Leonid Lecca

Tuberculosis and chronic respiratory disease: a systematic review.

BACKGROUND Chronic respiratory disease causes substantial global morbidity and mortality. The contribution of pulmonary tuberculosis to the aetiology of chronic respiratory disease is rarely considered, but may be important in tuberculosis-endemic areas. METHODS We performed a systematic literature review to assess the association between a history of tuberculosis and the presence of chronic obstructive pulmonary disease (COPD) or chronic suppurative lung disease (bronchiectasis). Study quality was evaluated using the National Heart Lung and Blood Institute quality assessment tool. Meta-analysis was performed using the DerSimonian and Laird random effects model. RESULTS We identified 9 eligible studies for COPD and 2 for bronchiectasis. Overall, there was a significant association between a history of tuberculosis and the presence of COPD in adults aged over 40 years (pooled odds ratio 3.05 (95% confidence interval 2.42, 3.85). Among individual COPD studies the strongest associations were found in countries with a high incidence of tuberculosis, as well as among never smokers and younger people. CONCLUSION In tuberculosis endemic areas, tuberculosis is strongly associated with the presence of chronic respiratory disease in adults. Efforts to improve long-term lung health should be part of tuberculosis care.

The Effect of HIV-Related Immunosuppression on the Risk of Tuberculosis Transmission to Household Contacts

BACKGROUND Coinfection with human immunodeficiency virus (HIV) may modify the risk of transmitting tuberculosis. Some previous investigations suggest that patients coinfected with HIV and tuberculosis are less likely to transmit infection, whereas others do not support this conclusion. Here, we estimated the relative risk of tuberculosis transmission from coinfected patients compared to HIV-negative patients with tuberculosis. METHODS Between September 2009 and August 2012, we identified and enrolled 4841 household contacts of 1608 patients with drug-sensitive tuberculosis in Lima, Peru. We assessed the HIV status and CD4 counts of index patients, as well as other risk factors for infection specific to the index patient, the household, and the exposed individuals. Contacts underwent tuberculin skin testing to determine tuberculosis infection status. RESULTS After adjusting for covariates, we found that household contacts of HIV-infected tuberculosis patients with a CD4 count ≤250 cells/µL were less likely to be infected with tuberculosis (risk ratio = 0.49 [95% confidence interval, .24-.96]) than the contacts of HIV-negative tuberculosis patients. No children younger than 15 years who were exposed to HIV-positive patients with a CD4 count ≤250 cells/µL were infected with tuberculosis, compared to 22% of those exposed to non-HIV-infected patients. There was no significant difference in the risk of infection between contacts of HIV-infected index patients with CD4 counts >250 cells/µL and contacts of index patients who were not HIV-infected. CONCLUSIONS We found a reduced risk of tuberculosis infection among the household contacts of patients with active tuberculosis who had advanced HIV-related immunosuppression, suggesting reduced transmission from these index patients.

Adaptation of a web-based, open source electronic medical record system platform to support a large study of tuberculosis epidemiology.

BackgroundIn 2006, we were funded by the US National Institutes of Health to implement a study of tuberculosis epidemiology in Peru. The study required a secure information system to manage data from a target goal of 16,000 subjects who needed to be followed for at least one year. With previous experience in the development and deployment of web-based medical record systems for TB treatment in Peru, we chose to use the OpenMRS open source electronic medical record system platform to develop the study information system. Supported by a core technical and management team and a large and growing worldwide community, OpenMRS is now being used in more than 40 developing countries. We adapted the OpenMRS platform to better support foreign languages. We added a new module to support double data entry, linkage to an existing laboratory information system, automatic upload of GPS data from handheld devices, and better security and auditing of data changes. We added new reports for study managers, and developed data extraction tools for research staff and statisticians. Further adaptation to handle direct entry of laboratory data occurred after the study was launched.ResultsData collection in the OpenMRS system began in September 2009. By August 2011 a total of 9,256 participants had been enrolled, 102,274 forms and 13,829 laboratory results had been entered, and there were 208 users. The system is now entirely supported by the Peruvian study staff and programmers.ConclusionsThe information system served the study objectives well despite requiring some significant adaptations mid-stream. OpenMRS has more tools and capabilities than it did in 2008, and requires less adaptations for future projects. OpenMRS can be an effective research data system in resource poor environments, especially for organizations using or considering it for clinical care as well as research.

Bacillus Calmette-Guérin and Isoniazid Preventive Therapy Protect Contacts of Patients with Tuberculosis

RATIONALE Individuals living with patients with tuberculosis (TB) are at elevated risk of infection and disease, with children at greatest risk. The World Health Organization recommends isoniazid preventive therapy (IPT) for HIV-positive contacts and those younger than 5 years. Despite these recommendations, household-level IPT programs are rarely implemented in high TB burden settings. Evidence is scarce about the age-specific efficacy of interventions, such as IPT and bacillus Calmette-Guérin (BCG) vaccination for preventing TB disease among exposed contacts. OBJECTIVES We estimate the age-specific efficacy of IPT and BCG for preventing TB disease using data from a large observational prospective cohort study of household contacts of patients with TB in Lima, Peru. METHODS We identified all adults (>15 yr) with incident pulmonary TB (index cases) diagnosed at 106 public health centers in Lima from September 2009 to August 2012. Among 14,041 household contacts (of 3,446 index cases) assessed for infection and disease during the year-long follow-up period, we identified 462 additional TB cases. We estimate risk ratios (RR) for pulmonary TB associated with BCG, IPT, and latent TB infection. MEASUREMENTS AND MAIN RESULTS BCG confers protection against coprevalent and incident TB among HIV-negative children younger than 10 years (RR, 0.35; 95% confidence interval, 0.19-0.66). IPT confers protection against incident TB among HIV-negative contacts younger than 30 years (RR, 0.33; 95% confidence interval, 0.20-0.54). Risk of incident TB associated with latent TB infection is greatest for children younger than 5 years and decreases with age. CONCLUSIONS These findings support the use of IPT in older children and young-adult household contacts, in addition to children younger than 5 years.

A cross sectional study of knowledge and attitudes towards tuberculosis amongst front-line tuberculosis personnel in high burden areas of Lima, Peru.

Introduction Tuberculosis, reported as the second most common infectious cause of death worldwide, is a key mortality contributor in developing countries and globally. The disease is endemic in Peru and while relative success was achieved during the 1990s in its control, this slowed as new complications, such as multi drug resistant TB arose. Health centre workers participating in the national DOTS program, create the front-line TB work-force in Peru meaning their knowledge and attitudes about the disease are key in its control. Methods A Spanish language, multiple choice knowledge and attitudes survey was designed based on previous successful studies and the national Peruvian TB control guidelines. It was applied to two health networks in Lima, Peru amongst 301health workers participating in the national TB control program from 66 different health centres. The study results were analysed to test mean knowledge scores amongst different groups, overall gaps in key areas of TB treatment and control knowledge, and attitudes towards the disease and the national TB control program. Results A mean knowledge score of 10.1 (+/- 1.7) out of 15 or 67.3% correct was shown. Demographics shown to have an effect on knowledge score were age and level of education. Major knowledge gaps were noted primarily in themes relating to treatment and diagnostics. Greater community involvement including better patient education about TB was seen as important in implementing the national TB control program. Participants were in disagreement about the current distribution of health resources throughout the study area. Discussion Serious knowledge gaps were identified from the survey; these reflect findings from a previous study in Lima and other studies from TB endemic areas throughout the world. Understanding these gaps and observations made by front-line TB workers in Lima may help to improve the national TB control program and other control efforts globally.

Cigarette smoking among tuberculosis patients increases risk of transmission to child contacts.

SETTING Observational cohort study in Lima, Peru. OBJECTIVE To determine the association between exposure to a smoking tuberculosis (TB) case and latent tuberculous infection (LTBI). METHOD Between September 2009 and August 2012, we identified 2132 patients with drug-susceptible TB and their 2054 child household contacts. Data were collected on active and secondhand smoking status and other risk factors for infection specific to the index case, the household and the exposed contacts. Contacts underwent a tuberculin skin test (TST) to determine their tuberculous infection status at baseline, 6-month and 12-month follow-up. We estimated the association between exposure to a smoking index case and LTBI using a modified Poisson regression model. RESULTS The 21 children (age ⩿15 years) exposed to smoking index TB patients were more likely to be TST-positive at baseline (RR 2.64, 95%CI 1.78-3.91), by 6 months (RR 1.91, 95%CI 1.40-2.60) and by 12 months (RR 1.48, 95%CI 1.07-2.06), than those who were not exposed. TST positivity among children at these time points did not vary with secondhand smoke exposure. CONCLUSIONS TB patients who smoke may be more likely to transmit infection to their contacts. Interventions designed to reduce smoking among TB patients may minimise further spread of the disease.

Impact of Vitamin A and Carotenoids on the Risk of Tuberculosis Progression

Key Points Vitamin A deficiency was associated with a 10-fold increase in risk of developing TB disease after household exposure. Vitamin A supplementation among high risk individuals might represent an effective means of preventing progression from TB infection to TB disease.

Modifiable factors associated with tuberculosis disease in children: a case-control study.

We conducted a case-control study among children in Lima, Peru to identify factors associated with tuberculosis disease. Known close contact with someone with tuberculosis disease, prior hospitalization, and history of anemia were associated with a higher tuberculosis disease rate. Consumption of fruits/vegetables ≥5 days/week was associated with a lower rate. Isoniazid uptake was low among children with a known contact.

Age-Specific Risks of Tuberculosis Infection From Household and Community Exposures and Opportunities for Interventions in a High-Burden Setting

We analyzed data from a large population-based prospective cohort study of household contacts of tuberculosis patients in Lima, Peru, to estimate the importance of within-household transmission relative to community-based transmission. We identified all adults (older than 15 years of age) who had incident pulmonary tuberculosis diagnosed at any of 106 public health centers in Lima from September 2009 to August 2012. A total of 14,041 household contacts of 3,446 index patients were assessed for tuberculosis infection and disease. We compared the prevalence of latent tuberculosis infection (LTBI) among persons who had received the Bacillus Calmette-Guérin vaccine in households with and without a microbiologically confirmed index case to estimate the age-specific risk of infection and excess risk of LTBI from household and community exposures. We found that the risk of infection from household and community sources increased from birth until 20 years of age. However, a large proportion of infections among child and young-adult household contacts could have been the result of household exposure. Excess infection risk associated with household exposure accounted for 58% (95% confidence interval: 47, 66) of LTBI prevalence among exposed children younger than 1 year of age, 48% (95% confidence interval: 39, 57) among 10-year-old children, and 44% (95% confidence interval: 34, 51) among 15-year-old adolescents. These findings suggest that expanded access to preventive therapy for older children and young-adult household contacts of known tuberculosis cases may be beneficial.

Pharmacokinetic Evidence from the HIRIF Trial To Support Increased Doses of Rifampin for Tuberculosis

ABSTRACT Rifamycins exhibit concentration-dependent killing of Mycobacterium tuberculosis; higher exposures potentially induce better outcomes. We randomized 180 tuberculosis patients in Peru to receive rifampin at 10, 15, or 20 mg/kg/day. A total of 168 had noncompartmental pharmacokinetic analyses; 67% were sampled twice, and 33% were sampled six times. The doses administered were well tolerated. The median area under the concentration-time curve from 0 to 6 h (interquartile range) was 24.9 (17.6 to 32.1), 43.1 (30.3 to 57.5), or 55.5 (35.7 to 73.2) h · μg/ml. The median maximum drug concentration in serum in the experimental arms reached the target of 8 μg/ml. Continued investigation of higher rifampin doses is warranted. (This study has been registered at ClinicalTrials.gov under registration no. NCT01408914.)