Treatment Of Latent Tuberculosis Infection Research Articles

Economic evaluation of diagnosis and treatment for latent tuberculosis infection among contacts of pulmonary tuberculosis patients in Thailand

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expression were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest that suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA.

Adherence to Preventive Treatment for Latent Tuberculosis Infection in Close Contacts of Pulmonary Tuberculosis Patients: A Cluster-Randomized Controlled Trial in China

ObjectivesThis study examined adherence rates to tuberculosis preventive treatment (TPT) among close contacts of individuals with pulmonary tuberculosis (PTB) and identified factors associated with TPT adherence in China. MethodsA multicenter, cluster-randomized, open-label control trial was carried out across three sites involving 34 counties in China. Close contacts of bacteriologically confirmed rifampin and isoniazid-susceptible PTB cases were identified and screened for latent tuberculosis infection (LTBI). Eligible participants were randomly assigned to either the 3H2P2 group, which consisted of a three-month, twice-weekly regimen of rifapentine and isoniazid, or the 6H group, which entailed a six-month daily regimen of isoniazid. To assess the factors influencing adherence, a two-level logistic regression model was utilized. ResultsOut of the 2,434 close contacts who initiated TPT, 2,121 (87.1%) completed the regimen. Of the 313 individuals who did not complete TPT, 60.1% refused to continue, and 27.8% discontinued due to adverse effects. The two-level logistic regression model revealed several factors associated with enhanced TPT adherence: enrollment in the 3H2P2 group (odds ratio (OR)=2.09), management by a TB dispensary responsible for TPT (OR=2.55), supervision by healthcare workers (OR=6.40), and clinician incentives (OR=2.49). Conversely, the occurrence of any adverse effects (OR=0.08) was identified as a risk factor for non-adherence. ConclusionsAdministering TPT to individuals with LTBI is feasible among close contacts. Adherence to TPT can be enhanced through shorter, safer treatment regimens and supportive interventions, such as directly supervised therapy for TPT recipients and incentives for healthcare providers managing TPT.

One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: a randomized controlled trial

ObjectivesThe weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. MethodsThis randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. ResultsA total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46–50.79] vs. 22.94 [14.67–31.65], p 0.018) and 6 hours (26.13 [15.80–53.06] vs. 29.83 [18.13–34.01], p 0.047) after dosing. DiscussionIn non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.

The Cascade of Care in Management of Solid Organ Transplant Candidates With Latent Tuberculosis Infection.

Solid organ transplant (SOT) candidates should be screened and treated for latent tuberculosis infection (LTBI) to prevent tuberculosis (TB) reactivation after transplantation. We aimed to assess the steps from positive QuantiFERON (QFT) through LTBI treatment (cascade of care) in the SOT population. We conducted a retrospective study of SOT recipients older than 18 y with a positive QFT during pretransplant evaluation at the Mayo Clinic from January 2010 to June 2023. We analyzed each cascade step to determine associated drop-out factors for LTBI management. Of 629 patients who had positive QFT results, 587 (93%) were evaluated by an infectious disease (ID) specialist, 478 (76%) were recommended to start LTBI treatment, 473 (75%) initiated LTBI treatment, and 457 (73%) completed LTBI treatment. LTBI treatment was not recommended in 109 patients evaluated by infectious disease, most of whom had previously received either LTBI (n = 72) or TB (n = 14) treatment. LTBI treatment was initiated before or after transplantation for 45% and 55% of patients, respectively. Isoniazid monotherapy was the most common regimen (92%), and adverse events were rare (7%). Seven patients developed active TB infection posttransplantation under various circumstances (3 without LTBI treatment, 1 during LTBI treatment, and 3 after completing LTBI treatment). Our findings demonstrate the variability of LTBI management in SOT recipients with positive QFT. When recommended, most patients completed LTBI treatment successfully. Nonetheless, active TB was noted regardless of whether patients received LTBI treatment. This study highlights the importance of optimizing LTBI management in this population.

HLA-DPB1*05:01 and HLA-A*11:01 Is Associated with Adverse Drug Reactions to Isoniazid and Rifampin for Treatment of Latent Tuberculosis Infection in South Korea.

Background: Screening and treating healthcare workers (HCWs) for latent tuberculosis infection (LTBI) are essential for tuberculosis (TB) infection control. Adverse drug reactions (ADRs) to anti-TB drugs present challenges to patient safety and treatment completion. Objective: This study investigated the association between human leukocyte antigen (HLA) alleles and the risk of ADRs, especially drug hypersensitivity (DHS) and hepatotoxicity, in HCWs with LTBI receiving isoniazid (INH) and rifampin (RIF) therapy. Methods: Korean HCWs with LTBI who received a 3 month INH and RIF regimen were included in this study. HLA genotyping was performed on HCWs who experienced ADRs during treatment, as well as the control group consisted of individuals who did not develop ADRs. Results: Of the 67 patients, 29 (43.2%) experienced ADRs during INH and RIF therapy. The HLA-A*11:01 allele was more frequent in patients with DHS without hepatotoxicity (DSH+/H-) compared to the control group (DHS-/H-) (4/9, 44.4% vs. 3/38, 7.9%; odd ratio [OR], 8.554; 95% confidence interval [CI], 1.415-59.869; p = 0.018). Conversely, HLA-DPB1*05:01 was associated with an increased risk of hepatotoxicity regardless of DHS (10/20, 50% vs. 5/38, 13.2%; OR, 5.323; 95% CI, 1.493-21.518; p = 0.011). In the DHS with hepatotoxicity group (DHS+/H+), HLA-DPB1*05:01 was present in a higher proportion (3/5, 60% vs. 5/38, 13.2%; OR, 8.912; 95% CI, 1.110-92.993; p = 0.037), whereas HLA-A*11:01 was not observed in this group. Conclusions: The HLA-A*11:01 allele was associated with an increased risk of DHS without hepatotoxicity, whereas the HLA-DPB1*05:01 allele was associated with an increased risk of hepatotoxicity.

Novel Thrice-Weekly Isoniazid plus Rifapentine Short-Course Regimen for the Treatment of Latent Tuberculosis Infection in a Murine Model

Novel Thrice-Weekly Isoniazid plus Rifapentine Short-Course Regimen for the Treatment of Latent Tuberculosis Infection in a Murine Model

Progress Toward Tuberculosis Elimination and Tuberculosis Program Performance - National Tuberculosis Indicators Project, 2016-2022.

Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.

A Mycobacterium bovis outbreak among exhibition animals at a zoo in the Republic of Korea: the first contact investigation of zoonotic tuberculosis.

Between July 2, 2021, and September 20, 2022, a Mycobacterium bovis outbreak occurred among exhibition animals at a zoo in the Republic of Korea. This study was conducted to assess the likelihood of M. bovis transmission to human contacts through a contact investigation and to implement preventive treatment for latent tuberculosis infection (LTBI). In this descriptive study, the Korea Disease Control and Prevention Agency conducted a contact investigation, which included interviews, interferon-gamma release assay (IGRA) tests, and chest X-rays. Contacts underwent IGRA testing on 2 occasions: initial testing of 29 contacts (15 in the first cluster of infection and 14 in the second cluster) and follow-up testing of the 15 contacts in the first cluster. The study included 29 participants, 18 of whom were male (62.1%) and 11 female (37.9%). The mean participant age was 37.3 years (standard deviation, 9.6 years). In the initial IGRA tests, 6 of the 29 participants tested positive, indicating a prevalence of 20.7%. Following prolonged exposure, 1 additional positive case was detected in follow-up testing, raising the prevalence of LTBI to 24.1%. None of the contacts had active tuberculosis. Among the 7 individuals with positive results, 2 (28.6%) underwent treatment for LTBI. This study faced challenges in confirming the transmission of M. bovis infection from infected animals to humans in the Republic of Korea. Nevertheless, adopting a One Health approach necessitates the implementation of surveillance systems and infection control protocols, particularly for occupational groups at high risk of exposure.

Latent tuberculosis diagnostics: current scenario and review.

This review presents a comprehensive examination of the contemporary landscape pertaining to latent tuberculosis infection (LTBI) diagnostics, with a particular emphasis on the global ramifications and the intricacies surrounding LTBI diagnosis and treatment. It accentuates the imperative of bolstering diagnostic, preventive, and treatment modalities for tuberculosis (TB) to fulfill the ambitious targets set forth by the World Health Organization aimed at reducing TB-related mortalities and the incidence of new TB cases. The document underscores the significance of addressing LTBI as a means of averting the progression to active TB, particularly in regions burdened with high TB prevalence, such as India. An in-depth analysis of the spectrum delineating latent and active TB disease is provided, elucidating the risk factors predisposing individuals with LTBI to progress towards active TB, including compromised immune functionality, concurrent HIV infection, and other immunosuppressive states. Furthermore, the challenges associated with LTBI diagnosis are elucidated, encompassing the absence of a definitive diagnostic assay, and the merits and demerits of tuberculin skin testing (TST) and interferon-γ release assays (IGRAs) are expounded upon. The document underscores the necessity of confronting these challenges and furnishes a meticulous examination of the advantages and limitations of TST and IGRAs, along with the intricacies involved in interpreting their outcomes across diverse demographics and settings. Additionally, attention is drawn towards the heritability of the interferon-γ response to mycobacterial antigens and the potential utility of antibodies in LTBI diagnosis.

Izoniazidom navodené poškodenie pečene sprevádzané ikterom

Summary: Isoniazid belongs to the first line antituberculosis drugs and can be used for the treatment of both active and latent tuberculosis infections. It is a part of combined regimens, for the preventive treatment of tuberculosis isoniazid can be used in monotherapy as well. Even though elevations in serum aminotransferases levels during isoniazid therapy are seen frequently, the development of symptomatic hepatitis is rare, according to specialised literature. This article describes a case of a patient who developed drug-induced liver injury accompanied by jaundice during the isoniazid preventive treatment of tuberculosis. It also provides a summary of the currently known risk factors, pathogenesis, and incidence of hepatotoxicity observed throughout therapy with this antituberculosis drug. We also illustrate the process of diagnosing drug--induced liver injury in clinical practice settings with the utilisation of the updated RUCAM score. Key words: jaundice – isoniazid – drug-induced liver injury – tuberculosis preventative therapy – updated RUCAM score.

Management of Isoniazid Monoresistant Tuberculosis

lsoniazid (INH) is one of the main first-line drugs used for the treatment of active tuberculosis (TB) and latent TB infection because it has bactericidal capabilities and a good level of safety. The presence of TB germs that are resistant to INH will reduce the effectiveness of TB treatment. The treatment mix for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx given for 6 months. If a health facility provides loose TB medication, the patient can be given a combination of treatment without INH (R-Z-E-Lfx). In conditions where the Lfx drug cannot be used because there is severe intolerance (serious adverse events) or there are contra indications, the treatment given is the R-H-Z-E combination for 6 months. Clinical monitoring for patients with INH monoresistant TB follows the same principles as treatment of drug-sensitive TB. In conclusion, the treatment guide for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx for 6 months.

Patient navigator’s role in latent tuberculosis infection at a New York City Health Department Chest Clinic

BackgroundPhilippines is one of the top ten countries of birth among individuals with tuberculosis in New York City (NYC). The NYC Health Department (HD) screened Filipino-born New Yorkers for latent TB infection (LTBI), but few of those tested positive completed evaluation and treatment. ObjectiveTo increase the proportion of Filipinos with a positive QuantiFeron-TB Gold Plus (QFT-Plus) complete LTBI evaluation and treatment. MethodsNine community-based LTBI screening events were conducted during September-December 2021. Patients with positive QFT-Plus results were offered no-cost LTBI evaluation and treatment at HD Chest Clinic. The HD engaged culturally- and linguistically-competent Filipino patient navigators (PN) to facilitate LTBI evaluation and treatment. ResultsOf 77 Filipinos screened, 17 (22%) tested positive. Fourteen (82%) were evaluated for LTBI; eight of the 14 (57%) completed LTBI treatment. ConclusionsPairing patients with culturally- and linguistically- competent Filipino PNs contributed to an increase in the proportion of Filipinos with a positive QFT-Plus who completed LTBI evaluation and treatment. TB prevention programs may wish to consider PNs in LTBI patient care.

Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-like Reactions During Treatment of Latent Tuberculosis Infection.

Flu-like reactions can occur after exposure to rifampin, rifapentine, or isoniazid. Prior studies have reported the presence of antibodies to rifampin, but associations with underlying pathogenesis are unclear. We evaluated PREVENT TB study participants who received weekly isoniazid + rifapentine for 3 months (3HP) or daily isoniazid for 9 months (9H) as treatment for M. tuberculosis infection. Flu-like reaction was defined as a grade ≥2 of any of flu-like symptoms. Controls (3HP or 9H) did not report flu-like reactions. We developed a competitive enzyme-linked immunosorbent assays (ELISA) to detect antibodies against rifapentine, isoniazid, rifampin, and rifapentine metabolite. Among 128 participants, 69 received 3HP (22 with flu-like reactions; 47 controls) and 59 received 9H (12 with flu-like reactions; 47 controls). In participants receiving 3HP, anti-rifapentine IgG was identified in 2/22 (9%) participants with flu-like reactions and 6/47 (13%) controls (P = 0.7), anti-isoniazid IgG in 2/22 (9%) participants with flu-like reactions and 4/47 (9%) controls (P = 0.9), and anti-rifapentine metabolite IgG in 2/47 (4%) controls (P = 0.9). Among participants receiving 9H, IgG and IgM anti-isoniazid antibodies were each present in 4/47 (9%) controls, respectively, but none among participants with flu-like reactions; anti-rifapentine IgG antibodies were not present in any participants with flu-like reactions or controls. We detected anti-rifapentine, anti-isoniazid, and anti-rifapentine metabolite antibodies, but the proportions of participants with antibodies were low, and did not differ between participants with flu-like reactions and those without such reactions. This suggests that flu-like reactions associated with 3HP and 9H were not antibody-mediated.

Latent TB treatment regimens in 2023: Wetmore TB clinic in New Orleans

The USPSTF has updated Latent TB Infection (LTBI) screening and treatment recommendations in 2023; describing treatment courses, side effects and benefits associated with each regimen. Overall, rifampin-containing shortened regimens are the preferred modality for LTBI treatment. A recent study in 2023 evaluated adherence and tolerance of the isoniazid(INH) + rifapentine(RPT), or “3HP” regimen and identified patient groups that may be at higher risk for non-completion of this regimen. It emphasized the need for targeted education at the beginning of treatment, to avoid early discontinuation. Our experience in New Orleans demonstrated that the 3HP is well-tolerated, with higher completion rates than other LTBI regimens. Utilizing a retrospective chart review model, we reviewed 756 patients who were treated for LTBI over a two-year period from 1/2021––12/2022. The three possible treatment regimens included isoniazid (INH) alone, rifampin (RIF) alone, or INH + RPT (3HP). Of these regimens, the highest completion rate was in the 3HP group, despite literature suggesting this regimen is difficult to tolerate. Our experience suggests that this may still be an efficacious regimen that is well-tolerated if there is good access to clinicians to discuss mitigating side effects. More data is needed to determine factors that led to the success or failure for each regimen. Our clinic does have increased availability of nursing and medical staff to discuss side effects and answer questions, which may have contributed to our relatively higher success rate. In addition, we applied the review recommendations to our patient population, and would recommend the consideration of diabetes, heavy alcohol use, and tobacco use as risk factors for patients that would benefit from LTBI screening and treatment.

Interpreter usage and associations with latent tuberculosis infection treatment acceptance and completion in the USA among non-U.S.-born persons, 2012-2017.

Latent tuberculosis infection (LTBI) screening and treatment interventions that are tailored to optimize acceptance among the non-U.S.-born population are essential for U.S. tuberculosis elimination. We investigated the impact of medical interpreter use on LTBI treatment acceptance and completion among non-U.S.-born persons in a multisite study. The Tuberculosis Epidemiologic Studies Consortium was a prospective cohort study that enrolled participants at high risk for LTBI at ten U.S. sites with 18 affiliated clinics from 2012 to 2017. Non-U.S.-born participants with at least one positive tuberculosis infection test result were included in analyses. Characteristics associated with LTBI treatment offer, acceptance, and completion were evaluated using multivariable logistic regression with random intercepts to account for clustering by enrollment site. Our primary outcomes were whether use of an interpreter was associated with LTBI treatment acceptance and completion. We also evaluated whether interpreter usage was associated treatment offer and whether interpreter type was associated with treatment offer, acceptance, or completion. Among 8,761 non-U.S.-born participants, those who used an interpreter during the initial interview had a significantly greater odds of accepting LTBI treatment than those who did not use an interpreter. There was no association between use of an interpreter and a clinician's decision to offer treatment or treatment completion once accepted. Characteristics associated with lower odds of treatment being offered included experiencing homelessness and identifying as Pacific Islander persons. Lower treatment acceptance was observed in Black and Latino persons and lower treatment completion by participants experiencing homelessness. Successful treatment completion was associated with use of shorter rifamycin-based regimens. Interpreter type was not associated with LTBI treatment offer, acceptance, or completion. We found greater LTBI treatment acceptance was associated with interpreter use among non-U.S.-born individuals.

Latent tuberculosis prevalence, diagnosis and treatment in Multiple Sclerosis as a strategy for reducing infection reactivation during immunosuppressant therapy

BackgroundTuberculosis is an infectious disease with a risk of reactivation in Multiple Sclerosis patients on immunosuppressant therapy. Diagnosis and treatment of Latent Tuberculosis Infection (LTBI) prevents the infection. ObjectiveTo diagnose and treat LTBI in Multiple Sclerosis (MS). MethodsCross-sectional study of the prevalence and treatment of LTBI in MS, between February 2021 and June 2023. LTBI was defined as an absence of symptoms, positive PPD or IGRA and normal chest X-ray. ResultsOf the 58 patients with MS, 17 (29.3 %) were diagnosed with LTBI, 15 with PPD > 5 mm and 2 with positive IGRA, 10 (58.8 %) female and 7 (41.1 %) male, mean age of 41.3 (SD ±13.4) years. All patients with LTBI were treated with immunomodulators or immunosuppressants: Fingolimod 5 (29.4 %), Natalizumab 5 (29.4 %), Cladribine 2 (11.8 %), Glatiramer 2 (11.8 %), Ocrelizumab 2 (11.8 %), and Interferon beta 1 (5.9 %). Steroids therapy for relapses, were used in 5/17 (93.8 %) with LTBI and 30/37 (81.1 %) without LTBI. To treat LTBI, 11 (64.7 %) received Isoniazid and 6 (35.3 %) Isoniazid plus Rifapentine. Hepatotoxicity occurred in 3 (17.6 %) with INH. There were no interruptions of ILTB treatment during the study. ConclusionThe prevalence of LTBI was found to be high and treatment proved safe.

Diagnosis and Management of Latent Tuberculosis Infection: Updates.

India has the largest problem of tuberculosis (TB) infection globally (estimated at about 35-40 crores cases), and around 18-36 lakh develop active tuberculosis annually. Latent TB is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens with no evidence of clinically manifested active TB. The progression of a latent infection to active tuberculosis increases several-fold in children < 5 years of age and in people with some or the other form of an immunocompromising condition. Therefore, to cater to this gigantic problem of tuberculosis, it is necessary to have awareness about latent tuberculosis infection (LTBI) amongst clinicians and to prioritise its diagnosis and treatment in high-risk groups. India plans to end TB well before the deadline set by the World Health organisation (WHO). However, this can only be achieved with effective strategies targeting LTBI. Multiple treatment regimens have been approved for LTBI treatment, and all have comparable efficacy. The selection of one regimen over the other depends on various factors, such as availability, risk of adverse events, age, and drug interactions. Recently, the WHO, as well as the Revised National TB Control Programme (RNTCP), have updated their guidelines on TB preventive treatment in 2020 and 2021, respectively. This review has been especially prepared to acknowledge the differences in approach to LTBI in developed and developing countries.

Association Studies of Serum Levels of TNF- α, IL-10, IFN-γ and CXCL 5 with Latent Tuberculosis Infection in Close Contacts.

Early recognition and treatment of latent tuberculosis infection(LTBI) is key to tuberculosis(TB) prevention. However, the emergence of LTBI is influenced by a combination of factors, of which the role of individual immune cytokines remains controversial. The aim of this study is to explore the influencing factors of LTBI and their effects with cytokines on LTBI. Close contacts of tuberculosis in Urumqi City from 2021 to 2022 were selected for the study to conduct a field survey. It used logistic regression model to analyse the influencing factors of LTBI, principal component analysis to extract a composite indicators of cytokines, and structural equation modelling to explore the direct and indirect effects of cytokines and influencing factors on LTBI. LTBI infection rate of 33.3% among 288 TB close contacts. A multifactorial Logistic model showed that factors influencing LTBI included education, daily contact hours, eating animal liver, and drinking coffee (P<0.05); After controlling for confounding factors and extracting composite indicators of cytokines using principal component analysis, CXCL5 and IFN-γ is a protective factor for LTBI(OR=0.572, P=0.047), IL-10 and TNF-α is a risk factor for LTBI(OR=2.119, P=0.010); Structural equation modelling shows drinking coffee, eating animal liver, daily contact hours, and IL-10 and TNF-α had direct effects on LTBI and educations had indirect effects on LTBI(P<0.05). IL-10 and TNF-α are involved in the immune response and are directly related to LTBI. By monitoring the cytokine levels of TB close contacts and paying attention to their dietary habits and exposure, we can detect and intervene in LTBI at an early stage and control their progression to TB.

Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.