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BackgroundThe implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries.MethodsObservational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes.ResultsBetween February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07).ConclusionsThis study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Objective: To investigate a multi-institutional outbreak of highly resistant tuberculosis and evaluate patient outcome.Design: Epidemiologic investigation of every tuberculosis case reported in New York City.Setting: Patients cared for at all public and nonpublic institutions from January 1, 1990, to August 1, 1993 (43 months).Patients: We reviewed medical and public health records and conducted clinical, epidemiologic, drug susceptibility, and restriction fragment length polymorphism (RFLP) analyses. A case was defined as tuberculosis in a patient with an isolate resistant to isoniazid, rifampin, ethambutol hydrochloride, and streptomycin (and rifabutin, if sensitivity testing included it), and, if RFLP testing was done, a pattern identical to or closely related to strain W.Main Outcome Measures: Patient survival and the conversion of sputum cultures from positive to negative.Results: Of the 357 patients who met the case definition, 267 had identical or nearly identical RFLP patterns; isolates from the other 90 patients were not available for RFLP testing. Among these 267 patients, 86% were human immunodeficiency virus (HIV)-infected, 7% were HIV-negative, and 7% had unknown HIV status. All-cause mortality was 83%. Epidemiologic linkages were identified for 70% of patients, of whom 96% likely had nosocomially acquired disease at 11 hospitals. Survival was prolonged among patients who received medications to which their isolate was susceptible, especially capreomycin sulfate, and among patients with a CD4+ T-lymphocyte count greater than 0.200 x 10(9)/L (200/microL). Treatment with isoniazid and a fluoroquinolone antibiotic was also independently associated with longer survival.Conclusions: This outbreak accounted for nearly one fourth of the cases of multidrug-resistant tuberculosis in the United States during a 43-month period. Most patients had nosocomially acquired disease, were infected with HIV, and unless promptly and appropriately treated, died rapidly. With appropriate directly observed treatment, especially combinations including an injectable medication, even severely immunocompromised patients had culture conversion and prolonged, tuberculosis-free survival. [ABSTRACT FROM AUTHOR]

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1 st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Introduction: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases., Discussion: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic., Conclusions: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The international community has committed to end the tuberculosis (TB) epidemic by 2030. To facilitate the meeting of the global incidence and mortality indicators set by the World Health Organization's End TB Strategy, the Stop TB Partnership launched the three 90-(90)-90 diagnostic and treatment targets in 2014. In this paper, we argue that a 'fourth 90'-Ensuring that 90% of all people successfully completing treatment for TB can have a good health-related quality of life'-should be considered. Many individuals who successfully complete anti-TB treatment are burdened with lifelong comorbidities-human immunodeficiency virus (HIV) and diabetes mellitus, obstructive and restrictive lung disease, involving lung destruction, cavitation, fibrosis and bronchiectasis, that either pre-existed or developed as a result of TB (e.g., chronic pulmonary aspergillosis), permanent disabilities such as hearing loss resulting from second-line anti-TB drugs, and mental health disorders. These need to be identified during TB treatment and appropriate care and support provided after anti-TB treatment is successfully completed. A 'fourth 90' has also been proposed for the UNAIDS 90-90-90 targets similar in scope to what is being suggested here for TB. Adoption by both HIV and TB control programmes would highlight the current focus on integrated person- and family-centred services.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in line with the sustainable development goals targets and has been implemented in the World Health Organization (WHO) Western Pacific Region since 2015. Significant progress has been made in implementing this strategy. However, several challenges still remain. In 2016, an estimated 1.8 million people developed TB in the region, and of these about 20% were missed by national TB programmes. The gap in diagnosis and enrolment as well as treatment completion is greater with drug-resistant TB. Many TB-affected families face catastrophic costs due to the disease. Sustaining financing for TB care is a long-term challenge in many countries. This article emphasizes targeted interventions in high-risk populations, including systematic screening and patient-centred TB care. Several other approaches including improving TB diagnostic tools and algorithm, and engaging all care providers are suggested to find missing TB patients. Drug-resistant TB requires additional resourcing for laboratories, enrolment and patient support. Specific measures are required at different levels to mitigate financial burden due to TB including linking TB to overall social protection schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the global agenda, forge partnerships and move towards universal health coverage., (© 2018 Asian Pacific Society of Respirology.)

Tuberculosis (TB), as the major infectious disease in the world, has devastating consequences for not only humans, but also cattle and several wildlife species. This disease presents additional challenges to human and veterinary health authorities given the zoonotic nature of the pathogens responsible for the disease across species. One of the main public health challenges regarding zoonotic TB (ZTB) caused by Mycobacterium bovis is that the true incidence of this type of TB in humans is not known and is likely to be underestimated. To effectively address challenges posed by ZTB, an integrated One Health approach is needed. In this manuscript, we describe the rationale, major steps, timeline, stakeholders, and important events that led to the assembling of a true integrated multi-institutional and interdisciplinary team that accomplished the ambitious goal of developing a ZTB roadmap, published in October, 2017. It outlines key activities to address the global challenges regarding the prevention, surveillance, diagnosis, and treatment of ZTB. We discuss and emphasize the importance of integrated approaches to be able to accomplish the short (year 2020) and medium term (year 2025) goals outlined in the ZTB roadmap.

Mycobacterium tuberculosis is recognised as the primary cause of human tuberculosis worldwide. However, substantial evidence suggests that the burden of Mycobacterium bovis, the cause of bovine tuberculosis, might be underestimated in human beings as the cause of zoonotic tuberculosis. In 2013, results from a systematic review and meta-analysis of global zoonotic tuberculosis showed that the same challenges and concerns expressed 15 years ago remain valid. These challenges faced by people with zoonotic tuberculosis might not be proportional to the scientific attention and resources allocated in recent years to other diseases. The burden of zoonotic tuberculosis in people needs important reassessment, especially in areas where bovine tuberculosis is endemic and where people live in conditions that favour direct contact with infected animals or animal products. As countries move towards detecting the 3 million tuberculosis cases estimated to be missed annually, and in view of WHO's end TB strategy endorsed by the health authorities of WHO Member States in 2014 to achieve a world free of tuberculosis by 2035, we call on all tuberculosis stakeholders to act to accurately diagnose and treat tuberculosis caused by M bovis in human beings., (Copyright © 2017 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Background: As part of its policy to shift monitoring of antiretroviral therapy (ART) to primary health care (PHC) workers, the Ministry of Health of the Democratic Republic of Congo (DRC) tested the feasibility of using dried blood spots (DBS) for viral load (VL) quantification and genotypic drug resistance testing in off-site high-throughput laboratories., Methods: DBS samples from adults on ART were collected in 13 decentralized PHC facilities in the Nord-Kivu province and shipped during program quarterly supervision to a reference laboratory 2000 km away, where VL was quantified with a commercial assay (m2000rt, Abbott). A second DBS was sent to a World Health Organization (WHO)-accredited laboratory for repeat VL quantification on a subset of samples with a generic assay (Biocentric) and genotypic drug resistance testing when VL >1000 copies per milliliter., Findings: Constraints arose because of an interruption in national laboratory funding rather than to technical or logistic problems. All samples were assessed by both VL assays to allow ART adjustment. Median DBS turnaround time was 37 days (interquartile range: 9-59). Assays performed unequally with DBS, impacting clinical decisions, quality assurance, and overall cost-effectiveness. Based on m2000rt or generic assay, 31.3% of patients were on virological failure (VF) and 14.8% presented resistance mutations versus 50.3% and 15.4%, respectively., Conclusion: This study confirms that current technologies involving DBS make virological monitoring of ART possible at PHC level, including in challenging environments, provided organizational issues are addressed. Adequate core funding of HIV laboratories and adapted choice of VL assays require urgent attention to control resistance to ART as coverage expands.

A modified presentation of the impact assessment framework is proposed that improves accessibility while continuing to provide a checklist of the evidence needed to support policy decisions on the implementation of new tools for the diagnosis of tuberculosis., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a 'syndemic' due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the 'MPOWER' package recommended by the World Health Organization's Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking.

Background: The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes., Methods and Findings: A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001). No other important differences were observed., Conclusions: This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB., Trial Registration: Controlled-Trials.com ISRCTN79888843.

The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organisation involved in the fight against tuberculosis. In 2008, the Institute of The Union was challenged to think boldly about the future and to develop a diverse work portfolio covering a wide spectrum of lung health and other disease-related problems. The vision adopted by The Union at that time was 'Health solutions for the poor'. More recently, there has been lengthy debate about the need for the Union to concentrate just on its core mandate of tuberculosis and lung health and for the Union's vision to reflect this narrower spectrum of activity as 'Lung health solutions for the poor'. In this viewpoint article we outline our reasons for believing that this narrower vision is incompatible with The Union's mission statement, and we argue that making such a change would be a mistake.

Setting: Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin., Results: The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities., Conclusion: The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Setting: Benin, where 20 of 54 tuberculosis (TB) clinics caring for 80% of all TB patients began providing integrated human immunodeficiency virus (HIV) care in 2005., Objective: To describe the characteristics and TB treatment outcomes of the first cohorts of TB-HIV patients, and to assess programmatic outcomes., Methods: Retrospective cohort study using data from the TB register and the register of co-infected patients., Results: During the study period, 8368 TB patients were registered, 7787 (93%) were tested for HIV and 1255 (16%) were HIV-positive, including 385 (32%) who already knew their positive status. Most patients (88%) were tested within 15 days of TB diagnosis. Female and young patients were overrepresented among the co-infected. Cotrimoxazole preventive therapy was administered to 1152 patients (95%) during anti-tuberculosis treatment, and antiretroviral treatment (ART) to 469 (42%). The likelihood of receiving ART increased as initial CD4 lymphocyte counts decreased. Fifteen per cent of TB-HIV patients died during anti-tuberculosis treatment. Patients already on ART prior to anti-tuberculosis treatment experienced the worst outcomes. Patients who initiated ART early during anti-tuberculosis treatment or in the timeframe recommended by the guidelines fared the best., Conclusion: HIV care has been successfully and sustainably integrated into TB services in Benin. However, ensuring the access of co-infected patients to more favourable treatment outcomes still represents significant challenges.

Setting: Three regional referral hospitals in Uganda with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) cases., Objective: To determine the treatment outcomes of TB retreatment cases and factors influencing these outcomes., Design: A retrospective cohort study of routinely collected National Tuberculosis Programme data between 1 January 2009 and 31 December 2010., Results: The study included 331 retreatment patients (68% males), with a median age of 36 years, 93 (28%) of whom were relapse smear-positive, 21 (6%) treatment after failure, 159 (48%) return after loss to follow-up, 26 (8%) relapse smear-negative and 32 (10%) relapse cases with no smear performed. Treatment success rates for all categories of retreatment cases ranged between 28% and 54%. Relapse smear-positive (P = 0.002) and treatment after failure (P = 0.038) cases were less likely to have a successful treatment outcome. Only 32% of the retreatment cases received a Category II treatment regimen; there was no difference in treatment success among patients who received Category II or Category I treatment regimens (P = 0.73)., Conclusion: Management of TB retreatment cases and treatment success for all categories in three referral hospitals in Uganda was poor. Relapse smear-positive or treatment after failure cases were less likely to have a successful treatment outcome.

In this manuscript, we report the current situation of tuberculosis globally and in Brazil, the need for new strategies toward tuberculosis control, focusing on new diagnostic technologies. Critical comments are given on the state of the art regarding the evaluation of new health technologies, degree of scientific evidence needed, evaluation of clinical impact, cost-effectiveness of incorporation into the health system and the social impact., (Copyright © 2013 Elsevier Editora Ltda. All rights reserved.)

Xpert ® MTB/RIF offers new and important possibilities for the diagnosis of sputum smear-negative tuberculosis (TB) and/or rifampicin (RMP) resistance, and many are encouraging rapid and widespread implementation. This simple test can be implemented almost everywhere, and it provides results within a few hours. In low-income countries (LICs), however, its cost, environmental limitations (stable and regular electricity, adequate room temperature) and difficulties involved in supply and maintenance are major obstacles. While it may be suitable for major reference hospitals, operational research is needed to evaluate the test and its additional yield above high-quality smear microscopy and clinical algorithms before its use at the peripheral level. In the meantime, direct microscopy should remain the initial diagnostic test for TB suspects. In most LICs, the prevalence of RMP resistance among new TB patients is very low; an Xpert MTB/RIF result indicating RMP resistance will thus always need confirmation by another test. In a population at high risk of RMP resistance (> 15%), however, the positive predictive value for RMP resistance by Xpert MTB/RIF is high, and identification of RMP resistance is an excellent proxy for multidrug-resistant TB (MDR-TB). The assay should be widely used for this purpose if, and only if, excellent MDR-TB management is available, both for ethical reasons and to reduce the risk of extensively drug-resistant TB.

Background: Zimbabwe has been severely affected by the HIV/AIDS and tuberculosis epidemics, with an estimated 80% of tuberculosis patients being HIV infected. We set out to use annual population-mortality records from the cities of Harare and Bulawayo to describe trends and possible causes of mortality from 1979 to 2008. The specific objectives were to document overall, sex and age-specific mortality, proportion of deaths attributed to AIDS and tuberculosis, and changes in death rates since the start of antiretroviral therapy in 2004., Methods: This retrospective descriptive study used existing mortality records of the Health Services departments in Harare and Bulawayo. Data points included: estimated yearly total population; groupings by sex and age; deaths (total and by sex and age groups for each year of the study period); and most frequently reported causes of death (for age groups <15 years, 15-44 years and ≥ 45 years). Data on deaths were aggregated by year, and crude, sex- and age-specific death rates were calculated per 1000 population. Tuberculosis and HIV-related disease-specific death rates and proportion of deaths attributed to these conditions were computed., Results: In both cities, crude death rates were lowest in the late 1980s, increased three- to five-fold by the early 2000s, and began a slow and, in the case of Bulawayo, intermittent decline from 2004. Sex-specific death rates followed a similar trend, being higher in males than in females. The death rates in the age groups <5 years, 15-44 years and ≥ 45 years showed significant increases, with a gradual levelling off and decline from 2002 onwards; death rates in those aged 5-14 years were relatively unaffected. Tuberculosis and HIV caused 70% of deaths in the age group of 15-44 years from the early 1990 s., Conclusions: This study used routinely collected population-mortality data that are rare in resource-limited settings, and it described, for the first time in Zimbabwe, the effects of the HIV/AIDS epidemic and the introduction of antiretroviral therapy on death rates in two large cities. After a substantial rise in crude mortality rates, there has been a decline associated with the introduction of ART. Such routine population data must continue to be collected, collated and analyzed.

Operational research (OR) has become a hot topic at national meetings, international conferences and donor fora. The International Union Against Tuberculosis and Lung Disease (The Union) and Médecins Sans Frontières (MSF) Operational Centre Brussels strongly promote and implement OR with colleagues in low- and middle-income countries. Here we describe how the two organisations define OR, and explain the guiding principles and methodology that underpin the strategy for developing and expanding OR in those countries. We articulate The Union's and MSF's approach to supporting OR, highlighting the main synergies and differences. Then, using the Malawi National Tuberculosis Control Programme as an example, we show how OR can be embedded within tuberculosis control activities, leading to changes in policy and practice at the national level. We discuss the difficult, yet vitally important, issue of capacity building, and share our vision of a new paradigm of product-related training and performance-based OR fellowships as two ways of developing the necessary skills at country level to ensure research is actually performed. Finally, we highlight the need to consider and incorporate into practice the ethical components of OR. This is a key moment to be involved in OR. We are confident that in partnership with interested stakeholders, including the World Health Organization, we can stimulate the implementation of quality, relevant OR as an integral part of health service delivery that in turn will lead to better health for people, particularly for those living in the poorer parts of the world.

Setting: One peri-urban and four rural districts in Uganda., Objectives: To determine the level of and factors associated with human immunodeficiency virus (HIV) testing among tuberculosis (TB) patients., Design: A cross-sectional study was conducted in five selected districts from August to November 2007. Patients aged > or = 18 years returning for TB treatment refills at facilities offering TB and HIV services were included. Patients were excluded if they were very sick or unable to speak English or any of the local study languages. The outcome was self-reported HIV testing after TB diagnosis, validated using clinic registers., Results: Of 261 patients analysed, 169 (65%) had been tested for HIV following TB diagnosis. In a multivariate analysis, age >45 years (OR 0.27, 95%CI 0.08-0.87), not receiving information about the TB-HIV association (OR 0.35, 95%CI 0.15-0.77), not being offered HIV testing by health provider (OR 0.02, 95%CI 0.006-0.042), dissatisfaction with privacy (OR 2.49, 95%CI 1.11-5.55) and spending 30-60 min at the clinic (OR 4.48, 95%CI 1.66-12.10) significantly influenced level of HIV testing., Conclusion: The level of HIV testing among TB patients was suboptimal, as per policy all patients should be tested. The Uganda Ministry of Health should continue to scale-up HIV testing and other collaborative TB-HIV services at health facilities.

The International Union Against Tuberculosis and Lung Disease (The Union) is the oldest international non-governmental organization involved in the fight against tuberculosis. This review documents the history and structure of The Union up to 2009, and describes the achievements that have taken place in the field of tuberculosis and lung health. The progress made in tackling the major killer (pneumonia) of children less than 5 years of age, the barrier to affordable essential asthma medicines, the complex issue of tobacco control, the move into the realm of HIV and AIDS, and new ideas and activities around the increasingly important domain of operational research are described and discussed. Finally, as with many institutions that have seen a rapid phase of growth, expansion and decentralisation to regional offices around the world, the review highlights the internal strategic initiative that aims to fine-tune the organisational structure, clarify lines of authority, create more efficient business, human resource and financial systems and revise, where necessary, The Union's guiding mission, vision and values for the future.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

In 2005, the World Health Assembly resolved that all Member States should ensure that all persons with tuberculosis (TB) "have access to the universal standard of care based on proper diagnosis, treatment and reporting consistent with the DOTS strategy..." The purpose of the International Standards for Tuberculosis Care (ISTC) is to define the widely accepted level of care of persons either suspected of, or diagnosed with, TB by all health practitioners, especially those in the private sector, who often lack guidance and systematic evaluation of outcomes provided by government programs. Since their publication in 2006 on World TB Day, the standards have been endorsed by the major international health organizations as well as many country-level professional societies. The intention is to complement local and national control polices consistent with those of the World Health Organization: they are not intended to replace local guidelines, but are written to accommodate local differences in practice. The ISTC comprise seventeen evidence-based standards on tuberculosis diagnosis and treatment, as well as the responsibility of the public health sector. These are based on the basic principles of TB care: prompt and accurate diagnosis, standardized treatment regimens of proven efficacy, appropriate treatment support and supervision, monitoring of response to treatment and the carrying out of essential public health responsibilities. The relevance of the ISTC to the Japanese context is highlighted, in terms of when persons should be suspected of TB; the appropriate diagnostic modalities, including the use of chest radiographs; the advantages of fixed dose combinations; the importance of follow-up laboratory tests to document response to treatment, the importance of recordkeeping and reporting to public health authorities, the value of HIV testing of TB patients and the use of anti-retrovirals for those dually infected; and the assessment of drug resistance and the appropriate treatment of multidrug-resistant tuberculosis. Finally, some proposals were made on the way forward for Japan.

Extensive drug resistance in TB is not a new phenomenon. It is created when patients with multidrug-resistant TB (MDR-TB) are treated with second-line anti-TB drugs but fail to be cured. The first principle in managing the risk of extensively drug-resistant TB (XDR-TB) is 'do not generate XDR-TB'. Once it is created, every effort must be made to prevent it from spreading. Health workers and care givers in long-term care facilities and prisons may have a considerable risk of exposure to TB, including XDR-TB. The principles in the control of TB transmission in healthcare settings, long-term care facilities and prisons include early identification and isolation of infectious TB patients, effective treatment of TB as soon as possible, environmental control with proper ventilation and personal protection of healthcare workers and others. Patients with the highest risk of developing XDR-TB are those MDR-TB patients who failed treatment using a second-line regimen and TB patients who have a history of contact with XDR-TB patients. The core principles in managing the risk of XDR-TB for health workers and care givers are reducing the risks of exposure to XDR-TB, becoming infected and developing XDR-TB. If TB has developed, the principles include promptly diagnosing XDR-TB and starting proper treatment.

Setting: In 1993, the New York City (NYC) Bureau of Tuberculosis Control developed the cohort review process as a quality assurance method to track and improve patient outcomes., Methods: The Bureau Director reviews every tuberculosis (TB) case quarterly in a multi-disciplinary staff meeting. In 2004 we also began collecting details on issues identified at cohort review to quantify how this process directly impacts TB control efforts., Results: From 1992 to 2004, NYC TB cases decreased by 72.7% and treatment success rates significantly increased by 26.7%. Implementing the cohort review was key to improving case management, thus leading to these results. For the 1039 patients in 2004, 596 issues were identified among 424 patients; 55.0% were incorrect, unclear or unknown patient information, 13.8% were treatment issues, 12.4% were case management issues and 10.6% were incomplete contact investigations. Most (76.5%) issues were addressed within 30 days of the cohort reviews., Conclusion: A systematic review of every TB case improves the quality of patient information, enhances patient treatment and ensures accountability at all levels of the TB control program.

Background: Two drug-resistance surveys showed a very high prevalence of drug resistance among isolates obtained from patients with tuberculosis in 1991 and 1994 in New York, New York., Methods: A cross-sectional survey in April 1997 and a survey of incident cases in April-June 2003 were conducted. The trend in the proportion of drug resistance in the 4 surveys was examined separately for prevalent and incident cases. Risk factors for drug resistance in incident cases were also assessed., Results: The number of patients was 251 in the 1997 survey and 217 in the 2003 survey. Among prevalent cases, the percentage of cases with resistance to any antituberculosis drug decreased from 33.5% in 1991 to 23.8% in 1994 and to 21.5% in 1997 (P < .001, by test for trend); cases of multidrug-resistant tuberculosis also decreased significantly, from 19% in 1991 to 6.8% in 1997 (P < .001, by test for trend). Among incident cases in the 4 surveys, the decrease in resistance to any antituberculosis drugs was not statistically significant; however, the decrease in multidrug-resistant tuberculosis (from 9% in 1991 to 2.8% in 2003) was statistically significant (P = .002, by test for trend). However, in 2003, a worrisome increase in incident cases of multidrug-resistant tuberculosis (an increase of 23%) was seen among previously treated patients with pulmonary tuberculosis not born in the United States. Human immunodeficiency virus infection, a strong predictor for drug resistance in 1991 and 1994, was not associated with drug resistance in subsequent surveys., Conclusions: Intensive case management, including directly observed therapy, adherence monitoring, and periodic medical review to ensure appropriate treatment for each patient, should be sustained to prevent acquired drug resistance.

Because of the increasing availability of antiretroviral (ARV) agents for HIV in low-income countries, many clinicians now need training on their use. This is especially true for clinicians caring for individuals with tuberculosis (TB), given its close relationship with HIV/AIDS. This article summarizes the key decisions facing clinicians who manage HIV-infected persons, with particular reference to issues regarding those dually infected with TB. Health care provider-initiated diagnostic testing using rapid HIV tests should be offered to all individuals with symptoms and signs suggesting HIV infection, including all persons with TB. Issues to be included in pre- and post-test counseling sessions are discussed. HIV-infected patients should be evaluated to determine clinical staging of HIV; certain laboratory examinations should ideally be performed to assess the degree of immunosuppression and to aid decisions about when best to start ARV therapy and preventive therapies. The recommended ARV regimens and guidance on proposed patient follow-up are presented. Good adherence to ARVs is required and factors that induce and reinforce compliance are suggested. The treatment of TB is a high priority, and follows the same principles whether the patient is HIV-infected or not. Suggestions are made about ARV use in patients with TB. A standardized and complementary information system should be developed to monitor management of HIV-TB patients and performance of joint TB and HIV care efforts. By diagnosing and managing additional HIV cases detected through the portal of the TB control programme, clinicians will contribute to diminishing the burden of HIV, and thus, TB.

Infection with HIV drives the tuberculosis epidemic, especially in sub-Saharan Africa, where up to 75% of individuals with tuberculosis are co-infected with HIV. This article reviews the epidemiological link between the conditions, how tuberculosis diagnosis and treatment differ between HIV-infected versus -uninfected individuals and the span of additional measures required to prevent and control HIV-related tuberculosis. Tuberculosis chemotherapy using standard short-course regimens is highly effective in both groups, and treatment follows the same principles. It differs in certain aspects, such as when antiretroviral treatment should be started in HIV-infected individuals with tuberculosis and consideration of drug-drug interactions between the rifamycins and certain antiretroviral drugs. Control of HIV-related tuberculosis requires, fundamentally, control of HIV transmission. Meanwhile, it is necessary to make concentrated efforts to intensify high-quality tuberculosis services employing the directly observed treatment, short-course (DOTS) strategy, carry out extensive research towards an evidence-based model for the expanded scope of collaborative tuberculosis and HIV/AIDS interventions, and ensure efficient implementation of the findings and recommended policies. The challenge is gigantic, and both robust within-country and international leadership and competent management capabilities will be required, in addition to substantial human and financial resources.

Injection drug users (IDUs) were heavily affected by the tuberculosis (TB) resurgence in New York City in the 1990s. We assessed the effectiveness of screening for latent TB infection in methadone users and of selective treatment with isoniazid. Risk for future TB was classified as low or high on the basis of tuberculin, anergy, and HIV test results. The cohort of 2212 IDUs was followed up for a median of 4.2 years; 25 IDUs, of whom 20 (80%) were infected with human immunodeficiency virus (HIV), developed TB. In an adjusted Cox proportional hazards model of high-risk IDUs, the risk of TB was associated with HIV infection (HR 10.3; 95% CI, 3.4-31.3); receipt of <6 months of isoniazid therapy (HR 7.6; 95% CI, 1.02-57.1); a CD4+ T lymphocyte count of <200 cells/mm3 (HR 6.6; 95% CI, 1.7-25.9); and tuberculin positivity (HR 4.0; 95% CI, 1.6-10.2). Treatment with isoniazid was beneficial in HIV-infected, tuberculin-positive IDUs.

Objective: To determine factors associated with no contacts identified for homeless patients in New York City., Design: Culture-confirmed pulmonary tuberculosis cases in persons >18 years old diagnosed in 1997-1999 were included. Demographic and clinical characteristics of tuberculosis patients associated with the number of contacts identified according to homeless status were analyzed using unconditional logistic regression., Results: Homeless patients (n = 152) had a significantly lower median number of contacts than non-homeless patients (n = 2836) (1 vs. 4, P < 0.001). Among homeless patients, having AFB smear-positive sputum with cavitary lesions reduced the likelihood of having no contacts identified. Homeless patients who lived on the street at the time of diagnosis were more likely to have no contacts identified compared to those with contacts identified (61.4% vs. 56.1%); however, the difference was not statistically significant (P = 0.506). Unlike non-homeless patients, being hospitalized at the time of tuberculosis diagnosis was not associated with having contacts identified in homeless patients., Conclusions: Homelessness independently predicted the likelihood of having no contacts identified. Strategies such as interviews that focus on location rather than persons may be more effective for identifying contacts. Furthermore, being homeless at the time of diagnosis should be used as an indicator for prioritizing prompt contact evaluation.

Objective: To determine the prevalence of and risk factors for tuberculin skin test positivity and conversion among New York City Department of Health and Mental Hygiene employees., Design: Point-prevalence survey and prospective cohort analysis. Sentinel surveillance was conducted from March 1, 1994, to December 31, 2001., Participants: HCWs in high-risk and low-risk settings for occupational TB exposure., Results: Baseline tuberculin positivity was 36.2% (600 of 1,658), 15.5% (143 of 922) among HCWs born in the United States, and 48.5% (182 of 375) among HCWs not born in the United States. There were 36 tuberculin conversions during 2,754 observation-years (rate, 1.3 per 100 person-years). For HCWs born in the United States, the risk for tuberculin conversion was greater in high-risk occupational settings compared with low-risk settings (OR, 5.7; CI95, 1.7-19.2; P < .01). HCWs not born in the United States and those employed at the Office of the Chief Medical Examiner (OCME) were at high risk for baseline tuberculin positivity (OR, 3.2; CI95, 1.7-5.8; P < .001); OCME HCWs (OR, 4.7; CI95, 2.3-9.4; P < .001), those of Asian ethnicity (OR, 4.3; CI95, 1.4-13.5; P < .01), and older HCWs (OR, 1.0; CI95, 1.0-1.1; P < .05) were at a higher risk for conversion., Conclusions: Although the prevalence of tuberculin positivity decreased after the peak of the recent TB epidemic in New York City, the conversion rate among HCWs in high-risk occupational settings for TB exposure was still greater than that among HCWs in low-risk settings. Continued surveillance of occupational TB infection is needed, especially among high-risk HCWs.

Setting: A large urban tuberculosis control program., Objectives: To examine changes in tuberculosis incidence and characteristics of cases in New York City (NYC), and assess the epidemiology of tuberculosis among non-US-born persons., Design: Tuberculosis surveillance data (1995-1999) for NYC were analyzed., Results: Tuberculosis incidence decreased by 56.6% in US-born and 19.6% in non-US-born persons (age-adjusted) over the study period. The decline in tuberculosis incidence among US-born persons was more substantial in the first half of the study period (23-24%) than in the second half (13-15%). The greatest decline in incidence was among US-born Hispanic or Black males aged 25-64. However, although there was an overall decline in incidence among non-US-born persons, there was no significant change in any sex or racial/ethnic subgroup. The percent of multidrug-resistant (MDR) cases among non-US-born patients remained stable, but recent arrivals accounted for 79% of non-US-born MDR-TB patients in 1999, a significant increase from 16% in 1997., Conclusions: Continuing current tuberculosis control efforts and treatment of immigrants with latent tuberculosis infection are of highest priority for reducing incident cases in NYC. Global collaboration towards earlier detection and treatment of active tuberculosis cases in high incidence countries is also essential.

Setting: New York City., Objective: To evaluate the yield of continued monthly sputum monitoring after culture conversion., Design: A retrospective review of tuberculosis patients verified between 1 January 1995 and 31 December 1996 who had: 1) pulmonary tuberculosis with organisms susceptible to isoniazid and rifampin; 2) culture conversion; and 3) completed therapy. We assessed time to smear and culture conversion and number of persons who developed a positive culture after culture conversion (culture reversion)., Results: Of 1440 patients, 379 were cared for by tuberculosis control program providers and 1061 were cared for by other providers; 813 (56%) were initially smear-positive. After the fifth month, 44 (5.3%) were smear-positive; four of these were culture-positive. Eighteen (1.3%) had culture reversions; eight were smear-positive. Excluding one specimen per patient collected at treatment completion, 7967 sputum samples were collected after culture conversion. The minimum estimated cost per culture reversion detected was $26,557., Conclusion: Continued monthly monitoring of sputum after culture conversion identified a very small number of patients who had culture reversion. However, patients who cannot tolerate or adhere to a standard regimen may need continued monitoring to assess response to treatment. For all patients a specimen should be collected at the end of treatment to document cure.