Ernesto Jaramillo

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.

Alcohol use as a risk factor for tuberculosis – a systematic review

BackgroundIt has long been evident that there is an association between alcohol use and risk of tuberculosis. It has not been established to what extent this association is confounded by social and other factors related to alcohol use. Nor has the strength of the association been established. The objective of this study was to systematically review the available evidence on the association between alcohol use and the risk of tuberculosis.MethodsBased on a systematic literature review, we identified 3 cohort and 18 case control studies. These were further categorized according to definition of exposure, type of tuberculosis used as study outcome, and confounders controlled for. Pooled effect sizes were obtained for each sub-category of studies.ResultsThe pooled relative risk across all studies that used an exposure cut-off level set at 40 g alcohol per day or above, or defined exposure as a clinical diagnosis of an alcohol use disorder, was 3.50 (95% CI: 2.01–5.93). After exclusion of small studies, because of suspected publication bias, the pooled relative risk was 2.94 (95% CI: 1.89–4.59). Subgroup analyses of studies that had controlled for various sets of confounders did not give significantly different results and did not explain the significant heterogeneity that was found across the studies.ConclusionThe risk of active tuberculosis is substantially elevated in people who drink more than 40 g alcohol per day, and/or have an alcohol use disorder. This may be due to both increased risk of infection related to specific social mixing patterns associated with alcohol use, as well as influence on the immune system of alcohol itself and of alcohol related conditions.

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.

WHO's new end TB strategy.

On May 19, 2014, the 67th World Health Assembly (WHA) adopted WHO’s “Global strategy and targets for tuberculosis prevention, care and control after 2015”. This post-2015 global tuberculosis strategy, labelled the End TB Strategy, was shaped during the past 2 years. A wide range of stakeholders—from ministries of health and national tuberculosis programmes to technical and scientifi c institutions, fi nancial and development partners, civil society and health activists, non-governmental organisations, and the private sector—contributed to its development. The strategy has a vision of making the world free of tuberculosis, with zero deaths, disease, and suff ering due to the disease (see appendix p 1 for summary of the End TB Strategy). In 2013, 9 million people fell ill with tuberculosis and 1·5 million died; about a quarter of them were HIV positive. Poor and deprived groups also bore the brunt of the enormous socioeconomic burden imposed by the disease and deaths. Concerned by this persistent human suff ering due to tuberculosis, but encouraged by the progress achieved during the past two decades and recognising the need to mount a multisectoral response to eff ectively address the problem, the health ministers at the WHA approved WHO’s proposal to push the limit of ambition to “end the global tuberculosis epidemic” by 2035, marked by well defi ned milestones and targets set along the way. Ending the tuberculosis epidemic implies bringing the levels of tuberculosis in the whole world down to converge with those already attained by many rich countries: fewer than ten new tuberculosis cases occurring per 100 000 population per year amounting to 90% reduction in tuberculosis incidence and tuberculosis deaths reduced by 95%. The rich countries achieved remarkable reductions in the tuberculosis burden not only by delivering adequate tuberculosis services, but also by pursuing universal access to health care and social protection while rapidly improving nutrition and economic conditions. Ending the tuberculosis epidemic in high-incidence countries needs a similar approach that guarantees access to high-quality tuberculosis care and prevention to all while simul taneously addressing the social determinants of tuberculosis. To this eff ect, elimination of catastrophic costs that tuberculosis-aff ected families face is an important milestone to be achieved under the End TB Strategy well within the next decade. Importantly, though, achievement of universal access to currently available methods of tuberculosis care and prevention will not be enough to end the epidemic within two decades. Global investments and eff orts are also essential to develop improved methods to diagnose, treat, and prevent tuberculosis. Equal emphasis on achievement of universal access to tuberculosis care and prevention, addressing of weaknesses in health systems and social determinants of tuberculosis, and pursuing of research and innovation for improved approaches and strategies constitute the core of the End TB Strategy. The achievements of the past two decades provide the basis for further progress. The DOTS (directly observed treatment, short-course) strategy of 1995 expanded access to high-quality tuberculosis care. The Stop TB Strategy of 2006 widened its scope to address management of all forms of tuberculosis including HIV-associated and drug-resistant tuberculosis, through engagement of communities, involvement of all care providers, strengthening of health systems, and fostering of research. Subsequently, the tuberculosis-related Millennium Development Goal to “halt and begin to reverse the incidence of tuberculosis” was achieved; 37 million lives were saved between 2000 and 2013; and a new rapid molecular test to simultaneously diagnose tuberculosis and rifampicin resistance was developed and two novel drugs were introduced. These achievements notwithstanding, the enormity of the task ahead cannot be overemphasised. Overall, the current 2% annual reduction in the global tuberculosis incidence is too slow to achieve an end to the epidemic in the foreseeable future. Tuberculosis remains a top infectious killer of men and women. A third of estimated incident tuberculosis cases go un-notifi ed or undiagnosed and close to half a million multidrug-resistant cases emerge each year. HIV-associated tuberculosis aff ects more than a million people a year. An estimated 2 billion people with latent tuberculosis infection form a reservoir that sustains the global epidemic. Analyses of constraints to global tuberculosis control bring four major persisting barriers to the fore. First, weak health systems including the unregulated non-state sector prevent reaching the currently available methods of diagnosis and treatment to all sections of the populations and a lack of universal health coverage and social protection inhibit provision of comprehensive tuberculosis care and prevention without further impoverishment to those who need it most. Second, determinants such as poverty, under nutrition, migration, and ageing populations enhance vulnerability and maintain the cycle of infection and disease. The risk of tuberculosis is further enhanced by non-communicable health problems such as diabetes, harmful use of alcohol, and tobacco smoking. Third, the lack of optimum methods—a point-of-care test for rapid diagnosis of disease and latent infection; better and safer drug regimens to shorten treatment; and a vaccine to prevent Lancet 2015; 385: 1799–801

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

Multidrug-resistant tuberculosis management in resource-limited settings.

Managing MDRTB through national programs can yield results similar to those seen in wealthier settings.

MDR Tuberculosis: Critical Steps for Prevention and Control

ultidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of Mycobacterium tuberculosis that are at least resistant to treatment with isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by multidrug-resistant strains that are also resistant to treatment with any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin). MDR tuberculosis and XDR tuberculosis are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade. 1,2 In 2008, an estimated 440,000 cases of MDR tuberculosis emerged globally. 1 India and China carry the greatest estimated burden of MDR tuberculosis, together accounting for almost 50% of the world’s total cases. More than three quarters of the estimated cases of MDR tuberculosis occur in previously untreated patients. The proportion of MDR cases among new cases and previously treated cases of tuberculosis reported globally from 1994 through 2009 ranged from 0 to 28.3% and from 0 to 61.6%, respectively (Fig. 1). The highest proportions of MDR cases, and the most severe drug-resistance patterns, appear in the countries of the former Soviet Union. By 2009, a total of 58 countries had reported at least one case of XDR tuberculosis. In eight countries, reported cases of XDR tuberculosis account for more than 10% of all cases of MDR tuberculosis, and six of these countries were part of the former Soviet Union. By far the largest number of cases of XDR tuberculosis has been reported from South Africa (10.5% of all cases of MDR tuberculosis in that country), owing to rapid spread among people infected with the human immunodeficiency virus (HIV). National programs are failing to diagnose and treat MDR tuberculosis. Globally, just under 30,000 cases of MDR tuberculosis were reported to the World Health Organization (WHO) in 2008 (7% of the estimated total), of which less than one fifth were managed according to international guidelines. The vast majority of the remaining cases probably are not diagnosed or, if diagnosed, are mismanaged. This problem remains despite the evidence that management of MDR tuberculosis is cost-effective 3 and that treatment of MDR tuberculosis, and even treatment of XDR tuberculosis, is feasible in persons who are not infected with HIV. 4,5

Financial burden for tuberculosis patients in low- and middle-income countries: a systematic review

In order to inform the development of appropriate strategies to improve financial risk protection, we conducted a systematic literature review of the financial burden of tuberculosis (TB) faced by patients and affected families. The mean total costs ranged from

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

55 to

World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update

8198, with an unweighted average of