Tuberculosis report among injection drug users and their partners in Kazakhstan.

OBJECTIVES: Tuberculosis (TB) is a major threat to global public health. Kazakhstan has the second highest percentage of multidrug-resistant tuberculosis (MDR-TB) cases among incident tuberculosis cases in the world (WHO 2013). A high burden of MDR-TB suggests TB prevention, control, and treatment programs are failing. This study provides an epidemiologic profile of TB among injection drug users (IDUs), a high-risk and chronically underserved population, in Kazakhstan. STUDY DESIGN: Cross-sectional study. METHODS: The authors studied the characteristics and risk environment of IDUs with self-reported previous active TB and their primary sexual partners in Almaty, Kazakhstan. 728 individuals (364 couples) participated in a couple-based study in 2009. RESULTS: 16.75% of participants reported at least one positive TB test (x-ray) in their lifetime. In a multivariable logistic regression adjusting for couple-based sampling, persons with positive TB test were significantly more likely to be older (odds ratio (OR) 7.26, 95% confidence interval (CI): 1.73, 30.43), male (OR 5.53, 95% CI: 2.74, 11.16), have a shorter duration of injection drug use (OR 0.17, 95% CI: 0.04, 0.65), have received high social support from their significant other (OR 2.13, 95% CI: 1.03, 4.40) and more likely (non-significantly) to have been incarcerated (OR 7.03, 95% CI: 0.64, 77.30). CONCLUSIONS: Older men with a history of incarceration and recent injection drug use were more likely to have positive TB test in Kazakhstan. Social network support, while potentially positive for many aspects of population health, may increase risk of TB among IDUs in this context. Public health policies that target high-risk populations and their at-risk networks may be necessary to stem the rise of MDR-TB in Central Asia.

Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report.

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Strategic response to COVID-19 in Ethiopia.

COVID-19, the novel coronavirus, has posed a major threat to low- and middle-income countries (LMICs) due to inadequate health infrastructure and human resources. Ethiopia, a low-income country with the second largest population in Africa, has coordinated a strategic response, leveraging existing infrastructure and health systems and mobilizing public health professionals and specialist expert physicians for a multifaceted, unified government approach and adaptive response. Resource limitations, particularly in critical care, have still posed challenges, but the public health and clinical interventions thus far have prevented the catastrophic toll that many predicted. As the pandemic continues, Ethiopia expects to use a triple care model integrated at all levels, consisting of COVID-19 care, isolation care for suspected cases, and essential health services, and urges intensified non-pharmaceutical interventions alongside equitable global vaccine distribution as the ultimate answers to pandemic control. This paper draws on existing data, national planning and guidelines, and expertise from health leadership to describe this response in hopes of providing an example of how future large-scale health challenges might be faced in LMICs, using Ethiopia's successes and challenges in facing the pandemic.

COVID-19, le nouveau coronavirus, a représenté une menace majeure pour les pays à revenu faible et intermédiaire (LMIC) en raison de l'insuffisance des infrastructures de santé et des ressources humaines. L'Éthiopie, un pays à faible revenu dont la population est la deuxième plus importante d'Afrique, a coordonné une réponse stratégique, en tirant parti des infrastructures et des systèmes de santé existants et en mobilisant des professionnels de la santé publique et des médecins experts spécialisés pour une approche gouvernementale unifiée à multiples facettes et une réponse adaptative. Les ressources limitées, notamment en matière de soins intensifs, ont encore posé des problèmes, mais les interventions cliniques et de santé publique menées jusqu'à présent ont permis d'éviter le bilan catastrophique que beaucoup prédisaient. Alors que la pandémie se poursuit, l'Éthiopie prévoit d'utiliser un modèle de soins triple intégré à tous les niveaux, composé de soins COVID-19, de soins d'isolement pour les cas suspects et de services de santé essentiels, et préconise l'intensification des interventions non pharmaceutiques parallèlement à une distribution équitable des vaccins à l'échelle mondiale comme réponses ultimes au contrôle de la pandémie. Cet article s'appuie sur les données existantes, la planification et les directives nationales, et l'expertise des responsables de la santé pour décrire cette réponse dans l'espoir de fournir un exemple de la manière dont les futurs défis sanitaires à grande échelle pourraient être relevés dans les LMIC, en utilisant les succès et les défis de l'Éthiopie face à la pandémie.

Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis.

Tuberculosis following solid organ transplantation.

BACKGROUND: Organ transplantation places patients at risk for tuberculosis (TB), which constitutes a challenge to physicians due to its atypical and extrapulmonary presentations, complicated treatment issues, and high morbidity and mortality. METHODS: We identified all patients with TB following solid organ transplantation at a large university medical center in New York. Demographic data, transplant characteristics (type of organ and donor), underlying medical conditions, immunosuppressive drugs, rejection and opportunistic infections were analyzed, and a nested case-control study was performed to identify factors associated with the development of TB. RESULTS: From 1988 to 2007, 4925 transplants were performed at Columbia University Medical Center: 1858 kidney, 857 liver, 1714 heart, 460 lung, and 36 heart/lung. Thirteen patients developed TB, for a cumulative incidence of 264/100,000. Of the 13 patients who developed TB, 10 had a kidney transplant, 2 had a lung transplant, and 1 had a heart transplant. The median time to develop TB was 11.2 (interquartile ratio: 4.4-23.0) months following transplantation. These cases were compared with 52 randomly selected control patients who had transplants not complicated by TB. Patients with TB were more likely to be renal transplant recipients (adjusted odds ratio [OR]: 4.59; 95% confidence interval [CI]: 1.07-19.67) and to be non-Caucasians (adjusted OR: 3.94; 95% CI: 0.99-15.56) than controls. CONCLUSIONS: The incidence of TB in post-transplant patients is much higher than the overall background incidence in the United States. Non-Caucasian and kidney transplant recipients appear to be at increased risk of developing TB. This may be associated with prior exposure to TB before transplant in these populations.

The value of end-of-treatment chest radiograph in predicting pulmonary tuberculosis relapse.

SETTING: Patients with cavitary pulmonary tuberculosis (TB) on baseline chest radiograph (CXR) who remain culture-positive after 8 weeks of treatment are at high risk of relapse. The role of end-of-treatment (EOT) CXR in predicting relapse is unclear. OBJECTIVE: To determine whether EOT CXR independently predicts TB relapse. DESIGN: We conducted a secondary analysis of a randomized trial of intermittent treatment using rifapentine in the continuation phase of TB treatment among 1004 human immunodeficiency virus seronegative adults with culture-proven pulmonary TB. RESULTS: Relapse occurred in 17.3% of subjects with persistent cavity on EOT CXR, in 7.6% of subjects with a cavity that resolved by EOT, and 2.5% (P=0.002 for trend) of subjects who never had a cavity. In multivariable analysis, patients with persistent cavity on EOT CXR were significantly more likely to relapse than patients with no cavity on baseline or 2-month CXR (hazard ratio [HR] 4.22, 95%CI 2.00-8.91), and were more likely to relapse than subjects whose early cavity had resolved by EOT CXR (HR 1.92, 95%CI 1.09-3.39). CONCLUSION: A persistent cavity after 6 months of TB treatment was independently associated with disease relapse after controlling for other variables. EOT CXR may help predict those likely to relapse.

Early responses to infection: chemokines as mediators of inflammation.

Chemokines are a superfamily of small related protein molecules that are secreted by a variety of cells and that have, among their diverse biological properties, the ability to recruit a wide range of immune cells to the sites of infection and disease. Chemokines are secreted in response to bacterial, viral, parasitic, and mycobacterial pathogens. Our recent progress in understanding the patterns of chemokine secretion in response to various pathogens and their impact on disease manifestations is likely to lead to the development of novel therapeutic approaches for a variety of serious infections.

Risks for tuberculosis in Kazakhstan: implications for prevention.

SETTING: Four regions in Kazakhstan where participants were recruited from June 2012 to May 2014. OBJECTIVE: To examine associations between incarceration history and tobacco, alcohol, and drug consumption, and human immunodeficiency virus (HIV) infection and diabetes mellitus (DM) with TB. DESIGN: This matched case-control study included 1600 participants who completed a survey on sociodemographics, history of incarceration, tobacco, alcohol and drug use, and HIV and DM diagnosis. Conditional logistic regression analysis was used to examine associations between a TB diagnosis and risk factors. RESULTS: Participants who had ever smoked tobacco (aOR 1.73, 95%CI 1.23-2.43, P  0.01), ever drank alcohol (aOR 1.41, 95%CI 1.03-1.93, P  0.05), were HIV-positive (aOR 36.37, 95%CI 2.05-646.13, P  0.05) or had DM (aOR 13.96, 95%CI 6.37-30.56, P  0.01) were more likely to have TB. CONCLUSIONS: The association between TB and tobacco use, alcohol use, HIV and DM in Kazakhstan suggests a need for comprehensive intervention and prevention approaches that also address tobacco and alcohol use, DM and HIV.

Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors.

SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population.

Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.

In 2013, 86% of patients with newly diagnosed tuberculosis (TB) successfully completed treatment and were discharged from care. However, long-term studies in industrialised and resource-poor countries all point to a higher risk of death in TB survivors than in the general population. The likely explanation is chronic restrictive and obstructive lung disease consequent to TB. We call for better linkages between TB control programmes and respiratory medicine services, a better understanding of the burden of respiratory disability at the end of anti-tuberculosis treatment, and political, programmatic, clinical and research action to improve the quality of life of affected patients.

Transmission trends for human immunodeficiency virus associated tuberculosis in New York City.

SETTING: Since 1992, tuberculosis (TB) control measures have reduced incidence rates in New York City and elsewhere. Nevertheless, trends have not been uniform in all demographic groups. OBJECTIVE: To characterize the epidemiology of human immunodeficiency virus (HIV) associated TB in New York during the 1990s, we analyzed social, demographic and clinical characteristics and genetic data on Mycobacterium tuberculosis isolates among persons with known HIV-status. DESIGN: A retrospective case-control study to compare patients with HIV-associated TB and patients with TB alone. RESULTS: Of 546 patients (70.5%) in the Department of Health Tuberculosis Control Registry treated for TB, 385 also had documented HIV status; 198 were HIV-infected (51%) and 187 (49%) were not. Genotype analysis of the 385 M. tuberculosis isolates identified 200 (52%) clustered strains, representing recent transmission. Although the overall percentage of TB cases associated with restriction fragment length polymorphism (RFLP) clustering fell over the period studied, HIV-associated cases were still much more likely to be associated with clustering than non-HIV-associated cases. CONCLUSIONS: Continued attention is required to contain the spread of TB in this vulnerable population.

DOT and timely treatment completion among Asian-born immigrant tuberculosis patients.

SETTING: A large urban tuberculosis (TB) control program. OBJECTIVES: To identify factors associated with directly observed therapy (DOT) participation and to quantify how early use of DOT affected treatment duration. DESIGN: A retrospective study of 731 Asian-born patients with drug-susceptible Mycobacterium tuberculosis isolates who were verified in New York City between 1993 and 1997 and completed treatment. RESULTS: Overall, 297 (41%) of 731 patients in the study participated in DOT for some or all of their TB treatment. DOT participation was significantly associated with TB disease in a pulmonary site (adjusted odds ratio [aOR] 2.85, 95% CI 1.86-4.35), more recent year of diagnosis (aOR 1.70, 95% CI 1.50-1.94) and male sex (aOR 1.86, 95% CI 1.30-2.66). Patients who received > or = 70% of their TB treatment at a health department chest clinic were also significantly more likely to participate in DOT (aOR 3.83, 95% CI 2.55-5.74). Among 297 DOT patients, those who completed treatment by 9 months received a greater amount of treatment by DOT during the first 4 months of treatment than those who took longer to complete treatment. CONCLUSION: Earlier DOT participation can lead to overall shorter treatment duration. Health care providers should encourage TB patients to participate in DOT as early as possible in their TB treatment.

Clinical utility of the polymerase chain reaction in the diagnosis of infections due to Mycobacterium tuberculosis.

OBJECTIVE: To evaluate the clinical utility of the polymerase chain reaction (PCR) in the diagnosis of infections due to Mycobacterium tuberculosis. DESIGN: Clinical specimens were assayed by PCR for the presence of the insertion element IS6110, a DNA sequence unique to the M tuberculosis complex of organisms. The PCR results were then correlated with acid-fast bacilli (AFB) smears, cultures, pathology, and clinical histories. SETTING: Bellevue Hospital, a large municipal teaching hospital. PATIENTS: Inpatients on the Bellevue Chest Service. MEASUREMENTS AND RESULTS: Sixty-five patients were evaluated. The PCR for M tuberculosis was positive in 37 patients and negative in 28. When correlated with smears, cultures, pathology, and clinical history, the sensitivity of PCR for a diagnosis of active tuberculosis (TB) was 100 percent. However, the specificity for a diagnosis of active TB was only 70 percent, as the PCR assay was positive in a number of patients with only prior, treated TB, or asymptomatic tuberculous infection. For a diagnosis of any TB infection (active, treated, or asymptomatic), sensitivity of PCR was 87.5 percent and specificity was 90 percent. CONCLUSIONS: The PCR assay for TB is extremely sensitive, but it lacks specificity for a diagnosis of active TB. Its role in clinical practice will likely be limited to well-defined situations, such as HIV-positive patients with intrathoracic adenopathy, and it may be most useful in excluding active TB from consideration in selected patients. Given the cost of the assay and the labor intensity it requires, it should not be part of the routine initial evaluation of patients with suspected pulmonary TB.

Screening by specialists to reduce unnecessary test ordering in patients evaluated for tuberculosis.

STUDY OBJECTIVE: To determine if screening by specialists could reduce unnecessary test ordering and reduce costs related to diagnostic workup in patients undergoing evaluation for tuberculosis. DESIGN: Prospective evaluation of expert opinion in consecutive patients suspected of having tuberculosis. SETTING: A large municipal hospital. PATIENTS: Patients for whom sputum acid-fast smears were ordered. INTERVENTION: For patients from whom sputum acid-fast bacilli smears and cultures were requested, the chest radiograph and a brief clinical history were presented separately to two pulmonologists with considerable experience in tuberculosis. Each expert reviewed each case independently (and was blinded to the opinion of the other) and indicated if he thought sputum smear examination and culture was, in fact, necessary. Final clinical diagnosis and microbiological information were correlated with the experts' opinion. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients had sputum smears ordered and had chest radiographs available for review. The two experts believed that sputum examination (smear and culture) was indicated in only 51.5% and 52.6% of cases, respectively. Interobserver agreement was 84.4%. Ultimately, six cases of active tuberculosis were diagnosed. Each expert detected all proven cases of tuberculosis, although one case occurred in a patient with a poor quality radiograph about which the experts offered no opinion. CONCLUSIONS: Screening by experienced clinicians may be effective in reducing unnecessary test ordering and reducing costs related to diagnostic workup in patients evaluated for tuberculosis.

DNA fingerprints from Mycobacterium tuberculosis isolates of patients confined for therapy noncompliance show frequent clustering.

STUDY OBJECTIVE: To test the hypothesis that individuals chronically noncompliant with antituberculous chemotherapy are vectors for ongoing transmission of the disease in the community. DESIGN: Cohort study. SETTING: A large public hospital with a tuberculosis detention unit for patients with repeated and prolonged nonadherence to therapy. PATIENTS: Mycobacterium tuberculosis isolates from patients confined on the detention unit were obtained from the hospital's mycobacteriology laboratory. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A standardized IS6110-based Southern blot hybridization protocol was used to genotype M tuberculosis isolates recovered from patients confined on the detention unit at the hospital. Each DNA fingerprint pattern was compared with the IS6110-fingerprint database at the Public Health Research Institute Tuberculosis Center, which has archived fingerprint patterns from over 2,500 M tuberculosis isolates collected from New York City patients in the past 5 years. Eighty percent of available isolates from detained patients belonged to an identifiable DNA fingerprint cluster, suggesting an epidemiologic link between the detainees and other New York City tuberculosis patients. CONCLUSIONS: Chronic noncompliance with therapy is associated with ongoing spread of tuberculosis in the community. Aggressive measures, including detention, for the small number of recalcitrant, noncompliant patients may interrupt a chain of transmission and contribute to a decline in the spread of tuberculosis in urban areas.

Time to detection of Mycobacterium tuberculosis in sputum culture correlates with outcome in patients receiving treatment for pulmonary tuberculosis.

STUDY OBJECTIVE: The purpose of this study was to determine whether the time to detection (TTD) of Mycobacterium tuberculosis in sputum culture correlates with the response to antituberculous treatment in patients with pulmonary tuberculosis. STUDY DESIGN: Twenty-six consecutive patients were studied who had active pulmonary tuberculosis and sufficient sputum cultures and clinical follow-up to allow adequate assessment. RESULTS: Following initiation of antituberculous therapy, 13 patients (group 1, responders) had a complete response to treatment, and the TTD of M tuberculosis using the mycobacterial growth indicator tube increased steadily. The remaining 13 patients (group 2, nonresponders) had persistent evidence of active disease and demonstrated little or no increase in the TTD with treatment unless an additional therapeutic intervention was implemented (surgery, improved compliance with medications, or a change in medications). The presence of HIV infection, intravenous drug use, multidrug resistance, treatment with second-line therapy, extensive radiographic involvement, and cavitary disease were associated with a delayed increase in the TTD. CONCLUSIONS: The TTD was superior to clinical, radiographic, or conventional bacteriologic evaluation in determining treatment outcome. The TTD closely correlates with the overall response to treatment for pulmonary tuberculosis and may represent a useful adjunct to predict outcome in these patients.

Tuberculosis and HIV infection: epidemiology, immunology, and treatment.

Tuberculosis and HIV have combined to present a major threat to global public health. Each disease has a negative effect on the other, and mortality in patients with both tuberculosis and HIV is higher than that caused by either condition alone. In regions such as sub-Saharan Africa, as many as a third or more of all patients with tuberculosis have concomitant HIV infection. In urban centers in developed nations, HIV co-infection may also be quite common. Treatment of latent tuberculosis infection in persons with HIV is successful in preventing many cases of active disease, and newer ultra-short course regimens, such as those consisting of 2 months of rifampin and pyrazinamide, should aid in this effort. Diagnosis and treatment of active tuberculosis in HIV-infected patients may be difficult. Although treatment of active tuberculosis is generally successful in patients with HIV, drug interactions between anti-tuberculosis medications and antiretrovirals often complicate the matter, and expert guidance should be sought for proper management.

Cytokine-based approaches to the treatment of multidrug-resistant tuberculosis.

The most disturbing aspect of the current epidemic of tuberculosis (TB) is the appearance of large numbers of strains of Mycobacterium tuberculosis that are resistant to one or more of the first-line agents used to treat the disease. Mortality associated with a multidrug-resistant strain of tuberculosis (MDR-TB) infection is reported to be extremely high, in many cases no different from the mortality of tuberculosis in the pre-antibiotic era. Infection control measures have limited the spread of MDR-TB. However, many outbreaks over the last several years have created a large reservoir of MDR-TB infection. In order to treat the cases of MDR-TB that are occurring now and which will undoubtedly occur in the future, new approaches to treatment will be needed. Recent research into the immunopathogenesis of tuberculosis has provided insight into the important constituents of the host immune system needed to control the infection in vivo. These elements include CD4+ and CD8+ T cells as well as cytokines such as interferon gamma (IFNgamma), interleukin-12 (IL-12), and tumour necrosis factor (TNF). IL-2, IFNgamma and M. vaccae vaccination have all shown promising effects in small preliminary studies. Evidence suggests that TNF antagonists and IL-12 may also prove useful in the treatment of drug-susceptible TB and MDR-TB. Further studies are needed to determine the precise role of these recombinant proteins in the treatment of TB.