Negative Tuberculin Skin Test Research Articles

Evaluating Treatment Outcomes and Tuberculosis Infection Risks: A Comparative Study of Centralized Hospitalization vs. Home-Based Treatment.

Background: Guizhou Province in Southwest China has experimented with a centralized hospitalization (CH) treatment for active and severe cases of pulmonary tuberculosis (PTB). The objective of this study was to compare treatment outcomes of patients with tuberculosis (TB) receiving care in a CH setting with those receiving home-based (HB) care. In addition, this study aimed to assess the probability of their household contacts contracting tuberculosis infection. Method: A retrospective review of medical records was undertaken for patients with TB who completed their treatment in four counties in Guizhou, China, spanning from January 2022 to August 2023. In addition, a cross-sectional survey was conducted on the tuberculin skin test (TST) among household contacts of new patients with TB who had completed their treatment. Results: In the retrospective study, 94.8% had successful CH treatment, and 93.1% had successful HB treatment (p value = 0.70). In the prospective study, 559 and 448 household contacts of patients receiving CH treatment had 16 positive and 89 negative TST results, whereas those with HB treatment showed 26 positive and 74 negative TST results. Regarding a logistic regression analysis, the CH group was nearly two times more likely to test negative on the TST, 1.95 (95% CI: 0.98, 3.92). After adjusting for confounding variables, the odds ratio increased significantly to 4.42 (95% CI: 1.22, 16.04). Conclusions: CH for treatment of TB did not show superior success rates, but it may reduce the risk of transmitting tuberculosis infection to household contacts compared to home treatment.

Tuberculosis among children visiting friends & relatives.

Most paediatric tuberculosis (TB) cases in low-TB-incidence countries involve children born to migrant families. This may be partially explained by trips to their countries of origin for visiting friends and relatives (VFR). We aimed to estimate the risk of latent TB infection (LTBI) and TB in children VFR. We conducted a prospective multicentric observational study in Catalonia (Spain) from 06/2017 to 12/2019. We enrolled children aged < 15years with a negative tuberculin skin test (TST) at baseline and at least one parent from a high-TB-incidence country, and who had travelled to their parent's birth country for ≥21days. TST and QuantiFERON-TB Gold Plus (QFT-Plus) were performed within 8-12weeks post-return. LTBI was defined as a TST ≥5mm and/or a positive QFT-Plus. Five hundred children completed the study, equivalent to 78.2 person-years of follow-up (PYFU). Thirteen children (2.6%) were diagnosed with LTBI (16.6/per100 PYFU,95%CI = 8.8-28.5), including two cases (0.4%) of TB (2.5/per100 PYFU, 95%CI = 0.3-9.3). LTBI incidence rates remained high after excluding BCG-vaccinated children (9.7/per100 PYFU,95%CI = 3.9-20.0). Household tobacco smoke exposure was associated with LTBI (aOR = 3.9, 95%CI = 1.1-13.3). The risk of LTBI in children VFR in high-TB-incidence countries may equal, or perhaps even exceed, the infection risk of the native population. The primary associated risk factor was the presence of smokers in the household. Furthermore, the incidence rate of active TB largely surpassed that of the countries visited. Children VFR in high-TB-incidence countries should be targeted for diagnostic and preventive interventions.

Miliary Tuberculosis as Postmortem Diagnosis in Solid Organ Transplant Recipient: Case Report and Review of the Literature

The diagnosis of tuberculosis (TB) in solid organ transplant (SOT) recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin test or/and interferon-gamma release assays, and negative sputum smear results despite active disease. The treatment poses challenges due to pharmacokinetic interactions, allograft-related toxicity, and inadequate immune response. We report the case of a 70-year-old man after kidney transplantation in 2012. The patient was transferred from the urology unit with deteriorating renal function and presumed urosepsis. His pulmonary chest X-ray showed hilar pulmonary infiltrates. Computed tomography of the chest/abdomen/pelvis revealed mediastinal lymphadenopathy, pulmonary infiltrates, pulmonary effusion, and splenomegaly. His blood results showed pancytopenia and high inflammatory and renal markers. He was treated with broad-spectrum antibiotics covering bacterial, fungal, and viral infections. Despite initial clinical improvement, his kidney function deteriorated, and he required hemodialysis. His temperature continued to spike. On physical examination, he was confused and lethargic. He was scheduled to have a mediastinoscopy with lymph node biopsy, but he died the day before. The postmortem examination revealed miliary tuberculosis with tuberculosis of many organs: kidney transplant, native kidney, bone marrow, mediastinal lymph nodes, lungs, and spleen. The diagnosis of active TB in transplant recipients requires a high index of suspicion and invasive procedures. The majority of all cases of active TB after SOT are disseminated or occur at extrapulmonary sites. Only a small minority of patients have classic cavitary changes on pulmonary imaging.

Tubercolosi vertebrale atipica: un caso clinico e revisione della letteratura

Background - Rates of Extrapulmonary Tuberculosis (TB) are higher in paediatric patients, especially in those from endemic areas. Bone TB is mostly located in the spine and in children may cause rapid bone destruction with severe deformity and neurological deficits. Case report - The paper reports the case of a 14-year-old male patient from Pakistan presenting with neurological symptoms and neuroradiological features suspicious for malignant tumour. After surgical removal of the mass, PCR test showed spinal TB. Tuberculin skin test (TST) and Interferon-Gamma Release Assays (IGRA) resulted negative. Discussion - False negative IGRA and TST test results can occur due to several factors, including immunodeficiency disorders. Some cases of spinal TB do not have typical radiological features, causing diagnostic delays or mistakes. Non-typical spinal TB features include: (1) involvement of the posterior elements of the spinal column; (2) skip lesions; (3) non-osseous TB involving spinal cord, cauda equina, and/or meninges. Conclusion - The differential diagnosis between spinal TB and malignancy might be challenging. Consequently, considering TB in children with neurological symptoms and/or vertebral neoformation, especially in patients coming from endemic areas, is recommended. TB diagnosis should not be excluded in case of non-typical radiological features, negative TST and IGRA or history of anti-TB vaccination. This approach should facilitate a timely diagnosis for appropriate treatment, avoiding neurological sequalae and delayed deformities.

Tubercular Serpiginous-Like Choroiditis in Patients with Negative TB-Immunoreactivity Tests

ABSTRACT Background Serpiginous-like choroiditis (SLC) denotes ocular tuberculosis (TB), in the presence of positive tuberculin skin test (TST) or interferon gamma release assay (IGRA). Methods Retrospective review of SLC patients from a TB-endemic country, with negative TST and IGRA tests, but responsive to anti-TB therapy. Results Fifteen patients (13 bilateral) with active SLC were included. Eleven (73.3%) patients had received corticosteroids ± immunosuppressive therapy prior to presentation. Chest radiographic abnormalities were found in four (26.7%) patients. We treated all patients with a combination of anti-TB therapy (ATT) and corticosteroids. Paradoxical worsening was noted in nine (60%) patients, complete resolution of lesions in 12 (80%), persistent inflammation (post-ATT) in one, while two were yet to complete ATT. None had recurrence after complete resolution of lesions (median follow-up of 71 weeks [range 15–676 weeks]). Conclusions TB-SLC may present with negative TST and IGRA tests but may still have clinical appearance, and treatment response, like test-positive disease.

Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among Mycobacterium tuberculosis exposed persons living with HIV.

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization to Mycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. Since there was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT, we focused on the 6h timepoint. When compared to uninfected PMN, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated differentially expressed genes (DEGs) (absolute cutoff of a log2FC of 0.2, FDR < 0.05) whereas PMNHIT demonstrated 3816 significantly upregulated and 3794 significantly downregulated DEGs following 6h Mtb infection. Contrasting the log2FC 6h infection response to Mtb from PMNHITTIN against PMNHIT, 2285 genes showed significant differential response between the two groups. Overall PMNHITTIN had a lower fold change response to Mtb infection compared to PMNHIT. According to pathway enrichment, Apoptosis and NETosis were differentially regulated between HITTIN and HIT PMN responses after 6h Mtb infection. To corroborate the blunted NETosis transcriptional response measured among HITTIN, fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMNHITTIN compared to PMNHIT, showing that PMNHITTIN have a distinct response to Mtb.

Postvaccination immune responses and risk of primary total hip arthroplasty—A population-based cohort study

To investigate the relationship between individual postvaccination immune responses and subsequent risk of total hip arthroplasty (THA) due to idiopathic osteoarthritis (OA) or rheumatoid arthritis (RA). Results of tuberculin skin tests (TSTs) following the Bacille Calmette-Guerin (BCG) vaccination were used as a marker of individual immune responses. TST results from the mandatory mass tuberculosis screening program 1948-1975 (n=236 770) were linked with information on subsequent THA during 1987-2020 from the Norwegian Arthroplasty Register. The multivariable Cox proportional hazardregression was performed. A total of 10 698 individuals received a THA during follow-up. In men, there was no association between TST and risk of THA due to OA (Hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.92-1.12 for positive versus negative TST and HR 1.06, 95% CI 0.95-1.18 for strong positive vs negative TST), while the risk estimates increased with increasingly restrictive sensitivity analyses. In women, there was no association with THA due to OA for positive versus negative TST (HR 0.98, 95% CI 0.92-1.05), while a strong positive TST was associated with reduced risk of THA (HR 0.90, 95% CI 0.84-0.97). No significant associations were observed in the sensitivity analysis for women or for THA due to RA. Our results suggestthat an increased postvaccination immune response is associated with a nonsignificant trend of increased risk of THA among men and a decreased risk among women, although risk estimates were small.

Differentially expressed transcript isoforms associate with resistance to tuberculin skin test and interferon gamma release assay conversion.

A mechanistic understanding of uncommon immune outcomes such as resistance to infection has led to the development of novel therapies. Using gene level analytic methods, we previously found distinct monocyte transcriptional responses associated with resistance to Mycobacterium tuberculosis (Mtb) infection defined as persistently negative tuberculin skin test (TST) and interferon gamma release assay (IGRA) reactivity among highly exposed contacts (RSTR phenotype). Using transcript isoform analyses, we aimed to identify novel RSTR-associated genes hypothesizing that previous gene-level differential expression analysis obscures isoform-specific differences that contribute to phenotype. Monocytes from 49 RSTR versus 52 subjects with latent Mtb infection (LTBI) were infected with M. tuberculosis (H37Rv) or left unstimulated (media) prior to RNA isolation and sequencing. RSTR-associated gene expression was then identified using differential transcript isoform analysis. We identified 81 differentially expressed transcripts (DETs) in 70 genes (FDR <0.05) comparing RSTR and LTBI phenotypes with the majority (n = 79 DETs) identified under Mtb-stimulated conditions. Seventeen of these genes were previously identified with gene-level bulk RNAseq analyses including genes in the IFNγ response that had increased expression among LTBI subjects, findings consistent with a clinical phenotype based on IGRA reactivity. Among the subset of 23 genes with positive differential expression among Mtb-infected RSTR monocytes, 13 were not previously identified. These novel DET genes included PDE4A and ZEB2, which each had multiple DETs with higher expression among RSTR subjects, and ACSL4 and GAPDH that each had a single transcript isoform associated with RSTR. Transcript isoform-specific analyses identify transcriptional associations, such as those associated with resistance to TST/IGRA conversion, that are obscured when using gene-level approaches. These findings should be validated with additional RSTR cohorts and whether the newly identified candidate resistance genes directly influence the monocyte Mtb response requires functional study.

Risk of tuberculosis in children with rheumatologic diseases treated with biological agents: A cross-sectional cohort study.

This study aimed to evaluate the risk of tuberculosis (TB) disease in children receiving biological agents for rheumatologic diseases, focusing on appropriate screening tests in a high-priority country for TB control. One hundred nine children (56 females, 53 males; range, 3.4 to 16.2 years) who received any biological agent for rheumatologic diseases for more than two years between May 2012 and October 2021 were included in this retrospective study. Patients were screened for TB infection using tuberculin skin test (TST) or interferon-gamma release assay (IGRA). Following the initial evaluation, patients were clinically examined for TB every three months by a comprehensive medical history and physical examination, and every 12 months using TST or IGRA. At the initiation of the biological agent, the patients' mean age was 12.4±4.5 years. The average follow-up duration was 3.6±1.3 years (range, 2.6 to 10.2 years) for patients treated with biological agents. Each patient had a documented Bacillus Calmette-Guérin vaccination. Before the initiating of therapy, TST was performed alone in 45 (41.3%) patients and in combination with IGRA in 64 (58.7%) patients. In the 64 patients who underwent both TST and IGRA, IGRA revealed nine (14.1%) positive results. Six (66.7%) of these nine patients, however, had negative baseline TST. Four (7.3%) of the 55 individuals whose initial IGRA results were negative also had positive TST results. Overall, no TB disease was observed after a follow-up period. This study reveals that biological agents were not associated with an increased risk of TB disease in closely monitored children. Additionally, the concomitant use of TST and IGRA for screening of TB is reasonable in patients receiving biological agents.

Cutaneous Sarcoidosis Masquerading as Papular Amyloidosis Revealed Post--Hair Removal.

Cutaneous Sarcoidosis Masquerading as Papular Amyloidosis Revealed Post--Hair Removal.

1435. Incidence of Tuberculosis Infection Among New Prisoners in Southern Thailand

Abstract Background Tuberculosis in prisons was reported to be 100 times higher than the normal population. Late diagnosis, overcrowding, and poor ventilation encourage the transmission of tuberculosis. Five percent of new tuberculosis infections turn into active disease within two years. This study was conducted to determine the incidence of tuberculosis infection among new prisoners in southern Thailand. Methods A prospective cohort study was planned for January 2020‒December 2021 at Songkhla Provincial Prison. However, due to the emerging COVID-19 pandemic, the study was terminated early in February 2021. All new prisoners aged ≥15 years were included. Subjects were excluded if they had any history of a previous diagnosis of tuberculosis, household contact with a tuberculosis patient, or a history of repeated imprisonment. Chest radiography together with a 2-step tuberculin skin test (TST) was done within 2 weeks after imprisonment and at 6 months using the one-step TST. A positive TST was defined by a skin reaction ≥1.5 cm. Prisoners with negative TST had a repeat TST at 6 months. New tuberculosis infection was defined by conversion of TST to positive after 6 months of imprisonment without evidence of active tuberculosis from chest radiography. Results The number of new prisoners during the study period was 602. All prisoners were men with an average age of 31.11 (range 18‒75) years Fifty-one prisoners were excluded. Three hundred and eighty-five prisoners completed the 2-step TST. A total of 11.07% (61/551) of subjects had initially tested positive. Three hundred and seventy prisoners were followed. The COVID-19 pandemic caused a total shutdown of the study because access to the prison was blocked. Therefore, only 53 (9.6%) prisoners completed the study protocol at 6 months. Five prisoners (9.4%) were tuberculin converters with no evidence of active tuberculosis from chest radiography Conclusion The incidence of tuberculosis infection in new prisoners was 9.4%. This study has limitations. Due to the emerging COVID-19 pandemic, 90.4% of subjects were lost to follow-up and some prisoners were released before 6 months, which caused low power of the study. Further studies are needed to identify the incidence of new tuberculosis infection in new prisoners. Disclosures All Authors: No reported disclosures.

Implementation of a Routine Screening Program for Latent Tuberculosis Infection among Patients with Acute Leukemia at a Canadian Cancer Center

Screening for latent tuberculosis infection (LTBI) in patients with hematological malignancy is recommended because of their increased risk of tuberculosis (TB). We assessed the utility of tuberculin skin test (TST) screening in patients with acute leukemia and subsequent outcomes of LTBI treatment. We retrospectively evaluated patients ≥16 years of age with acute leukemia from 2013-2014 with a TST planted and read prior to the initiation of antineoplastic chemotherapy treatment. Demographics, clinical information and treatment outcomes of LTBI therapy were compared between patients with positive TST (≥10 mm induration) and negative TST. A total of 389 patients with acute leukemia were included in the cohort. Of them, 37/389 (9.5%) had a positive TST. Only 3.4% (8/235) of individuals originating from North and South America as well as the Caribbean were TST positive, while 21% (20/95) of individuals from Asia were TST positive. Diagnostic imaging findings consistent with prior tuberculosis infection were higher in TST positive patients compared to TST negative ones (29.7% versus 9.4%, p < 0.0001). Furthermore, 31/38 patients (81.6%) who were TST positive received LTBI therapy, which was well tolerated. There was no significant difference in overall survival among those who received LTBI therapy compared to those who did not. No patients developed active TB. Universal screening with TST may be of low yield in individuals with acute leukemia unless patients originate from a TB endemic country. When therapy for LTBI is prescribed, patients with acute leukemia do not experience drug-induced liver toxicity and are likely to complete the intended duration of therapy, thus preventing the development of active tuberculosis.

Tuberculin skin test versus QuantiFERON-TB gold in-tube for latent tuberculosis screening in people living with HIV in a resource-limited setting.

To compare QuantiFERON-TB Gold-in-Tube (QFT) and tuberculin skin test (TST) in the diagnosis of latent tuberculosis infection (LTBI) among people living with HIV (PLWHIV). A cross-sectional study was carried out between 2017-2018. Tuberculin skin test and QFT were performed and their concordance was measured. The gold standard for LTBI was defined as positivity to any of the tests. A logistic regression model was carried out to predict the QFT result in patients with a negative TST. A total of 510 PLWHIV were included, with 409 (80.2%) being male. The mean age of the patients was 41.3 ± 11.8years. The median time since HIV diagnosis was 5years (IQR 2-10), with a median CD4+ count of 541 (IQR 340-757) cells/mm3. Overall, 20 patients had an isolated TST+, 22 an isolated QFT+ and 15 had both positive. Concordance between tests showed a kappa coefficient of .37. Overcrowding was the only predictor for a positive QFT after a negative TST (p = .003). There was fair agreement between tests in PLWHIV. In conditions of limited access to QTF, a TST-based strategy could be considered, with sequential use of QTF in high-risk patients with a negative result, especially those who live in overcrowded conditions.

Gene expression profiling identifies candidate biomarkers for new latent tuberculosis infections. A cohort study.

To determine the gene expression profile in individuals with new latent tuberculosis infection (LTBI), and to compare them with people with active tuberculosis (TB) and those exposed to TB but not infected. A prospective cohort study. Recruitment and follow-up were conducted between September 2016 to December 2018. Gene expression and data processing and analysis from April 2019 to April 2021. Two male Colombian prisons. 15 new tuberculin skin test (TST) converters (negative TST at baseline that became positive during follow-up), 11 people that continued with a negative TST after two years of follow-up, and 10 people with pulmonary ATB. Gene expression profile using RNA sequencing from PBMC samples. The differential expression was assessed using the DESeq2 package in Bioconductor. Genes with |logFC| >1.0 and an adjusted p-value < 0.1 were differentially expressed. We analyzed the differences in the enrichment of KEGG pathways in each group using InterMiner. The gene expression was affected by the time of incarceration. We identified group-specific differentially expressed genes between the groups: 289 genes in people with a new LTBI and short incarceration (less than three months of incarceration), 117 in those with LTBI and long incarceration (one or more years of incarceration), 26 in ATB, and 276 in the exposed but non-infected individuals. Four pathways encompassed the largest number of down and up-regulated genes among individuals with LTBI and short incarceration: cytokine signaling, signal transduction, neutrophil degranulation, and innate immune system. In individuals with LTBI and long incarceration, the only enriched pathway within up-regulated genes was Emi1 phosphorylation. Recent infection with MTB is associated with an identifiable RNA pattern related to innate immune system pathways that can be used to prioritize LTBI treatment for those at greatest risk for developing active TB.

Retinitis due to Rickettsia infection

A 67-year-old woman with type 2 diabetes presented to our hospital with decreased left vision for 7 days. On examination, right visual acuity was 20/30, and left visual acuity was 20/50. Intraocular pressures were both normal. Anterior chambers were deep and uninflamed, with bilateral nuclear sclerotic cataracts. There was mild left vitritis, but none in the right eye. Right fundoscopy was normal. Left fundoscopy showed one-disc diameter of unifocal retinitis along the superior vascular arcade (figure A). Left fluorescein angiography revealed late staining in the area of retinitis. The patient was treated presumptively with anti-toxoplasmosis and anti-herpes therapy (oral pyrimethamine [100 mg for the first day then 50 mg daily] and oral sulfadiazine [1 g three times daily] for toxoplasmosis, and intravenous aciclovir [800 mg three times daily] for herpetic retinitis), while awaiting laboratory results. PCR testing of anterior chamber taps were negative for Herpes simplex virus and toxoplasmosis. Negative Treponema pallidum hemagglutination and venereal disease research laboratory test excluded syphilis. Negative QuantiFERON-TB Gold test and tuberculin skin test were negative, and eliminated tuberculosis as a possible cause. Serum angiotensin converting enzyme and lysozyme were normal, which made sarcoidosis an unlikely explanation for the clinical findings. The patient's vision worsened to 20/200 in the left eye. Fundoscopy showed ongoing retinitis with a new retinal haemorrhage and serous macular detachment. She subsequently disclosed having episodes of malaise, headache, myalgia, skin rash (figure B), and fever (maximum 39·5°C; unresponsive to amoxicillin 500 mg three times a day), following travel to rural Algeria. Serology for Rickettsia conorii showed an elevated IgG titer of 1024 g/L, but was negative for IgM. Anterior tap PCR and cutaneous biopsy were negative for Rickettsia. Fundoscopy improved markedly after 7 days of treatment with doxycycline (200 mg daily). After 2 months, visual acuity was 20/20 and the retinitis resolved fully. This case illustrates the importance of careful history taking, and maintaining an index of suspicion for Rickettsia in patients who have travelled to an endemic area and present with fever, skin rash, and retinitis.

Incomplete contact investigation and risk of developing TB among healthcare professionals.

BACKGROUND: Data on the impact of incomplete contact investigation on TB incidence among healthcare professionals (HCPs) after TB exposure are limited.METHODS: This was a prospective cohort study with 2-year follow-up among Thai HCPs exposed to TB to determine TB incidences and factors associated with TB development.RESULTS: Of the 398 HCPs with TB exposure, 367 (92%) participated in the study; 342 HCPs were included in the final analysis; 311 participated in contact investigations; 303 underwent chest X-ray; 252 completed baseline TB and latent TB infection screening using tuberculin skin test (TST); 210 had negative baseline TST; and 45 completed follow-up tests at 3 months. Altogether, 20 HCPs developed TB (2.92/100 person-years). TB incidences in HCPs not participating in or not completing the investigation at any step were higher than in those who completed the evaluation (11.29 and 2.90, respectively, vs. 0/100 person-years; P < 0.05). No participation in contact investigation and no baseline chest X-ray were independent factors associated with TB development (adjusted odds ratio [aOR] 6.7; P < 0.001 and aOR 8.9; P = 0.01, respectively).CONCLUSION: Study findings indicate increased risks of TB development among HCPs not undergoing or not completing contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.

Discordance between TST and QFT-TBGold Plus for Latent Tuberculosis Screening among Under-Five Children: An Interim Analysis

To analyze the agreement between tuberculin skin test (TST) and fourth-generation QuantiFERON (QFT)-TB Gold Plus [interferon gamma (INF-γ) release assays (IGRA)] for latent tuberculosis infection (LTBI) diagnosis among under-five children who are undernourished and/or who have history of contact with active tuberculosis (TB) patients. Children from the age group of 6 months to 5 years (undernourished or tuberculosis household contacts) were screened through anganwadis (government playschools) and TB Health posts from Mumbai, India during September 2019 to January 2021. Both TST and QFT-TB Gold Plus test were carried out to diagnose LTBI. Out of the total 299, 35 (11.7%) (95% CI 8.1-15.3%) children tested positive by IGRA (QFT-TB Gold Plus) and 68 (22.7%) (95% CI 18.0-27.4%) by TST, suggestive of moderate concordance (κ = 0.483) between both tests. IGRA and TST showed moderate concordance in children <24 months (κ = 0.478). Moreover, 26 (21.1%) children with TB contact had both TST and IGRA positive with moderate concordance (κ = 0.550). A fair concordance (κ = 0.396) was observed between IGRA and TST in undernourished children. Also, 45 (15.0%) children showed discordance of which 39 (13.0%) had positive TST but negative IGRA and 6 (2.0%) had negative TST but positive IGRA. The study strongly recommends both TST and QFT-TB Gold Plus test for the diagnosis of LTBI in under-five children. A moderate concordance in children <24 months endorses the reliability of QFT-TB Gold Plus in diagnosing LTBI in this age group. This study highlights the need for screening undernourished children for LTBI to consider repeating IGRA testing for TST positives as per the window period and risk of ongoing exposure.

798. Incomplete Contact Investigation and Risk of Developing Tuberculosis Among Healthcare Professionals After Tuberculosis Exposure

BackgroundTuberculosis (TB) contact investigation is recommended for healthcare professionals (HCPs) after TB exposure. However, association between no participation in or incomplete contact investigation and subsequent TB development has not been well-described. This study aims to determine TB incidences and factors associated with TB development among HCPs requiring contact investigations.MethodsWe conducted a prospective cohort study among Thai HCPs with TB exposure from January 2013 to December 2017. Contact investigations, including baseline TB and latent tuberculosis infection (LTBI) screening and follow-up at 3 months after TB exposure, were recommended to all HCPs. The two-step tuberculin skin test (TST) was used for LTBI testing. All HCPs were followed for 2 years for TB development.ResultsOf the 342 HCPs with TB exposure included in the study, 311 (91%) participated in the contact investigations and 252 (74%) completed baseline TB and LTBI screening. Among the 210 HCPs with negative baseline TST, 45 (21%) completed the follow-up tests. The overall incidence of TB was 2.92/100 person-years. HCPs who did not complete follow-up TST had significantly higher TB incidence than those completed baseline and follow-up TST (3.55 vs. 0/100 person-years; P=0.01). No participation in the contact investigation and no chest radiograph performed at baseline were the independent factors associated with TB development among the HCPs [adjusted odds ratio (aOR) 6.69; P< 0.001 and aOR 8.85; P=0.01, respectively]. Contact with an index patient with concomitant TB at extrapulmonary sites (aOR 49.76, 10.03-246.99; P< 0.001) and with negative sputum AFB but positive sputum GeneXpert MTB/RIF (aOR 3.18, 1.35-7.50; P=0.008) were independently associated with no participation in the contact investigation.ConclusionThe findings indicate the risk of TB development among the HCPs who did not undergo or complete contact investigations and underscore the need for interventions to improve contact investigation participation and completeness.Disclosures All Authors: No reported disclosures

Brief Report: Yield of Repeat Tuberculin Skin Testing for People Living With HIV in Brazil.

In Brazil, annual tuberculin skin tests (TSTs) are recommended for people living with HIV (PLWH) with CD4 >350, with tuberculosis preventive therapy provided on test conversion. We aimed to determine the yield of repeat TSTs for PLWH. Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT) to prevent tuberculosis (TB). We analyzed data from newly registered PLWH with negative baseline TST results. We calculated the number of TST conversions after 1 and/or 2 years among patients eligible for follow-up TSTs, the proportion of converters initiating IPT, and incidence of TB/death. Among 1770 PLWH with a negative baseline TST, 679 (38%) were female and median age was 36 years (IQR 29-43). Eighty-six (5%) developed TB or died within 1 year. Among 1684 eligible for a follow-up 1-year TST, 582 (35%) were tested and 53 (9%) were positive. Forty-nine converters (92%) started IPT. Of 529 patients with a negative 1-year TST, 7 (1%) developed TB or died over the following year. Of 522 patients eligible for a 2-year TST, 158 (30%) were tested and 13 (8%) were positive. Ten converters (77%) started IPT. Of 1102 patients who did not receive a 1-year TST, 33 (3%) developed TB or died. Of the 1069 patients eligible for a 2-year TST, 259 (24%) were tested and 34 (13%) were positive. Thirty converters (88%) started IPT. In this cohort of PLWH in Brazil, TST conversion was high among those retested, but only 48% received a follow-up TST within 2 years.

Performance of 4 methods for screening of latent tuberculosis infection in patients with chronic inflammatory arthritis under TNF\u03b1 inhibitors: a 24-month prospective study

BackgroundThe reactivation rate of tuberculosis in patients with chronic inflammatory arthritis (CIA) on TNFα inhibitors (TNFi) and baseline negative screening for latent tuberculosis infection (LTBI) is higher than in the general population.AimTo compare the performance of tuberculin skin test (TST), TST-Booster, ELISPOT (T-SPOT.TB) and QuantiFERON-TB Gold in tube (QFT-IT) to detect LTBI in patients with CIA on TNFi.Patients and methodsA total of 102 patients with CIA [rheumatoid arthritis (RA), n = 40; ankylosing spondylitis (AS), n = 35; psoriatic arthritis (PsA), n = 7; and juvenile idiopathic arthritis (JIA), n = 20] were prospectively followed-up for 24 months to identify incident LTBI cases. Epidemiologic data, TST, T-SPOT.TB, QFT-IT and a chest X-ray were performed at baseline and after 6 months of LTBI treatment.ResultsThirty six percent (37/102) of patients had positive TST or Interferon Gamma Release Assays (IGRAs) tests. Agreement among TST and IGRAs was moderate (k = 0.475; p = 0.001), but high between T-SPOT.TB and QFT-IT (k = 0.785; p < 0.001). During the 24-Month follow-up, 15 (18.5%) incident cases of LTBI were identified. In comparison to TST, the IGRAs increased the LTBI diagnosis power in 8.5% (95% CI 3.16–17.49). TST-Booster did not add any value in patients with negative TST at baseline. After 6-Month isoniazid therapy, IGRAs results did not change significantly.ConclusionsAlmost 20% of CIA patients had some evidence of LTBI, suggesting higher conversion rate after exposition to TNFi. TST was effective in identifying new cases of LTBI, but IGRAs added diagnostic power in this scenario. Our findings did not support the repetition of IGRAs after 6-Month isoniazid therapy and this approach was effective to mitigate active TB in 2 years of follow-up.