platform for this exchange of experiences, promoting common approaches.

Experience establishing tuberculosis laboratory capacity in a developing country setting.

OBJECTIVE: To describe the experience of strengthening laboratory diagnosis of tuberculosis (TB) in a resource-limited country with high TB-HIV (human immunodeficiency virus) and multidrug-resistant TB (MDR-TB) prevalence. METHODS: In the Kingdom of Lesotho, which is confronted with high levels of TB, MDR-TB and HIV prevalence, between 2006 and 2008 a coalition of the Foundation for Innovative New Diagnostics, Partners In Health and the World Health Organization renovated the National TB Reference Laboratory and reinforced microscopy services, streamlined conventional culture and drug susceptibility testing (DST) and introduced modern TB diagnostic methods. FINDINGS: It was feasible to establish a biosafety level three facility for solid culture and DST and an external quality assessment programme for smear microscopy within 4 months, all in 2007. Liquid culture and DST were introduced a month later. Preliminary results were comparable to those found in laboratories in industrialised countries. A year later, line-probe assay for the rapid detection of MDR-TB was introduced. DISCUSSION: Through strong political commitment and collaboration, it is possible to rapidly establish quality assured TB diagnostic capacity, including current methods, in a resource-limited setting. Case detection and management for TB and MDR-TB have been greatly enhanced. From a low baseline, TB culture throughput in the laboratory increased ten-fold and has been sustained. This experience has served as a catalyst to translate policy into practice with new diagnostic technologies. It supports global policy setting to enhance and modernise laboratory work in developing countries.

Trends in tuberculosis incidence and their determinants in 134 countries.

OBJECTIVE: To determine whether differences in national trends in tuberculosis incidence are attributable to the variable success of control programmes or to biological, social and economic factors. METHODS: We used trends in case notifications as a measure of trends in incidence in 134 countries, from 1997 to 2006, and used regression analysis to explore the associations between these trends and 32 measures covering various aspects of development (1), the economy (6), the population (3), behavioural and biological risk factors (9), health services (6) and tuberculosis (TB) control (7). FINDINGS: The TB incidence rate changed annually within a range of +/-10% over the study period in the 134 countries examined, and its average value declined in 93 countries. The rate was declining more quickly in countries that had a higher human development index, lower child mortality and access to improved sanitation. General development measures were also dominant explanatory variables within regions, though correlation with TB incidence trends varied geographically. The TB incidence rate was falling more quickly in countries with greater health expenditure (situated in central and eastern Europe and the eastern Mediterranean), high-income countries with lower immigration, and countries with lower child mortality and HIV infection rates (located in Latin America and the Caribbean). The intensity of TB control varied widely, and a possible causal link with TB incidence was found only in Latin America and the Caribbean, where the rate of detection of smear-positive cases showed a negative correlation with national incidence trends. CONCLUSION: Although TB control programmes have averted millions of deaths, their effects on transmission and incidence rates are not yet widely detectable.