Case reports of chronic myeloid leukemia and tuberculosis: Is imatinib the link between the two?

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

A Novel In Vitro Mouse Model to Study Mycobacterium tuberculosis Dissemination Across Brain Vessels: A Combination Granuloma and Blood-Brain Barrier Mouse Model.

In vitro culture models of the blood-brain barrier (BBB) provide a useful platform to test the mechanisms of cellular infiltration and pathogen dissemination into the central nervous system (CNS). We present an in vitro mouse model of the BBB to test Mycobacterium tuberculosis (Mtb) dissemination across brain endothelial cells. One-third of the global population is infected with Mtb, and in 1%-2% of cases bacteria invade the CNS through a largely unknown process. The "Trojan horse" theory supports the role of a cellular carrier that engulfs bacteria and carries them to the brain without being recognized. We present for the first time a protocol for an in vitro BBB-granuloma model that supports the Trojan horse mechanism of Mtb dissemination into the CNS. Handling of bacterial cultures, in vivo and in vitro infections, isolation of primary astroglial and endothelial cells, and assembly of the in vitro BBB model is presented. These techniques can be used to analyze the interaction of adaptive and innate immune system cells with brain endothelial cells, cellular transmigration, BBB morphological and functional changes, and methods of bacterial dissemination. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolation of primary mouse brain astrocytes and endothelial cells Basic Protocol 2: Isolation of primary mouse bone marrow-derived dendritic cells Support Protocol 1: Validation of dendritic cell purity by flow cytometry Basic Protocol 3: Isolation of primary mouse peripheral blood mononuclear cells Support Protocol 2: Isolation of primary mouse spleen cells Support Protocol 3: Purification and validation of CD4+ T cells from PBMCs and spleen cells Basic Protocol 4: Isolation of liver granuloma supernatant and determination of organ load Support Protocol 4: In vivo and in vitro infection with mycobacteria Basic Protocol 5: Assembly of the BBB co-culture model Basic Protocol 6: Assembly of the combined in vitro granuloma and BBB model.

Mycobacterium tuberculosis and Pseudoramibacter alactolyticus coinfection in brain after dental extraction: A case report.

INTRODUCTION: More than 1200 different types of microbes were found in the human mouth, only some of these microorganisms were associated with intracranial bacterial infection. However, there are limited data available about the Pseudoramibacter alactolyticus (P alactolyticus) or Mycobacterium tuberculosis (MTB) intracranial infections oral origin. PATIENT CONCERNS: Here, we reported a rarely case with P alactolyticus and MTB coinfection in central nervous after dental extraction. The 44-year-old man presented with progressive headache over the last 2 weeks and a sustained fever >39°C, with a dental extraction performed 2 days before the onset of headache. DIAGNOSIS: P alactolyticus and MTB were confirmed by real-time polymerase chain reaction targeting the16S ribosomal RNA gene. The presence of MTB was also demonstrated by positive acid-fast staining of the purulent discharge. INTERVENTIONS: The patient was treated by metronidazole and anti-TB treatment OUTCOMES:: The patient fully recovered without sequela. CONCLUSION: In conclusion there should be awareness of the possibility of P alactolyticus or MTB intracranial infections following tooth extraction.

Experimental animal models of central nervous system tuberculosis: A historical review.

Animal models are and will remain valuable tools in medical research because their use enables a deeper understanding of disease development, thus generating important knowledge for developing disease control strategies. Central nervous system tuberculosis (CNS TB) is the most devastating disease in humans. Moreover, as the variability of signs and symptoms delay a timely diagnosis, patients usually arrive at the hospital suffering from late stage disease. Therefore, it is impossible to obtain fresh human tissue for research before an autopsy. Because of these reasons, studies on human CNS TB are limited to case series, pharmacological response reports, and post mortem histopathological studies. Here, we review the contribution of the different animal models to understand the immunopathology of the disease and the host-parasitic relationship, as well as in the development of new strategies of vaccination and to test new drugs for the treatment of CNS TB.

Tuberculous encephalopathy: a reappraisal.

Forty years ago Dastur and Udani described a form of diffuse cerebral damage in tuberculosis, which they called tuberculous encephalopathy. Their pathological and clinical observations led them to propose an immune pathogenesis. Although there have been no convincing independently reported series, the entity is now established in the tuberculosis literature. We review the literature on tuberculous encephalopathy, and suggest alternative aetiopathogenetic explanations for the appearances of the brain in these cases. We propose that tuberculosis is one of many infections which may be associated with a range of immune, drug-related, hypoxic-ischaemic and toxic diffuse brain pathologies.

[Tuberculous orchiepididymitis and CNS complication]. / Die tuberkulöse Epididymoorchitis und die Zentralnervensystemkomplikation.

INTRODUCTION: Hydrocephalus as a complication of tuberculous orchiepididymitis is extremely rare. In this reported case, hydrocephalus was the consequence of a disseminated tuberculous process. CASE REPORT: A 28-year-old man was treated for a left-sided orchiepididymitis. He developed the signs of increased intracranial pressure. Computer tomography (CT) of the brain showed a hydrocephalus. The diagnostics that followed confirmed disseminated tuberculosis (Tbc). CONCLUSIONS: Urogenital system is at the present rarely affected by Tbc. Especially rare is disseminated Tbc, which affects at the same time three different organ systems. Disseminated Tbc presented with many different but non-specific clinical symptoms, sometimes mimicking neoplasm. This makes diagnosis and therapy more difficult. We point out that in any case of orchiepididymitis not responding to standard antimicrobial therapy Tbc must be taken into consideration as the one of the differential diagnostic possibilities.

Tuberculous brain abscess in AIDS patients: report of three cases and literature review.

OBJECTIVE: Clinical description of tuberculous brain abscess in patients with acquired immunodeficiency syndrome (AIDS). METHODS: Clinical case report and review of the literature from January 1981 to January 2003 using the MEDLINE database. RESULTS: The authors report three cases of tuberculous brain abscess in AIDS patients and review nine similar cases. The mean age was 30 years (range: 18-56 years) with seven patients being male. Five (42%) were intravenous drug users, had prior history of extra-cerebral tuberculosis, and presented alterations on chest radiograph. Tuberculin skin test was anergic in six (75%) of eight patients. Three patients of nine had a CD4+ cell count higher than 200 cells/microL, and three had a CD4+ cell count lower than 100 cells/microl. All but one patient had a brain computerized tomography scan with a single lesion. All patients received anti-tuberculous treatment and underwent surgical procedures. Most patients (75%) showed appropriate clinical responses. CONCLUSION: Tuberculous brain abscess must be considered in the differential diagnosis of intracranial mass in AIDS patients. A careful epidemiological, clinical and laboratory evaluation may guide a diagnostic suspicion. Surgery combined with specific anti-tuberculosis treatment seems to determine a good outcome.

Pathogenesis, diagnosis, treatment, and outcome aspects of cerebral tuberculosis.

Cerebral tuberculosis or tuberculosis of the brain manifests predominantly as tuberculous meningitis followed by tuberculoma, tuberculous abscess, and other concomitant forms such as cerebral miliary tuberculosis, tuberculous encephalopathy, tuberculous encephalitis, and tuberculous arteritis. Different forms of cerebral tuberculosis are mainly caused by Mycobacterium tuberculosis and also by non-tuberculous mycobacteria such as M. avium-intracellulare in human immunodeficiency virus-infected persons. Cerebral tuberculosis is diagnosed based on clinical features, cerebrospinal fluid studies combined with radiological images. Early diagnosis, prompt institution of anti-tubercular treatment, and the clinical stage at which the patient presents are important and deciding factors for final outcome. The present review highlights the pathogenesis, recent strides made in diagnosis, including sensitive and specific molecular diagnostic (immunologic and polymerase chain reaction) tests, treatment, and outcome aspects of cerebral tuberculosis.

[Neurological manifestations of tuberculosis]. / Nevrologicheskie proiavleniia tuberkuleza.

One hundred and forty-four new cases of pulmonary tuberculosis were examined. The examination revealed the following neurological syndromes: vegetovascular dystonia, disseminated cerebral microsymptoms, focal lesion of the brain, sensory polyneuropathy. The presence of positive specific basophilic degranulation reactions and intracutaneous tuberculin test suggests that the body shows allergic reactions in response to Mycobacteria tuberculosis. And since connective tissue that presents in the vessels and tunics in the nervous system is involved into a pathological process in allergy, neurological disorders are always secondary in tuberculosis and due to the primary vascular wall lesion that following the type of secondary allergic vasculitis.

Tuberculous encephalopathy. A rare complication of pulmonary tuberculosis.

A case of tuberculous encephalopathy, a rare form of neuro-tuberculosis, is reported in a 16-year-old girl who had pulmonary tuberculosis and extensive cerebral demyelination. The clinical, laboratory and pathological features of this entity are highlighted and the pathogenesis discussed.

Central nervous system (CNS) tuberculosis following allogeneic stem cell transplantation.

Tuberculosis is an uncommon infectious complication after stem cell transplantation. We report a patient who presented with a brain mass, 3 months after pulmonary tuberculosis had been diagnosed and while he was receiving triple antituberculous therapy. He had extensive chronic GVHD. The diagnosis was made after biopsy of the lesion. The cerebral mass was excised, antituberculous treatment was maintained and the patient made a complete neurologic recovery. Six months later, he died of gram-negative septic shock. Mycobacterial infections should be considered in allograft recipients with chronic GVHD and solid lesions in the brain. Bone Marrow Transplantation (2000) 25, 567-569.

Infection of the central nervous system by Mycobacterium tuberculosis in patients infected with human immunodeficiency virus (the new neurotuberculosis).

Neurologic complications of HIV infection are numerous. This review focuses on the clinical presentation, diagnostic particularities and therapeutic issues of neurotuberculosis. The pertinent literature describing this important infection is succinctly summarized with a particular emphasis on the discussion of differences in clinical presentation between HIV-infected and -uninfected patients.