Dissemination Of Mycobacterium Tuberculosis Research Articles

Disseminated Tuberculosis with Testes Involvement: An Intriguing Case Report

Background: Disseminated tuberculosis (TB) is the presence of two or more noncontiguous sites resulting from hematogenous dissemination of Mycobacterium tuberculosis. We report a case of disseminated TB with testicular involvement. Case: A 21-year-old male patient presented to the outpatient department with bilateral testicular enlargement and tenderness for last six months. It was suspected to be a case of epididymo-orchitis and empirical antimicrobial therapy was initiated. However, ultrasonography findings were inconsistent with epididymo-orchitis. Two weeks later the patient again presented with increased nodularity in the right testes. Non-seminomatous germ cell tumor was suspected. However, tumor markers came back normal. Magnetic resonance imaging revealed enlarged lymph nodes in the right inguinal and retroperitoneal region raising a suspicion of testicular lymphoma. Positron emission tomography with computed tomography showed multiple lymphadenopathies. Histopathology of the left axillary lymph node finally confirmed the diagnosis to be tuberculosis. No drug resistance were found and the patient responded well to anti-tubercular drugs. Conclusion: Diagnosing disseminated TB is difficult as it mimics conditions, such as infarction, cancer, torsion, etc. Attention to small details is necessary. We faced a similar situation in our patient. The patient went through a myriad of tests before finally being diagnosed with TB. Histopathological study was able to get it whereas cytology could not. Similar and totally opposite cases were found in the literature. This highlights the difficulty and importance of these type of cases.

Pneumothorax revealing miliary tuberculosis: A case report

Pulmonary tuberculosis can take several clinical and radiological forms; spontaneous pneumothorax is a serious complication of tuberculosis, and tuberculous miliary is a severe form of secondary tuberculosis due to hematogenous dissemination of Mycobacterium tuberculosis. We report a case of tuberculous miliary revealed by pneumothorax. The patient was 57 years old and a farmer. He was been presented to the emergency department of Mohamed VI University Hospital in Marrakech with acute dyspnea associated with chest pain. Clinical examination and imaging revealed a spontaneous pneumothorax that complicated tuberculous miliary. Treatment consisted of a combination of anti-tuberculosis chemotherapy, chest drainage, and kinesrespiratory therapy. The outcome was favorable, with improvement in clinical and radiological signs. Pneumothorax complicating TM requires careful diagnosis and prompt management to improve prognosis.

Cerebral Tuberculomas Mimicking A Brain Tumor: Report of Two Cases

Introduction : Cerebral tuberculoma, a seldom encountered and severe manifestation of tuberculosis (TB), arises from the dissemination of Mycobacterium tuberculosis through the bloodstream. Its symptoms and radiological characteristics lack specificity, often resulting in diagnostic errors. Management predominantly involves medical intervention, with the treatment duration for cerebral tuberculoma ranging from 6 to 36 months. In specific instances, surgical intervention may be advised. Case presentation: We reported two cases of cerebral tuberculoma occurring in patients who presented with seizures, with space-occupying lesions evident on magnetic resonance imaging of the brain. There were no symptoms of concurrent extra cranial TB. Surgery was performed on both of the cases and anti-TB treatment began as soon as the diagnosis was made with corticosteroid as adjuvant treatment. Conclusion: : A combination of clinical, radiological, and histopathological examination is needed to confirm the diagnosis and determine the appropriate therapy. If ICP is increased as a result of the lesion and medical therapy has failed, surgical excision is required.

Mycobacterium tuberculosis sepsis with multiple intermuscular abscesses and respiratory failure as the main manifestations: a case report

BackgroundTuberculous sepsis is uncommon in individuals without human immunodeficiency virus (HIV) infection, and some patients may not exhibit clinical signs and symptoms of suspected sepsis upon admission, leading to delayed diagnosis and treatment.Case presentationThis report present the case of a 60-year-old female patient who presented with erythema, edema, and pain in her right upper limb accompanied by fever and chills. Further evaluation revealed multiple intermuscular abscesses caused by suspected gram-positive bacteria. Despite receiving anti-infection treatment, the patient rapidly progressed to septic shock and respiratory failure. Metagenomic next-generation sequencing (mNGS) analysis of blood samples detected Mycobacterium tuberculosis complex groups (11 reads). Additionally, mNGS analysis of fluid obtained from puncture of the abscess in the right upper extremity also suggested Mycobacterium tuberculosis complex groups (221 981 reads). Consequently, the patient was diagnosed with tuberculous sepsis resulting from hematogenous dissemination of Mycobacterium tuberculosis. Following the administration of anti-tuberculosis treatment, a gradual recovery was observed during the subsequent follow-up period.ConclusionIt is noteworthy that atypical hematogenous disseminated tuberculosis can be prone to misdiagnosis or oversight, potentially leading to septic shock. This case illustrates the importance of early diagnosis and treatment of tuberculosis sepsis. Advanced diagnostic techniques such as mNGS can aid clinicians in the early identification of pathogens for definitive diagnosis.

DISSEMINATED TUBERCULOSIS PRESENTING AS AN ACUTE ABDOMEN

Mycobacterium tuberculosis is a widespread infection in developing countries like India. Tuberculosis is primarily a chronic condition but can present with acute and unusual manifestations. Disseminated tuberculosis is defined as having two or more non-contiguous sites resulting from lymphohematogenous dissemination of mycobacterium tuberculosis ex.: Miliary TB. Before COVID-19, tuberculosis was the worlds leading cause of death due to a single infectious agent. Especially in India because India accounts for one-quarter of the global burden and prevalence, the incidence rate of Latent TB Infection (LTBI) and active tuberculosis is 33% & 36% respectively in India which is quite high, therefore it is important to consider tuberculosis as an etiological agent if symptom indicates and subsequent work up consideration. Here we are reporting a rare presentation of disseminated tuberculosis in an emergency department at a tertiary care center with sub-acute intestinal obstruction to emphasize the importance of clinical examination and history to evaluate for the cause, for the management of patients even in acute settings like emergency.

Dominant negative biologics normalise the tumour necrosis factor (TNF-α) induced angiogenesis which exploits the Mycobacterium tuberculosis dissemination

BackgroundTumor necrosis factor (TNF) is known to promote T cell migration and increase the expression of vascular endothelial growth factor (VEGF) and chemokines. The administration of Xpro-1595, a dominant-negative TNF (DN-TNF) engineered to selectively inactivate soluble TNF (solTNF), has been extensively studied and proven effective in reducing TNF production without suppressing innate immunity during infection. The literature also supports the involvement of glutamic acid-leucine-arginine (ELR+) chemokines and VEGF in angiogenesis and the spread of infections.Materials and methodsIn this study, we administered Xpro-1595 to guinea pigs to selectively inhibit solTNF, aiming to assess its impact on Mycobacterium tuberculosis (M.tb) dissemination, bacterial growth attenuation, and immunological responses. We conducted immunohistochemical analyses, immunological assays, and colony enumeration to comprehensively study the effects of Xpro-1595 by comparing with anti-TB drugs treated M.tb infected guinea pigs. Throughout the infection and treatment period, we measured the levels of Interleukin-12 subunit alpha (IL-12), Interferon-gamma (IFN-γ), TNF, Tumor growth factor (TGF), and T lymphocytes using ELISA.ResultsOur findings revealed a reduction in M.tb dissemination and inflammation without compromising the immune response during Xpro-1595 treatment. Notably, Xpro-1595 therapy effectively regulated the expression of VEGFA and ELR + chemokines, which emerged as key factors contributing to infection dissemination. Furthermore, this treatment influenced the migration of CD4 T cells in the early stages of infection, subsequently leading to a reduced T cell response and controlled proinflammatory signalling, thus mitigating inflammation.ConclusionOur study underscores the pivotal role of solTNF in the dissemination of M.tb to other organs. This preliminary investigation sheds light on the involvement of solTNF in the mechanisms underlying M.tb dissemination, although further in-depth research is warranted to fully elucidate its role in this process.

Transcriptomic and proteomic analyses of Mycobacterium tuberculosis strains isolated from tuberculous meningitis patients.

Tuberculous meningitis (TBM) is caused by the dissemination of Mycobacterium tuberculosis (MTB) from the primary site of infection to the central nervous system. However, the bacterial factors associated with the pathogenesis of TBM remain unclear. This study employed transcriptomic and proteomic methods to comprehensively analyze the changes in genes and proteins and their associated pathways in MTB strains isolated from cerebrospinal fluid (CSF) of TBM and sputum of pulmonary TB (PTB) cases. Five MTB strains were subjected to OMICs (transcriptomic and proteomic) analysis. Among five MTB strains, two were isolated from CSF and sputum samples of the same patient with PTB and TBM infections, one from the sputum of a different PTB patient, and a strain obtained from the CSF of another TBM patient. H37Rv was used as a reference strain. The reliability of transcriptomic results was validated by real time polymerase chain reaction with selected genes from 100 MTB isolates (CSF, 50 and sputum, 50). The transcriptomic study revealed that overlapping differentially expressed genes of MTB strains isolated from TBM patients showed featured enrichment in benzoate degradation, lysine degradation, tryptophan metabolism, fatty acid degradation, ATP binding cassette transporters, microbial metabolism in diverse environments, biosynthesis of antibiotics, and metabolic pathways. Eleven genes were upregulated, and four were downregulated in MTB strains isolated from TBM compared to PTB. From proteomic analysis, we identified three candidate proteins belonging to plasminogen binding proteins (PBP) (enolase, dnaK, and isocitrate lyase 1) that were significantly upregulated in MTB strains isolated from TBM. Overall, the transcriptomic and proteomic analyses provided an important base for understanding the unique feature of TBM pathogenesis. To the best of our knowledge, this is the first report highlighting the importance of PBPs on TBM pathogenesis.

Rare Presentation of Disseminated Tuberculosis in the Present Era of Modern Tuberculosis Management

Background: Disseminated tuberculosis (TB) is defined as two or more noncontiguous sites resulting from lymphohematogenous dissemination of Mycobacterium tuberculosis. In an immunocompetent host, it is uncommon. The presentation varies, and non-specific early infection symptoms can be noted on chest radiography. Early medication beginning is linked to significantly better outcomes in cases of disseminated tuberculosis. The current case report describes the series of incidents that resulted from a 50-year-old man's excessive usage of the corticosteroid medication tablet Betamethasone, which he was taking for a cough and cold related to his chronic obstructive pulmonary disease (COPD).
 Case Presentation: A 50-year-old Indian male patient with osteoporosis, drug-induced adrenal insufficiency, and bilateral pleural effusion who is receiving anti-tuberculosis therapy which he is on now is presented to the outpatient department of a tertiary hospital with complaints of fever associated with shivering on & off for 4 months, generalized tiredness. He had a history of loose stools for 2-3 days, small joint pain, left knee joint pain and swelling, loss of weight, and loss of appetite.
 Conclusion: The right diagnosis, treatment, patient counseling, diet, and family support helped him recover despite his turbulent recovery phase. As far as steroid therapy is concerned, it is a double-edged sword, meaning that taking (OTC) over-the-counter steroid drugs without first seeking adequate medical advice could have serious negative effects.

A CASE OF DISSEMINATED TUBERCULOSIS IN A IMMUNOCOMPETENT PATIENT: TB MENINGITIS, PLEURAL TB, INTESTINAL/PERITONEAL TB

Disseminatedtuberculosis (TB)isdenedas thepresenceoftwo or more noncontiguous sites resulting from hematogenous dissemination of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation of a latent focus with subsequent spread or rarely through iatrogenic origin. Nowadays, the term miliary TB also refers to progressive and widely spread forms of pulmonary TB. It entails a hematogenous spreadofthediseasetoseveral organ.

Fungal esophagitis associated with tuberculous pericarditis in an human immunodeficiency virus-positive patient: a case report

BackgroundOpportunistic infections are frequent in people living with the human immunodeficiency virus who either do not have access to antiretroviral therapy (ART) or use it irregularly. Tuberculosis is the most frequent infectious disease in PLHIV and can predispose patients to severe fungal infections with dire consequences.Case presentationWe describe the case of a 35-year-old Brazilian man living with human immunodeficiency virus (HIV) for 10 years. He reported no adherence to ART and a history of histoplasmosis with hospitalization for 1 month in a public hospital in Natal, Brazil. The diagnosis was disseminated Mycobacterium tuberculosis infection. He was transferred to the health service in Recife, Brazil, with a worsening condition characterized by daily fevers, dyspnea, pain in the upper and lower limbs, cough, dysphagia, and painful oral lesions suggestive of candidiasis. Lymphocytopenia and high viral loads were found. After screening for infections, the patient was diagnosed with tuberculous pericarditis and esophageal candidiasis caused by Candida tropicalis. The isolated yeasts were identified using the VITEK 2 automated system and matrix-assisted laser desorption/ionization time-of-flight–mass spectrometry. Antifungal microdilution broth tests showed sensitivity to fluconazole, voriconazole, anidulafungin, caspofungin, micafungin, and amphotericin B, with resistance to fluconazole and voriconazole. The patient was treated with COXCIP-4 and amphotericin deoxycholate. At 12 days after admission, the patient developed sepsis of a pulmonary focus with worsening of his respiratory status. Combined therapy with meropenem, vancomycin, and itraconazole was started, with fever recurrence, and he changed to ART and tuberculostatic therapy. The patient remained clinically stable and was discharged with clinical improvement after 30 days of hospitalization.ConclusionFungal infections should be considered in patients with acquired immunodeficiency syndrome as they contribute to worsening health status. When mycoses are diagnosed early and treated with the appropriate drugs, favorable therapeutic outcomes can be achieved.

Superinfection with SARS-CoV-2 Has Deleterious Effects on Mycobacterium bovis BCG Immunity and Promotes Dissemination of Mycobacterium tuberculosis.

ABSTRACTAn estimated one-third of the world’s population is infected with Mycobacterium tuberculosis, with the majority being vaccinated with Mycobacterium bovis BCG. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a threat, and we must understand how SARS-CoV-2 can modulate both BCG immunity and tuberculosis pathogenesis. Interestingly, neither BCG vaccination nor tuberculosis infection resulted in differences in clinical outcomes associated with SARS-CoV-2 in transgenic mice. Surprisingly, earlier M. tuberculosis infection resulted in lower SARS-CoV-2 viral loads, mediated by the heightened immune microenvironment of the murine lungs, unlike vaccination with BCG, which had no impact. In contrast, M. tuberculosis-infected tissues had increased bacterial loads and decreased histiocytic inflammation in the lungs following SARS-CoV-2 superinfection. SARS-CoV-2 modulated BCG-induced type 17 responses while decreasing type 1 and increasing type 2 cytokines in M. tuberculosis-infected mice. These findings challenge initial findings of BCG’s positive impact on SARS-CoV-2 infection and suggest potential ramifications for M. tuberculosis reactivation upon SARS-CoV-2 superinfection.IMPORTANCE Prior to SARS-CoV-2, M. tuberculosis was the leading infectious disease killer, with an estimated one-third of the world’s population infected and 1.7 million deaths a year. Here, we show that SARS-CoV-2 superinfection caused increased bacterial dissemination in M. tuberculosis-infected mice along with immune and pathological changes. SARS-CoV-2 also impacted the immunity of BCG-vaccinated mice, resulting in decreased interleukin-17 (IL-17) levels, while offering no protective effect against SARS-CoV-2. These results demonstrate that SARS-CoV-2 may have a deleterious effect on the ongoing M. tuberculosis pandemic and potentially limit BCG’s efficacy.

Case Report on Congenital Heart Disease with Miliary Tuberculosis

Background: Miliary tuberculosis is the widespread dissemination of Mycobacterium tuberculosis. It is the result of hematogenous dissemination and is characterized by extensive miliary mottling of lungs and involvement of the spleen, liver, and other tissues. It may be found as pulmonary type or septicemic type or meningitic type. Coarctation of the Aorta is a distinct narrowing or long segment hypoplasia of the aortic arch, usually distal to the subclavian artery. The narrow aortic lumen may exist as preductal or postductal obstruction which depends upon the position of the obstruction about the ductus arteriosus. The lesion obstructs blood flow through the aorta, resulting in increased pressure and effort of the left ventricle. Patient presentation: We are presenting an 8-year-old male child who visited the pediatric outpatient unit with the symptoms of fever, cough, and increased work of breathing, he was admitted to PICU. He was a known case of congenital heart disease. He was diagnosed to have congenital heart disease at the age of 3 years when he was admitted to the hospital due to the bluish coloration of his palms and soles. He had a fever (100 degrees F), cough, and increased work of breathing for 15 days during normal daily activities. The patient had undergone a 2-D Echo showing a parachute mitral valve. He was treated with antibiotics and maintained saturation on O2 by CPAP. Symptoms such as Respiratory distress and cough are relieved after maintaining saturation O2 and medications. Conclusion: Coarctation of the Aorta is typically present at birth (congenital heart defect). Mild to severe symptoms are possible. The illness might not be discovered until an adult. Coarctation of the Aorta frequently coexists with other congenital cardiac abnormalities. There are different methods employed for the treatment of CoA in adults, including surgical or percutaneous balloon angioplasty with or without stent placement, and medical therapy. Miliary Tuberculosis is one type of tuberculosis. This condition is rare in people with a normal immune system. It’s more common in people whose immune system isn’t working right. This is called being immunocompromised. Often your lungs, bone marrow, and liver are affected by miliary TB, but it can also spread to the lining of your heart, your spinal cord and brain, and other parts of your body. Treatment strategies in a patient with Miliary tuberculosis require the same treatment as Tuberculosis (Antibiotics).

POS-065 DISSEMINATED TUBERCULOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS: A RARE PRESENTATION AS A PULMONARY-RENAL SYNDROME

Disseminated tuberculosis (TB) is defined as the presence of two or more noncontiguous sites resulting from hematogenous dissemination of Mycobacterium tuberculosis. Higher rates of TB infection (both pulmonary and extra pulmonary) are observed in individuals with SLE compared with the general population. This has been attributed to the immunodysregulatory effects of SLE as well as to the immunosuppressive agents used in its treatment. We describe a case of SLE who succumbed to an unfortunate interplay between active lupus and disseminated tuberculosis.

Tuberculosis Presenting as Intestinal Granulomas in a Patient from West Virginia

uberculosis (TB) is relatively uncommon in West Virginia compared to surrounding Appalachia and the rest of the country. Despite the low prevalence, it is essential to diagnose promptly given the high potential for significant disease burden. Miliary TB is a form of disseminated Mycobacterium tuberculosis infection resulting from hematogenous spread of the organism. Known risk factors for developing disseminated TB include immunosup-pressant medications, human immunodeficiency virus infection, and extremes of age. We present a case in which a patient without identifiable risk factors for TB developed intestinal TB that had been misdiagnosed as Crohn's disease. Shortly after being started on immunosuppressant therapy for the presumed inflammatory bowel disease, the patient developed significant miliary TB

Retrospective assessment of the patients with disseminated tuberculosis

Background: Disseminated tuberculosis (TB) is defined as the presence of two or more noncontiguous sites resulting from hematogenous dissemination of Mycobacterium tuberculosis, occurring as a result of progressive primary infection, reactivation of a latent focus with subsequent spread, or rarely through iatrogenic origin. Hence; the present study was undertaken for assessing the patients with disseminated tuberculosis. Materials & methods: A total of 50 patients who reported to the department and were confirmed with diagnosis of disseminated tuberculosis in the past one year. Complete demographic and clinical data of all the subjects was enrolled. Clinical profile of all the patients was recorded. Assessment of all the results was done using SPSS software. Results: Fever, malaise, weight loss and poor appetite were seen in 66 percent, 30 percent, 24 percent and 20 percent of the patients respectively. Cough, dyspnea, myalgia and joint pain was seen in 20 percent, 12 percent, 14 percent and 18 percent of the patients respectively. On chest imaging, consolidation, fibrotic change, miliary lesion and nodular change was seen in 16 percent, 10 percent, 50 percent and 8 percent of the patients respectively. Conclusion: Majority of the patients demonstrate clinical findings suggestive of disseminated TB.

Donor-Derived Disseminated Mycobacterium Tuberculosis Infection in a Lung Transplant Recipient Three Months After Transplant

<h3>Introduction</h3> Reactivation of latent mycobacterium tuberculosis (MTB) infection in lung transplant recipients is common, which is why pre-transplant screening is recommended to guide treatment. However, MTB transmission from a donor organ is much rarer and there is no consistent screening process of donors. We describe a consequence of this, a rare case of donor-derived disseminated MTB infection in a bilateral lung transplant (BLTx) recipient. <h3>Case Report</h3> A 61-year-old female three months post BLTx complicated by post-operative right lung torsion requiring pneumonectomy presented with a swollen and tender right index finger, tender nodules along her occiput, and a recurrent left sided pleural effusion, which was drained on presentation and culture negative. She improved initially with linezolid and ceftriaxone for presumed septic arthritis, however re-presented two weeks later with similar features, which prompted further evaluation. CT and subsequently MRI of the abdomen demonstrated multiple rim-enhancing liver lesions. A finger aspirate and liver biopsy were obtained that were both culture and smear positive for MTB. Sputum acid fast bacilli samples were negative, and she was started on quadruple therapy with rifabutin, isoniazid, pyrazinamide, and ethambutol with clinical improvement, including resolution of her culture-negative pleural effusion. We suspect that this was a donor-derived infection as the donor lived in an endemic region for many years and the recipient was latent TB negative pre-transplant. <h3>Summary</h3> Donor-derived MTB infection can be difficult to diagnosis due to the atypical way it can present, especially in patients who reside in non-endemic areas. As the world becomes more globalized, and access to lung transplant more accessible, we believe that more donor organs will come from individuals who have lived in endemic areas increasing the risk of donor-derived MTB infections making this an important diagnosis to consider.

A Dual Role of Heme Oxygenase-1 in Tuberculosis.

Iron metabolism is vital for the survival of both humans and microorganisms. Heme oxygenase-1 (HO-1) is an essential stress-response enzyme highly expressed in the lungs, and catabolizes heme into ferrous iron, carbon monoxide (CO), and biliverdin (BV)/bilirubin (BR), especially in pathological conditions which cause oxidative stress and inflammation. Ferrous iron (Fe2+) is an important raw material for the synthesis of hemoglobin in red blood cells, and patients with iron deficiency are often associated with decreased cellular immunity. CO and BR can inhibit oxidative stress and inflammation. Thus, HO-1 is regarded as a cytoprotective molecule during the infection process. However, recent study has unveiled new information regarding HO-1. Being a highly infectious pathogenic bacterium, Mycobacterium tuberculosis (MTB) infection causes acute oxidative stress, and increases the expression of HO-1, which may in turn facilitate MTB survival and growth due to increased iron availability. Moreover, in severe cases of MTB infection, excessive reactive oxygen species (ROS) and free iron (Fe2+) due to high levels of HO-1 can lead to lipid peroxidation and ferroptosis, which may promote further MTB dissemination from cells undergoing ferroptosis. Therefore, it is important to understand and illustrate the dual role of HO-1 in tuberculosis. Herein, we critically review the interplay among HO-1, tuberculosis, and the host, thus paving the way for development of potential strategies for modulating HO-1 and iron metabolism.

Disseminated Mycobacterium tuberculosis: An Unusual Presentation with Associated Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal, and systemic hyperinflammatory syndrome with exacerbated and uncontrolled activation of histiocytes and lymphocytes against mature cells. Secondary HLH can occur in association with a myriad of underlying infections or malignancies. Our patient is a 38-year-old male prisoner with poorly controlled diabetes and no known other medical conditions. He was referred to our emergency department with three-week history of worsening malaise, weight loss, fever, bruising, and shortness of breath; imaging showed pneumomediastinum, lung nodule, and adrenal mass. Biopsy of the lung nodule revealed acid-fast bacilli. Furthermore, bone marrow biopsy showed foci of necrosis with associated acid-fast bacilli and hemophagocytosis highlighted by CD163 stain; consequently, secondary HLH was suggested. Hence, lab results were reviewed and found to satisfy five of the eight secondary HLH criteria. Moreover, ferritin was >10,000 ng/ml, which has been suggested to be highly suspicious for HLH. The patient was started on anti-MAC therapy. Unfortunately, the patient's status declined rapidly; he developed multi-organ failure and succumbed to disease. Later, his culture confirmed Mycobacterium tuberculosis. In conclusion, we presented a rare and challenging case of secondary HLH associated with disseminated Mycobacterium tuberculosis. A high index of suspicion is required for early diagnosis and treatment, and pathologists should be aware of Mycobacterium tuberculosis' association with secondary HLH.

Mycobacterium Abscessus Masquerading as Disseminated Mycobacterium Tuberculosis Infection

Disseminated infection caused by mycobacterium abscessus is a rare condition, observed in immunodeficient or immunosuppressed individuals. We report a case of disseminated mycobacterium abscessus infection, which occurred in a nine-year-old boy with a ventriculoperitoneal shunt. He presented with features of meningitis, ascites and later developed pleural effusion. This infection closely mimics mycobacterium tuberculosis infection, which is endemic in India. Multidrug therapy with macrolides and aminoglycosides, for prolonged duration, can help to eradicate the organism. Mycobacterium abscessus infections can occur following neurosurgical interventions, with surgical shunts and prostheses acting as the portals of entry, thus prompting strong disinfection and sterilization measures in the operating room.

Identifying innate immune regulators of Mycobacterium tuberculosis pathogenesis in macrophages

Abstract Tuberculosis (TB) is a leading infectious disease that contributes to approximately 1.4 million deaths annually worldwide. In the present situation of the COVID-19 pandemic and disrupted healthcare services, mathematical modelling predicts that there will be an additional 6.3 million new cases and 1.4 million more TB deaths by the end of 2025. Innate immune cells like macrophages are the frontline responders in host defense against Mycobacterium tuberculosis (MTB) and may also play a major role in disease establishment. A major roadblock in developing effective strategies against TB is the inability of current anti-TB drugs to target both replicating and non-replicating bacteria. We have found that lack of specific components of the host innate sensing machinery has a major impact on intracellular bacterial growth and the production of IL-1β and IFN-β during MTB infection of macrophages; the latter cytokines play major roles in host-protective and host-detrimental outcomes of infection respectively. RNA seq reveals that these innate immune modules differentially control the expression of genes implicated in host protein synthesis and MTB dissemination and escape from the granuloma. Ongoing work is utilizing Path-Seq for quantitative profiling of the MTB transcriptome within infected macrophages and investigating macrophage-dependent mechanisms of MTB restriction and persistence in vivo. Our study will potentially identify immune regulators that make the macrophage environment either permissive or restrictive for intracellular replication of MTB with important implications for developing combinatorial targeting approaches for host-directed treatment of TB.