Health in Persons Deprived of Their Liberty in South America: A Painful Reflection of Our Public Health.

Objectives: To describe sociodemographic characteristics and health-related data in persons deprived of liberty (PDL) from South America in the last five years. Methods: Documentary descriptive study. Results: There are 1.5 million PDL in Latin America and the Caribbean; the average overcrowding is 64%; 58% do not sleep in beds, 20% do not have access to clean water and 29% do not receive medical care. In Peru, during 2021, there were 87,245 PDL and 69 penal institutions. The national average overcrowding is 120%, the second-highest in South America. In South America, the prevalence of tuberculosis is 2.0% SD = 0.64 and the median of illegal substances prevalence is 34.6 (IQR = 7.5-41.4). In Peru, the prevalence of tuberculosis has decreased since 2016 (4.3%), 2018(3.5%), and 2021(2.5%). Among the health problems by country, there were more data on substance use: 8/10, and tuberculosis, 7/10 countries. Cardiovascular diseases had the least available data. Regarding COVID-19, during the first wave in Peru, 54% of the total PPL were infected, and by the end of the wave, 446 PDL and 46 members of the prison staff had died. In Colombia, between April and October 2020, there were 16,804 cases (80 in ICU) and 136 deaths. In Brazil, up to March 2021, 340 people had died, and there were over 67,000 infections. Conclusions: Overcrowding is an unresolved problem; tuberculosis and substance use are the most frequent issues. Data are limited in quality, homogeneity and availability. Greater effort is needed from health authorities to improve health management and information systematization. Source: MesH.

Prevalence of pulmonary tuberculosis and HIV infections and risk factors associated to tuberculosis in detained persons in Antananarivo, Madagascar.

The incidence rate of tuberculosis in prisons is estimated to be 8 times greater than that in the general population in Madagascar. Our objectives were to estimate the prevalence of pulmonary tuberculosis and HIV infection among prisoners and to identify risk factors associated with tuberculosis. We conducted a cross-sectional study at the central prison of Antananarivo from March to July 2021. Individual male and female inmates aged ≥ 13 years who had lived in the prison for at least three months prior to the study period were included as participants. Acid-fast bacilli detection by microscopy and/or culture, an intradermal tuberculin test, a chest X-ray, and a rapid diagnostic orientation test for HIV were performed. Among 748 participants, 4 (0.5%) were confirmed to have pulmonary tuberculosis. Overall, 14 (1.9%) patients had "confirmed" or "probable" tuberculosis [0.90-2.84, 95% CI]. The proportion of participants with latent tuberculosis infection was 69.6% (517/743) based on a positive tuberculin test without clinical symptoms or radiography images indicating tuberculosis. Out of 745 HIV screening tests, three showed reactive results (0.4%). Age (OR = 4.4, 95% CI [1.4-14.0]) and prior tuberculosis treatment (or episodes) were found to be associated with confirmed and probable tuberculosis.

Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation.

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention.

Predictors of quality of life of TB/HIV co-infected patients in the Northern region of Ghana.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-morbidity continues to be a serious worldwide health issue, particularly in Sub-Saharan Africa. Studies on the quality of life (QOL) of TB/HIV co-infected patients guide stakeholders on the delivery of patient-centred healthcare. This study evaluated QOL of TB/HIV co-infected individuals and its contributing factors. METHODS: We conducted a cross-sectional study among TB/HIV co-infected patients, receiving treatment at clinics in the Northern Region of Ghana. Simple random sampling technique was used to select 213 patients from 32 clinics. We gathered information on patients' QOL using the World Health Organization QOL-HIV BREF assessment tool. At a 5% level of significance, multiple logistic regression analyses were carried out to find correlates of QOL among the patients. RESULTS: The mean age of the patients was (38.99 ± 14.00) years with most, 33.3% (71/213) aged 30-39 years. Males constituted 54.9% (117/213). About 30.0% (64/213) of the patients reported a good QOL. Being employed (aOR = 5.23, 95% CI: 1.87 - 14.60), and adhering to treatment (aOR = 6.36, 95% CI: 1.51 - 26.65) were significantly associated with a good QOL. Being depressed (aOR = 0.02, 95% CI: 0.03 - 0.29), stigmatized (aOR = 0.31, 95% CI : 0.11 - 0.84), and not exercising (aOR = 0.28, 95% CI: 0.12 - 0.67) were negatively associated with a good QOL. CONCLUSION: Less than one-third of TB/HIV co-infected patients in the region have good QOL. To guarantee good QOL, modifiable predictors such as patients' physical activity and medication adherence should be targeted by the National AIDS and TB Control Programs.

Disparities in Tuberculosis Incidence by Race and Ethnicity Among the U.S.-Born Population in the United States, 2011 to 2021 : An Analysis of National Disease Registry Data.

BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Tuberculosis prevalence and demographic characteristics of population in Azad Jammu and Kashmir (Pakistan): A retrospective study.

Tuberculosis (TB) remains a serious problem for public health and a leading cause of death after COVID-19 and superior to even HIV/AIDS. It is a social health issue and can cause stigma and economic loss as the person cannot perform professionally due to lethargy caused by disease. It is a retrospective study done on data from National TB program Muzaffarabad chapter. The details were noted on SPSS and analysis was done to find important demographic characteristics. The total number of patients was 3441; among which 48.76% were males. Most of them (81.11%) belonged to the Muzaffarabad division of Azad Jammu and Kahmir (AJK). The microbiologically or culture positive cases were 440. Rifampicin resistance was present in 147 cases, further categorized as high (n = 143), very high (n = 3), or true positive (n = 1) resistance. Muti drug resistance was found in 19 cases. The microscopy culture is more sensitive (AUC = 0.511) than MTB/RIF or serology (AUC = 0.502) according to ROC. The rate of positive smear results is not very satisfactory in the present study as it cannot detect dormant or latent cases. There is a need to establish more sensitive tests for detection of cases and more research to combat the disease.

Tuberculosis treatment outcomes and associated factors among tuberculosis patients treated at healthcare facilities of Motta Town, Northwest Ethiopia: a five-year retrospective study.

Tuberculosis (TB) remains a significant public health concern, particularly in low-resource settings. The treatment outcome is a crucial indicator of the effectiveness of TB treatment programs. Assessing the current treatment outcome and its associated factors is essential for improving patient care and reducing the spread of TB. Therefore, this study aimed to assess TB treatment outcomes and their associated factors among TB patients who received treatment at public healthcare facilities in Motta Town, Northwest Ethiopia. A facility-based retrospective cross-sectional study design was employed in two TB treatment centers in Motta town from January 2017 to December 2021. The study participants were all patients diagnosed with TB who received treatment. A p-value of 0.05 with a 95% confidence interval (CI) was used to determine statistical significance. A total of 362 TB patients were included in the study. The overall treatment success rate was 88.4% (95% CI 85.1, 91.7). Male gender (AOR = 2.40, 95% CI 1.16, 4.98), normal nutritional status (AOR = 3.11, 95% CI 1.33, 7.25), HIV negative status (AOR = 3.35, 95% CI 1.31, 8.60), and non-presumptive drug resistance to TB (AOR = 3.72, 95% CI 1.74, 7.98) were significantly associated with successful TB treatment outcomes (p < 0.05). In the current study, nine out of ten study participants had successful TB treatment outcome rates. Male gender, normal nutritional status, non-presumed drug resistance to TB, and HIV-negative status were significantly associated with successful TB treatment outcomes. By taking risk factors associated with poor treatment outcomes like those found in this study into account, patient management and treatment can be optimized. Sufficient TB control measures for populations are imperative and could significantly reduce the nation's total TB burden.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study.

BACKGROUND: Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection. DESIGN: PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis. SETTING AND PARTICIPANTS: The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya. RESULTS: The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions. CONCLUSION: Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

Obesity-related indicators and tuberculosis: A Mendelian randomization study.

PURPOSE: Obesity is a strong risk factor for many diseases, with controversy regarding the cause(s) of tuberculosis (TB) reflected by contradictory findings. Therefore, a larger sample population is required to determine the relationship between obesity and TB, which may further inform treatment. METHODS: Obesity-related indicators and TB mutation data were obtained from a genome-wide association study database, while representative instrumental variables (IVs) were obtained by screening and merging. Causal relationships between exposure factors and outcomes were determined using two-sample Mendelian randomization (MR) analysis. Three tests were used to determine the representativeness and stability of the IVs, supported by sensitivity analysis. RESULTS: Initially, 191 single nucleotide polymorphisms were designated as IVs by screening, followed by two-sample MR analysis, which revealed the causal relationship between waist circumference [odds ratio (OR): 2.13 (95% confidence interval (CI): 1.19-3.80); p = 0.011] and TB. Sensitivity analysis verified the credibility of the IVs, none of which were heterogeneous or horizontally pleiotropic. CONCLUSION: The present study determined the causal effect between waist circumference and TB by two-sample MR analysis and found both to be likely to be potential risk factors.

Prevalence and association of HIV and tuberculosis status in older adults in South Africa: an urgent need to escalate the scientific and political attention to aging and health.

Objectives: This study examined the prevalence and sociodemographic factors among older adults with HIV and TB status in South Africa. Methods: This data was cross-sectional and obtained from the 2019 General Household Surveys in South Africa. Adults 50 years and over with reported HIV and TB status were included (N = 9,180,047). We reported statistical analyses of the descriptive, Chi-square and Fisher's exact tests, and binary logistic regression. Results: The study has found a prevalence rate of HIV to be 5.3% and TB to be 2.9% among older adults aged 50 years and above in South Africa. However, the study found HIV and TB to be highest among older adults residing in Gauteng, KwaZulu-Natal and Eastern Cape provinces. For HIV status, the female gender [AOR = 0.80*, CI 95% = 0.80-0.80] and secondary education [AOR = 0.57, CI 95% = 0.56-0.58] have lower odds of association among older adults with HIV. Regarding TB status, primary education [AOR = 1.08*, CI 95% = 1.06-1.10] and diabetes [AOR = 1.87*, CI 95% = 1.82-1.91] have lower likelihoods of associations among older adults with TB. Conclusion: There is an urgent need to escalate scientific and political attention to address the HIV/TB burden in older adults and, public health policymakers need to take cognizance of the interdependence of inequality, mobility, and behavioural modification among this high-risk population.

Global analysis of an age-structured tuberculosis model with an application to Jiangsu, China.

Diagnostic delay for TB infected individuals and the lack of TB vaccines for adults are the main challenges to achieve the goals of WHO by 2050. In order to evaluate the impacts of diagnostic delay and vaccination for adults on prevalence of TB, we propose an age-structured model with latent age and infection age, and we incorporate Mycobacterium TB in the environment and vaccination into the model. Diagnostic delay is indicated by the age of infection before receiving treatment. The threshold dynamics are established in terms of the basic reproduction number R 0 . When R 0 < 1 , the disease-free equilibrium is globally asymptotically stable, which means that TB epidemic will die out; When R 0 = 1 , the disease-free equilibrium is globally attractive; there exists a unique endemic equilibrium and the endemic equilibrium is globally attractive when R 0 > 1 . We estimate that the basic reproduction number R 0 = 0.5320 (95% CI (0.3060, 0.7556)) in Jiangsu Province, which means that TB epidemic will die out. However, we find that the annual number of new TB cases by 2050 is 1,151 (95%CI: (138, 8,014)), which means that it is challenging to achieve the goal of WHO by 2050. To this end, we evaluate the possibility of achieving the goals of WHO if we start vaccinating adults and reduce diagnostic delay in 2025. Our results demonstrate that when the diagnostic delay is reduced from longer than four months to four months, or 20% adults are vaccinated, the goal of WHO in 2050 can be achieved, and 73,137 (95%CI: (23,906, 234,086)) and 54,828 (95%CI: (15,811, 206,468)) individuals will be prevented from being infected from 2025 to 2050, respectively. The modeling approaches and simulation results used in this work can help policymakers design control measures to reduce the prevalence of TB.

Lessons Learned from Public Health and State Prison Collaborations during COVID-19 Pandemic and Multifacility Tuberculosis Outbreak, Washington, USA.

The large COVID-19 outbreaks in prisons in the Washington (USA) State Department of Corrections (WADOC) system during 2020 highlighted the need for a new public health approach to prevent and control COVID-19 transmission in the system's 12 facilities. WADOC and the Washington State Department of Health (WADOH) responded by strengthening partnerships through dedicated corrections-focused public health staff, improving cross-agency outbreak response coordination, implementing and developing corrections-specific public health guidance, and establishing collaborative data systems. The preexisting partnerships and trust between WADOC and WADOH, strengthened during the COVID-19 response, laid the foundation for a collaborative response during late 2021 to the largest tuberculosis outbreak in Washington State in the past 20 years. We describe challenges of a multiagency collaboration during 2 outbreak responses, as well as approaches to address those challenges, and share lessons learned for future communicable disease outbreak responses in correctional settings.

Diabetes mellitus and human immunodeficiency virus (HIV) infection in people with tuberculosis in Odisha, India.

BACKGROUND: Modelling studies have indicated that approximately 20% of all tuberculosis (TB) cases may suffer from diabetes mellitus (DM). DM increases the risk of developing active TB disease by 2-3 times. People living with HIV (PLHIV) are more likely to develop TB disease, and TB is a leading cause of hospitalization and death among PLHIV. Despite the substantial burden of DM and HIV in India, few studies have evaluated the prevalence of DM and HIV among active cases of TB, and its impact on the treatment outcome for TB. This study evaluated the burden of HIV and DM in TB cases from Odisha during 2019, and its impact on the TB treatment outcome. METHODS: The study utilized data on TB patients of Odisha during 2019, from the NIKSHAY portal, the health management information system (HMIS) of TB in India. This is a retrospective observational registry-based cohort study, which evaluated a linkage between socio-demographic predictors, clinical diagnostic and treatment predictors, time of treatment predictors, and co-morbidity with TB. Data were retrieved electronically in Microsoft-Excel and analysis was done using STATA 16 (StataCorp. 2019, College Station, TX: StataCorp LLC). RESULTS: Data for 47,831 TB cases of Odisha as study population was extracted from the Nikshay application for the year 2019. The highest prevalence (31.1%, 14,863/47,831) of TB was observed among young participants aged 15-30 years, whereas the prevalence was least among children <14 years (4.4%, 2124/47,831). Males had a higher prevalence of TB (66.7%, 31,878/47,831). Of the 47,831 TB cases included in the study, 7.6% (3659/47,831) had diabetes mellitus (DM), along with TB. 1.2% (571/47,831) had HIV along with TB, while only 0.08% (37/47,831) had both DM and HIV along with TB. 88.2% (3148/3569) of cases with DM and TB had a favorable outcome, compared to 82.3% (449/541) of cases with HIV and TB. People with TB who did not have DM had a significantly higher favorable outcome (OR 1.6, 95% CI 1.5-1.8) compared to those with TB and DM. Similarly, TB cases who did not have HIV infection had a significantly higher favorable outcome (OR 2.4, 95% CI 1.9-3.0) compared to those with TB and HIV. CONCLUSION: Our study showed that presence of DM and/or HIV in TB patients had an impact on the TB treatment outcome. There is a crucial need to prevent comorbidities such as DM and HIV from occurring and to prioritize early diagnosis and management of these conditions.

"Harm reduction approach for tuberculosis and substance use disorders: A review of approaches and implications in the Indian context".

There are limitations to traditional treatment approaches in addressing the needs of individuals with dual comorbidity of TB and SUD. The concept of harm reduction as a distinct approach to addressing substance use, focusing on minimising the negative consequences associated with it rather than advocating for complete abstinence. Different harm reduction strategies, such as opioid substitution therapy, needle and syringe programmes, testing for viral infections etc. have been effectively employed for SUDs in past. Similarly, TB risk minimization approaches like improving housing and nutrition and focused testing strategies are considered as harm reduction strategies for TB management. The relationship between tuberculosis (TB) and substance use disorders (SUDs) involves a complex interplay of biopsychosocial factors. It is crucial to prioritise integrated and closely monitored care in order to address the treatment challenges and potential drug interactions that may arise. In light of the acknowledged challenges like limited awareness, infrastructure, drug resistance, and stigma, it is imperative to explore potential avenues for the implementation of harm reduction strategies targeting individuals with comorbid TB and SUD in India. Potential strategies for addressing the issue includes a range of measures, such as augmenting investments in healthcare, integrating policies, tackling social determinants, and establishing shared platforms for psychosocial rehabilitation.

India marching towards TB elimination: How far we are.

Tuberculosis continues to be the leading cause of death worldwide. India shares twenty five percent of total tuberculosis population. Programmatic approach to fight against tuberculosis started in this country in the form of National Tuberculosis Program (NTP). In due course of time India adopted many strategic changes in its fight against tuberculosis. The current program named National tuberculosis elimination program (NTEP) has been set up to eliminate TB by 2025. There are some challenges which India need to overcome to achieve its target five years ahead of the sustainable development goals. Insufficient budget, inadequate diagnostic facilities, under-reporting, low success rate, high dropout rate, social stigma are some of the major challenges in the path to achieve a TB elimination status. Besides that, all the backlogs demand for swift performance in identification, notification, and treatment of TB cases. India has all the potential to eliminate tuberculosis. Strengthening of health system, mainstreaming of private sectors, enhancing diagnostic facilities, inclusion of latest diagnostic techniques, addressing social hindrances, and advocacy for higher budget are some of the program strengthening measures, if followed properly, can take India towards a TB free status.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease.

Importance: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. Objective: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. Design, Setting, and Participants: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. Exposures: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Main Outcomes and Measures: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. Results: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). Conclusions and Relevance: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.