Increase In Risk Of Tuberculosis Research Articles

Alcohol consumption and risk of tuberculosis: a systematic review and meta-analysis.

To perform a systematic review and meta-analysis of the association between alcohol consumption and risk of tuberculosis (TB). Medline, EMBASE and Web of Science were searched for observational studies from 2005 to April 2018. Reference lists of included studies were screened. Forty-nine studies were included. Compared with people with low or no alcohol intake, the risk of TB in people with high or any alcohol consumption was increased by relative odds of 1.90 (95%CI 1.63-2.23). Substantial levels of heterogeneity were seen (I² = 82%); however, there was no evidence of publication bias (P = 0.54). Sensitivity analysis restricted to studies using no alcohol drinking as a reference group found a slightly lower but still increased risk (OR 1.60, 95%CI 1.39-1.84). Subgroup analyses revealed no significant differences in relation to study design and quality, geographic location, publication year or adjustment for confounders. A pooled analysis of a further four studies reporting hazard ratios (HRs) found a nearly three-fold increase in risk of TB in relation to alcohol consumption during follow-up (HR 2.81, 95%CI 2.12-3.74). An exposure-response analysis showed that for every 10-20 g daily alcohol intake, there was a 12% increase in TB risk. Alcohol consumption is an important risk factor for the development of TB.

P439 Diagnosis and management of latent and active tuberculosis in the context of biologic therapy in inflammatory bowel disease

Background: Anti-TNF treatments have improved the outcomes for patients with inflammatory bowel disease (IBD). However, they are associated with an increase in risk of Tuberculosis (TB). The aim of this study is to determine the proportion of latent TB infections (LTBI) in our IBD cohort treated with anti-TNFs and the management of these patients. We also examined the effect of different immunosuppressive drugs on the indeterminate rate of the interferon-gamma release assays (IGRA) in LTBI screening Methods: We conducted a retrospective review of all patients treated with biologics between March 2007 and November 2015. Patient notes and electronic records were reviewed. LTBI screening was assessed using a risk assessment form, chest x-ray, and tuberculin skin test (TST) or IGRA for the screening for LTBI and the nature of the immunosuppressive treatment was documented. Results: 732 patients with IBD were screened for LTBI before starting a biological treatment during the study period. 31 of 732 (4%) IBD patients were diagnosed and treated for LTBI with no significant side effects. 596 of 732 received their biologic treatment with a median delay of 86 days in initiating biologics. 6 of 596 patients who received biologic treatment developed active TB; 5 of whom were Caucasian. 247 patients were screened with an IGRA test. 6 were positive, 162 were negative and 79 patients were indeterminate. 45% with indeterminate IGRA had a repeat; half were negative and half remained indeterminate. 73% of the patients were receiving immunosuppressive (IMM) medication(s). There was a higher indeterminate rate of the IGRA in the IMM group compared to the no-IMM group (32% compared to 9%). The combination of steroids and thiopurines gave the highest rate of an indeterminate IGRA. High and low doses of steroids were equally likely to result in an indeterminate IGRA result. Conclusions: 4% of patients screened had LTBI and 1% of patients treated with biologics developed active TB. Delays in initiating biologics due to LTBI screening may have detrimental effects on the IBD management. Almost one third of patients on immunosuppressants had an indeterminate IGRA, which supports the need for a guideline incorporating a risk stratification strategy based on factors such as country of birth and local TB prevalence. There is a need to remain vigilant for TB regardless of baseline LTBI results or epidemiological factors.

Diabetes and Tuberculosis.

The increase in type 2 diabetes mellitus (DM) patients in countries where tuberculosis (TB) is also endemic has led to the reemerging importance of DM as a risk factor for TB. DM causes a 3-fold increase in TB risk and a 2-fold increase in adverse TB treatment outcomes. Given the sheer numbers of DM patients worldwide, there are now more TB patients with TB-DM comorbidity than TB-HIV coinfection. There is an urgent need to implement strategies for TB prevention and control among the millions of DM patients exposed to Mycobacterium tuberculosis. This chapter summarizes the current epidemiological, clinical, and immunological knowledge on TB and DM and their clinical and public health implications. These include the underlying mechanisms for TB risk in DM patients and their clinical and sociodemographic characteristics that distinguish them from TB patients without DM. TB-DM comorbidity is posing a new challenge for integrating the short-term care for TB with the long-term care for DM, particularly in low- and middle-income countries.

The Characteristics of TB Epidemic and TB/HIV Co-Infection Epidemic: A 2007-2013 Retrospective Study in Urumqi, Xinjiang Province, China.

ObjectiveThis study was aimed to find out epidemiologic characteristic of tuberculosis (TB) cases, and Human Immunodeficiency Virus (HIV) positive cases among TB patients (TB/HIV co-infection) through demographic, temporal, and spatial study in Urumqi.MethodsDescriptive statistics and multivariate logistic regression were applied to identify the epidemiologic characteristics and risk factors of TB epidemic and TB/HIV co-infection epidemic. All addresses of each TB case, TB/HIV co-infection case, and administrative street were transformed into geographical coordinate. Subsequently, the geocoded address for 82 streets was transformed into a dot map used as the basis of spatial datasets. In addition, the paper also used quantile map and the spatial scan statistic in order to identify the spatial distribution and spatial clusters of TB epidemic and TB/HIV co-infection epidemic.ResultThere was a declining trend of the notification rates of TB epidemic from 2007 to 2009, as well as a rising trend from 2010 to 2013. However, the notification rates of TB/HIV co-infection epidemic showed a rising trend from 2007 to 2010, and a declining trend from 2011 to 2013. Moreover, a significant share of TB epidemic and TB/HIV co-infection epidemic happened between the age of 15 to 45 years old, indicating an increase in risk of TB and TB/HIV infection. It is worth noting that the risk of HIV infection for male TB patients was 2.947 times (95% CI [2.178, 3.988]) than that of female patients. Han ethnicity and Uygur ethnicity in urban region accounted for a large proportion of total TB and TB/HIV co-infection cases. Most of the TB cases of minorities in Urumqi showed a statistically significant increase in risk of HIV infection than Han ethnicity in Urumqi. In addition, the spatial distribution of TB epidemic and TB/HIV co-infection epidemic was highly skewed. Most of the local clusters were located in urban area and rural-urban continuum where showed an increase in risk of TB and TB/HIV infection.ConclusionThe epidemiologic and spatial-temporal analysis of TB epidemic and TB/HIV co-infection epidemic demonstrates a potential connection between TB and HIV in Urumqi. Demographic, temporal, geographic factors are the reasons of causing TB and TB/HIV co-infection epidemic.

Incident tuberculosis in HIV-positive children, adolescents and adults on antiretroviral therapy in South Africa.

To evaluate the association between age and incident tuberculosis (TB) among human immunodeficiency virus (HIV) infected patients receiving antiretroviral treatment (ART) in South Africa. Prospective cohort analysis among HIV-infected patients initiating ART between April 2004 and April 2012. Generalized estimating equations (GEE) were used with modified Poisson regression clustered by treatment site as a function of sex, age, nucleoside reverse transcriptase inhibitor, CD4 count, hemoglobin levels and year of ART initiation. Cumulative incidence functions stratified by age and controlling for death as a competing risk were used to graphically display incident TB. Although non-significant, GEE models showed that patients aged <1 year had a 40% increase in risk of TB compared to those aged 30-39.9 years. Results also showed that male patients, those with low CD4, those with low hemoglobin and those who initiated ART before 2010 were at increased risk of TB. Our results show that patients aged <1 year, males, patients with low CD4 and those with low hemoglobin at ART initiation are at increased risk of incident TB in the first 24 months of ART. Given the known transmission risk factors for children living in households with a TB contact, reducing TB incidence in HIV-positive adults could substantially impact the risk of TB in young children.

Health Care Visits as a Risk Factor for Tuberculosis in Taiwan: A Population-Based Case-Control Study.

To assess whether health care visits of nontuberculous patients are a risk factor for contracting tuberculosis. We conducted a case-control study nested within the cohort of 1 million individuals from the health insurance database in Taiwan between 2003 and 2010. We identified incident cases of tuberculosis through International Classification of Diseases, Ninth Revision (ICD-9) codes and prescription of antituberculosis drugs. We identified 4202 case participants and 16 808 control participants matched by age, gender, and date of diagnosis to estimate the association between frequency of health care visits and incidence of tuberculosis. Frequency of health care visits was associated with increased risk of tuberculosis in a dose-dependent manner after adjustment for other medical comorbidities (P for trend < .001). Compared with individuals with fewer than 5 visits per year, those with more than 30 had a 77% increase in tuberculosis risk (adjusted odds ratio = 1.77; 95% confidence interval [CI] = 1.60, 1.97). Frequent health care visits of nontuberculous patients appear to be a risk factor for contracting tuberculosis. Efforts should focus on educating the general population to avoid unnecessary hospital visits, strengthening active case finding, and intensifying infection control in all health care settings.

The Risk of Tuberculosis in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor-α Antagonist: A Metaanalysis of Both Randomized Controlled Trials and Registry/Cohort Studies.

Tumor necrosis factor-α (TNF-α) antagonists have significantly improved treatment results in rheumatoid arthritis (RA), but have also increased the risk of tuberculosis (TB). Etanercept (ETN), adalimumab (ADA), infliximab (IFX), golimumab, and certolizumab pegol are the 5 drugs currently available on the market. This article aimed to evaluate the risk of TB infection from these 5 drugs for patients with RA. We searched PubMed, EMBASE, COCHRANE library, OVID, and EBSCO for randomized controlled trials (RCT) of TNF-α antagonist versus control and registry/longitudinal cohort studies of 1 TNF-α antagonist versus another. The Mantel-Haenszel test was adopted to analyze risk ratio (RR) in this metaanalysis. Fifty RCT and 13 non-RCT were included in this study. No significant difference in TB risk was found in the RCT because of the short observational periods. In the non-RCT, TNF-α antagonist was associated with a higher TB risk in patients with RA (RR 4.03, 95% CI 2.36-6.88), and the TB incidence rates of IFX and ADA were 2.78 and 3.88 times, respectively, higher than that of ETN. Further, preventive treatment for latent TB infection (LTBI) was shown to reduce the TB risk by 65% (RR 0.35, 95% CI 0.15-0.82). This study demonstrated a significant increase in TB risk in patients with RA treated with TNF-α antagonists; among them, ETN is least likely to cause active TB. The study also proposes the necessity of LTBI prophylaxis in patients with RA.

Year in review 2012: Lung cancer, respiratory infections, tuberculosis, pleural diseases, bronchoscopic intervention and imaging

This Year in Review series addresses the most relevant articles published in Respirology and other respiratory medicine journals during 2012 concerning five specific areas that we consider to be of importance to practicing pulmonologists, namely lung cancer, respiratory infections, tuberculosis (TB), pleural diseases, and interventional pulmonology and imaging. Some important findings that will be commented on more in depth are that: 1) screening for lung cancer using low-dose computed tomography (CT) in high risk populations is promising, although not firmly established, 2) an enhanced CURB (which stands for confusion, urea, respiratory rate, blood pressure) score as well as the Japanese A-DROP (age, dehydration, respiratory failure, orientation disturbance, and pressure) prognostic scale are as accurate as the pneumonia severity index (PSI) scoring system to predict mortality in patients with community-acquired pneumonia (CAP), 3) randomized trials are urgently needed to optimize multidrug-resistant (MDR)-TB treatment, 4) the use of video-assisted thoracoscopic surgery (VATS) to quantify pleural tumor burden and, if feasible, perform an intrathoracic cytoreduction in patients with malignant effusions secondary to ovarian cancer (OC) may have a significant impact on further patient management plans, and 5) respiratory endoscopy and its different diagnostic and therapeutic modalities, is a safe procedure with overall complication rates less than 1%.

Abdominal Pain and Weight Loss After Adalimumab Therapy

Question: A 70-year-old Spanish woman with a history of rheumatoid arthritis has been treated for 1 year with adalimumab 40 mg subcutaneously every 2 weeks, prednisone 10 mg orally daily, and methotrexate 10 mg orally every week. She was admitted owing to abdominal pain and severe weight loss of 2-month duration. Physical examination was remarkable for a temperature of 37.2°C and distended abdomen with marked mesogastric tenderness to palpation. Laboratory tests showed mild anemia (11.4 g/dL) and elevated sedimentation rate (120 mm), in addition to an elevation of serum CA 125 (584.40 IU/mL; normal range, 0–35). Contrast-enhanced computed tomography showed smooth and uniform thickening of peritoneum (Figures A and B, arrowheads) and ascitic fluid in the pelvic recesses. Screening test results for tuberculosis (TB) screening before adalimumab therapy (chest radiograph and tuberculin skin test [TST] with booster) were negative and the patient denied previous history or known exposure to TB. Repeat chest radiograph and TST, as well as interferon-gamma release assay, were negative for TB. What is the most likely diagnosis? Look on page 189 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Laparoscopy showed whitish miliary nodules on the peritoneum and small bowel (Figures C and D). Histopathologic examination revealed noncaseating epithelioid granulomas (Figure E; stain: H&E; original magnification, ×200), and mycobacteria were not identified by acid-fast bacillus staining. Although bacteriologic culture, auramine stain, and detection of DNA with polymerase chain reaction were negative for TB, empirical anti-TB treatment was started. Mycobacterium tuberculosis grew on culture 5 weeks later. Adalimumab was discontinued and anti-TB therapy was completed for 9 months. The risk of TB increases 5-fold after the use of anti–tumor necrosis factor (TNF)-α, especially in 3 groups1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar: (1) Patients with occupational exposure, such as healthcare workers, (2) patients native from Sub-Saharan Africa and Asia, where TB is endemic,2Mankia S. Peters J.E. Kang S. et al.Tuberculosis and anti-TNF treatment: experience of a central London Hospital.Clin Rheumatol. 2011; 30: 399-401Crossref PubMed Scopus (17) Google Scholar and (3) patients born in countries with high prevalence of latent TB infection (LTBI), principally Spain and Portugal.3Gomez-Reino J.J. Carmona L. Valverde V.R. et al.Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.Arthritis Rheum. 2003; 48: 2122Crossref PubMed Scopus (913) Google Scholar Additionally, the lack of utility of chest radiograph and TST to identify LTBI is demonstrated by growing cases of adalimumab-induced TB (most of them native from Spain or Asia) in immunosuppressed rheumatic patients after negative TB screening. As such, emerging recommendations balance the need for systematic TB chemoprophylaxis in high-risk, immunosuppressed patients on anti–TNF-α therapy.1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar Although this strategy seems rational in Asian or African immigrants <35 years old in their 4 first years after entry,1British Thoracic Society Standards of Care CommitteeBTS recommendations for assessing risk and for managing M. tuberculosis infection and disease in patients due to start anti-TNF-alpha treatment.Thorax. 2005; 60: 800-805Crossref PubMed Scopus (402) Google Scholar it remains to be proven cost effective for other groups. Furthermore, concomitant intake of azathioprine or methotrexate can increase the risk of hepatotoxicity. As indications for adalimumab use grow in inflammatory bowel disease, a careful epidemiologic and clinical history, beside TB screening at the very outset of the disease (inmmunosuppressant-naive state), combining TST and interferon-gamma release assay, are required to enhance the diagnosis of LTBI. Likewise, inactive inflammatory bowel disease on anti–TNF-α and either fever of unknown origin or atypical symptoms should lead to a diagnostic workup for TB. Negative results do not preclude TB, owing to its paucibacillary expression, and histopathology should be sought quickly. Of note, early concurrent anti-TB treatment should be started under TB suspicion until microbiological confirmation. The authors thank Dr Lucia Ferrando-Lamana, Department of Anatomic Pathology, Hospital San Pedro de Alcantara, Caceres, Spain, for providing the histopathology image and Dr Javier P. Gisbert, for his useful comments on this manuscript.

Tuberculosis risk factors and mortality for HIV-infected persons receiving antiretroviral therapy in South Africa

To determine important risk factors for and impact of tuberculosis on survival in HIV-infected patients starting antiretroviral therapy (ART) in South Africa. Prospective trial of 1771 HIV-infected patients with either CD4 cell count less than 200 cells/microl or a prior AIDS-defining illness, enrolled in randomized trial of four antiretroviral regimens. Data collected from patient records. A history of tuberculosis at study entry was reported by 27% of patients and correlated with poor baseline health status. A history of tuberculosis at baseline was associated with subsequent tuberculosis and death during ART, but was not itself an independent risk factor for poor outcome. Tuberculosis was diagnosed during ART in 14% of patients and was more frequent during the first 3 months. Tuberculosis during therapy was independently associated with increased hazard of other AIDS-defining events and death, regardless of when during ART tuberculosis occurred. ART that consistently suppressed circulating viremia reduced but did not eliminate tuberculosis risk. In HIV-infected patients who started ART at low CD4 cell counts, tuberculosis at baseline was a predictor of death, but was not independent of other factors indicating poor baseline health status. Tuberculosis during follow-up was, in contrast, an independent predictor of death even after adjustments for baseline risk factors, including CD4 cell count and viral load. Virologic failure during ART was associated with a 55% increase in risk of tuberculosis. Thus, tuberculosis is a major marker for poor outcome both at baseline and during ART and is not completely eliminated by fully suppressive ART.

Effects of duration of HIV infection and secondary tuberculosis transmission on tuberculosis incidence in the South African gold mines

HIV increases the risk of tuberculosis directly, through immunosuppression, and indirectly, through onward transmission of Mycobacterium tuberculosis from the increased caseload. We assess the contribution of these two mechanisms by time since seroconversion to HIV. The incidence of new pulmonary tuberculosis was estimated in a retrospective cohort study of South African gold miners over 14 years. HIV tests were done in random surveys in 1992-1993, and in clinics. One thousand nine hundred fifty HIV positive men with seroconversion intervals of less than 3 years were identified and linked to medical, demographic and occupational records. They were compared with men who were HIV-negative in a survey, with no later evidence of HIV. Analyses were censored when men were diagnosed with tuberculosis, died or left the mine. Tuberculosis incidence rose soon after HIV infection, reaching 1.4/100 person-years (95% confidence interval 1.1-1.9) within 2 years, and 10.0/100 person-years (95% confidence interval 6.5-15.5) at 10 or more years. By 11 years from seroconversion, nearly half the men had had tuberculosis. Among 5702 HIV-negative men, tuberculosis incidence was 0.48/100 person-years (95% confidence interval 0.33-0.70) in 1991-1993 and doubled over the period of the study (after adjusting for age). Age-adjusted model estimates suggest that half the increase in tuberculosis incidence by time since HIV infection was attributable to increasing incidence over calendar period--the indirect effect. For the first time, we have shown that the increase in tuberculosis risk by time since seroconversion reflects both direct effects of HIV increasing susceptibility, and indirect effects due to onward transmission. Innovative and sustained public health measures are needed to reduce Mycobacterium tuberculosis transmission.

Impact of lifestyle on tuberculosis

Abstract: Tuberculosis (TB) is well known to be associated with poverty and multiple social factors. However, relatively little attention has been paid to the behavioural factors, apart from those associated with drug abuse, alcoholism and HIV infection. In recent years, the roles of other lifestyle‐related factors have been increasingly recognized. In particular, smoking has been associated with excess risks of TB infection, disease and mortality. Only limited evidence is available for the association between TB disease and passive smoking or the use of biomass fuels. Nutrition status also plays an important role. Malnutrition or underweight is associated with increased risk of TB disease, and obesity appears to be protective. On the other hand, diabetes mellitus increases the risk of TB disease, but mainly among those with poor diabetic control. Although the increase in TB risk is only modest for most lifestyle factors, their prevalences are increasing rapidly in some Asian communities. Furthermore, as much as one‐third of the world population is thought to be latently infected with the tubercle bacillus. The successful introduction of directly observed therapy—short course (DOTS) might have rapidly reduced the ongoing risk of transmission in many parts of Asia. However DOTS alone is unlikely to eliminate the continuing emergence of infectious tuberculosis cases through endogenous reactivation among the large pool of latently infected subjects in the Asia–Pacific region. With the close interaction between lifestyle, aging population and aging TB epidemic, promotion of healthy lifestyle may help to complement the DOTS strategy in the control of TB.

Risk factors for bovine tuberculosis in New Zealand cattle farms and their relationship with possum control strategies

This paper reports the investigation of farm-level risk factors for confirmed bovine tuberculosis (TB), based on a retrospective cohort study of a population of cattle in the lower North Island of New Zealand. Data were obtained from the TB testing surveillance programme operational in this area since the mid-1970s and comprised 190,665 cattle-years at risk from July 1980 to June 2004 (inclusive). A mixed-effects Poisson regression model was used to investigate the influence of farm-level covariates on the number of cattle confirmed with TB throughout the study period. This model was interpreted in context of depopulation strategies for the wildlife reservoir for TB, the brushtail possum Trichosurus vulpecula, that were applied in this area. The model showed that, despite intensification of possum control strategies over time, proximity to forest parks (a principal possum habitat in this area) remained a significant predictor of the number of confirmed cases of TB detected per farm per year. Our analyses showed a significant, three-fold increase in TB risk in dairy cattle relative to beef conditional on the size of local possum habitat, and confirmed the positive influence of cattle population size and the presence of previous infection status as a determinant of the number of confirmed TB cases per farm per year.

Tumor Necrosis Factor Blockade: Mechanism of Action

Modulation of the immune response with tumor necrosis factor (TNF) blockers is not a new treatment strategy for many inflammatory disorders; however, relatively little is known about their specific mechanism of action. Understanding the mode of action, pharmacology, and pharmacokinetics of the monoclonal TNF antibodies, infliximab and adalimumab, and the soluble TNF receptor, etanercept, may therefore enable us to account for their differing clinical profiles. The aim of this supplement is to explore the roles and mechanisms of TNF and TNF blockade using in vitro pharmacological and in vivo animal modeling experiments, and in vivo studies of the effects of etanercept on the inflammatory cascade in patients with psoriasis.

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

Does bacille Calmette-Guérin scar size have implications for protection against tuberculosis or leprosy?

Setting: Total population study in Karonga District, northern Malawi, in which the overall vaccine efficacy of bacille Calmette-Guérin (BCG) has been found to be −7% against tuberculosis and 54% against leprosy. Objective: To examine the relationship between BCG scar size and protection against tuberculosis and leprosy. Design: Cohort study in which 85 134 individuals were screened for tuberculosis and 82 265 for leprosy between 1979 and 1984, and followed up between 1986 and 1989. Results: Of the BCG scar positive individuals whose scars were measured, 31 3 2471 were later identified with tuberculosis and 81 31 879 with leprosy. In 19 114 individuals, of whom 17 developed tuberculosis, tuberculin induration was measured at first examination. Mean scar sizes increased with increasing tuberculin induration in all except the oldest individuals. Mean scar sizes were lowest in individuals aged < 10 years, highest in individuals aged 10–29 years and intermediate in older individuals. There was some evidence ( P = 0.08) for an increase in tuberculosis risk with increasing scar size, which probably reflects the known correlation between scar size and tuberculin status at the time of vaccination. There was no clear association between BCG scar size and leprosy incidence. Conclusions: We find no evidence that increased BCG scar size is a correlate of vaccine-induced protective immunity against either tuberculosis or leprosy.