An assessment of current tuberculosis patient care and support policies in high-burden countries.

CONTEXT: Adherence to treatment for tuberculosis (TB) is an important predictor of treatment outcomes. The World Health Organization guidelines recommend a patient-centred approach to adherence support; however, the extent to which policies in high-burden countries facilitate this approach remains uncertain.DESIGN: A cross-sectional survey of current national patient care and support policies in high TB burden countries was performed.RESULT: Responses were provided by TB care programmes in 23 of the 30 high TB burden countries, comprising 77.4% of TB cases globally. Clinic-based and household adherence support and patient education were recommended in all countries, while policies for digital technologies and social supports have been adopted in a small minority of countries. Financial or material support (such as reimbursement for transportation) and psychological support to patients-if included in the policies-was mainly recommended only for specific sub-groups of patients.CONCLUSION: National policies in many countries have not yet fully adopted global recommendations for patient care and support. Further scale-up of evidence-based approaches to care is required to improve quality of care for patients in high TB burden settings.

Treatment as prevention and other interventions to reduce transmission of multidrug-resistant tuberculosis.

Drug-resistant tuberculosis (DR-TB) represents a major programmatic challenge at the national and global levels. Only ∼30% of patients with multidrug-resistant TB (MDR-TB) were diagnosed, and ∼25% were initiated on treatment for MDR-TB in 2016. Increasing evidence now points towards primary transmission of DR-TB, rather than inadequate treatment, as the main driver of the DR-TB epidemic. The cornerstone of DR-TB transmission prevention should be earlier diagnosis and prompt initiation of effective treatment for all patients with DR-TB. Despite the extensive scale-up of Xpert® MTB/RIF testing, major implementation barriers continue to limit its impact. Although there is longstanding evidence in support of the rapid impact of treatment on patient infectiousness, delays in the initiation of effective DR-TB treatment persist, resulting in ongoing transmission. However, it is also imperative to address the burden of latent drug-resistant tuberculous infection because it is estimated that many DR-TB patients will become infectious before seeking care and encounter various diagnostic delays before treatment. Addressing latent DR-TB primarily consists of identifying, treating and following the contacts of patients with MDR-TB, typically through household contact evaluation. Adjunctive measures, such as improved ventilation and use of germicidal ultraviolet technology can further reduce TB transmission in high-risk congregate settings. Although many gaps remain in our biological understanding of TB transmission, implementation barriers to early diagnosis and rapid initiation of effective DR-TB treatment can and must be overcome if we are to impact DR-TB incidence in the short and long term.

Widespread use of incorrect PCR ramp rate negatively impacts multidrug-resistant tuberculosis diagnosis (MTBDRplus).

The scale-up of rapid drug resistance testing for TB is a global priority. MTBDRplus is a WHO-endorsed multidrug-resistant (MDR)-TB PCR assay with suboptimal sensitivities and high indeterminate rates on smear-negative specimens. We hypothesised that widespread use of incorrect thermocycler ramp rate (speed of temperature change between cycles) impacts performance. A global sample of 72 laboratories was surveyed. We tested 107 sputa from Xpert MTB/RIF-positive patients and, separately, dilution series of bacilli, both at the manufacturer-recommended ramp rate (2.2 °C/s) and the most frequently reported incorrect ramp rate (4.0 °C/s). Mycobacterium tuberculosis-complex DNA (TUB-band)-detection, indeterminate results, accuracy, and inter-reader variability (dilution series only) were compared. 32 respondents did a median (IQR) of 41 (20-150) assays monthly. 78% used an incorrect ramp rate. On smear-negative sputa, 2.2 °C/s vs. 4.0 °C/s improved TUB-band positivity (42/55 vs. 32/55; p = 0.042) and indeterminate rates (1/42 vs. 5/32; p = 0.039). The actionable results (not TUB-negative or indeterminate; 41/55 vs. 28/55) hence improved by 21% (95% CI: 9-35%). Widespread use of incorrect ramp rate contributes to suboptimal MTBDRplus performance on smear-negative specimens and hence limits clinical utility. The number of diagnoses (and thus the number of smear-negative patients in whom DST is possible) will improve substantially after ramp rate correction.

The devil we know: is the use of injectable agents for the treatment of MDR-TB justified?

For decades, second-line injectable agents (IAs) have been the cornerstone of treatment for multidrug-resistant tuberculosis (MDR-TB). Although evidence on the efficacy of IAs is limited, there is an expanding body of evidence on the serious adverse events caused by these drugs. Here, we present the results of a structured literature review of the safety and efficacy of IAs. We review the continued widespread use of these agents in the context of therapeutic alternatives-most notably the newer TB drugs, bedaquiline and delamanid-and from the context of human rights, ethics and patient-centered care. We conclude that there is limited evidence of the efficacy of IAs, clear evidence of the risks of these drugs, and that persons living with MDR-TB should be informed about these risks and provided with access to alternative therapeutic options.

FAST implementation in Bangladesh: high frequency of unsuspected tuberculosis justifies challenges of scale-up.

SETTING: National Institute of Diseases of the Chest and Hospital, Dhaka; Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Dhaka; and Chittagong Chest Disease Hospital, Chittagong, Bangladesh. OBJECTIVE: To present operational data and discuss the challenges of implementing FAST (Find cases Actively, Separate safely and Treat effectively) as a tuberculosis (TB) transmission control strategy. DESIGN: FAST was implemented sequentially at three hospitals. RESULTS: Using Xpert® MTB/RIF, 733/6028 (12.2%, 95%CI 11.4-13.0) patients were diagnosed with unsuspected TB. Patients with a history of TB who were admitted with other lung diseases had more than twice the odds of being diagnosed with unsuspected TB as those with no history of TB (OR 2.6, 95%CI 2.2-3.0, P < 0.001). Unsuspected multidrug-resistant TB (MDR-TB) was diagnosed in 89/1415 patients (6.3%, 95%CI 5.1-7.7). Patients with unsuspected TB had nearly five times the odds of being diagnosed with MDR-TB than those admitted with a known TB diagnosis (OR 4.9, 95%CI 3.1-7.6, P < 0.001). Implementation challenges include staff shortages, diagnostic failure, supply-chain issues and reliance on external funding. CONCLUSION: FAST implementation revealed a high frequency of unsuspected TB in hospitalized patients in Bangladesh. Patients with a previous history of TB have an increased risk of being diagnosed with unsuspected TB. Ensuring financial resources, stakeholder engagement and laboratory capacity are important for sustainability and scalability.

Tuberculosis in migrants in low-incidence countries: epidemiology and intervention entry points.

As tuberculosis (TB) rates continue to decline in native populations in most low TB incidence countries, the proportion of TB patients born outside their country of residence ('foreign-born') increases. Some low-incidence countries have experienced a substantial increase in TB rates related to recent increases in the number of asylum seekers and other migrants from TB-endemic countries. However, average TB rates among the foreign-born in low-incidence countries declined moderately in 2009-2015. TB in foreign-born individuals is commonly the result of reactivation of latent infection with Mycobacterium tuberculosis acquired outside the host country. Transmission is generally low in low-incidence countries, and transmission from migrants to the native population is often modest. Variations in levels and trends in TB notifications among the foreign-born are likely explained by differences and fluctuations in the number and profile of migrants, as well as by variations in TB control, health and social policies in the host countries. To optimise TB care and prevention in migrants from endemic to low-incidence countries, we propose a framework for identifying possible TB care and prevention interventions before, during and after migration. Universal access to high-quality care along the entire migration pathway is critical. Screening for active TB and latent tuberculous infection should be tailored to the TB epidemiology, adapted to the needs of specific migrant groups and linked to treatment. Ultimately, the long-term TB elimination goal can be reached only if global health and socio-economic inequalities are dramatically reduced. Low-incidence countries, most of which are among the wealthiest nations, need to contribute through international assistance.

Multidrug-resistant tuberculosis and migration to Europe.

Multidrug-resistant tuberculosis (MDR-TB) in low-incidence countries in Europe is more prevalent among migrants than the native population. The impact of the recent increase in migration to EU and EEA countries with a low incidence of TB (<20 cases per 100 000) on MDR-TB epidemiology is unclear. This narrative review synthesizes evidence on MDR-TB and migration identified through an expert panel and database search. A significant proportion of MDR-TB cases in migrants result from reactivation of latent infection. Refugees and asylum seekers may have a heightened risk of MDR-TB infection and worse outcomes. Although concerns have been raised around 'health tourists' migrating for MDR-TB treatment, numbers are probably small and data are lacking. Migrants experience significant barriers to testing and treatment for MDR-TB, exacerbated by increasingly restrictive health systems. Screening for latent MDR-TB is highly problematic because current tests cannot distinguish drug-resistant latent infection, and evidence-based guidance for treatment of latent infection in contacts of MDR patients is lacking. Although there is evidence that transmission of TB from migrants to the general population is low-it predominantly occurs within migrant communities-there is a human rights obligation to improve the diagnosis, treatment and prevention of MDR-TB in migrants. Further research is needed into MDR-TB and migration, the impact of screening on detection or prevention, and the potential consequences of failing to treat and prevent MDR-TB among migrants in Europe. An evidence-base is urgently needed to inform guidelines for effective approaches for MDR-TB management in migrant populations in Europe.

Anaemia is highly prevalent among unselected internal medicine inpatients and is associated with increased mortality, earlier readmission and more prolonged hospital stay: an observational retrospective cohort study.

BACKGROUND: Anaemia is associated with adverse outcomes in elderly community-dwelling individuals, but this problem is less well characterised in the inpatient setting. AIMS: To determine the prevalence of anaemia and its associations in a well-defined cohort of internal medicine inpatients. METHODS: A retrospective cohort study of non-elective admissions under internal medicine at Palmerston North Hospital, New Zealand, was conducted for 4 months of 2008 with outcome analysis on 1 March 2010. RESULTS: At admission, 497 of 1491 (33.3%) patients were anaemic by World Health Organization criteria (haemoglobin <130 g/L for males; <120 g/L for females). Anaemia was more prevalent in males (38.1%) than females (28.2%), P < 0.001, in patients aged 65 years or older (41%) than in those under 65 (21.3%), P < 0.001, in New Zealand Europeans (34.3%) than in Maori and people from the Pacific Islands (26.4%), P= 0.04, and in patients admitted primarily because of malignancy, endocrine/metabolic disease, infection, and acute coronary syndrome/congestive heart failure (P < 0.001). Anaemia was independently associated with increased length of hospital stay (7.3 days vs 5.1 days in non-anaemic patients; P < 0.001), with mortality (P < 0.001) and unplanned hospital readmission (P < 0.001) during the follow-up period. Anaemia was infrequently acknowledged or investigated. Secondary analysis using a haemoglobin threshold of 110 g/L showed similar results. CONCLUSIONS: Anaemia is highly prevalent among medical inpatients with variation because of gender, age, race and reason for admission. Anaemia independently predicts for prolonged hospital stay, increased mortality and shorter time to readmission, but is usually not documented or investigated in this setting.