Late Tuberculosis Reactivation After Severe Covid-19.

Background: Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic. Case description: The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased. Discussion: Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated. LEARNING POINTS: Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.

When the Lightning Strikes Twice: Navigating the Complex Terrain of Cerebral Tuberculosis.

Tuberculosis (TB), a Mycobacterium tuberculosis (Mtb) infection, remains a significant global health concern despite a declining incidence. This report highlights a complex case involving a 24-year-old patient from Angola who presented with a constellation of symptoms, including fever, weight loss, and neurological deficits. The patient had been on chronic corticosteroid therapy, a known risk factor for the reactivation of latent TB infection (LTBI). Her clinical course was marked by diagnostic challenges, such as a previous diagnosis of Kikuchi's disease and paradoxical progression despite appropriate tuberculostatic chemotherapy. Miliary TB, characterized by widespread dissemination of Mtb from the primary site of infection, can manifest in various extrapulmonary locations. Central nervous system (CNS) involvement, particularly TB meningitis, is the most severe form of TB, associated with significant morbidity and mortality. The diagnosis of miliary and CNS TB can be elusive due to nonspecific clinical presentations and imaging findings. This case underscores the importance of a high index of suspicion, especially in immunocompromised individuals, and the need for comprehensive microbiological analysis, including cerebrospinal fluid (CSF) examination, to confirm CNS involvement. Furthermore, this case illustrates the challenges associated with TB treatment, including the risk of drug toxicity, medication adherence, and the potential for drug resistance. Treatment duration for miliary TB is extended, typically lasting nine months to a year, and may require adaptation based on the patient's clinical response and drug penetration into the CNS. Corticosteroids play a critical role as adjuvant therapy, particularly in cases with perilesional edema or paradoxical reactions during treatment. This case underscores the complexity of diagnosing and managing miliary and CNS TB, emphasizing the importance of considering TB as a diagnostic possibility in patients with nonspecific symptoms and risk factors. Early identification, multidisciplinary collaboration, and tailored therapeutic strategies are essential for achieving optimal outcomes in such challenging cases. Additionally, screening for latent TB infection should be a priority for patients requiring immunosuppressive therapy to mitigate the risk of reactivation.

Shift in Tissue-Specific Immune Niches and CD137 Expression in Tuberculoma of Pembrolizumab-Treated Nasopharyngeal Carcinoma Patients.

The use of immune checkpoint inhibitors (ICIs) in cancer treatment has shown promise but can also have unintended consequences, such as reactivating latent tuberculosis (TB). To develop treatments that address ICIs-related adverse events, it is essential to understand cellular heterogeneity across healthy and pathological tissues. We performed cross-tissue multiplexed staining analysis on samples from two patients with TB reactivation during pembrolizumab treatment for metastatic nasopharyngeal carcinoma. CD8+ T cells, rather than CD4+ T cells, accumulated preferentially in the tuberculoma and were associated with increased production of IFNγ and expression of CD137. Additionally, CD137 enrichment played a role in the spatial organization of the tuberculoma, with specific interaction limited to spatial proximal cells between IFNγ+ CD137+ CD8+ T cells and IL12+ CD137+ type-1 macrophages. This unique feature was not observed in non-tumoral or tumoral tissues. Our analysis of public transcriptomic datasets supported the notion that this cellular interaction was more prominent in patients with durable ICI responses compared to those with non-ICI-related TB. We suggest that shifts towards CD137-rich immune niches are correlated with both off-target immune-related adverse events and anti-tumor efficacy. Targeting the tumor microenvironment through conditional activation of anti-CD137 signaling in combination with ICIs can modulate the reactivity of T cells and macrophages for localized tumor killing without the potential off-target immune-related risks associated with ICIs alone.

Ureteral obstruction may activate kidney latent tuberculosis. A qualitative study.

Objectives: To analyze the hypothesis that ureteral obstruction may activate kidney latent tuberculous though qualitative study of Urogenital Tuberculosis patients. Methods: A qualitative study was conducted using semistructured interviews in eight patients with Urogenital Tuberculosis. The progression of the disease from the initial symptoms was characterized through the analysis of the clinical and radiological data. The presence of ureteral obstruction prior to the onset of renal tuberculosis was observed in three patients. Results: Patient 1: A 58-year-old female had five episodes of acute left ureteral lithiasis in two years prior to left kidney tuberculosis. Patient 2: A 55-year-old male patient had a 1.2 cm proximal left ureteral stone and in the following six months, the diagnosis of tuberculosis was made in a nonfunctioning left kidney with ureteral thickening and stenosis. Patient 3: A 47-year-old male patient had a 1.2 cm stone in the proximal right ureter and developed urinary tuberculosis with a nonfunctioning right kidney and a contracted bladder. Conclusion: Kidney tuberculosis may appear in the same kidney that had previously suffered stone ureteral obstruction, which may have created local conditions for the activation of latent foci of renal tuberculosis.

Miliary Tuberculosis during R-MPV Therapy in an Elderly Patient with Primary Central Nerve System Lymphoma: A Case Report.

Most elderly patients with tuberculosis (TB) have previously been infected with Mycobacterium tuberculosis, which remains dormant in the body for decades and may reactivate when their immunity declines due to underlying diseases. Elderly cancer patients are at a high risk for TB, and the treatment of TB reactivation in these patients is challenging. Among cancer patients, the incidence of TB reactivation is the highest in lymphoma patients. However, the impact of chemotherapy on TB reactivation in lymphoma patients is unknown. We report the case of an immunocompetent elderly patient with primary central nervous system lymphoma (PCNSL) having no prior history of TB, who developed miliary TB during multiagent chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine (R-MPV therapy). Retrospectively, the chest computed tomography showed calcification of the pleura, suggesting that the patient had a latent tuberculosis infection (LTBI) and developed miliary TB from the reactivation of TB triggered by the R-MPV therapy. Our case emphasizes that when chemotherapy is administered to patients with PCNSL, interferon-gamma release assay (IGRA) should be performed if there are findings on chest examination suggestive of LTBI, such as pleural calcification, and if IGRA is positive, chemotherapy should be given concurrently with LTBI treatment.

Association of ambient PM2.5 concentration with tuberculosis reactivation diseases-an integrated spatio-temporal analysis.

Objectives: While the plausible role of ambient particulate matter (PM)2.5 exposure in tuberculosis (TB) reactivation has been inferred from in vitro experiments, epidemiologic evidence is lacking. We examined the relationship between ambient PM2.5 concentration and pulmonary TB (PTB) in an intermediate TB endemicity city dominated by reactivation diseases. Methods: Spatio-temporal analyses were performed on TB notification data and satellite-based annual mean PM2.5 concentration in Hong Kong. A total of 52,623 PTB cases from 2005-2018 were mapped to over 400 subdistrict units. PTB standardized notification ratio by population subgroups (elderly aged ≥65, middle-aged 50-64, and young adults aged 15-49) was calculated and correlated with ambient PM2.5 concentration. Results: Significant associations were detected between high ambient PM2.5 concentration and increased PTB among the elderly. Such associations were stable to the adjustment for socio-economic factors and other criteria pollutants. Unstable patterns of association between PM2.5 and PTB risk were observed in the middle-aged population and young adults, for which the observed associations were confounded by other criteria pollutants. Conclusion: With elderly PTB almost exclusively attributable to reactivation, our findings suggested that increased TB reactivations have occurred in association with high ambient PM2.5 exposure, lending support to preventive measures that minimize PM2.5-related TB reactivation.

Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

Disseminated Tuberculosis With an Atypical Cutaneous Manifestation in a Hematopoietic Cell Transplant Patient in the Early Posttransplant Period: Case Report and Review of the Literature.

We describe an unusual case of posttransplant tuberculosis reactivation in a man who underwent allogeneic hematopoietic cell transplant. Concomitant with disseminated adenovirus infection, reactivation of tuberculosis manifested as disseminated, nonfollicular pustules on day +49. Skin biopsy was obtained on day +50. Initial histopathologic evaluation did not suggest mycobacterial infection, but tissue stain showed acid-fast organisms, which were subsequently identified as Mycobacterium tuberculosis. Shortly after the cutaneous presentation of tuberculosis, the patient died on day +52. Our case is among a paucity of reports describing tuberculosis reactivation in hematopoietic cell transplant patients in the early posttransplant period. It highlights the difficulty of diagnosing contemporaneous systemic infections, and it presents a rare and atypical cutaneous manifestation of tuberculosis in a hematopoietic cell transplant patient. Our case and review of the literature emphasize the need for further research to elucidate risk factors associated with early posttransplant reactivation of tuberculosis, and the importance of remaining vigilant for active tuberculosis in hematopoietic cell transplant patients with epidemiologic risk factors.

A Case of Pleural Tuberculosis vs Latent Tuberculosis Reactivation as a Result of COVID-19 Infection and Treatment.

The reactivation of latent tuberculosis occurs when a patient living with Mycobacterium tuberculosis enters a state where the immune system is suppressed. Since early 2021, the standard of care has been to provide corticosteroids in patients with COVID-19 infection in hospitalized patients receiving supplemental oxygen or mechanical ventilation. The immunomodulatory effects of corticosteroids are potentially detrimental for patients with latent vs active tuberculosis, with concomitant SARS-CoV2 infection. We present one of the first few cases in the literature detailing a case of reactivation of latent tuberculosis vs. pleural tuberculosis as a consequence of COVID-19, and who underwent subsequent corticosteroid treatment.

Reactivation of Pulmonary Tuberculosis in a Patient With COVID-19: Case Report and Review of Literature.

Given COVID-19 rise in populations with high burden of tuberculosis infection, the interplay between COVID-19 and tuberculosis reactivation needs further investigation. We report a case of a 64-year-old man who developed acute respiratory distress syndrome due to severe COVID-19 infection. He was managed with intubation, prone-position mechanical ventilation, inhaled nitric oxide, and methylprednisolone 40 mg intravenous twice daily for 5 days. He developed unexplained persistent fever and leukocytosis that failed to respond to empiric broad-spectrum antibacterial, antifungal agents, and a 3-day course of intravenous methylprednisolone 1000 mg for possible usual interstitial pneumonitis. His endotracheal aspiration samples tested positive for Mycobacterium tuberculosis, and antituberculosis regimen was started. The patient died as result of decision to withdraw life support. This report establishes the clinical picture of a tuberculosis reactivation in a COVID-19 patient. The complex interaction between COVID-19, steroids, and tuberculosis is a clinical dilemma of great significance.

Tuberculosis reactivation at ileum following immune checkpoint inhibition with pembrolizumab for metastatic nasopharyngeal carcinoma: a case report.

BACKGROUND: Tuberculosis (TB) reactivation has been increasingly identified following immune checkpoint inhibitor (ICI) therapy for cancer patients. However there has been no report on TB reactivation in the gastrointestinal tract. In the report, we describe a patient who developed TB ileitis after pembrolizumab for her metastatic nasopharyngeal carcinoma (NPC). Rechallenge with pembrolizumab after its temporary interruption together with anti-TB therapy produced continuous tumor response but without further TB reactivation. CASE PRESENTATION: A 29-year-old lady with metastatic NPC involving the cervical nodes, lungs and bones started pembrolizumab after failure to multiple lines of chemotherapy. She complained of sudden onset of abdominal pain, vomiting and bloody diarrhea with mucus 21 months after pembrolizumab. Colonoscopy revealed terminal ileitis with multiple caseating granulomas with Langerhan cells. Serum interferon gamma release assay was strongly positive. She was treated with anti-TB medication and was later rechallenged with pembrolizumab for her progressive lung metastases without further TB relapse while her lung metastases were brought under control again. CONCLUSION: To date, this is the first gastrointestinal TB reactivation after ICI therapy for cancer. Guidelines to screen for TB before initiation of ICIs in endemic areas should be established.

Latent tuberculosis infection reactivation in patients with multiple sclerosis in use of disease-modifying therapies: A systematic review.

BACKGROUND: Tuberculosis (TB) is an infectious-contagious disease caused by Mycobacterium tuberculosis. This disease can act acutely or in latent form as granuloma. Multiple Sclerosis (MS) is a chronic inflammatory disease more common in the Central Nervous System (CNS). Its treatment involves disease-modifying therapies (DMTs), which can predispose MS patients to a higher risk of infections by interfering in the immune system. Patients undergoing MS treatment could be more susceptible to Latent Tuberculosis Infection (LTBI) reactivation. This study aims to elucidate the possible relationship between MS and LTBI through a systematic review of the literature. METHODS: MEDLINE/PubMed, Cochrane, ScienceDirect, LILACS, and SciELO were systematically reviewed from 2010 to 2020 and Google Scholar from 2015 to 2020 to detect eligible papers. The following keywords were used for this search: "LTBI and MS"; "Multiple Sclerosis and Latent Tuberculosis"; "Multiple Sclerosis and Latent Tuberculosis infection reactivation"; "Multiple Sclerosis and Pulmonary Tuberculosis"; "Multiple Sclerosis and Active Tuberculosis"; "Multiple Sclerosis and Tuberculosis Reactivation" for MEDLINE/Pubmed and ScienceDirect; and "Multiple Sclerosis and Latent Tuberculosis Infection" for Google Scholar, Cochrane, SCIELO, and LILACS. The filter for "review articles," "research articles," and "case reports" was applied in ScienceDirect. RESULTS: Fourteen (14) studies describing the relationship between MS and LTBI were included in qualitative synthesis: case-report (2), prevalence (2), non-systematic review (4), expert consensus (2), and case-control (4) studies. CONCLUSION: The reactivation of LTBI is well understood, but hardly any literature addressed the association between the contagious disease and MS' treatment. The selected articles are observational studies that offer limited data and differ in many aspects detailed over this study. These divergences make it challenging to compare articles' results. Nevertheless, most reports recommend screening for LTBI before starting MS treatment, mainly in high incidence countries.

Reactivation of intraabdominal tuberculous lymphadenopathy after drug-eluting beads transcatheter arterial chemoembolization in a patient with hepatocellular carcinoma.

Owing to effective treatments and sanitary improvements, the incidence of latent tuberculosis infection (LTBI) has decreased. However, approximately one-quarter of the world's population is thought to have LTBI, and the reactivation of tuberculosis (TB) sometimes occurs in immunocompromised hosts. A 54-year-old man presented with a fever. The patient had past histories of alcoholic and hepatitis C virus-related cirrhosis and hepatocellular carcinoma (HCC). He was treated with drug-eluting beads transarterial chemoembolization (DEB-TACE) for HCC three times, beginning 10 months before his current visit. A computed tomography scan showed enlarged intraabdominal lymph nodes with calcification, and the interferon-gamma release assay for TB infection was positive. The patient was diagnosed with tuberculous reactivation. Anti-TB therapy was administered to the patient, after which we restarted TACE and the TB infection remains controlled. In this case, we presumed that DEB-TACE is associated with the reactivation of TB infection and that anthracycline increases the risk of reactivating TB infection. In summary, we experienced a case of TB reactivation during the clinical course of a patient with HCC who was treated with DEB-TACE. When patients with HCC are treated with TACE, their symptoms, laboratory data, and imaging results should be monitored when latent TB infections are suspected.

Characteristics Predicting Tuberculosis Risk under Tumor Necrosis Factor-α Inhibitors: Report from a Large Multicenter Cohort with High Background Prevalence.

OBJECTIVE: Screening strategies for latent tuberculosis (TB) before starting tumor necrosis factor (TNF)-α inhibitors have decreased the prevalence of TB among patients who are treated with these agents. However, despite vigilant screening, TB continues to be an important problem, especially in parts of the world with a high background TB prevalence. The aim of this study was to determine the factors related to TB among a large multicenter cohort of patients who were treated with anti-TNF. METHODS: Fifteen rheumatology centers participated in this study. Among the 10,434 patients who were treated with anti-TNF between September 2002 and September 2012, 73 (0.69%) had developed TB. We described the demographic features and disease characteristics of these 73 patients and compared them to 7695 patients who were treated with anti-TNF, did not develop TB, and had complete data available. RESULTS: Among the 73 patients diagnosed with TB (39 men, 34 women, mean age 43.6 ± 13 yrs), the most frequent diagnoses were ankylosing spondylitis (n = 38) and rheumatoid arthritis (n = 25). More than half of the patients had extrapulmonary TB (39/73, 53%). Six patients died (8.2%). In the logistic regression model, types of anti-TNF drugs [infliximab (IFX), OR 3.4, 95% CI 1.88-6.10, p = 0.001] and insufficient and irregular isoniazid use (< 9 mos; OR 3.15, 95% CI 1.43-6.9, p = 0.004) were independent predictors of TB development. CONCLUSION: Our results suggest that TB is an important complication of anti-TNF therapies in Turkey. TB chemoprophylaxis less than 9 months and the use of IFX therapy were independent risk factors for TB development.

Tuberculosis reactivation in hepatocellular carcinoma: association with transarterial chemoembolization.

Transarterial chemoembolization (TACE) is an important therapeutic option for patients with hepatocellular carcinoma (HCC). We discuss five patients with HCC and tuberculosis (TB) reactivation following TACE. Screening patients for latent TB infection at diagnosis of cirrhosis or HCC should be considered because of the immunosuppression inherent in both the diseases and their treatments.

Reactivation of pulmonary tuberculosis during cancer treatment.

Reactivation of Mycobacterium tuberculosis can occur in patients with latent tuberculosis (TB) with risk factors including chronic disease (i.e., malignancy). We herein describe the case of an immigrant from Hong Kong with lung cancer and no known TB disease who presents with reactivation of TB in the setting of chemotherapy and radiation therapy.