Risk Of Active Tuberculosis Disease Research Articles

Prediabetes and risk of active tuberculosis: a cohort study from Northern Taiwan.

Diabetes mellitus (DM) is a well-established risk factor for active tuberculosis (TB) infection. Despite the worldwide rapid increase in the prevalence of prediabetes, its impact on the risk of active TB remains largely unknown. This study aimed to investigate the relationship between prediabetes and risk of active TB in a large cohort study. A total of 119 352 participants were screened from a community-based health screening programme in Northern Taiwan. Diabetes mellitus and prediabetes were defined by baseline fasting plasma glucose (FPG) and prescription of anti-diabetic drugs. Incident cases of active TB were identified from the National Tuberculosis Registry. Kaplan-Meier curves and Cox regression analysis were employed to estimate the hazard ratios for prediabetes and DM compared with normoglycaemia. Spline regression was performed to investigate the dose-response relationship between FPG level and risk of TB disease. At baseline, 27 404 (22.96%) participants had prediabetes and 10 943 (9.17%) participants had DM. After an average follow-up of 7.2 years, 322 TB cases occurred. The adjusted hazard ratio of developing active TB disease was 0.73 [95% confidence interval (CI) 0.55-0.97] for prediabetic and 1.48 (95% CI 1.11-1.98) for diabetic participants compared with normoglycaemic individuals. Spline regression revealed a U-shaped association between FPG level and risk of active TB disease, with the lowest risk at FPG around110 mg/dl. Sensitivity analyses were conducted to exclude factors such as potential confounders (including body mass index), misclassification of glycaemic level, and selection bias, and results showed that those factors could not explain the lower risk of active TB. Prediabetes was associated with a 27% reduced risk of active TB disease compared with normoglycaemia. The biological mechanism of this inverse association and its implication for global nutrition transition and TB control should be further investigated.

Systems biology approaches to investigate the role of granulomas in TB-HIV coinfection.

The risk of active tuberculosis disease is 15-21 times higher in those coinfected with human immunodeficiency virus-1 (HIV) compared to tuberculosis alone, and tuberculosis is the leading cause of death in HIV+ individuals. Mechanisms driving synergy between Mycobacterium tuberculosis (Mtb) and HIV during coinfection include: disruption of cytokine balances, impairment of innate and adaptive immune cell functionality, and Mtb-induced increase in HIV viral loads. Tuberculosis granulomas are the interface of host-pathogen interactions. Thus, granuloma-based research elucidating the role and relative impact of coinfection mechanisms within Mtb granulomas could inform cohesive treatments that target both pathogens simultaneously. We review known interactions between Mtb and HIV, and discuss how the structure, function and development of the granuloma microenvironment create a positive feedback loop favoring pathogen expansion and interaction. We also identify key outstanding questions and highlight how coupling computational modeling with in vitro and in vivo efforts could accelerate Mtb-HIV coinfection discoveries.

Nationwide trends in the incidence of tuberculosis among people with disabilities in Korea: a nationwide serial cross-sectional study.

Studies on the association between disabilities and tuberculosis (TB) are scarce. We aimed to assess the risk of active TB disease among people with disabilities. We conducted a nationwide serial cross-sectional study using national registry linkage databases from 2008 to 2017. The crude and age-standardized and sex-standardized incidence rates of TB were analyzed for each year according to the presence, type, and severity of disabilities. The crude incidence rate and odds of developing TB disease were examined with a multivariable logistic regression model using data from 2017. The overall incidence of active TB decreased between 2008 and 2017. The age- and sex-standardized incidence rates of TB disease among people with disabilities were significantly higher than among those without disabilities throughout all observed years (p<0.001). As of 2017, the population with disabilities had a higher crude incidence rate of active TB disease than that without disabilities (119.9/100,000 vs. 48.5/100,000 person-years, p<0.001), regardless of sex, income level, and place of residence. Compared to those without disabilities, those with disabilities had higher odds of active TB (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.15 to 1.24). Individuals with mental disabilities (aOR, 1.51; 95% CI, 1.24 to1.84) had the highest odds of active TB incidence, followed by those with developmental disabilities (aOR, 1.30; 95% CI, 1.09 to 1.55). People with disabilities are at a greater risk of developing TB disease. Active screening and care for TB cases would be beneficial for people with disabilities.

Tuberculosis risk among people with diabetes mellitus in Sub-Saharan Africa: A systematic review.

ObjectivesPeople with diabetes mellitus (DM) have a higher tuberculosis (TB) risk, but the evidence from sub‐Saharan Africa (SSA) was scarce until recently and not included in earlier global summaries. Therefore, this systematic review aims to determine the risk of active TB disease among people with DM in SSA and whether HIV alters this association.MethodsMedline, Embase, CINAHL, Web of Science, Global Health and African Index Medicus were searched between January 1980 and February 2021. Cohort, case‐control and cross‐sectional studies from SSA, which assessed the association between DM and active TB, were included if adjusted for age. Two researchers independently assessed titles, abstracts, full texts, extracted data and assessed the risk of bias. Estimates for the association between DM and TB were summarised using a random effects meta‐analysis. PROSPERO: CRD42021241743.ResultsNine eligible studies were identified, which reported on 110,905 people from 5 countries. Individual study odds ratios (OR) of the TB–DM association ranged from 0.88 (95% CI 0.17–4.58) to 10.7 (95% CI 4.5–26). The pooled OR was 2.77 (95% CI 1.90–4.05). High heterogeneity was reduced in sensitivity analysis (from I 2 = 57% to I 2 = 6.9%), by excluding one study which ascertained DM by HbA1c. Risk of bias varied widely between studies, especially concerning the way in which DM status was determined.ConclusionsThere is a strong positive association between DM and active TB in SSA. More research is needed to determine whether HIV, a key risk factor for TB in SSA, modifies this relationship.

Use of Calcium Channel Blockers and Risk of Active Tuberculosis Disease: A Population-Based Analysis.

Calcium channel blockers (CCBs) are known to reduce the availability of iron-an important mineral for intracellular pathogens. Nonetheless, whether the use of CCBs modifies the risk of active tuberculosis in the clinical setting remains unclear. To determine whether CCBs may modify the risk of active tuberculosis disease, we conducted a nested case-control study using the National Health Insurance Research Database of Taiwan between January 1999 and December 2011. Conditional logistic regression and disease risk score adjustment were used to calculate the risk of active tuberculosis disease associated with CCB use. Subgroup analyses investigated the effect of different types of CCBs and potential effect modification in different subpopulations. A total of 8164 new active tuberculosis cases and 816 400 controls were examined. Use of CCBs was associated with a 32% decrease in the risk of active tuberculosis (relative risk [RR], 0.68 [95% CI, 0.58-0.78]) after adjustment with disease risk score. Compared with nonuse of CCBs, the use of dihydropyridine CCBs was associated with a lower risk of tuberculosis (RR, 0.63 [95% CI, 0.53-0.79]) than nondihydropyridine CCBs (RR, 0.73 [95% CI, 0.57-0.94]). In contrast, use of β-blockers (RR, 0.99 [95% CI, 0.83-1.12]) or loop diuretics (RR, 0.88 [95% CI, 0.62-1.26]) was not associated with lower risk of tuberculosis. In subgroup analyses, the risk of tuberculosis associated with the use of CCBs was similar among patients with heart failure or cerebrovascular diseases. Our study confirms that use of dihydropyridine CCBs decreases the risk of active tuberculosis.

Advances in the diagnosis and treatment of latent tuberculosis infection.

This review describes the major developments in the rationale for treating latent tuberculosis infection; new approaches to identifying persons with latent infection who are most likely to progress to active disease; and the development of novel short-course regimens for treatment of latent tuberculosis. As many as one-third of the world's population has latent infection with Mycobacterium tuberculosis. Models demonstrate that tuberculosis will not be eliminated without large-scale treatment of persons with latent TB. Current tools for identifying persons at risk for active tuberculosis disease include TST and IGRA, which have poor positive predictive values. Newer approaches using gene expression profiling show promise and are being studied in the ongoing trials. Development of short-course regimens are a major advance in treatment of latent TB. Three months of rifapentine with isoniazid, 4 months of rifampin, and 1 month of rifapentine with isoniazid have been found to be noninferior to the standard 9 months of isoniazid. Progress towards TB elimination can be accelerated by instituting public health measures that take into account new developments in identifying and treating persons with latent tuberculosis infection who are most likely to progress to active disease.

Cytomegalovirus Antibody Responses Associated With Increased Risk of Tuberculosis Disease in Ugandan Adults.

Recent evidence highlights human cytomegalovirus (HCMV) and immune activation as risk factors for tuberculosis disease. It is not known whether other herpesviruses are also implicated, nor whether a dose-response relationship exists between tuberculosis risk and herpes coinfection. This nested case-control study used stored serum samples from 25 persons with tuberculosis up to 10 years before tuberculosis diagnosis and between 3 and 6 matched controls without tuberculosis from a rural Ugandan cohort. Samples were investigated for Epstein-Barr virus, herpes simplex virus, and HCMV-specific immunoglobulin G (IgG), serum markers of inflammation, and mycobacterial antibody levels. Humoral response to HCMV, but not Epstein-Barr or herpes simplex virus, was associated with increased risk of active tuberculosis disease up to 10 years before diagnosis. Individuals with medium HCMV IgG were 2.8 times more likely to have tuberculosis (P = .055), and those with high HCMV IgG 3.4 times more likely to have tuberculosis (P = .007). Mycobacterial antibody levels were not associated with differences in odds of tuberculosis disease. Interferon-induced protein 10 was independently associated with increased odds of tuberculosis (odds ratio, 4.2; P = .009). These data provide evidence of a dose response between magnitude of HCMV IgG with risk of tuberculosis disease. An inflammatory environment, characterized by serum interferon-induced protein 10 and interleukin 1α, is independently associated with increased risk of tuberculosis disease.

Mitochondrial DNA haplogroup C4 can increase the risk of active tuberculosis disease in Southwest China.

<sec> <title>BACKGROUND</title> Tuberculosis (TB) remains a serious health problem worldwide. Host genetic factors are reported to be correlated with tuberculous infection. However, few mitochondrial genetic studies of TB patients have been carried out. </sec> <sec> <title>OBJECTIVE</title> To investigate the role of mitochondrial DNA (mtDNA) in tuberculous infection. </sec> <sec> <title>DESIGN</title> We recruited 243 TB patients and 261 normal controls (NCs) to compare their mtDNA haplogroups and copy numbers. </sec> <sec> <title>RESULTS</title> The frequency of mtDNA haplogroup C4 was significantly higher in TB patients (7%) than in NCs (2.8%, P = 0.042). However, this difference disappeared when TB patients were separated into male and female groups and compared with sex-matched NCs. When TB patients were divided into five subgroups for further analyses, the mtDNA haplogroup C4 showed different frequencies among the five subgroups. The frequency of the haplogroup C4 was much lower in the pulmonary TB (pTB) and pleural TB (plTB) group (1.4%) than in the non-pTB and plTB group (9.3%, P = 0.027). mtDNA copy numbers were significantly higher in TB patients than in NCs (99.09 ± 54.54 vs. 73.90 ± 43.92; P < 0.0001); results in male/female/total TB patients and matched NCs were similar. </sec> <sec> <title>CONCLUSION</title> mtDNA haplogroups and copy numbers were found to have an important role in active TB disease. </sec>.

Tuberculosis progression rates in U.S. Immigrants following screening with interferon-gamma release assays.

BackgroundInterferon-gamma release assays may be used as an alternative to the tuberculin skin test for detection of M. tuberculosis infection. However, the risk of active tuberculosis disease following screening using interferon-gamma release assays in immigrants is not well defined. To address these uncertainties, we determined the incidence rates of active tuberculosis disease in a cohort of high-risk immigrants with Class B TB screened with interferon-gamma release assays (IGRAs) upon arrival in the United States.MethodsUsing a retrospective cohort design, we enrolled recent U.S. immigrants with Class B TB who were screened with an IGRA (QuantiFERON ® Gold or Gold In-Tube Assay) at the San Francisco Department of Public Health Tuberculosis Control Clinic from January 2005 through December 2010. We reviewed records from the Tuberculosis Control Patient Management Database and from the California Department of Public Health Tuberculosis Case Registry to determine incident cases of active tuberculosis disease through February 2015.ResultsOf 1233 eligible immigrants with IGRA screening at baseline, 81 (6.6 %) were diagnosed with active tuberculosis disease as a result of their initial evaluation. Of the remaining 1152 participants without active tuberculosis disease at baseline, 513 tested IGRA-positive and 639 tested IGRA-negative. Seven participants developed incident active tuberculosis disease over 7730 person-years of follow-up, for an incidence rate of 91 per 100,000 person-years (95 % CI 43–190). Five IGRA-positive and two IGRA-negative participants developed active tuberculosis disease (incidence rates 139 per 100,000 person-years (95 % CI 58–335) and 48 per 100,000 person-years (95 % CI 12–193), respectively) for an unadjusted incidence rate ratio of 2.9 (95 % CI 0.5–30, p = 0.21). IGRA test results had a negative predictive value of 99.7 % but a positive predictive value of only 0.97 %.ConclusionsAmong high-risk immigrants without active tuberculosis disease at the time of entry into the United States, risk of progression to active tuberculosis disease was higher in IGRA-positive participants compared with IGRA-negative participants. However, these findings did not reach statistical significance, and a positive IGRA at enrollment had a poor predictive value for progressing to active tuberculosis disease. Additional research is needed to identify biomarkers and develop clinical algorithms that can better predict progression to active tuberculosis disease among U.S. immigrants.

The increased risk of active tuberculosis disease in patients with dermatomyositis - a nationwide retrospective cohort study.

The risk of active tuberculosis (TB) in patients with dermatomyositis (DM) is poorly understood. The cohort study aimed to investigate the association between DM and the risk of active TB disease. We conducted a population based study on 4,958 patients with newly diagnosed DM and 19,832 matched controls according to age, sex, and index date between 1998 and 2008. The hazard ratios (HRs) and cumulative incidences of active TB disease between DM patients and controls were analyzed. During the study period, a total of 85 (1.7%) DM patients developed active TB disease, which was significantly higher than that of non-DM patients (0.64%). The incidence rate of active TB disease was higher among DM patients than controls (incidence rate ratio 2.95; 95% confidence interval [CI], 2.24 to 3.88). The Cox regression model demonstrated significantly higher active TB disease rate among DM patients compared with controls (adjusted HR, 2.64; 95% CI, 1.97 to 3.54; p < 0.001) after adjusting for age, sex, and underlying medical disorders. The most significant risk factors for developing active TB included male sex, diabetes mellitus comorbidity, and use of corticosteroids and azathioprine in DM patients. In conclusion, DM patients are at a greater risk for active TB disease.

Hepatitis C Virus Infection Is Associated With an Increased Risk of Active Tuberculosis Disease: A Nationwide Population-Based Study.

Tuberculosis (TB) and hepatitis C virus (HCV) infection contribute to major disease mortality and morbidity worldwide. However, the causal link between HCV infection and TB risk remains unclear. We conducted a population-based cohort study to elucidate the association between HCV infection and TB disease by analyzing Taiwan National Health Insurance Database. We enrolled 5454 persons with HCV infection and 54,274 age- and sex-matched non-HCV-infected persons between January 1998 and December 2007. Time-dependent Cox proportional hazards regression analysis was used to measure the association between HCV infection and active TB disease. Incidence rate of active TB disease was higher among HCV infection than in control (134.1 vs 89.1 per 100,000 person-years; incidence rate ratio 1.51; P = 0.014). HCV infection was significantly associated with active TB disease in multivariate Cox regression (adjusted hazard ratio [HR] 3.20; 95% confidence interval [CI], 1.85-5.53; P < 0.001) and competing death risk event analysis (adjusted HR 2.11; 95% CI, 1.39-3.20; P < 0.001). Multivariate stratified analysis further revealed that HCV infection was a risk of active TB disease in most strata. This nationwide cohort study suggests that HCV infection is associated with a higher risk of developing active TB disease.

Hepatitis C virus infection is associated with an increased risk of active tuberculosis disease

Hepatitis C virus infection is associated with an increased risk of active tuberculosis disease

High Prevalence of Tuberculosis Infection in HIV-1 Exposed Kenyan Infants

Infants born to HIV-1 infected mothers may have increased risk for tuberculosis (TB), but the prevalence of TB infection in this population is undefined. In contrast to tuberculin skin tests that are confounded by recent bacille Calmette-Guérin (BCG) vaccination, TB interferon gamma release assays (IGRAs) do not cross-react with BCG and enable detection of TB infection in infancy. In a nested observational cohort of HIV-1 infected Kenyan mothers and their infants, we conducted T-SPOT.TB assays on cryopreserved peripheral blood mononuclear cells from 6-month-old infants without prior active TB. Maternal and infant correlates of infant TB infection were assessed. One hundred and eight-two infants were tested with T-SPOT.TB. Of 128 infants with determinate T-SPOT.TB results, the prevalence of a positive T-SPOT.TB was 10.9% [95% confidence interval (CI): 6.1-17.7%]. All infants were BCG-vaccinated and 7.0% were HIV-1 infected. Positive infant T-SPOT.TB was associated with maternal active TB (odds ratio: 15.5, 95% CI: 1.3-184; P = 0.04) and prolonged infant fever (>1 month) (odds ratio: 18.8, 95% CI: 1.6-223; P = 0.03). We observed a high prevalence of TB infection in 6-month-old HIV-1 exposed infants. Improved TB detection and prevention are warranted in HIV-1 exposed infants at high risk for active TB disease.

Using Tuberculin Skin Test as an Entry Point to Screen for Latent and Active Tuberculosis in Thai People Living With HIV

Tuberculin skin test (TST) identifies patients highly likely to benefit from isoniazid preventive therapy and tuberculosis (TB) prevalence may differ by TST status. We evaluated latent and active TB screening and diagnosis strategies among people living with HIV (PLHIV) incorporating TST as the initial screening step. PLHIV attending services at the Thai Red Cross Anonymous Clinic during September 2006 to January 2008 were enrolled. TB disease was defined as any positive Mycobacterium tuberculosis (MTB) specimen culture from sputum, urine, stool, lymph node aspiration, and blood. The performance of symptom screening (>1 of: any cough, any fever, night sweats lasting 3 or more weeks in the preceding 4 weeks) and laboratory screening (sputum smear followed by chest radiography and CD4 count) for active TB disease were evaluated according to TST status. We enrolled 604 PLHIV. TST was positive in 151 PLHIV (25.0%). TB disease was diagnosed in 33 PLHIV, including 22 (14.6%) TST-positive and 11 (2.4%) TST-negative PLHIV. We found that an approach of performing MTB culture for all TST-positive PLHIV and symptom screening followed by laboratory screening for all TST-negative PLHIV would identify 196 (32.4%) of 604 PLHIV who would need MTB culture to correctly diagnose 29 (87.9%) of 33 active TB cases. TST can be used as an initial screening test among PLHIV to identify those at highest risk of active TB disease. Access to MTB culture or other sensitive tests to exclude TB disease is urgently needed to improve TB screening and prevention in resource-limited settings.

Evidence for waning of latency in a cohort study of tuberculosis

BackgroundTo investigate how the risk of active tuberculosis disease is influenced by time since original infection and to determine whether the risk of reactivation of tuberculosis increases or decreases with age.MethodsCohort analysis of data for the separate ten year birth cohorts of 1876-1885 to 1959-1968 obtained from Statistics Norway and the National Tuberculosis Registry. These data were used to calculate the rates and the changes in the rates of bacillary (or active) tuberculosis. Data on bacillary tuberculosis for adult (20+) age groups were obtained from the National Tuberculosis Registry and Statistics Norway from 1946 to 1974. Most cases during this period arose due to reactivation of remote infection. Participants in this part of the analysis were all reported active tuberculosis cases in Norway from 1946 to 1974 as recorded in the National Tuberculosis Registry.ResultsTuberculosis decreased at a relatively steady rate when following individual birth cohorts, but with a tendency of slower decline as time passed since infection. A mean estimate of this rate of decline was 57% in a 10 year period.ConclusionsThe risk of reactivation of latent tuberculosis decreases with age. This decline may reflect the rate at which latent tuberculosis is eliminated from a population with minimal transmission of tubercle bacilli. A model for risk of developing active tuberculosis as a function of time since infection shows that the rate at which tuberculosis can be eliminated from a society can be quite substantial if new infections are effectively prevented. The findings clearly indicate that preventative measures against transmission of tuberculosis will be the most effective. These results also suggest that the total population harbouring live tubercle bacilli and consequently the future projection for increased incidence of tuberculosis in the world is probably overestimated.

Mycobacterium tuberculosis in Solid Organ Transplant Recipients

Mycobacterium tuberculosis in Solid Organ Transplant Recipients

DIAGNOSIS: TUBERCULOSIS

Home care staff frequently become anxious when a patient with active infectious tuberculosis is referred for home care. Using a home care patient case study, this article reviews tuberculosis epidemiology, pathophysiology, treatment, and infection control. It also discusses home health staff's role in case finding because home care patients with chronic disease and immunosuppression conditions are at risk for active tuberculosis disease.

Tuberculosis risk varies with the duration of HIV infection: a prospective study of European drug users with known date of HIV seroconversion.

It is not known whether the risk of active tuberculosis disease varies with the length of time that individuals are infected with HIV. To study how, independently of CD4 T cell count, the risk of tuberculosis varies with the duration of HIV infection. Using Poisson regression analysis, the incidence of and risk factors for tuberculosis were studied in 683 injecting drug users (IDU) with a documented date of HIV seroconversion followed in seven cohorts in six European countries until 1998. Overall incidence was 11.5/1000 person-years. Adjusted for CD4 T cell count and geographic region, the risk ratio (RR) for tuberculosis (both pulmonary and extrapulmonary), compared with the first 3 years of HIV infection, was 2.8 for years 4 to 6 of HIV infection [95% confidence interval (CI), 1.3-6.3], 1.2 for year 7 to 9 (95% CI, 0.3-4.2) and 4.6 after 9 years (95% CI, 1.4-15.0). The adjusted RR for geographic region was 13.1 (95% CI, 4.3-40.0) for Amsterdam and 15.8 (95% CI, 4.8-52.0) for the Valencian region of Spain compared with all other sites combined. The risk of tuberculosis is increased relatively early in HIV infection (year 4 to 6) and also later (after year 9) with possibly a relatively silent period between. As expected, IDU in Southern Europe have a substantially higher risk of tuberculosis than IDU in Northern and Central Europe. Amsterdam forms an exception for Northern Europe, with very high incidence rates.