Progression Of Latent Tuberculosis Infection Research Articles

A modified multiple-criteria decision-making approach based on a protein-protein interaction network to diagnose latent tuberculosis

BackgroundDNA microarrays provide informative data for transcriptional profiling and identifying gene expression signatures to help prevent progression of latent tuberculosis infection (LTBI) to active disease. However, constructing a prognostic model for distinguishing LTBI from active tuberculosis (ATB) is very challenging due to the noisy nature of data and lack of a generally stable analysis approach.MethodsIn the present study, we proposed an accurate predictive model with the help of data fusion at the decision level. In this regard, results of filter feature selection and wrapper feature selection techniques were combined with multiple-criteria decision-making (MCDM) methods to select 10 genes from six microarray datasets that can be the most discriminative genes for diagnosing tuberculosis cases. As the main contribution of this study, the final ranking function was constructed by combining protein-protein interaction (PPI) network with an MCDM method (called Decision-making Trial and Evaluation Laboratory or DEMATEL) to improve the feature ranking approach.ResultsBy applying data fusion at the decision level on the 10 introduced genes in terms of fusion of classifiers of random forests (RF) and k-nearest neighbors (KNN) regarding Yager’s theory, the proposed algorithm reached a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. Finally, with the help of cumulative clustering, the genes involved in the diagnosis of latent and activated tuberculosis have been introduced.ConclusionsThe combination of MCDM methods and PPI networks can significantly improve the diagnosis different states of tuberculosis.Clinical trial numberNot applicable.

Progression of tuberculosis among patients with rheumatic diseases – A systematic review and meta-analysis

BackgroundTuberculosis is a contagious disease that ranks among the top ten killers of humans worldwide. Mycobacterium tuberculosis is an etiological agent of tuberculosis. The prognosis of tuberculosis in patients with autoimmune diseases is high due to treatment with anti-TNF-alpha therapy. Methods and materialsWe analyzed the studies based on the Preferred Reporting Items and Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methods of eligibility criteria, search criteria and critical analyses, biased and challenges, and intervention. ResultsWe observed the tuberculosis incidence of 595 (3.25%; 95% CI- 2.9 – 3.5) cases in systemic lupus erythematosus, 332 (4.54%; 95% CI - 4.07 - 5.01) in rheumatoid arthritis, and 25 (1.9%; 95% CI - 1.16 – 2.64) in multiple sclerosis out of 26,870 study populations in the various studies, and a total of 93 (7.2%; 95% CI - 5.8 – 8.6) cases in MS, and 10 (0.05%; 95% CI - 0.02 – 0.08) in SLE reported of TB indeterminate results. ConclusionThis systematic review comprehensively analyzed the recent studies of the disease progression of latent tuberculosis infection to active tuberculosis is high in treatments with glucocorticoid, azathioprine, prednisone, and leflunomide among patients with autoimmune diseases. Key findingsWe summarized recent studies emphasizing the risk factors of tuberculosis to be found the disease-modifying anti-rheumatic drug (DMARD), immunosuppressive treatments given to biologic-naive patients as the dominant factor associated with the risk of TB and treatment with a tumor necrosis factor inhibitor.

Prospects for tuberculosis elimination in Ethiopia: feasibility, challenges, and opportunities

To end the global tuberculosis (TB) epidemic and eliminate TB, countries around the world committed to significantly expanding the scope of their efforts, including rapid uptake of new tools, interventions, and strategies, and envisioned a world free of TB. Between 2010 and 2020, Ethiopia experienced a 5% average annual decline in TB incidence. However, at that current rate, ending the TB epidemic (<10 TB cases/100,000 population) may not be possible soon. As a high TB and TB/HIV burden country, Ethiopia's TB epidemic is characterized by a high rate of transmission in the general population and hard-to-reach areas and progression of latent TB infection (LTBI) rather than cross-border migration. Studies suggest that a combination of interventions, such as intensive household screening with TB preventive therapy, has the potential to significantly decrease the incidence of TB. The feasibility of reducing the population-level TB incidence by a combination of interventions in Ethiopia is unknown. Based on the World Health Organization's TB elimination framework and the END TB strategic documents and previously published reviews in TB elimination we conducted a narrative review to summarize and estimated the effect of a combined intervention package (community-based TB screening for active case finding and TB and LTBI prevention and treatment among high-risk groups like household and close contacts). The projected annual decline of TB incidence was above 16%. With this level of impact and nationwide scale-up of the interventions, Ethiopia aligns well with ending the TB epidemic before 2035 and shifting toward TB elimination in the foreseeable future. In the Ethiopia setting, we recommend future studies generating evidence on the impact of the combination intervention package to reduce TB incidence in Ethiopia, which is aiming to shift from control to TB elimination.

Defective expansion and function of memory like natural killer cells in HIV+ individuals with latent tuberculosis infection.

PurposeTuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development. NK cells have an important role in T cell independent immunity against TB, but the exact role of NK cell subsets in LTBI and HIV is not well characterized.MethodsIn this study, we compared the expansion and function of memory like NK cells from HIV-LTBI+ individuals and treatment naïve HIV+LTBI+ patients in response to Mtb antigens ESAT-6 and CFP-10.ResultsIn freshly isolated PBMCs, percentages of CD3-CD56+ NK cells were similar in HIV+LTBI+ patients and healthy HIV-LTBI+ individuals. However, percentages of CD3-CD56+CD16+ NK cells were higher in healthy HIV-LTBI+ individuals compared to HIV+LTBI+ patients. HIV infection also inhibited the expansion of memory like NK cells, production of IL-32α, IL-15 and IFN-γ in response to Mtb antigens in LTBI+ individuals.ConclusionWe studied phenotypic, functional subsets and activation of memory like-NK cells during HIV infection and LTBI. We observed that HIV+LTBI+ patients demonstrated suboptimal NK cell and monocyte interactions in response to Mtb, leading to reduced IL-15, IFN-γ and granzyme B and increased CCL5 production. Our study highlights the effect of HIV and LTBI on modulation of NK cell activity to understand their role in development of interventions to prevent progression to TB in high risk individuals.

Association between Birth Region and Time to Tuberculosis Diagnosis among Non-US-Born Persons in the United States.

Approximately 90% of tuberculosis (TB) cases among non–US-born persons in the United States are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated whether birthplace is associated with time to disease progression among non–US-born persons in whom TB disease developed. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 birth regions, adjusting for sex, birth year, and age at entry. After adjusting for age at entry and birth year, the median time to TB diagnosis was lowest among persons from Middle Africa, 128 months (95% CI 116–146 months) for male persons and 121 months (95% CI 108–136 months) for female persons. We found time to TB diagnosis among non–US-born persons varied by birth region, which represents a prognostic indicator for progression of latent TB infection to TB disease.

Latent Tuberculosis Infection Status of Pregnant Women in Uganda Determined Using QuantiFERON TB Gold-Plus.

Background The risk of progression of latent tuberculosis infection (LTBI) to active disease increases with pregnancy. This study determined the prevalence and risk factors associated with LTBI among pregnant women in Uganda.MethodsWe enrolled 261 pregnant women, irrespective of gestational age. Participants who had known or suspected active tuberculosis (TB) on the basis of clinical evaluation or who had recently received treatment for TB were excluded. LTBI was defined as an interferon-γ concentration ≥0.35 IU/mL (calculated as either TB1 [eliciting CD4+ T-cell responses] or TB2 [eliciting CD8+ T-cell responses] antigen minus nil) using QuantiFERON TB Gold-Plus (QFT-plus) assay.ResultsLTBI prevalence was 37.9% (n = 99) (95% confidence interval [CI], 32.3–44.0). However, 24 (9.2%) subjects had indeterminate QFT-plus results. Among participants with LTBI, TB1 and TB2 alone were positive in 11 (11.1%) and 18 (18.2%) participants, respectively. In multivariable analysis, human immunodeficiency virus (HIV) infection (adjusted odds ratio [aOR], 4.4 [95% confidence interval {CI}, 1.1–18.0]; P = .04) and age 30–39 years (aOR, 4.0 [95% CI, 1.2–12.7]; P = .02) were independently associated with LTBI. Meanwhile, smoking status, alcohol use, nature of residence, crowding index, and TB contact were not associated with LTBI.ConclusionsOur findings are in keeping with the evidence that HIV infection and advancing age are important risk factors for LTBI in pregnancy. In our setting, we recommend routine screening for LTBI and TB preventive therapy among eligible pregnant women.

Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis

ABSTRACT Host immune factor plays an important role in the progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. However, whether global gene expression measured in blood biomarkers allows the identification of prospective signatures for TB risk remains unknown. Hence, we aimed to assess the ability of the transcriptome signatures in the human peripheral blood mononuclear cells (PBMCs) of LTBI subjects to differentiate future TB progressors from non-progressors. In a randomized clinical trial of TB preventive treatment of 513 participants with silicosis, we randomly collected PBMC samples from 50 LTBI subjects in the observational group, which was monitored for TB disease progression for 37 months. The prospective signatures of TB risk between the two participants who developed active TB (progressors) and four matched individuals who remained healthy (non-progressors) were compared using differential expression analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Weighted Gene Co-expression Network Analysis. The 20 TB-specific differentially expressed genes, which were significantly downregulated in TB progressors, were revealed to be associated with interferon-gamma response-related genes. Therefore, the PBMC transcriptome profiles analyzed in this study may help identify LTBI individuals who are at risk of progressing to active TB among silicosis patients and may provide new insights for targeted intervention to prevent disease progression. Clinical trial registration www.clinicaltrials.gov (NCT02430259)

Time Since Infection and Risks of Future Disease for Individuals with Mycobacterium tuberculosis Infection in the United States.

Risk of tuberculosis (TB) declines over time since Mycobacterium tuberculosis infection, but progression to clinical disease is still possible decades later. In the United States, most TB cases result from the progression of latent TB infection acquired over 2 years ago. We synthesized evidence on TB natural history and incidence trends using a transmission-dynamic model. For the 2020 US population, we estimated average time since infection and annual, cumulative, and remaining lifetime risks of progression to TB, by nativity and age. For a newly infected adult with no other risk factors for progression to TB, estimated rates of progression declined from 38 (95% uncertainty interval: 33, 46) to 0.38 (0.32, 0.45) per 1000 person-years between the first and 25th year since infection. Cumulative risk over 25 years from new infection was 7.9% (7.0, 8.9). In 2020, an estimated average age of individuals with prevalent infection was 62 (61, 63) for the US-born population, 55 (54, 55) for non-US-born, and 57 (56, 58) overall. Average risks of developing TB over the remaining lifetime were 1.2% (1.0, 1.4) for US-born, 2.2% (1.8, 2.6) for non-US-born, and 1.9% (1.6, 2.2) for the general population. Risk estimates were higher for younger age groups. Our analysis suggests that, although newly infected individuals face appreciable lifetime TB risks, most US individuals with latent TB infection were infected long ago, and face low future risks of developing TB. Better approaches are needed for identifying recently infected individuals and those with elevated progression risks.

Ethical issues in expanding latent TB management in high burden countries.

Global efforts are being made to eliminate tuberculosis (TB) as a public health problem by 2030. These efforts are being thwarted by the challenge of effective management to minimise the progression of latent TB infection (LTBI) to TB, thereby interrupting the chain of transmission. Approximately 5%-10% LTBI cases eventually develop TB in their lifetime with the risk being higher in children, people living with HIV/AIDS (PLHIV), undernourished people, and patients with diabetes, chronic kidney disease, silicosis, and other comorbid conditions. Apart from operational barriers, complex ethical issues govern decision-making processes in either retaining current LTBI management practices or advocating implementation of the latest World Health Organization guidelines, which suggest extending treatment to vulnerable groups who have a higher risk of progression to TB. Newer LTBI treatment regimens have a diminished risk of toxicity that allays threats to patient safety. Public health justification for treating LTBI can also override patient autonomy, but the lack of a patient-centred approach is associated with poor adherence and treatment outcomes. Cost-effectiveness studies need to evaluate the gains and losses accruing from funding treatment of LTBI versus similar costs in nutritional interventions for managing undernutrition. Similarly, the impact of diverting resources available for management of the existing active TB control programmes to expanding LTBI treatment also needs to be assessed. In conclusion, a comprehensive LTBI treatment strategy built on the basis of high-quality evidence is the best way forward for resolving the ethical considerations at the heart of LTBI management in the developing world. Keywords: Tuberculosis; India; Latent TB; Medical ethics.

Serial T-SPOT.TB in household contacts of tuberculosis patients: a 6-year observational study in China.

BACKGROUND: Screening tuberculosis (TB) contacts is a priority for TB control; however, it remains inadequate in most regions of China.OBJECTIVE: To investigate the progression of latent TB infection (LTBI) using the interferon-gamma release assay (IGRA) in contacts of active TB patients.DESIGN: This longitudinal prospective observational study included 159 household contacts aged ≥14 years without preventive treatment who were followed up for 6 years to compare their conversion and reversion rates using the T-SPOT®.TB IGRA to diagnose LTBI.RESULTS: Among the 159 household contacts, LTBI positivity was 47.5%. Age was independently associated with LTBI (OR 3.6, 95%CI 1.81-7.14; P = 0.00). T-SPOT.TB conversion rates were respectively 29.4% and 18.8% at 3- and 6-year follow-up. The reversion rates were 9.4% of contacts during the 3-year follow-up period, which increased to 38.2% at the 6-year follow-up. A decreasing trend in spot-forming cells on T-SPOT.TB was observed in most patients at the 6-year follow-up.CONCLUSION: LTBI prevalence among household contacts was relatively high, particularly in elderly patients. Furthermore, serial IGRA testing was highly dynamic; however, this overall trend gradually decreased over time, even if preventive therapy was not prescribed.

Pulmonary Tuberculosis Screening in Patients with Diabetes Mellitus

Abstract Background and aims: Diabetes mellitus (DM) is a risk factor for pulmonary tuberculosis (TB), increasing the risk of progression of latent tuberculosis infection (LTBI) to active TB threefold, threatening the TB control, especially in developing countries. The aim of this study was to assess active and latent TB infection frequency in patients with DM. Material and methods: There were enrolled in this study 503 adult DM patients. Active TB screening was performed through anamnestic data, clinical examination and chest X-ray and latent TB infection screening was evaluated using the tuberculin skin tests (TST). Results: A number of 63 (12.5%) patients had type 1 DM and 440 (87.5%) had type 2 DM. Personal history of TB was present in 21 (4.2%) subjects, 5 (8.1%) with type 1 DM and 16 (3.6%) with type 2 DM. The TST was positive in 258 (51.5%) patients and 54 (10.7%) presented cough for more than two weeks at the time of examination. The chest X-ray revealed suggestive lesions for active TB in 4 (1%) subjects and lesions of inactive TB in 90 (22.4%) subjects. Conclusions: TB screening must receive proper attention in patients with DM, being essential for diagnosis in those with nonspecific symptoms.

Identification of unique key genes and miRNAs in latent tuberculosis infection by network analysis

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M.tb). New cases are now mainly caused by the progression of latent tuberculosis infection (LTBI). Thus, methods to diagnose and treat LTBI are urgently needed to prevent the development of active TB in infected individuals and the subsequent spread of the disease. In this study, a systems biology approach was utilized to obtain numerous microarray data sets for mRNAs and microRNAs (miRNAs) expressed in the peripheral blood mononuclear cells (PBMCs) of TB patients and individuals with LTBI. Within these data sets, we identified the differentially expressed mRNAs and miRNAs and further investigated which differentially expressed genes and miRNAs were uniquely expressed during LTBI. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to analyze the functional annotations and pathway classifications of the identified genes. To further understand the unique miRNA-gene regulatory network of LTBI, we constructed a protein–protein interaction (PPI) network for the targeted genes. The PPI network included 39 genes that were differentially and uniquely expressed in PBMCs of individuals with LTBI, and KEGG pathway enrichment analysis showed that these genes were predominantly involved in the PI3K-Akt signaling pathway, which plays an important role in chronic inflammation. DIANA TOOLs-mirPath analysis revealed that the identified miRNAs in the miRNA–gene regulatory network for LTBI were mainly associated with the Hippo signaling pathway, which functions in the development of inflammation. Quantitative real-time PCR verified the up expression of hsa-miR-212-3p and its predicted target gene —MAPK1 which had low expression and was a major component of the PPI network, and MAPK1 expression was correlated with the clinicopathological characteristics of LTBI by receiver operating characteristic (ROC) curve analysis. Therefore, MAPK1 has potential to be a new investigable marker during LTBI, which merits our further study and solution. The unique aberrant miRNA–gene regulatory network and the related PPI network identified in this study provide insight into the molecular mechanisms of the immune response to LTBI, and thus, may aid in the development of a novel treatment strategy.

Polymorphisms in Toll-Like Receptor 10 and Tuberculosis Susceptibility: Evidence from Three Independent Series

The toll-like receptor 2 (TLR2)-mediated immune response is critical for host defense against Mycobacterium tuberculosis. There is evidence that TLR10, a TLR2 signaling modulator, may be involved in progression of tuberculosis (TB). Using a self-validating case-control design, we tested for an association between seven TLR10 polymorphisms and susceptibility to TB in three independent series with two distinct populations. Single-nucleotide polymorphism (SNP) genotypes were determined by the SNPscanTM method. Three genetic models (additive, dominant, and recessive) as well as multiple-SNP score analyses were used to evaluate the risk of TB associated with the TLR10 SNPs. By comparing TB patients with healthy controls, we observed two SNPs (rs11466617 and rs4129009) that were associated with decreased risk of TB in the Tibetan population, but did not in the Chinese Han population. Further analysis demonstrated that the rs11466617 Chengdu cohort genotype served as a protective factor against the progression of latent TB infection (LTBI) to active TB under the recessive model. None of the SNPs were significantly different in comparisons of TB-uninfected people with LTBI individuals. Additionally, when the underlying four TB-associated loci were considered together in a multiple-SNP score analysis, we observed an allele dose-dependent decrease in TB risk in Tibetans. Variants of TLR10 may show an ethnic specificity on susceptibility to TB in Tibetan individuals. rs11466617 affected the susceptibility to progress from LTBI to active TB disease, but was not associated with the establishment of LTBI after M. tuberculosis exposure. More studies are needed to verify this genetic epidemiological result and unravel the role of TLR10 SNPs in the pathogenesis of TB.

Undernutrition & tuberculosis in India: Situation analysis & the way forward.

Undernutrition and tuberculosis (TB) are linked and have a bidirectional relationship. Undernutrition increases the risk of TB which in turn, can lead to malnutrition. Undernutrition not only is a risk factor for progression of latent TB infection to active disease, but also increases the risk of drug toxicity, relapse and death once TB develops. The dietary intake of TB patients in the country is inadequate. Nutritional supplementation in patients with TB is associated with faster sputum conversion, higher cure and treatment completion rates, significant gain in body weight and body composition as well as better performance status.The Government of India has various social support schemes (including nutrition supplementation schemes) and policies, at the Centre as well as State levels. Here we discuss some successful examples and suggest a few solutions to address this gap; like considering TB patients as a vulnerable group for “Targeted Public Distribution System” and providing extra rations for the duration of treatment. Recommendations for the research community, civil societies, government organizations, non-governmental and corporate sector on the actions needed to achieve the goals of the End TB Strategy are also provided. Ultimately, reduction of TB burden in India and its elimination will require improving the nutritional status of the community as a whole.

Differential expression of CD57 in antigen-reactive CD4+ T cells between active and latent tuberculosis infection

The development of diagnostic tests that predict the progression of latent tuberculosis infection to active disease is pivotal for the eradication of tuberculosis. As an initial step to achieve this goal, our study's aim was to identify biomarkers that differentiate active from latent tuberculosis infection. We compared active and latent tuberculosis infection groups in terms of the precursor frequency, functional subset differentiation, and senescence/exhaustion surface marker expression of antigen-specific CD4+ T cells, which were defined as dividing cells upon their encountering with Mycobacterium (M.) tuberculosis antigens. Among several parameters shown to have statistically significant differences between the two groups, the frequency of CD57-expressing cells could differentiate effectively between active disease and latent infection. Our results suggest that the expression of CD57 in M. tuberculosis-reactive CD4+ T cells could be a promising candidate biomarker with which to identify individuals with latent tuberculosis infection prone to progression to active disease.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Survival Experience and its Predictors among TB/HIV Co-infected Patients in Southwest Ethiopia

Background: HIV-TB co-infection is “bidirectional and synergistic”. HIV promotes the progression of latent tuberculosis infection to disease and tuberculosis accelerates the progression of HIV disease to its advanced stage. To date, there have been limited clinical data regarding survival rates among TB/HIV co-infected patients and the impact of antiretroviral therapy on clinical outcomes in developing countries. Therefore, this study assessed the predictors of TB/HIV associated mortality in a cohort of HIV infected patients treated with antiretroviral therapy in Jimma University Teaching Hospital. Methods: Retrospective study was conducted in Jimma University Teaching Hospital from September 01, 2010 to August 31, 2012. All records of adult TB-HIV co-infected patients who follow TB-HIV care in Jimma University Teaching Hospital between 01 September of 2010 and 31 August of 2012 were retrieved. Data were entered by Epidata and was exported to SPSS version 19. Data were analyzed using proportional hazards cox model with stepwise variable selection to identify independent predictors. P value below 0.05 was considered statistically significant in the final model. Results: Fifty five (20.2%) Tb HIV co-infected patients were died in the year September 2010 to August 2012, and 272 study subjects contributed 3, 082.7 person month observations. Age between 35-44 years (AHR=2.9; 95%CI: 1.08-7.6), being commercial sex worker (AHR=9.1; 95%CI: 2.7-30.7), bed ridden functional status (AHR=3.2; 95%CI: 1.2-8.7), and WHO stages 2 (AHR=0.2; 95%CI: 0.06-0.5), 3(AHR=0.3; 95%CI: 0.1-0.8) and 4(AHR=0.2; 95%CI: 0.04-0.55) were the independent factors affecting mortality of TB-HIV co-infected patients. Conclusions: More than 1 in 5 TB-HIV co-infected individuals died. The independent predictors were age between 35-44 years, being student and commercial sex worker, bed ridden functional status, and WHO stages 2, 3, and 4. Therefore, attention should be given to reduce the considerable amount of death, and specific intervention should be designed focusing on the independent predictors.

Comparison of screening strategies to improve the diagnosis of latent tuberculosis infection in the HIV-positive population: a cohort study

BackgroundHIV is the most important risk factor for progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB). Detection and treatment of LTBI is necessary to reduce the increasing burden...

Diagnosis of tuberculosis in patients with psoriasis: the need for a modified approach

To the Editors: We read with interest the TBNET consensus statement on the diagnosis and treatment of tuberculosis (TB) in patients screened for tumour necrosis factor (TNF)-α antagonist therapy [1]. Admittedly, accumulated evidence during the last decade demonstrates that adherence to such guidelines has minimised the risk of TB reactivation in patients receiving immunosuppressive regimens, including anti-TNF-α therapy. For TNF-α antagonists specifically, targeted preventive chemotherapy prior to the onset of therapy has significantly reduced the risk of progression of latent TB infection (LTBI) to overt disease, yet at the cost of increased risk for significant treatment-associated toxicity. Thus, in an effort to avoid possible over-treatment prior to treatment with TNF-α antagonists and to accurately identify patients who would benefit from anti-TB treatment, patient cohorts inherently predisposed to overdiagnosis of LTBI should be identified. In the TBNET consensus statement, the author panel concludes: “Screening for latent infection and preventive chemotherapy against TB should not be different for patients with different underlying disease […] who are candidates for …

Do We Have Evidence for Policy Changes in the Treatment of Children With Latent Tuberculosis Infection?

For more than 50 years, isoniazid has been prescribed to prevent the progression of latent tuberculosis infection (LTBI) to overt TB disease.1,2 Treating LTBI benefits the individual by preventing TB disease, and it benefits public health by diminishing the pool of infection that could become contagious TB disease in the future.3 In this issue of Pediatrics , Finnell et al4 point to rising Mycobacterium tuberculosis drug-resistance rates globally and question the standard regimen of 9 months of isoniazid treatment. From a cost/benefit analysis, they conclude that rifampin should replace isoniazid for treating LTBI in immigrant children from countries where the likelihood of being infected with isoniazid-resistant M tuberculosis exceeds 11%. An estimated 586 000 US children aged 1 to 14 years have LTBI, 70% of whom were born overseas.5 The worldwide epidemic of drug-resistant TB warrants consideration of alternative treatment regimens. For a proposed strategy to be effective, treatment should be efficacious, safe, acceptable to the patient, and cost-effective. Isoniazid fulfills these criteria. Cost/benefit models for treating LTBI are sensitive to several variables: (1) the proportion of … Address correspondence to John A. Jereb, MD, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS E-10, Atlanta, GA 30333. E-mail: jxj4{at}cdc.gov