REFINING THE DEFINITION OF MILIARY/DISSEMINATED TUBERCULOSIS IN CANADA.

OBJECTIVE: While a multi-site definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein we sought to generate that evidence. METHODS: We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively-diagnosed TB patients in Canada. Definitions were combined in a multi-variable logistic regression to determine risk factors for TB-related death in DTB. RESULTS: We applied two mutually exclusive definitions of DTB to our dataset: 1. 'strict' - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. 'multisite' - TB disease in two or more non-contiguous sites. Among 2877 notified TB patients, 110 (3.8%) met the 'strict' definition, while 168 (5.8%) met the 'multisite' definition. Of all 278 DTB patients only 135 (48.6%) were notified as DTB using International Classification of Disease codes, and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. DTB patients, by either definition, were less likely to achieve cure/treatment completion and more likely to die. Risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection. CONCLUSION: Our findings support the combination of both a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability.

Vigilance Needed in Treating a Child with Disseminated TB: A Case Report.

BACKGROUND: Tuberculosis is still one of the biggest causes of infection-related death around the world. Disseminated tuberculosis is a potentially fatal disease caused by the haematogenous spread of Mycobacterium tuberculosis. First-line anti-tuberculosis drugs in-clude isoniazid, rifampicin, pyrazinamide, and ethambutol. The first three drugs are known to cause hepatotoxicity. CASE PRESENTATION: We have, herein, reported a case of Drug-induced Liver Injury (DILI) due to anti-tuberculosis therapy in a one-year-old male child with disseminated tuberculosis. He was started on a fixed-dose combination of Anti-tuberculosis Therapy (ATT; isoniazid 50 mg, rifampicin 75 mg, and pyrazinamide 150 mg) and pyridoxine 10 mg orally. Initially, liver pa-rameters were normal, but later on with the course of the treatment, there was a rapid rise in liver enzymes, suggesting liver injury. DISCUSSION: The association between liver injury and anti-tuberculosis therapy has been con-firmed by applying various causality association scales. It is obvious that proper treatment of disseminated tuberculosis can avoid the development of drug-resistant strains that can be harm-ful, worsening the prognosis as there are fewer therapeutic alternatives available. At the same time, there is a need to monitor the patient with ATT-induced DILI. CONCLUSION: The diagnosis of tuberculosis in children is difficult because of the mild, nonspe-cific clinical presentation, which usually reflects the implicated underlying organ. In addition to prompt diagnosis and treatment of disseminated TB, careful monitoring is equally important.

Successful Management, in a Low-Resource Setting, of Disseminated Tuberculosis in a 3-Year Old Boy: A Case Report.

Disseminated or military tuberculosis (TB) is defined as the presence of at least two non-contiguous sites of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation and spread of a latent focus or due to iatrogenic origin. Disseminated TB represents a life-threatening condition, especially in at-risk children and when diagnosis and treatment are delayed. We report on a case of a 3-year old boy who presented with long-lasting unrecognised disseminated TB that was successfully managed in a low-resource setting.

Immune reconstitution inflammatory syndrome following disseminated TB with cerebral venous thrombosis in HIV-negative women during their postpartum period: a case report.

Immune reconstitution inflammatory syndrome (IRIS) is characterized by exuberant and dysregulated inflammatory responses to invading microorganisms. IRIS associated with tuberculosis (TB-IRIS) is widely known in HIV-positive patients after starting highly active antiretroviral therapy (HAART) therapy. However, IRIS has also been observed in solid organ transplant recipients, neutropenic patients, tumor necrosis factor antagonist recipients, and women during the postpartum period despite their HIV status. Case Presentation: We report an exceptional case of a 19-year-old HIV-negative lady who presented as IRIS following disseminated TB with cerebral venous thrombosis during her postpartum period. After 1 month of starting anti-TB therapy, we found a paradoxical worsening of her symptoms and further deterioration of radiological features showing extensive tubercular spondylodiscitis involving almost all the vertebral with extensive prevertebral and paravertebral soft tissue collections. Significant improvement was observed after 3 months of continuation of steroids along with an adequate dose of anti-TB therapy. Discussion: The possible mechanism that could explain this dysregulated and exuberant immune response in HIV-negative postpartum women would be rapidly changing immunologic repertoire, as the recovery of the immune system causes an abrupt shift of host immunity from an anti-inflammatory and immunosuppressive status toward a pathogenic proinflammatory state. Its diagnosis mostly depends on having a high degree of suspicion and ruling out alternative etiology. Conclusion: Therefore, clinicians should be aware of the paradoxical worsening of TB-related symptoms and/or radiological features at the primary site of infection or new location following an initial improvement in adequate anti-TB therapy despite HIV status.

Partial Sheehan's syndrome with abdominal tuberculosis presented with pancytopenia and fluctuating thyroid profile: a case report.

Sheehan's syndrome is a well-recognized cause of panhypopituitarism secondary to pituitary apoplexy, followed by postpartum hemorrhage. Depending upon the degree of ischemic injury, it can be either partial or complete. Case presentation: We report an interesting case of a 35-year-old woman admitted to our hospital with complaints of abdominal distension, which was later presumed to be due to disseminated tuberculosis (TB) after excluding the possible differentials. During the treatment course, she was going through repeated attacks of hypovolemic shock and hypoglycemia due to adrenocortical insufficiency. This, along with the history of prolonged amenorrhea 4 years back due to severe postpartum hemorrhage in her last pregnancy, has led us to our diagnosis of partial Sheehan's syndrome. After 1 month of starting steroid and anti-TB therapy, it was quite surprising when she presented with features of pancytopenia and antitubercular drug-induced hepatitis. Discussion: Sheehan's syndrome may have a varying degree of presentation depending upon the degree of damage to the pituitary gland, which includes amenorrhea, lactation failure, adrenocortical insufficiency, hyponatremia, hypoglycemia, as well as pancytopenia in some rare instances The hormone panel especially the thyroid profile should be monitored carefully. Such cases are often challenging to deal with because of their varying degrees of presentation and the delay in diagnosis due to a lack of clinical suspicion. Conclusion: Therefore, we believe that this rare presentation of pancytopenia in Sheehan's syndrome with fluctuating thyroid profile and abdominal TB in the background will let clinicians approach such a rare disease differently.

Bone graft tuberculosis outbreak in USA: Is it a concern in India?

Globally, 25% of the population is infected with tuberculosis, which poses a leading cause of death worldwide. The transmission of tuberculosis (TB) during organ transplant is reported in the literature whereas only one report has been published on the transmission of TB, during bone allograft transplantation. In the US, in May 2021, an outbreak of TB occurred in patients undergoing spine surgery with bone allograft. This bone graft was retrieved from 80 years deceased donor with latent TB, which was not diagnosed earlier. The recipients were started with a long course of anti-tuberculous drugs. This review narrates the pathway of TB spread among transplant recipients and the strategies to be followed while performing organ or tissue transplantation.

Disseminated Tuberculosis Post COVID-19 Infection: A Case Report.

Diagnosis of tuberculosis was affected during the coronavirus disease 2019 (COVID-19) pandemic. Several studies have shown an association between tuberculosis reactivation and COVID-19, but disseminated tuberculosis was rare. We present a case of a 17-year-old male hospitalized due to a fever of unknown origin for two weeks. The patient recovered from COVID-19 five weeks ago, and his nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was negative on current hospitalization. After investigations, diagnosis of disseminated tuberculosis was made by lymph node biopsy and radiological features. The patient was treated with four anti-tuberculosis medications and had a favorable outcome.

Transudative or masked exudative polyserositis in disseminated tuberculosis? A case report.

Introduction: Polyserositis in disseminated tuberculosis (TB) is an uncommon presentation. The exudative nature of effusion in disseminated TB can be masked by presence of malnutrition due TB. Case presentation: A 24-year-old female, diagnosed with disseminated TB, developed polyserositis with transudative nature of fluid. She was treated with anti-tubercular therapy (ATT). Clinical discussion: Polyserositis, though an uncommon presentation in disseminated TB, was the clinical manifestation in our case. But transudative nature of the fluid was an unexpected finding. Hypoalbuminemia as a result of malnutrition due to TB was the cause for masking exudative effusion in TB. Conclusions: Hypoalbuminemia as a result of malnutrition due to TB can be the reason for transudative nature of effusion in polyserositis.

Concurrent central nervous system involvement in immunocompetent adults with pulmonary miliary TB: a prospective analysis.

BACKGROUND: Wallgren's tuberculosis (TB) timetable demonstrated co-occurrence of miliary TB and tuberculous meningitis in children. To verify the same in immunocompetent adults, we prospectively evaluated the prevalence and spectrum of central nervous system (CNS) involvement in patients with pulmonary miliary TB. MATERIALS AND METHODS: This was a tertiary care, University hospital-based, prospective evaluation performed from December 2018 to June 2020. Newly diagnosed patients with pulmonary miliary TB were subjected to a detailed clinical, laboratory and MRI-based evaluation. All patients received treatment as per WHO guidelines. RESULTS: Out of 342 patients with pulmonary TB, 53 patients met the eligibility criteria. The median age at presentation was 32 y and approximately two-thirds of patients were female. Clinically, only two-fifths of patients had features of CNS involvement. Cerebrospinal fluid (CSF) and imaging abnormalities were noted in 46 patients each. Twelve (23.5%) patients were diagnosed with definite-category tuberculous meningitis. Presence of an infarct significantly correlated with neurological features. Mantoux positivity correlated significantly with the presence of choroid tubercles, CSF changes and brain tuberculomas. CONCLUSION: This is the first study to endorse Wallgren's observations in immunocompetent adults. A high index of suspicion, even in asymptomatic patients, may uncover tuberculous lesions involving the CNS and guide optimal monitoring of patients.

Stillbirth as the primary manifestation of disseminated tuberculosis in a young immunocompetent mother with multiple perforations of the ileum.

Tuberculosis (TB), a significant cause of morbidity and mortality worldwide, is particularly relevant in low/middle-income countries like India, where the disease is endemic. The female reproductive system is very vulnerable to this infection with, the clinical presentation being utterly silent in most patients. Symptoms of TB in pregnancy may initially be attributed to the gravidity itself besides temporary concealment of associated weight loss by the normally occurring weight gain during the pregnancy. Untreated TB may cause pregnancy loss by either placental damage or direct harm to both the mother and child. We report a case of latent disseminated TB in a young immunocompetent female that was revealed in the postpartum state (after full-term stillbirth delivery at home) as 20 ileal perforations secondary to intestinal TB. Due to ongoing sepsis and delayed presentation to the hospital, the patient could not be salvaged despite the best possible efforts.

Uncommon testicular localization of Disseminated TB: a case report from Mozambique.

Tuberculosis (TB) of the testicle is a rarely reported and poorly described disease localization. There are no well-defined clinical features suggestive of testicular TB, which makes the diagnosis difficult to establish, especially in low-income settings like Mozambique, where TB is endemic and often associated with HIV-infection; both considered leading causes of death worldwide. We reported the case of a 45-year-old male, HIV positive, naïve to antiretroviral treatment, admitted to the Department of Medicine of the Central Hospital of Beira to investigate chronic enlargement of the testicles.

Central nervous system Tuberculosis in a man from Cambodia with worsening headaches.

Central nervous system (CNS) tuberculosis should be considered in patients from endemic nations with worsening neurological symptoms. If imaging reveals possible CNS tuberculomas, potentially life-threatening lesions should be excised and analyzed. When disease is less severe, other tissues possibly infected should be biopsied first for diagnosis to avoid neurosurgery.

A rare presentation of disseminated tuberculosis: Prostatic abscess.

Involvement of the prostate by tuberculosis (TB) occurs rarely and tuberculosis prostate abscess is an even rarer occurrence. It has been reported in immunocompromised patients, mainly human immunodeficiency virus seropositive individuals. We are reporting a case of tuberculosis prostatic abscess in an immunocompetent patient with relapse of TB.

A study of the incidence of BCG vaccine complications in infants of Babol, Mazandaran (2011-2013).

BACKGROUND: BCG vaccination which is administered to prevent tuberculosis is sometimes associated with serious complications. This study aimed to determine the incidence of complications of BCG vaccination in Babol. METHODS: All infants who received BCG vaccination between 2011-2013 in health centers of Babol entered the study. Data regarding complications of vaccine were extracted according to the National Inventory of babies. All complicated cases were confirmed by the Academic Committee to review the adverse consequences of the vaccine. RESULTS: Among the 15984 vaccinated neonates, 150 (0.93%) cases presented lymphadenitis. 46.5% were females and 53.5% were males; 43% were rural residents and 57% were urban residents. No cases of lymphadenitis including 1% of lymphadenitis with abscess formation were recovered without treatment. Disseminated infection occurred in 3 cases of immune deficient patients who responded to the treatment. Most complications occurred during 4 months after vaccination. CONCLUSION: According to the results of this study, the prevalence of lymphadenitis in Babol was higher than the standard of WHO. This may be attributed to type and vaccine storage and injection technique. These findings justify further training of health-center workers.

Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications.

TB is the leading cause of HIV/AIDS-related deaths globally. New diagnostic tools are urgently needed to avert deaths from undiagnosed HIV-associated TB. Although simple assays that detect lipoarabinomannan (LAM) in urine have been commercially available for years, their specific role and utility were initially misunderstood, such that they have been slower to emerge from the diagnostics pipeline than otherwise might have been expected. In this article, we review and explain how urine-LAM assays should be understood as diagnostics for disseminated TB in HIV-positive patients with advanced immunodeficiency, in whom haematogenous TB dissemination to the kidneys serves as the primary mechanism by which LAM enters the urine. These insights are critical for the appropriate design of studies to evaluate these assays and to understand how they might be most usefully implemented. This understanding also supports the 2015 WHO recommendations on the restricted use of these assays in sick HIV-positive patients with advanced immunodeficiency.