Reactivation Of Latent Tuberculosis Research Articles

1636. Risk of Latent Tuberculosis Reactivation in Patients Treated with Checkpoint Inhibitors Immunotherapy Compared to Other Anti-Cancer Therapies including Hematopoietic Cell Transplantation

BackgroundThe risk of latent tuberculosis infection (LTBI) reactivation in cancer patients during checkpoint inhibitor immunotherapy (CPI) remains largely unknown. We sought to evaluate LTBI therapy and outcomes between cancer patients receiving CPI versus conventional chemotherapy (CC) and hematopoietic cell transplantation (HCT) recipients.MethodsWe conducted a retrospective cohort study of adult patients with LTBI (positive T-SPOT TB test) at MD Anderson Cancer Center between April 2016 and May 2020, who received CPI or combined with other conventional chemotherapy. Thereafter we compared each group to patients treated with other anti-cancer therapies including CC alone or HCT.ResultsWe identified 106 patients with LTBI, who were analyzed into 3 distinct groups: CPI (32 patients, 30%) CC alone (37 patients, 35%), and HCT (37 patients, 35% (7 autologous versus 30 allogeneic). The majority of patients in the CPI group (97%) had solid tumors compared to 54% in the CC group. Nivolumab was the most commonly used CPI agent in 13 patients (40%), followed by pembrolizumab 10 pts (31%). In the CPI group, 20 pts (62%) received LTBI therapy that included Isoniazid (INH), versus 18 patients (49%) in the HCT group and 16 patients (43%) in the CC group (p=0.26). Only 3 patients (CC group) had TB reactivations (8%; p=0.11). None of these 3 patients had received LTBI therapy or corticosteroids prior to the diagnosis. Immune-related adverse effect (IrAEs) were reported in 11 pts (34%) patients, and 9 (82%) of them received corticosteroids. Out of 20 of CPI patients whom received INH, 4 (20%) developed possible INH-induced liver toxicities leading to interruption of medication versus 1 (6%) patient which had mild hepatitis in CC group versus none of HCT patients (p=0.09).ConclusionOur data suggest that latent tuberculosis reactivation remains rare, especially in the severely immunocompromised patients on CPI, CC and steroids. However, hepatotoxicity is relatively common in patients treated with CPI and INH. Therefore, caution and close laboratory and clinical monitoring is required to avoid significant hepatic injury and interruption of LTBI therapy and lifesaving oncological therapy.Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

Trend of HIV-TB co-morbidity?in north-west region of Uttarakhand

Tuberculosis (TB) is the commonest opportunistic infection and the number one cause of death in HIV patients in developing countries. HIV co-infection is the most powerful known risk factor for progression of M. tuberculosis infection to active disease, increasing the risk of latent TB reactivation. The study was carried out to study the trend of Tuberculosis in HIV seropositive patients and determine HIV-TB co-morbidity in Dehradun, Uttarakhand. A retrospective study of standardized patient records was conducted from December 2017 to November 2018 of all HIV sero-positive patients registered to ART PLUS Centre Govt. Doon Hospital Dehradun. TB suspected patients were referred to RNTCP. Data was taken and analyzed by Microsoft Excel. Among total of 18319 HIV positive patients attending ART centre (ART and Pre- ART enrolled) during the study period, 585 patients were suspected of TB and were referred from ART to RNTCP. Total 128 (21.9%) patients were diagnosed with TB, of which 71(55.46%) patients were diagnosed for pulmonary TB and 57(44.5%) were Extra-Pulmonary TB. In our study Male predominance was seen and most of the cases were of age group 19-40 years, mostly belonging to rural areas. Keywords: HIV/AIDS, Tuberculosis, Co-infection.

The impact of HIV infection on tuberculosis transmission in a country with low tuberculosis incidence: a national retrospective study using molecular epidemiology.

BackgroundHIV is known to increase the likelihood of reactivation of latent tuberculosis to active TB disease; however, its impact on tuberculosis infectiousness and consequent transmission is unclear, particularly in low-incidence settings.MethodsNational surveillance data from England, Wales and Northern Ireland on tuberculosis cases in adults from 2010 to 2014, strain typed using 24-locus mycobacterial-interspersed-repetitive-units–variable-number-tandem-repeats was used retrospectively to identify clusters of tuberculosis cases, subdivided into ‘first’ and ‘subsequent’ cases.Firstly, we used zero-inflated Poisson regression models to examine the association between HIV status and the number of subsequent clustered cases (a surrogate for tuberculosis infectiousness) in a strain type cluster. Secondly, we used logistic regression to examine the association between HIV status and the likelihood of being a subsequent case in a cluster (a surrogate for recent acquisition of tuberculosis infection) compared to the first case or a non-clustered case (a surrogate for reactivation of latent infection).ResultsWe included 18,864 strain-typed cases, 2238 were the first cases of clusters and 8471 were subsequent cases. Seven hundred and fifty-nine (4%) were HIV-positive.Outcome 1: HIV-positive pulmonary tuberculosis cases who were the first in a cluster had fewer subsequent cases associated with them (mean 0.6, multivariable incidence rate ratio [IRR] 0.75 [0.65–0.86]) than those HIV-negative (mean 1.1).Extra-pulmonary tuberculosis (EPTB) cases with HIV were less likely to be the first case in a cluster compared to HIV-negative EPTB cases. EPTB cases who were the first case had a higher mean number of subsequent cases (mean 2.5, IRR (3.62 [3.12–4.19]) than those HIV-negative (mean 0.6).Outcome 2: tuberculosis cases with HIV co-infection were less likely to be a subsequent case in a cluster (odds ratio 0.82 [0.69–0.98]), compared to being the first or a non-clustered case.ConclusionsOutcome 1: pulmonary tuberculosis-HIV patients were less infectious than those without HIV. EPTB patients with HIV who were the first case in a cluster had a higher number of subsequent cases and thus may be markers of other undetected cases, discoverable by contact investigations.Outcome 2: tuberculosis in HIV-positive individuals was more likely due to reactivation than recent infection, compared to those who were HIV-negative.

Tuberculosis comorbidity with rheumatoid arthritis: Gene signatures, associated biomarkers, and screening.

Rheumatoid arthritis (RA) is known to be related to an elevated risk of infections because of its pathobiology and the use of immunosuppressive therapies. Reactivation of latent tuberculosis (TB) infection is a serious issue in patients with RA, especially after receiving anti-TNFs therapy. TNF blocking reinforces the TB granuloma formation and maintenance and the growth of Mycobacterium tuberculosis (Mtb). After intercurrent of TB infection, the standard recommendation is that the treatment with TNF inhibitors to be withheld despite its impressive effect on suppression of inflammation until the infection has resolved. Knowing pathways and mechanisms that are common between two diseases might help to find the mechanistic basis of this comorbidity, as well as provide us a new approach to apply them as therapeutic targets or diagnostic biomarkers. Also, screening for latent TB before initiation of an anti-TNF therapy can minimize complications. This review summarizes the shared gene signature between TB and RA and discusses the biomarkers for early detection of this infection, and screening procedures as well.

Association of Tuberculosis in Patients with Chronic Myeloid Leukemia, a Treatment Proposal Based on Literature Review

Introduction: Chronic Myeloid leukemia (CML) is a chronic myeloproliferative neoplasm with an increased undifferentiated proliferation of granulocytic lineage of the white blood cells. It is an acquired disorder of the hematopoietic stem cells due to a cytogenetic aberration known as the Philadelphia chromosome. It occurs due to a phenomenon of a reciprocal translocation between chromosomes t(9,22) and results in BCR/ABL fusion gene. The product of this gene has tyrosine kinase property, which predominantly causes the disease. Tyrosine kinase inhibitors (TKI) are the mainstay of the treatment to achieve remission, while bone marrow transplant is the only proven cure. Tuberculosis (TB), both active and reactivation of latent TB, remains the most common infectious disease worldwide and leads to high mortality. Currently, one-fourth of the global population has been infected by Mycobacterium tuberculosis. The incidence of TB has been reportedly increasing in patients with cancer. It has been mostly found in association with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Recently, the incidence increased in patients with CML during treatment with Imatinib (IM) has also been reported in a retrospective cohort study in Taiwan by Lui C-J et. al. and few other published cases in literature. This might be due to impairment of the T lymphocytes signal transduction leading to increased host susceptibility to TB, hepatitis B, and varicella-zoster infection. TB treatment is mainly based on the susceptibility of the Mycobacterium Tuberculosis to the anti-TB medications. First-line therapy includes of four drugs, Isoniazid (INH), Rifampicin (RIF), Pyrazinamide (PZA), and Ethambutol (EMB). Anti TB drugs administration also needs close monitoring because of potential side effects. These include, but not limited to hepatoxicity, optic neuritis, impaired color vision, peripheral neuropathy, and gastrointestinal disturbances. Their occurrence necessitate discontinuation of the culprit drug from the regimen. Certain anti TB drugs are also known to disrupt bioavailability of other drugs metabolized in the liver when concomitantly administered by influencing the hepatic cytochrome P450 enzyme. This happens while using anti-TB medication to treat concomitant TB infection in CML patients on tyrosine kinase inhibitors therapy. Methods and critical analysis of the reviewed study articles: The authors reviewed the current literature focusing on all articles addressing TB infections and their diagnosis and management in patients with CML (PubMed and Google Scholar between 2000 and 2020). Our review aimed to provide the necessary data to improve clinical diagnosis and clarify the management strategy of this condition. Conclusion and treatment proposal: Throughout our review of multiple research articles, it has been realized that patients with CML and other hematological malignancies and solid tumors (e.g., non-Hodgkin lymphoma, chronic lymphocytic leukemia, metastatic gastric tumors), have a higher risk of having TB infection. TB infection (pulmonary and extra-pulmonary) occurs 2-9 times more than the general population in patients with hematological malignancies. In CML patients, treatment therapy with Imatinib posed a higher risk of development of TB due to defective cellular immunity. Co-administration of 1st line anti Tb medications mainly rifampicin with standard TKIs therapy Imatinib and Dasatinib has resulted in sub-therapeutic levels of these drugs due to induction of CYP4503A enzyme. Either by changing the TB treatment regimen to a non-rifampicin based therapy line with a combination of a fluoroquinolone, increasing the dose, or switching to a different TKI class may result in clinical improvement. To the best of our knowledge, there are no randomized control trials, or FDA approved guidelines to treat concomitant TB infection in CML patients. Therefore, a clear strategy to deal with such a clinical condition is lacking. The immediate treatment for the concomitant disease has been suggested based on clinical experience and clinical response of some patients published in few case reports, case series, and retrospective cohort studies. After careful literature review, we put forth our management proposals, However it need further research studies and clinical trials to bring recommendations and guidelines. Disclosures No relevant conflicts of interest to declare.

Vitamin D deficiency predicts latent TB reactivation independent of preventive therapy: a longitudinal study.

BACKGROUND: Vitamin D deficiency is associated with progression of latent tuberculosis (TB) infection to active disease. The impact of preventive therapy on this association is unknown.METHOD: Serum 25-hydroxyvitamin D (25(OH)D) levels were retrospectively linked to adults diagnosed with latent TB between April 2010 and January 2019 in a hospital in London, UK. Individuals in the cohort who progressed to active TB were identified by matching to a national notification register. A logistic regression model was used to examine baseline vitamin D deficiency and use of preventive therapy with subsequent incidence of TB disease.RESULTS: Of 1509 latently infected individuals with 3902 patient-years of follow-up, 687 (45.5%) were identified as vitamin D deficient and 691 (45.8%) individuals had a LTBI regimen prescribed. There were 29 (1.9%) instances of TB reactivation. On multivariate analysis, profound (<25 nmol/L) vitamin D deficiency (aHR 5.68, 95%CI 2.18-14.82; P = 0.0003) and the absence of preventive therapy (aHR 3.84, 95%CI 1.46-10.08; P = 0.006) were associated with progression to active TB disease. There was no evidence that preventive therapy modified the association between vitamin D status and TB reactivation.CONCLUSION: Our results show an independent association between vitamin D deficiency and progression from latent TB infection to active disease.

Lymph nodes-The neglected battlefield in tuberculosis.

Lymph nodes, particularly thoracic lymph nodes, are among the most common sites of extrapulmonary tuberculosis (TB). However, Mycobacterium tuberculosis (Mtb) infection in these organs is understudied. Aside from being sites of initiation of the adaptive immune system, lymph nodes also serve as niches of Mtb growth and persistence. Mtb infection results in granuloma formation that disrupts and—if it becomes large enough—replaces the normal architecture of the lymph node that is vital to its function. In preclinical models, successful TB vaccines appear to prevent spread of Mtb from the lungs to the lymph nodes. Reactivation of latent TB can start in the lymph nodes resulting in dissemination of the bacteria to the lungs and other organs. Involvement of the lymph nodes may improve Bacille Calmette-Guerin (BCG) vaccine efficacy. Lastly, drug penetration to the lymph nodes is poor compared to blood, lung tissue, and lung granulomas. Future studies on evaluating the efficacy of vaccines and anti-TB drug treatments should include consideration of the effects on thoracic lymph nodes and not just the lungs.

CD4 T cells are important in protection against M. tuberculosis reinfection in cynomolgus macaques

Abstract Early human studies show individuals with latent M. tuberculosis (Mtb) infection are less likely to develop active tuberculosis (TB) compared to naïve individuals with similar levels of exposure. Using Mtb-barcoded libraries (Lib A as first and Lib B as second infection), we published that an existing Mtb infection in cynomolgus macaques protects against the establishment and progression of a second Mtb challenge. CD4 T cells are important in control of TB, and depletion results in worse acute infection and latent TB reactivation in macaques. We hypothesized that CD4 T cells play a major role in protection against a secondary Mtb challenge. To test this hypothesis, CD4 T cells were depleted in infected and treated macaques before a second Mtb challenge. As controls, one group received IgG and a naive group received only Lib B. The number of Lib B granulomas in the IgG group was significantly fewer than in the naïve group, while the αCD4 group was in between the two. The IgG group had the lowest lung bacterial burden followed by the αCD4 group (16-fold higher than IgG) and lastly the naïve group (57.5-fold higher than IgG). Both reinfected groups (αCD4 and IgG) had a higher frequency of CD8 T cells producing IFNγ and/or TNF in Lib B granulomas compared to naïve macaques but there was no significant difference when compared to each other. Because each Mtb bacterium has a unique barcode, we can track the spread of Mtb to different organs. Both naïve and αCD4 groups had a greater number of unique Lib B barcodes in the thoracic lymph nodes compared to the IgG group. These data suggest that CD4 T cells help limit the establishment, progression and dissemination of the second infection. However, they are not the only factor responsible for protection against reinfection.

Chronic Immune Activation in TB/HIV Co-infection.

HIV co-infection is the most critical risk factor for the reactivation of latent tuberculosis (TB) infection (LTBI). While CD4+ T cell depletion has been considered the major cause of HIV-induced reactivation of LTBI, recent work in macaques co-infected with Mycobacterium tuberculosis (Mtb)/simian immunodeficiency virus (SIV) suggests that cytopathic effects of SIV resulting in chronic immune activation and dysregulation of T cell homeostasis correlate with reactivation of LTBI. This review builds on compelling data that the reactivation of LTBI during HIV co-infection is likely to be driven by the events of HIV replication and therefore highlights the need to have optimum translational interventions directed at reactivation due to co-infection.

B cell-mediated Immunity against Tuberculosis Infection: A Mini Review Study

Mycobacterium tuberculosis (Mtb) is considered to be a major public health concern and a successful intracellular pathogen associated with high mortality worldwide. The Bacillus Calmette-Guerin (BCG) vaccine is the only available vaccine for the prevention of tuberculosis (TB) and tubercular meningitis in children. However, BCG is not adequately effective in the treatment of the adults affected to TB. According to the literature, there are controversial data on the potential role of B cells. B cells and humoral immune response play a key role in the amplification of the host immune response against TB. This review study aimed to discuss B cells and humoral immune responses in TB infection and assess its application as a therapeutic option. The monitoring of various B cell phenotypes in TB could be a reliable marker for the prediction of TB in individuals, especially in the latent form. According to the findings, the CMI response (especially Th1 activities) is not sufficient for efficient protection against TB, and B cells and Abs influence the innate immunocytes and Th1, while playing a pivotal role in various outcomes of exposure with tubercle bacilli. Although B cells may contribute to Mtb in the development of active TB, further investigations are required regarding the effects of B cells and humoral immunity on TB pathogenesis and the targeted harmful humoral-mediated response. Moreover, B cells and antibodies could be proper biomarkers to promote the studies regarding the detection of reliable diagnostic tools for the reactivation of latent TB, as well as use as a new generation of therapeutic options.

Disseminated tuberculosis in a pregnant immunocompetent healthcare worker

Health care workers (HCWs) have an increased risk of Mycobacterium Tuberculosis (TB) infection compared to general population. Pregnancy suppresses the Lymphocyte T-helper 1 (Th1) pro-inflammatory response. Frequent and consecutive pregnancies may also promote TB infection or reactivation of latent TB. But there is still no evidence of certain risk of severe disseminated infection. A 35-year-old pregnant woman, working as a laboratory officer, presented with fever, general weakness then acute respiratory failure. Miliary lung nodules were noted on chest X-ray. Under the impression of miliary tuberculosis, anti TB medication was administered. Likelihood of This diagnosis was due to her occupation, exposition to Mycobacterium Tuberculosis, clinical and radiologic findings. CT scan revealed cerebro-meningeal, pulmonary, splenic and ganglionary TB. The patient was treated successfully with ordinary anti TB combination regimen. Delivery and post partum was without complication. Cases of severe TB in an otherwise healthy pregnant woman are rare. This is an occupational disease to prevent.

Tuberculosis in patient with psoriasis receiving biologic therapy – case report

Introduction: The introduction of biological therapy has revolutionized the treatment of psoriasis. Due to its immunosuppressive effect, the following side effects might occur: injection-site reactions, exacerbation of autoimmune diseases, increased risk of malignant tumors and infections, including tuberculosis (TB). Aim: The aim of this report is to present a case of a patient who developed TB during tumornecrosis factor α (TNF-α) inhibitor therapy. Case study: A 52-year-old man was admitted to the Dermatology Clinic for re-qualification for biological treatment with adalimumab. The patient was treated with cyclosporin A and lefludomide combined with methotrexate with no effect and the adalimumab therapy was initiated with complete remission of psoriatic lesions. The patient was suspended in the drug program because of TB. TNF-α inhibitor therapy was resumed after antimycobacterial treatment, during which lymphadenopathy was observed and serous TB was confirmed. Three months after the treatment, the patient was rehospitalized because of suspicion of TB relapse. It was decided to requalify the patient for biological therapy after completion of antimycobacterial treatment. Due to the high risk of TB recurrence, switch to the interleukin-17 inhibitor was decided. Results and discussion: The proper qualification and thorough testing before biological treatment ensures patients’ safety and satisfactory therapeutic effect. It should be remembered that during longterm therapy with TNF antagonists, both reactivation of latent TB as well as new infection are serious problems. Therefore, regular tests should be performed, especially in countries with high prevalence of this disease. Conclusions: In patients who develop TB, particularly recurrent, switching to a drug with a different mechanism should be considered.

Risk of tuberculosis with anti-tumor necrosis factor-alpha therapy in patients with psoriasis and psoriatic arthritis in Indian population.

Anti-tumor necrosis factor-alpha (TNF-α) immunotherapy has revolutionized the treatment of inflammatory diseases, such as psoriasis and psoriatic arthritis. However, a major concern is that patients receiving this therapy have an increased risk of infection, particularly of reactivation of latent tuberculosis (TB). There were an estimated 10.4 million new cases of tuberculosis in 2016, worldwide, and India has one of the largest TB case burden with an estimated incidence of 2.79 million cases of TB in the same year. Anti-TNF agents like etanercept and infliximab are available in India approved for psoriasis and psoriatic arthritis. But long-term use of these agents possesses a risk of reactivation of latent TB. In this review article, we assessed the risk of TB with anti-TNF therapy especially in patients with psoriasis and psoriatic arthritis in India. At the end of the article, we have also suggested a recommendation for screening of latent tuberculosis and its management, before starting anti-TNF-α therapy.

&lt;p&gt;Role Of Vitamin-D Supplementation In TB/HIV Co-Infected Patients&lt;/p&gt;

ObjectiveThis review aimed to assess the role of vitamin D supplementation on the decrement of mortality and morbidity rate among tuberculosis (TB)/human immune deficiency virus (HIV) co-infected clients.Method: Pub Med, google scholar and google search were accessed to find out all document to describe this review article.ResultsNowadays TB/HIV co-infection has become a major global concern, particularly in low and middle-income countries. Mycobacterium tuberculosis and HIV infections are co-endemic and more susceptible to the progression of TB. Immunosuppression associated with HIV is a strong risk factor for the reactivation of latent TB to the active form. Immune cells like macrophages recognized Mycobacterium tuberculosis through TLR2/1, and it increases the expression of the vitamin D receptor (VDR) and CYP27B1. The synthesis of 1,25-dihydroxy vitamin D promotes VDR-mediated transactivation of the antimicrobial peptide cathelicidin and the killing of intracellular Mycobacterium tuberculosis. Cathelicidins have a direct antimicrobial effect through membrane disruption. Besides, it has also antiviral effects via inhibition of retrovirus (HIV) replication. In fact, as some studies showed, there was a lower induction of cathelicidin in monocytes who have low vitamin D levels.Conclusion: Therefore, vitamin D supplementation can be directly involved in the reduction of TB/HIV co-infection and its progression.

Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors.

Patients with autoimmune rheumatic diseases (ARD) have an increased risk for tuberculosis (TB). The use of tumor necrosis factor inhibitors (TNFi) and glucocorticoids in these patients has been associated with an increased prevalence of latent TB reactivation. Over the last few years, several biologic disease-modifying anti-rheumatic drugs (bDMARDs), other than TNFi (e.g. rituximab, abatacept, tocilizumab, secukinumab) and targeted synthetic DMARDs (tsDMARDs) [e.g. apremilast, Janus kinase (JAK) inhibitors] have been used for the treatment of patients with ARD. For many of these drugs, especially the newer ones like JAK inhibitors or antibodies against interleukin (IL)-23, most data stem from randomized clinical trials and few are available from real life clinical experience. We sought to review the current evidence for TB risk in patients with ARD treated with tsDMARDs or bDMARDs, other than TNFi. It seems that some of these drugs are associated with a lower TB risk, indirectly compared with TNFi treatment. In fact, it appears that rituximab, apremilast and inhibitors of IL-17 and IL-23 might be safer, while more data are needed for JAK inhibitors. As seen in TNFi, risk for TB is more pronounced in TB-endemic areas. Screening for latent TB must precede initiation of any tsDMARDs or bDMARDs. The growing use of non-TNFi agents has raised the need for more real-life studies that would compare the risk for TB between TNFi and other treatment modalities for ARD. Knowledge about the TB-safety profile of these drugs could help in the decision of drug choice in patients with confirmed latent TB infection or in TB endemic areas.

A Four-Year Hospital-Based Retrospective Study of the Predictors of Tuberculosis in People Living with HIV and Receiving Care at Bamenda Regional Hospital, Cameroon.

Background:Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infections place immense burdens on healthcare systems with particularly diagnostic and therapeutic challenges. TB is high among opportunistic diseases and the most leading cause of death among patients with HIV/AIDS. HIV infection is the most-known risk factor for Mycobacterium tuberculosis infection and progression to active disease, which increases the risk of latent TB reactivation by 20-fold. We present a four-year descriptive analysis of TB in people living with HIV in the Bamenda Regional Hospital (BRH) from 2012-2016.Methods:This was a hospital-based descriptive chart review. We conducted manual reviews of medical records of HIV/TB co-infected patients from June 2017-July 2017 at BRH’s AIDS Treatment Centre, North West region of Cameroon. Socio-demographic and clinical characteristics of cases were captured using a pre-tested data collection sheet and analyzed with Statistical Package for Social Sciences (SPSS) software, version 25.Results:Out of the 1078 HIV patients, 36.5% (393) of them were diagnosed with TB; 75% (808) of the People living with HIV (PLWHIV) were active; among the remaining 25%, 10.2% were bedridden, 13.0% were jobless, and 1.8% were retired. The greater proportion of the participants were females 65.5% (705).Conclusion and Global Health Implications:The baseline anemia, smoking tobacco, drinking alcohol, detectable (≥50copies/mL), CD4 count ≤ 200cells/µl and gender of the PLWHIV were associated with the incidence of TB. We recommend early diagnosis and treatment of anemia, modification of patient’s lifestyle, and strengthening of immunization programs to reduce the risk of TB occurrence among HIV-infected people.

1370. Concurrent Anti-PD -1 and Anti-tubercular Therapy in a Patient with Refractory Lymphoma and Pulmonary Tuberculosis: A Case Report

Backgroundsafety and efficacy of concurrent treatment for tuberculosis and checkpoint inhibitor drugs are unknown.Methodscase report.Results36-year-old gentleman presented with bulky adenopathy in December 2016. Work-up revealed classical Hodgkin’s lymphoma with extra-nodal sites of involvement including bone, lungs and skeletal muscle. After his disease proved refractory to the standard first and second-line treatments, complete remission was achieved with anti-CD 30 drug-toxin conjugate, brentuximab followed by consolidation with autologous stem cell transplant in February 2018. However, his lymphoma recurred in June 2018 with new bulky adenopathy and new bilateral nodular pulmonary infiltrates. PET imaging revealed multiple avid lymph nodes, liver and bone lesions. Biopsy of a neck node confirmed relapsed lymphoma. Cultures of sputa revealed drug-susceptible M. tuberculosis. Four drug treatment with Isoniazid, Rifampin, Ethambutol and Pyrazinamide was initiated in June 2018. Hospice enrollment was considered because of progressive lymphoma and poor functional status. In July 2018, patient elected for a trial of salvage treatment with Nivolumab, a PD-1 checkpoint inhibitor (CPI) while on anti-tubercular treatment. He was monitored for paradoxical worsening of symptoms. He tolerated the tuberculosis medications well for the entire 6-month course, follow-up sputa were culture negative. His lymphoma remains in remission on maintenance nivolumab as a donor search is underway.ConclusionAuto-immune reactions and immune-related adverse events are major side effects of CPI drugs. Our understanding of the interplay between checkpoint inhibitors and infectious risks continues to evolve. Among the few cases reported in the literature, patients on CPIs have experienced both reactivation of latent tuberculosis as well as severe, fatal paradoxical reactions during treatment of active tuberculosis. Despite the relatively uncomplicated course in our patient, tuberculosis in this group of patients poses many challenges in diagnosis and management and warrants close monitoring and follow-up.Disclosures All authors: No reported disclosures.

The Proportion of Latent Tuberculosis Infection in Naive Lung Cancer Patients at Persahabatan Hospital Jakarta

Background: Lung cancer and pulmonary tuberculosis (TB) are two major public health problems associated with significant morbidities and mortalities. The increased prevalence of active TB and latent TB reactivation in lung cancer patients and negative effect of pulmonary TB in lung cancer prognosis needed screening of lung cancer patients for latent TB infection (LTBI). This study aimed to determine the proportion of LTBI in lung cancer patients, their characteristics and the relationship between them.&#x0D; Methods: This study used cross-sectional design. Collecting sample used consecutive sampling of 86 newly diagnosed treatment-naive lung cancer patients from RSUP Persahabatan in 2015 to 2016. The presence of LTBI was determined by Quantiferon-TB Gold-In-Tube (QFT- GIT) after having Mycobacterium TB not detected result from Xpert MTB/RIF sputum test. Demographic characteristics and cancer-related factors associated with LTBI were investigated.&#x0D; Results: The results of latent TB tests were IGRA(+) 12.8%, IGRA(-) 68.6% and IGRA(I) 18.6%. Number of male patients with lung cancer with latent were 68.6%, as many as 55.8% were immunized with BCG, 4.6% had close contact with TB and 64% were using smoking. Most types of cancer were adenocarcinomas (77.9%) with advanced stage (82.6%) and general display status 2 (50%). The characteristics that show an association with IGRA results are the location of the cancer and the total lymphocyte count.&#x0D; Conclusion: The proportion of latent TB in lung cancer patients at the RSUP Persahabatan was 12.8%. The location of the cancer associated with the area of typical TB was related to latent TB, although it cannot be canceled. Results of IGRA(I) in lung cancer patients with low total lymphocyte counts prove IGRA sensitivity in the protection of latent TB infection in immunocompromised patients. (J Respir Indo. 2019; 39(4): 256-65)

1926 Gastrointestinal Bleeding in a Patient With Latent Tuberculosis and Remote T-Cell Lymphoma

INTRODUCTION: Immunosuppressed patients such as those with malignancies are susceptible to reactivation of tuberculosis (TB), which can affect the gut. CMV should also be considered as a cause of colitis in these patients. CASE DESCRIPTION/METHODS: A 68-year-old man with a history of T-cell lymphoma of the kidney and nasal cavity and latent TB presented with weight loss and cough. He was cachectic and had diffuse rhonchi in the lung bases. CT of the chest showed areas of cavitation. Multiple sputum cultures positive for acid-fast bacilli (AFB) and a positive mycobacterium tuberculosis (MTB) PCR confirmed active TB infection. The patient developed repeated episodes of melena with a hemoglobin level of 5.0 g/dL, MCV of 71.5 fL, iron of 4.5 ug/dL, transferrin saturation of 1%. Colonoscopy revealed extensive diverticulosis in the sigmoid colon and evidence of a prior cecectomy with ulceration of the ileocolonic anastomosis. Biopsies showed dense mature lymphocytic infiltrate and granulation tissue with no evidence of T-cell lymphoma. A CT revealed a 4 cm segment of terminal ileum with mild wall thickening, mucosal hyperenhancement and thickened folds of a distal loop of jejunum. Stool AFB culture and MTB PCR were both positive, indicating a probable diagnosis of TB enteritis. A push enteroscopy showed a 60 mm infiltrative lesion with ulcerated bases and three smaller lesions of similar appearance on the anterior wall of the stomach along with jejunal ulceration. Ulcer biopsies revealed large cells with inclusions consistent with CMV enteritis. Stains for AFB were also positive. Biopsies of the stomach lesions revealed an ulcerative oxyntic mucosa with dense atypical lymphoid infiltrate. Markers were consistent with a diagnosis of Burkitt’s Lymphoma (BL). The patient was treated with TB therapy, ganciclovir, and R-CHOP. DISCUSSION: Immunosuppression due to this patient’s BL likely led to dissemination and reactivation of latent TB and susceptibility to infection with CMV. The stomach and bowel are the most common sites of extranodal involvement in BL. The incidence of TB in malignancy is highest in non-Hodgkin’s lymphoma like BL. Bowel involvement in TB is seen in less than 5% of cases in the United States. Common endoscopic findings include ileal or ileocecal disease, non-confluent involvement of the colon, and nodular mucosa with areas of ulceration. The diagnosis can be made by biopsy showing caseating granulomas, a positive TB culture or PCR result, or by clinical suspicion with improvement following treatment.

Tests for latent tuberculosis in candidates for solid organ transplantation: A systematic review and meta-analysis.

Reactivation of latent tuberculosis following solid organ transplantation has serious consequences for the recipient. The most useful diagnostic test for latent TB is not clear. We conducted a systematic review and meta-analysis to assess the relative test performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) in people undergoing solid organ transplantation. The clinical or radiological risk factors were used as the proxy reference standard. Test performance was expressed as an odd ratio (OR). We identified 24 studies (N=7811), 12 studies compared IGRAs with TST directly, nine studies evaluated only TST and three studies only IGRAs. Direct comparison between tests and clinical risk factors indicated both tests were strongly associated with the presence of clinical risk factors for TB (TST: OR 3.17; 95%CI 1.55-6.48, IGRA: OR 2.78; 95%CI 1.55-5.01), and radiological evidence of past TB (TST: OR 3.26; 95%CI 1.85-5.73, IGRA: OR 3.85; 95%CI 2.16-6.86). Relative comparison indicated IGRAs positivity was more strongly associated with presence of radiological evidence of TB than TST (relative OR: 3.24; 95%CI 1.10-9.56). While there is no strong evidence in supporting use of IGRAs over TST for diagnosing latent TB, IGRAs positivity is more associated with the presence of radiological evidence of previous TB.