Months Of Isoniazid Research Articles

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

Hepatotoxicity, efficacy and completion rate between 3 months of isoniazid plus rifapentine and 9 months of isoniazid in treating latent tuberculosis infection: A systematic review and meta-analysis.

The mainstay therapy for latent tuberculosis infection is a 9-month regimen of daily isoniazid (9H) and a 3-month regimen of 12 once-weekly doses of isoniazid and rifapentine (3HP). We performed this updated meta-analysis to compare hepatotoxicity, efficacy and completion rate between these two regimens. We searched all literature in the major medical databases using the subject search terms "isoniazid" and "rifapentine", and performed a systemic review and meta-analysis. A total of 14 studies were eligible for the meta-analysis, which included 5600 (49%) patients who received the 3HP regimen and 5919 (51%) patients who received the 9H regimen. A total of 202 (2%) patients had a drug-induced liver injury (DILI) and 11 317 (98%) did not. The pooled odds ratio (OR) of DILI in the 3HP regimen was 0.18 (95% confidence interval [CI], 0.12-0.26; p < 0.0001), compared with the 9H regimen. This result remained consistent in subgroup analyses of ethnicity and study design. The 3HP regimen was superior to the 9H regimen in the prevention of active tuberculosis (OR, 0.38, 95% CI, 0.18-0.80, p = 0.01). Furthermore, the 3HP regimen was associated with a better completion rate than the 9H regimen (OR: 2.30, 95% CI, 2.10-2.53, p < 0.0001). The 3HP regimen is superior to the 9H regimen, with less hepatotoxicity, and better efficacy and completion rate in treating latent tuberculosis infection.

PERICARDIAL TB CAUSING RESTRICTIVE CARDIOMYOPATHY TREATED WITH RIFAMPIN, ISONIAZID, PYRAZINAMIDE, ETHAMBUTOL (RIPE) AND CORTICOSTEROIDS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pericardial tuberculosis presents in one to two percent of pulmonary tuberculosis (TB). Of these patients, approximately thirty to sixty percent develop constrictive pericarditis without treatment. This case presents a patient with constrictive pericarditis from reactivation of a prior pleural TB infection, treated with RIPE therapy and adjunctive steroids. CASE PRESENTATION: An 81 year old male from India with a history of pleural TB (treated with isoniazid, para-aminosalicylic acid and an unknown agent) and recent diagnosis of a large pericardial effusion without tamponade who presented with dyspnea. On presentation, he was hemodynamically stable. Physical exam was unremarkable. Labs significant for c-reactive protein of 166 mg/L and BNP of 508 pg/mL. Echocardiogram showed a small pericardial effusion with new constrictive pericarditis. Work up included a heart catheterization, consistent with constrictive physiology. Cardiac MRI revealed pericardial thickening, adhesions and fibrosis. A thoracoscopy with pericardial biopsy was performed and was negative for mycobacterium tuberculosis (MTB). Bronchoscopy with bronchoalveolar lavage was negative for MTB, however induced sputum post-bronchoalveolar was positive. He was treated with two months of RIPE therapy followed by four months of Isoniazid and Rifampin, in addition to prednisone 60 mg daily with a taper and Bactrim for Pneumocystis Jiroveci prophylaxis. After treatment initiation, sputum testing was negative. Repeat echocardiogram showed resolution of pericardial effusion without constriction. The patient tolerated treatment without complications. DISCUSSION: Tuberculosis pericarditis is diagnosed when any MTB is detected in the body in the setting of pericarditis. In this case, the patient underwent an extensive workup which revealed findings consistent with constrictive pericarditis, however the relation to tuberculosis was not established until his post-bronchoalveolar sputum despite negative pericardial biopsy. Negative pericardial biopsy results cannot rule out tuberculosis pericarditis as the sensitivity ranges from ten to sixty-four percent. A pericardiocentesis on initial presentation may have been helpful in an earlier diagnosis. Standard treatment is RIPE. However, the role of corticosteroids is controversial. Research supports the use of corticosteroids in patients who have or are at high risk of developing constrictive pericarditis. These patients include those with large pericardial effusions, high levels of inflammatory cells in pericardial fluid, and/or early signs of constriction. Corticosteroids have not become standard therapy due to significant side effects, with unclear benefits. CONCLUSIONS: Tuberculosis pericarditis is a rare and challenging diagnosis. Recommended treatment is with RIPE and the role of adjunct corticosteroids warrants further investigation. REFERENCE #1: Larrieu AJ, Tyers GF, Williams EH, Derrick JR. Recent experience with tuberculous pericarditis. Ann Thorac Surg 1980; 29:464. REFERENCE #2: Komsuoglu B, Goldeli O, Kulan K, Komsuoaylu SS. The diagnostic and prognostic value of adenosine deaminase in tuberculous pericarditis. Eur Heart J 1995; 16:1126. REFERENCE #3: Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis 2016; 63:e147. DISCLOSURES: No relevant relationships by Adetokunbo Adebayo, source=Web Response No relevant relationships by Alissa Ali, source=Web Response No relevant relationships by Jared Beaudin, source=Web Response No relevant relationships by Julie Nguyen, source=Web Response

Tuberculosis preventive therapy for people living with HIV: A systematic review and network meta-analysis.

Tuberculosis (TB) preventive therapy (TPT) is an essential component of care for people living with HIV (PLHIV). We compared efficacy, safety, completion, and drug-resistant TB risk for currently recommended TPT regimens through a systematic review and network meta-analysis (NMA) of randomized trials. We searched MEDLINE, Embase, and the Cochrane Library from inception through June 9, 2020 for randomized controlled trials (RCTs) comparing 2 or more TPT regimens (or placebo/no treatment) in PLHIV. Two independent reviewers evaluated eligibility, extracted data, and assessed the risk of bias. We grouped TPT strategies as follows: placebo/no treatment, 6 to 12 months of isoniazid, 24 to 72 months of isoniazid, and rifamycin-containing regimens. A frequentist NMA (using graph theory) was carried out for the outcomes of development of TB disease, all-cause mortality, and grade 3 or worse hepatotoxicity. For other outcomes, graphical descriptions or traditional pairwise meta-analyses were carried out as appropriate. The potential role of confounding variables for TB disease and all-cause mortality was assessed through stratified analyses. A total of 6,466 unique studies were screened, and 157 full texts were assessed for eligibility. Of these, 20 studies (reporting 16 randomized trials) were included. The median sample size was 616 (interquartile range [IQR], 317 to 1,892). Eight were conducted in Africa, 3 in Europe, 3 in the Americas, and 2 included sites in multiple continents. According to the NMA, 6 to 12 months of isoniazid were no more efficacious in preventing microbiologically confirmed TB than rifamycin-containing regimens (incidence rate ratio [IRR] 1.0, 95% CI 0.8 to 1.4, p = 0.8); however, 6 to 12 months of isoniazid were associated with a higher incidence of all-cause mortality (IRR 1.6, 95% CI 1.2 to 2.0, p = 0.02) and a higher risk of grade 3 or higher hepatotoxicity (risk difference [RD] 8.9, 95% CI 2.8 to 14.9, p = 0.004). Finally, shorter regimens were associated with higher completion rates relative to longer regimens, and we did not find statistically significant differences in the risk of drug-resistant TB between regimens. Study limitations include potential confounding due to differences in posttreatment follow-up time and TB incidence in the study setting on the estimates of incidence of TB or all-cause mortality, as well as an underrepresentation of pregnant women and children. Rifamycin-containing regimens appear safer and at least as effective as isoniazid regimens in preventing TB and death and should be considered part of routine care in PLHIV. Knowledge gaps remain as to which specific rifamycin-containing regimen provides the optimal balance of efficacy, completion, and safety.

Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

Low level of tuberculosis preventive therapy incompletion among people living with Human Immunodeficiency Virus in eastern Uganda: A retrospective data review

IntroductionIn most developing countries, tuberculosis (TB) is the leading cause of mortality among people living with the Human Immunodeficiency Virus (PLHIV). Uganda implements TB preventive therapy (TPT) using Isoniazid but data are limited about TPT incompletion. We, therefore, assessed the magnitude of TPT incompletion and the associated factors among PLHIV in a large rural referral health facility in rural eastern Uganda. Methods and materialsWe conducted a retrospective data review for PLHIV initiated on TPT between October 2018 and September 2019. The outcome variable was TPT incompletion defined as the failure to finish 6 consecutive months of Isoniazid or failure to finish 9 months of Isoniazid without stopping for more than 2 months at a time. We descriptively summarized numerical data using frequencies and percentages and compared differences in the outcome with independent variables using the Chi-square or fisher’s exact, and the Student’s t-tests. We used a generalized linear model to assess factors independently associated with TPT incompletion, reported using adjusted odds ratio (aOR) and 95% confidence interval (CI). ResultsWe enrolled 959 participants with a mean age of 41.1 ± 13.8 years, 561 (58.5%) were females, 663 (69.1%) married, 538 (56.1) travelled 5–10 km from their place of residence to the ART clinic, 293 (30.6%) had disclosed HIV status, 362 (37.7%) had been on ART for 5–9 years, and 923 (96.2%) were on first-line ART regimen. We found 26 (2.7%) participants had incomplete TPT. Non-adherence to ART clinic visits (aOR, 2.81; 95% CI, 1.09–7.73), history of switch in ART regimen (aOR, 9.33; 95% CI, 1.19–52.39), patient representation (aOR, 4.70; 95% CI, 1.35–13.99), and one unit increase in ongoing counselling session (aOR, 0.67; 95% CI, 0.46–0.91) were associated with TPT incompletion. ConclusionWe found low rates of TPT incompletion among PLHIV in rural eastern Uganda. Non-adherence to ART clinic visits, patient representation, and history of switch in ART regimen is associated with a higher likelihood of TPT incompletion while ongoing counselling is associated with a reduction in TPT incompletion. The health system should address non-adherence to ART clinic visits and patient representation, through ongoing psychosocial support.

Vikela Ekhaya: A Novel, Community-based, Tuberculosis Contact Management Program in a High Burden Setting.

BackgroundThe prevention of tuberculosis (TB) in child contacts of TB cases and people living with human immunodeficiency virus (HIV) is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.MethodsVikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases by using mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants’ homes.ResultsIn total, 945 contacts from 244 households were screened for TB symptoms; 72 (8%) contacts reported TB symptoms, and 5 contacts (0.5%) were diagnosed with prevalent TB. A total of 322 of 330 (98%) eligible asymptomatic household contacts initiated TPT. Of 322 contacts initiating TPT, 248 children initiated 3 months of isoniazid and rifampicin and 74 children and adults living with HIV initiated 6 months of isoniazid; 298 (93%) completed TPT. In clustered logistic regression analyses, unknown HIV status (adjusted odds ratio [aOR] 5.7, P = .023), positive HIV status (aOR 21.1, P = .001), urban setting (aOR 5.6, P = .006), and low income (aOR 5.9, P = .001) predicted loss from the cascade of care among TPT-eligible contacts.ConclusionVikela Ekhaya demonstrated that community-based TB household contact management is a feasible, acceptable, and successful strategy for TB screening and TPT delivery. The results of this study support the development of novel, differentiated, community-based interventions for TB prevention and control.

61-Year-Old Man With Shortness of Breath and Cough

A 61-year-old man presented with 3 weeks of shortness of breath and cough productive of occasional brown sputum. His medical comorbidities included Crohn colitis, deep vein thrombosis and pulmonary embolism on chronic anticoagulation, obstructive sleep apnea, obesity, impaired fasting glucose, depression, and latent tuberculosis status post 9 months of isoniazid. For the past year, his Crohn disease treatment regimen included methotrexate, and he received his first dose of ustekinumab 6 weeks before presentation.

Adverse events associated with weekly short course isoniazid and rifapentine therapy in pediatric patients with latent tuberculosis: A chart and literature review.

Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen's superior safety and adherence. We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving the 3HP regimen via DOT between 2017 and 2019. Frequencies of selected outcomes were compared to previously published data collected in a literature review. In this retrospective chart review, pediatric patients ages 2-20 years receiving 3HP with DOT for latent tuberculosis experienced frequent adverse events, more severe adverse events such as anaphylaxis, and higher treatment discontinuation than that which has been previously reported in the literature. Of note, our cohort's race/ethnicity differed from the cohorts described in the literature. Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the 3HP regimen's safety and tolerability.

Toward patient-centered tuberculosis preventive treatment: preferences for regimens and formulations in Lima, Peru

BackgroundTo ensure patient-centered tuberculosis preventive treatment, it is important to consider factors that make it easier for patients to complete treatment. However, there is little published literature about patient preferences for different preventive treatment regimen options, particularly from countries with high tuberculosis burdens.MethodsWe conducted a qualitative research study using a framework analysis approach to understand tuberculosis preventive treatment preferences among household contacts. We conducted three focus group discussions with 16 members of families affected by tuberculosis in Lima, Peru. Participants were asked to vote for preferred preventive treatment regimens and discuss the reasons behind their choices. Coding followed a deductive approach based on prior research, with data-driven codes added.ResultsIn total, 7 (44%) participants voted for 3 months isoniazid and rifapentine, 4 (25%) chose 3 months isoniazid and rifampicin, 3 (19%) chose 4 months rifampicin, and 2 (13%) chose 6 months isoniazid. Preferences for shorter regimens over 6 months of isoniazid were driven by concerns over “getting tired” or “getting bored” of taking medications, the difficulty of remembering to take medications, side effects, and interference with daily life. For some, weekly dosing was perceived as being easier to remember and less disruptive, leading to a preference for 3 months isoniazid and rifapentine, which is dosed weekly. However, among caregivers, having a child-friendly formulation was more important than regimen duration. Caregivers reported difficulty in administering pills to children, and preferred treatments available as syrup or dispersible formulations.ConclusionsThere is demand for shorter regimens and child-friendly formulations for tuberculosis preventive treatment in high-burden settings. Individual preferences differ, suggesting that patient-centered care would best be supported by having multiple shorter regimens available.

Cost of Delivering 12-Dose Isoniazid and Rifapentine Versus 6 Months of Isoniazid for Tuberculosis Infection in a High-Burden Setting.

BackgroundSuccessful delivery and completion of tuberculosis preventive treatment are necessary for tuberculosis elimination. Shorter preventive treatment regimens currently have higher medication costs, but patients spend less time in care and are more likely to complete treatment. It is unknown how economic costs of successful delivery differ between longer and shorter regimens in high-tuberculosis-burden settings.MethodsWe developed survey instruments to collect costs from program and patient sources, considering costs incurred from when household contacts first entered the health system. We compared the cost per completed course of preventive treatment with either 6 months of daily isoniazid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network tuberculosis program in Karachi, Pakistan, between October 2016 and February 2018.ResultsDuring this period, 459 individuals initiated 6H and 643 initiated 3HP; 39% and 61% completed treatment, respectively. Considering costs to both the program and care recipients, the cost per completed course was 394 US dollars (USD) for 6H and 333 USD for 3HP. Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP to 290 USD. Under varying assumptions about drug prices and costs incurred by care recipients, the cost per completed course was lower for 3HP in all scenarios, and the largest cost drivers were the salaries of clinical staff.ConclusionsIn a high-burden setting, the cost of successful delivery of 3HP was lower than that of 6H, driven by higher completion.

Safety and Efficacy of Rifampin or Isoniazid Among People With Mycobacterium tuberculosis Infection and Living With Human Immunodeficiency Virus or Other Health Conditions: Post Hoc Analysis of 2 Randomized Trials.

The safety and efficacy of rifampin among people living with human immunodeficiency virus (PLHIV) or other health conditions is uncertain. We assessed completion, safety, and efficacy of 4 months of rifampin vs 9 months of isoniazid among PLHIV or other health conditions. We conducted post hoc analysis of 2 randomized trials that included 6859 adult participants with Mycobacterium tuberculosis infection. Participants were randomized 1:1 to 10 mg/kg/d rifampin or 5 mg/kg/d isoniazid. We report completion, drug-related adverse events (AE), and active tuberculosis incidence among people living with HIV; with renal failure or receiving immunosuppressants; using drugs or with hepatitis; with diabetes mellitus; consuming >1 alcoholic drink per week or current/former smokers; and with no health condition. Overall, 270 (3.9%) people were living with HIV (135 receiving antiretroviral therapy), 2012 (29.3%) had another health condition, and 4577 (66.8%) had no condition. Rifampin was more often or similarly completed to isoniazid in all populations. AEs were less common with rifampin than isoniazid among PLHIV (risk difference, -2.1%; 95% confidence interval [CI], -5.9 to 1.6). This was consistent for others except people with renal failure or on immunosuppressants (2.1%; 95% CI, -7.2 to 11.3). Tuberculosis incidence was similar among people receiving rifampin or isoniazid. Among participants receiving rifampin living with HIV, incidence was comparable to those with no health condition (rate difference, 4.1 per 1000 person-years; 95% CI, -6.4 to 14.7). Rifampin appears to be safe and as effective as isoniazid across many populations with health conditions, including HIV. NCT00170209; NCT00931736.

Programmatic Effectiveness of Latent Tuberculosis Care Cascade in a Community Health Center.

Our aim was to quantify successful completion of steps of the latent tuberculosis (LTBI) care cascade in a community health center (CHC) with a large foreign-born population. We conducted a retrospective cohort study of individuals with a positive test for tuberculosis (TB) infection from 2015 to 2017 at Baltimore Medical Systems (BMS). During the study period, 3,984 individuals were tested for TB. Of the 418 individuals with positive tests, 152 (36%) were referred elsewhere for care, whereas 266 (64%) were retained in care at BMS. Treatment was prescribed for 157 of the 214 (73%) diagnosed with LTBI and retained in care at BMS (125/157 [80%] four months of rifampin; 32/157 [20%] nine months of isoniazid). One hundred forty-one patients (141/157, 90%) initiated treatment, of which 119 completed therapy (119/141, 84%). Our study identified several gaps in the LTBI care cascade in a CHC. Nonetheless, a large proportion of those treated for LTBI at the CHC completed therapy.

Advantage in privacy protection by using synchronous video observed treatment enhances treatment adherence among patients with latent tuberculosis infection

BackgroundTreatment of latent tuberculosis infection (LTBI) is an important strategy for active disease prevention. Conventional in-person DOT (CDOT) programs are challenged by patient dissatisfaction over problems of convenience and privacy. The present study assessed satisfaction to DOT program and treatment adherence of synchronous video observed treatment (SVOT) programs from patients’ perspectives. MethodsA two-part questionnaire was presented to 240 subjects with LTBI who received a 9-month isoniazid treatment regimen along with mandatory DOT monitoring during January 2014 to December 2017. ResultsSatisfactions with location arrangement (p<0.001), ensuring treatment adherence (p=0.027), and privacy issues (p=0.005) were superior in the SVOT group. The overall rate of LTBI treatment completion was 91.25%. One (1.25%) and 20 (12.50%) of the participants in the SVOT and CDOT groups, respectively, quit LTBI treatment (p=0.008). Development of adverse events [adjusted hazard ratio, aHR 8.01 (3.42–18.79)], and the concern of privacy infringement [aHR 5.86 (2.69–12.76)] by the DOT program independently increase the risk of withdrawal. SVOT program [aHR 0.21 (0.06–0.68)] and a belief in the importance of adherence on treatment efficacy [aHR 0.29 (0.08–0.98)] were independent predictors preventing patients from withdrawing from treatment. ConclusionsA comprehensive patient-centered DOT program enables high treatment adherence for the 9-month isoniazid LTBI treatment. Furthermore, SVOT was associated with superior patients’ satisfactions which translate into higher treatment completion rates. As treatment adherence is the key to the efficacy of LTBI treatment, SVOT should be a reasonable supplement for LTBI treatment.

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.

Four months of rifampin is noninferior to nine months of isoniazid for latent TB

Four months of rifampin is noninferior to nine months of isoniazid for latent TB

Expression of USP18 and IL2RA Is Increased in Individuals Receiving Latent Tuberculosis Treatment with Isoniazid.

Background The treatment of latent tuberculosis infection (LTBI) in individuals at risk of reactivation is essential for tuberculosis control. However, blood biomarkers associated with LTBI treatment have not been identified. Methods Blood samples from tuberculin skin test (TST) reactive individuals were collected before and after one and six months of isoniazid (INH) therapy. Peripheral mononuclear cells (PBMC) were isolated, and an in-house interferon-γ release assay (IGRA) was performed. Expression of chemokine ligand 4 (CCL4), chemokine ligand 10 (CXCL10), chemokine ligand 11 (CXCL11), interferon alpha (IFNA), radical S-adenosyl methionine domain-containing 2 (RSAD2), ubiquitin-specific peptidase 18 (USP18), interferon-induced protein 44 (IFI44), interferon-induced protein 44 like (IFI44L), interferon-induced protein tetratricopeptide repeats 1(IFIT1), and interleukin 2 receptor subunit alpha (IL2RA) mRNA levels were assessed by qPCR before, during, and after INH treatment. Results We observed significantly lower relative abundances of USP18, IFI44L, IFNA, and IL2RA transcripts in PBMC from IGRA-positive individuals compared to levels in IGRA-negative individuals before INH therapy. Also, relative abundance of CXCL11 was significantly lower in IGRA-positive than in IGRA-negative individuals before and after one month of INH therapy. However, the relative abundance of CCL4, CXCL10, and CXCL11 mRNA was significantly decreased and that of IL2RA and USP18 significantly increased after INH therapy, regardless of the IGRA result. Our results show that USP18, IFI44L, IFIT1, and IL2RA relative abundances increased significantly, meanwhile the relative abundance of CCL4, CXCL11, and IFNA decreased significantly after six months of INH therapy in TST-positive individuals. Conclusions Changes in the profiles of USP18, IL2RA, IFNA, CCL4, and CXCL11 expressions during INH treatment in TST-positive individuals, regardless of IGRA status, are potential tools for monitoring latent tuberculosis treatment.

Conversion of QuantiFERON-TB Gold Plus following Isoniazid Prophylaxis among Latent Tuberculosis Patients

OBJECTIVES: To evaluate the conversion of QuantiFERON-TB Gold plus (QFT-Plus) following Isoniazid prophylaxis among latent tuberculosis (LTB) patient. MATERIAL AND METHODS: We conducted a case series starting in December 2016 up to the present March 2019. Twenty asymptomatic cases were identified to have had exposure to active tuberculosis (TB) infection, undergone chest x-ray and QFT-Plus test. Those with positive test QFT-Plus results with negative chest x-ray reports were prescribed with Isoniazid 300mg tablet once daily for nine months. Post prophylaxis, chest x-ray and QFT-Plus were repeated to determine the conversion results. RESULT: All 20 participants were QFT-Plus test positive and chest x-ray negative. The average age was 47 ± 5.7 years and there were eighteen females and two males. Two had underlying conditions: valvular heart disease and peripheral neuropathy. All took the nine-month Isoniazid prophylaxis and repeated the QFT-Plus test and chest x-ray. Chest x-ray results again were all negative. Eighteen cases revealed persistence of positive QFT-Plus and two cases were negative. The initial conversion rate of QFT-Plus post treatment (2017) was ten percent. In the succeeding years (2018 and 2019), another ten percent conversion was reported and sixteen cases maintained their positive baseline score. CONCLUSION: To our knowledge this clinical series is the first to report 20% conversion rate of QFT-Plus among LTB participants prescribed with a nine-month Isoniazid prophylaxis. This study only evaluated the conversion of QFT-Plus with LTB participants being treated with 9-month Isoniazid. As there is no gold standard on the definition and distinction of conversion and reversion, further studies are warranted to optimize the correlation between the efficacy of varied latent tuberculosis infection (LTBI) and TB treatment regimen and conversion of QFT-Plus results.

Determinants of Latent Tuberculosis Treatment Acceptance and Completion in Healthcare Personnel.

US public health strategy for eliminating tuberculosis (TB) prioritizes treatment of latent TB infection (LTBI). Healthcare personnel (HCP) are less willing to accept treatment than other populations. Little is known about factors associated with HCP LTBI therapy acceptance and completion. We conducted a retrospective chart review to identify all employees with LTBI at time of hire at a large academic medical center during a 10-year period. Personal demographics, occupational factors, and clinic visit variables were correlated with LTBI treatment acceptance and completion rates using multivariate logistic regression. Of 470 HCP with LTBI for whom treatment was recommended, 193 (41.1%) accepted treatment, while 137 (29.1%) completed treatment. Treatment adherence was better with 4 months of rifampin than 9 months of isoniazid (95% vs 68%, P < .005). Increased age of the healthcare worker was independently associated with lower rates of treatment acceptance (odds ratio [95% confidence interval]: 0.97 [0.94-0.99] per year), as was having an occupation of clinician (0.47 [0.26-0.85]) or researcher (0.34 [0.19-0.64]). Male gender was associated with higher treatment acceptance (1.90 [1.21-2.99]). Treatment completion was associated with being from a low- (9.49 [2.06-43.73]) or medium- (8.51 [3.93-18.44]) TB-burden country. Geographic and occupational factors affect acceptance and completion of LTBI therapy. Short-course regimens may improve adherence. Physicians, researchers, and HCP from high-TB-burden countries have lower treatment rates than other HCP. Improving LTBI treatment in HCP will require attending to cultural and occupational differences.

Evaluation and treatment of latent tuberculosis infection among healthcare workers in Korea: A multicentre cohort analysis.

ObjectiveHealthcare workers (HCWs) are one of the target groups for systematic testing and treatment of latent tuberculosis infection (LTBI) in a setting of low TB incidence. We performed this study to describe the testing of HCWs for LTBI and analyse the acceptance and completion of treatment of LTBI.MethodsThis retrospective cohort study was conducted in four university-affiliated hospitals between January 1 and December 31, 2018. HCWs with positive interferon-gamma release assay (IGRA) during LTBI screening were analysed. We assessed the acceptance and completion of LTBI treatment.ResultsOverall, 893 HCWs were IGRA positive. Among them, 609 HCWs visited the clinic for evaluation of LTBI. Of 609 HCWs who were evaluated, 302 (49.6%) were offered treatment for LTBI. The proportion of acceptance for treatment was 64.5% (195 of 302 HCWs). The treatment course was completed by 143 of 195 HCWs (73.3%). Three months of isoniazid and rifampin (3HR) was used in 137 HCWs (70.3%) and 4 months of rifampin (4R) in 58 (29.7%). 72 HCWs (36.9%) experienced at least one adverse drug events, but there was no different characteristics between completer and non-completer.ConclusionThe acceptance and completion of LTBI treatment were unsatisfactory. Subjective perspective regarding obstacles to treatment of LTBI needs to be explored to increase compliance to LTBI treatment.