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Dash N, Manion M, Silverberg SL, Kitai I. Identification and Management of Paradoxical Reactions in Pediatric Tuberculosis. Pediatr Infect Dis J 2025; 44:e203-e206. [PMID: 40106771 DOI: 10.1097/inf.0000000000004805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Affiliation(s)
- Nabaneeta Dash
- From the Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Maura Manion
- Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Sarah L Silverberg
- From the Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Institute of Health Policy, Management and Evaluation
| | - Ian Kitai
- From the Division of Infectious Diseases, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
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2
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Zhang H, Hasan T, Dotel R, Ulbricht E, Gilroy N, Maddocks S. Central nervous system tuberculosis in Western Sydney: a 10-year retrospective cohort study. Intern Med J 2025; 55:822-832. [PMID: 40104936 PMCID: PMC12077587 DOI: 10.1111/imj.70017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 01/06/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Central nervous system tuberculosis (CNS-TB) is a rare complication of tuberculosis. There is a lack of data surrounding investigation and management of this in Australia. AIM To review CNS-TB cases in Western Sydney, Australia, and understand the epidemiology, investigation, diagnosis, management and outcomes in a low-prevalence setting. METHODS Retrospective cohort study of all CNS-TB patients managed in Western Sydney from 2013 to 2022. Demographics, risk factors, clinical presentation, investigations and management were reviewed. Clinical outcomes like hospital length-of-stay, adverse drug reactions, paradoxical reactions, functional disability and treatment outcomes, including cure, treatment failure, loss to follow-up and death, were also measured. RESULTS Thirty-nine CNS-TB cases were identified, with 16 (41%) confirmed by nucleic acid amplification test or culture of CNS specimens and 23 (59%) diagnosed presumptively without CNS microbiological confirmation. The median age was 32 years. Thirty-seven (95%) were overseas-born; 27 (69%) had no comorbidities. Presenting symptoms included fever (82%), headache (64%) and weight loss (51%). Twenty-five (64%) used fluoroquinolones and nine (23%) used high-dose rifampicin. Steroids were used in all patients. Six (15%) were prescribed aspirin for primary stroke prevention. Twenty-eight (73%) completed treatment, with one requiring re-treatment for presumed treatment failure. Six (15%) were lost to follow-up, and five (13%) died during their treatment course. Twenty-one (54%) experienced an adverse drug reaction. CONCLUSION Tuberculosis is an ongoing public health issue in Australia, with CNS-TB being its most devastating form, and all clinicians to be aware of this rare complication. The efficacy of newer treatment options requires further study.
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Affiliation(s)
- Hayden Zhang
- Infectious Diseases DepartmentBlacktown HospitalBlacktownNew South WalesAustralia
- School of MedicineWestern Sydney UniversityBlacktownNew South WalesAustralia
| | - Tasnim Hasan
- Infectious Diseases DepartmentBlacktown HospitalBlacktownNew South WalesAustralia
- Faculty of Health and MedicineUniversity of SydneySydneyNew South WalesAustralia
| | - Ravindra Dotel
- Infectious Diseases DepartmentBlacktown HospitalBlacktownNew South WalesAustralia
| | - Evan Ulbricht
- NSW Tuberculosis ProgramHealth Protection New South WalesSydneyNew South WalesAustralia
| | - Nicole Gilroy
- Centre for Infectious Diseases and MicrobiologyWestmead HospitalSydneyNew South WalesAustralia
| | - Susan Maddocks
- Faculty of Health and MedicineUniversity of SydneySydneyNew South WalesAustralia
- Centre for Infectious Diseases and MicrobiologyWestmead HospitalSydneyNew South WalesAustralia
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3
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Schregenberger S, Graup V, Schibli A, Preiswerk B, Laube I, Huber LC, Stüssi-Helbling M. Immune reconstitution inflammatory syndrome (IRIS): Case series and review of the literature. Respir Med Case Rep 2025; 55:102213. [PMID: 40276120 PMCID: PMC12019413 DOI: 10.1016/j.rmcr.2025.102213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2025] [Revised: 03/18/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025] Open
Abstract
Background Immune-reconstitution inflammatory syndrome (IRIS) is a dysregulated host inflammatory response following the initiation of appropriate therapy targeting an infectious disease. It is most commonly reported in human immunodeficiency virus patients following the initiation of antiretroviral therapy; however, IRIS can also be seen in immunocompromised patients without HIV, when the immune system is recovering. The diagnosis is confirmed using clinical and laboratory data after excluding differential diagnoses and concomitant infections. Case series Here, we describe three cases of patients with IRIS that were treated at our tertiary care center. The first case involves a paradoxical IRIS in an HIV-positive patient with TB, where the re-initiation of ART led to an inflammatory response despite effective anti-tuberculous treatment (ATT). The second case highlights unmasking IRIS in an HIV-positive patient, where the initiation of ART revealed an underlying Epstein-Barr virus (EBV)-associated B-cell lymphoma. The third case describes paradoxical worsening of pulmonary TB in an HIV-negative patient, expanding the scope of IRIS beyond its conventional association with HIV infection. Conclusion These cases illustrate the various manifestations of IRIS and emphasize the need for timely diagnosis and appropriate management strategies to mitigate the potentially severe outcomes associated with this syndrome. Our report highlights the challenges faced in the diagnosis of IRIS which impede prompt onset of therapy.
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Affiliation(s)
- Sebastian Schregenberger
- Department of Surgery, Division of Emergency Medicine, Hospital Buelach, Spitalstrasse 24, 8180, Buelach, Switzerland
| | - Vera Graup
- Department of Cardiology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland
| | - Adrian Schibli
- Department of Internal Medicine, Division of Infectious Diseases and Infection Prevention, City Hospital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Benjamin Preiswerk
- Department of Internal Medicine, Division of Infectious Diseases and Infection Prevention, City Hospital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Irène Laube
- Department of Internal Medicine, Division of Pulmonology, City Hospital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Lars C. Huber
- Department of Internal Medicine, Clinic for Internal Medicine, City Hospital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
| | - Melina Stüssi-Helbling
- Department of Internal Medicine, Clinic for Internal Medicine, City Hospital Zurich, Birmensdorferstrasse 497, 8063, Zurich, Switzerland
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4
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Yano K, Yokosuka K, Amemiya K, Sakashita K, Ishida T. Orbital Myositis as a Paradoxical Reaction to Anti-Tuberculosis Treatment. Balkan Med J 2025; 42:77-78. [PMID: 39600227 PMCID: PMC11725676 DOI: 10.4274/balkanmedj.galenos.2024.2024-7-10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 08/22/2024] [Indexed: 11/29/2024] Open
Affiliation(s)
- Koichi Yano
- Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan
| | - Kyoko Yokosuka
- Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan
| | - Kiyomi Amemiya
- Department of Radiology, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan
| | - Kentaro Sakashita
- Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan
- Department of Pulmonary Medicine, Takayama Red Cross Hospital, Takayama, Gifu, Japan
| | - Takuto Ishida
- Department of Internal Medicine, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan
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5
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Reasoner KC, Fiske CT, Yu J, Thomson DB, Staub MB. Mycobacterium tuberculosis Ankle Arthritis and Subsequent Immune-Reconstitution Inflammatory Syndrome. Am J Med 2024; 137:1063-1066. [PMID: 39074676 DOI: 10.1016/j.amjmed.2024.07.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 07/31/2024]
Affiliation(s)
- Kaitlyn C Reasoner
- Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tenn.
| | - Christina T Fiske
- Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tenn
| | - James Yu
- Tennessee Orthopaedic Alliance, Nashville
| | | | - Milner B Staub
- Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tenn; Infectious Diseases Section, Veteran Affairs Tennessee Valley Healthcare System, Nashville
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6
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Siahaan AMP, Nainggolan BWM, Rosa AB, Risfandi M, Pradana A, Silalahi DMR. Tuberculous ventriculitis as a devastating neurological manifestation of immune reconstitution inflammatory syndrome: A case report in immunocompetent patient. Int J Surg Case Rep 2024; 124:110493. [PMID: 39427403 PMCID: PMC11533677 DOI: 10.1016/j.ijscr.2024.110493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/17/2024] [Accepted: 10/18/2024] [Indexed: 10/22/2024] Open
Abstract
INTRODUCTION AND IMPORTANCE Tubercular Immune Reconstitution Inflammatory syndrome (TB-IRIS) is defined as the worsening of existing disease or new tuberculosis lesions during anti-tuberculosis therapy after excluding drug resistance, adherence issues, secondary infection, and malignancy. Ventriculitis is a rare and detrimental complication of cerebral tuberculosis. Here, we report a case of ventriculitis as a manifestation of TB-IRIS. CASE PRESENTATION A 46-year-old male presented to the emergency department with a decline in consciousness for four days prior to admission. He experienced a progressive headache accompanied by intermittent high-grade fever over the past week. He was diagnosed with rifampicin-sensitive pulmonary tuberculosis three months prior and was treated with a fixed-dose combination of anti-tuberculosis (ATT) regimen. His HIV test result was negative. A non-contrast computed tomography (CT) scan revealed ventriculitis and hydrocephalus. The patient subsequently received ATT and corticosteroids, along with external ventricular drainage (EVD) to alleviate intracranial pressure and address the intraventricular infection. Regrettably, the patient's condition progressively declined, resulting in his demise on the seventh day post-admission. CLINICAL DISCUSSION TB-IRIS is primarily characterized in individuals with HIV/tuberculosis coinfection; however, it does not exclude that TB-IRIS may occur in immunocompetent conditions. Tuberculous ventriculitis is a manifestation of CNS TB-IRIS, characterized by significant morbidity and mortality. The fundamental principle in managing ventriculitis is to control both the inflammation and the infection and reducing intracranial pressure. CONCLUSION This particular case does not significantly enhance the management of CNS-TB-IRIS; however, it does bring attention to the potential occurrence of this condition in immunocompetent patients.
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Affiliation(s)
| | | | - Ahmad Brata Rosa
- Department of Neurosurgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - Marsal Risfandi
- Faculty of Sport Sciences, Universitas Negeri Medan, Medan, Indonesia
| | - Andika Pradana
- Department of Pulmonology and Respiratory Medicine, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
| | - David M R Silalahi
- Intensive Care Unit Division, Imelda Pekerja Indonesia General Hospital, Medan, Indonesia
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Bohórquez JA, Jagannath C, Xu H, Wang X, Yi G. T Cell Responses during Human Immunodeficiency Virus/ Mycobacterium tuberculosis Coinfection. Vaccines (Basel) 2024; 12:901. [PMID: 39204027 PMCID: PMC11358969 DOI: 10.3390/vaccines12080901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/05/2024] [Accepted: 08/07/2024] [Indexed: 09/03/2024] Open
Abstract
Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as both targets for HIV infection and mediators of the immune response against both pathogens. This review aims to synthesize the current literature and provide insights into the effects of HIV/Mtb coinfection on T cell populations and their contributions to immunity. Evidence from multiple in vitro and in vivo studies demonstrates that T helper responses are severely compromised during coinfection, leading to impaired cytotoxic responses. Moreover, HIV's targeting of Mtb-specific cells, including those within granulomas, offers an explanation for the severe progression of the disease. Herein, we discuss the patterns of differentiation, exhaustion, and transcriptomic changes in T cells during coinfection, as well as the metabolic adaptations that are necessary for T cell maintenance and functionality. This review highlights the interconnectedness of the immune response and the pathogenesis of HIV/Mtb coinfection.
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Affiliation(s)
- José Alejandro Bohórquez
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA;
- Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA
- Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA
| | - Chinnaswamy Jagannath
- Department of Pathology and Genomic Medicine, Center for Infectious Diseases and Translational Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA;
| | - Huanbin Xu
- Tulane National Primate Research Center, Tulane University School of Medicine, Tulane University, Covington, LA 70112, USA; (H.X.); (X.W.)
| | - Xiaolei Wang
- Tulane National Primate Research Center, Tulane University School of Medicine, Tulane University, Covington, LA 70112, USA; (H.X.); (X.W.)
| | - Guohua Yi
- Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA;
- Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA
- Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA
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Sabzi F, Faraji R, Khoshnood S. Right atrial tuberculoma enclosed by thrombus. Glob Cardiol Sci Pract 2024; 2024:e202436. [PMID: 39351480 PMCID: PMC11439434 DOI: 10.21542/gcsp.2024.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 07/23/2024] [Indexed: 10/04/2024] Open
Abstract
Right atrial tuberculoma (RAT) are an exceedingly rare heart mass often caused by primary pulmonary tuberculosis (TB) in patients infected with human immunodeficiency virus (HIV). In HIV patients, the right atrium is not only a suitable location for tuberculoma formation, but also has a tendency for thrombus formation due to the thrombophilic state of HIV and the destructive effect of the HIV virus on the endothelial surface of the right atrium and subsequent thrombus formation. These masses can simply be detected by transthoracic echocardiography (TEE), but their differentiation from other cardiac pathologies requires histological examination. Herein, using a positive polymerase chain reaction test, we report a case of a previously diagnosed HIV-positive 24-year-old man who presented with a right atrial thrombus, dyspnea, and pleural effusion. Final histological examination identified the right atrial thrombus as a tuberculoma. The patient underwent open heart surgery to remove the mass and received prolonged postoperative TB therapy together with HIV drugs. Three-month follow-up showed some remaining dyspnea and lower extremity edema; however, TEE showed no recurrence of the RAT or thrombus.
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Affiliation(s)
- Freidoun Sabzi
- Department of General Surgery, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Reza Faraji
- Tuberculosis and Lung Diseases Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
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9
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Nayak B, Panda RK, Mohanty T, Sahu L. Incidence and pattern of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients on anti-retroviral therapy: An observational study. Indian J Tuberc 2024; 71:291-296. [PMID: 39111937 DOI: 10.1016/j.ijtb.2023.05.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 05/12/2023] [Accepted: 05/25/2023] [Indexed: 02/01/2025]
Abstract
BACKGROUND Tuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). METHODS This observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. RESULTS A total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. CONCLUSION People with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.
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Affiliation(s)
- Bikash Nayak
- Department of Pharmacology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
| | - Rajendra Kumar Panda
- Department of Pharmacology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
| | - Thitta Mohanty
- Department of Pulmonary Medicine, S.C.B. Medical College and Hospital, Cuttack, Odisha, India
| | - Lorika Sahu
- Department of Pharmacology, S.C.B. Medical College and Hospital, Cuttack, Odisha, India.
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10
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Guimarães AR, Bastos J, Santos L, Silva‐Pinto A. Lymph node tuberculosis-associated paradoxical immune reconstitution inflammatory syndrome in a non-HIV patient: Case report and review of literature. EJHAEM 2024; 5:593-598. [PMID: 38895068 PMCID: PMC11182407 DOI: 10.1002/jha2.912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 04/09/2024] [Indexed: 06/21/2024]
Abstract
Tuberculosis (TB) is a global health threat, especially in HIV patients who may experience immune reconstitution inflammatory syndrome (IRIS) upon Mycobacterium tuberculosis infection. Diagnosing and defining IRIS in non-HIV patients remains challenging. A 63-year-old male with acute leukaemia underwent induction therapy with a regimen containing fludarabine. Febrile neutropenia led to further investigations, revealing non-cavitary pulmonary TB, prompting anti-tuberculosis therapy (ATT) alongside resumed leukaemia treatment with sorafenib. Persistent extra-pulmonary TB, specifically lymph node involvement, were observed and IRIS was suspected, evidenced by enlarged lymphadenopathies, scrofula, and skin lesions that developed during the 13-month course of ATT, with no recurrence after its cessation. This article explores a case of lymph node TB-associated paradoxical IRIS in a non-HIV leukaemia patient, revealing the intricate interplay between tuberculosis and haematological malignancies and emphasizing the lack of standardized diagnostic criteria and treatment consensus. Challenges in lymph node TB diagnosis and management highlight the need for tailored therapeutic approaches. The report explores the potential immunomodulatory effects of fludarabine and sorafenib, questioning their roles in TB-IRIS. This case illuminates TB-IRIS dynamics in non-HIV patients, urging further research and collaborative efforts to enhance understanding and outcomes. As medical complexities persist, personalized therapeutic approaches and advancements in TB-IRIS research are crucial.
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Affiliation(s)
| | - Juliana Bastos
- Hematology Diseases DepartmentCentro Hospitalar Universitário de São JoãoPortoPortugal
| | - Lurdes Santos
- Infectious Diseases DepartmentCentro Hospitalar Universitário de São JoãoPortoPortugal
| | - André Silva‐Pinto
- Infectious Diseases DepartmentCentro Hospitalar Universitário de São JoãoPortoPortugal
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11
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Karnan A, Jadhav U, Ghewade B, Ledwani A, Beeravolu H. HIV Versus the Human Body: A Case Report of an Immunity-Compromised Patient. Cureus 2024; 16:e62942. [PMID: 39050280 PMCID: PMC11265968 DOI: 10.7759/cureus.62942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 06/23/2024] [Indexed: 07/27/2024] Open
Abstract
The immune system is the body's defense system against infection, pathogenic organisms, or foreign bodies. Human immunodeficiency virus (HIV) infection significantly reduces the number of cells involved in the immune system making the infected person prone to a greater number of infections like tuberculosis (TB). HIV infection reduces the CD4 T helper cell count and further replicates within the body. HIV-TB is a major health concern as there is more chance of progression to acquired immunodeficiency syndrome (AIDS) and the emergence of drug-resistant TB. In this case report, we see how the HIV-TB infection affects the body, significantly affecting the morbidity and mortality of the patient.
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Affiliation(s)
- Ashwin Karnan
- Pulmonary Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Ulhas Jadhav
- Respiratory Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Babaji Ghewade
- Respiratory Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Anjana Ledwani
- Pulmonary Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Harshith Beeravolu
- Respiratory Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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12
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Montero-Vega MT, Matilla J, Bazán E, Reimers D, De Andrés-Martín A, Gonzalo-Gobernado R, Correa C, Urbano F, Gómez-Coronado D. Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to Inactivated Mycobacterium tuberculosis H37Ra. Cells 2024; 13:536. [PMID: 38534380 PMCID: PMC10969755 DOI: 10.3390/cells13060536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 03/07/2024] [Accepted: 03/11/2024] [Indexed: 03/28/2024] Open
Abstract
Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients against developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMCs) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMCs, most monocytes/macrophages became foamy cells that overproduced NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMCs were exposed to Mtb H37Ra, a small subset of macrophages captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFNγ. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria, degraded them, markedly activated caspase-1 and elicited a potent IFNγ/cytotoxic response. In rabbits immunized with the same bacteria, fluvastatin increased the tuberculin test response. We conclude that statins may enhance macrophage efficacy to control Mtb, with the help of adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.
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Affiliation(s)
- María Teresa Montero-Vega
- Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (J.M.); (D.G.-C.)
| | - Joaquín Matilla
- Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (J.M.); (D.G.-C.)
| | - Eulalia Bazán
- Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (E.B.); (D.R.)
| | - Diana Reimers
- Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (E.B.); (D.R.)
| | - Ana De Andrés-Martín
- Servicio de Inmunología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain;
| | - Rafael Gonzalo-Gobernado
- Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), 28049 Madrid, Spain;
| | - Carlos Correa
- Unidad de Cirugía Experimental y Animalario, Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain;
| | - Francisco Urbano
- Servicio Interdepartamental de Investigación (SIdI), Facultad de Medicina, Universidad Autónoma, 28029 Madrid, Spain;
| | - Diego Gómez-Coronado
- Servicio de Bioquímica-Investigación, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; (J.M.); (D.G.-C.)
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13
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Lin N, Erdos T, Louie C, Desai R, Lin N, Ayzenberg G, Venketaraman V. The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV. Int J Mol Sci 2024; 25:2952. [PMID: 38474196 PMCID: PMC10932396 DOI: 10.3390/ijms25052952] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 02/25/2024] [Accepted: 02/28/2024] [Indexed: 03/14/2024] Open
Abstract
Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses.
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Affiliation(s)
- Nicole Lin
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
| | - Thomas Erdos
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
| | - Carson Louie
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
| | - Raina Desai
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
| | - Naomi Lin
- Creighton University School of Medicine, Creighton University, Omaha, NE 68178, USA;
| | - Gregory Ayzenberg
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
| | - Vishwanath Venketaraman
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA (T.E.); (C.L.); (R.D.); (G.A.)
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Enicker B, Aldous C. Factors associated with in-hospital mortality in HIV-infected children treated for tuberculous meningitis hydrocephalus. Childs Nerv Syst 2024; 40:695-705. [PMID: 37964056 PMCID: PMC10891234 DOI: 10.1007/s00381-023-06205-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 10/26/2023] [Indexed: 11/16/2023]
Abstract
PURPOSE The study aimed to investigate factors associated with in-hospital mortality in children diagnosed with tuberculous meningitis (TBM) hydrocephalus and HIV co-infection undergoing cerebrospinal fluid diversion procedures and their complications. METHODS Data were collected retrospectively and prospectively between 2007 and 2022. Data collected included demographics, clinical characteristics, antiretroviral therapy (ART) status, biochemistry results, CD4 count, radiology findings, CSF diversion procedures (and complications), length of hospital stay (LOHS), and in-hospital mortality. RESULTS Thirty-one children were included, with a mean age of 6.7 ± 5.3 years and 67.7% males. Median admission Glasgow Coma Scale (GCS) was 11 (IQR 9-15). Hypertonia (64.5%) and seizures (51.6%) were frequently observed clinical characteristics. Sixty-one percent of children were on ART. Cerebral infarcts and extra-meningeal TB were diagnosed in 64.5% and 19.3% of cases, respectively. The median CD4 count was 151 (IQR 70-732) cells/µL. Surgical procedures included ventriculoperitoneal shunt (VPS) in 26 cases and endoscopic third ventriculostomy (ETV) in five children. VPS complication rate was 27%. No complications were reported for ETV. Median LOHS was 7 days (IQR 4-21). Eleven children (35.5%) died during admission. Factors associated with mortality included GCS (p = 0.032), infarcts (p = 0.004), extra-meningeal TB (p = 0.003), VPS infection (p = 0.018), low CD4 count (p = 0.009), and hyponatremia (p = 0.002). No statistically significant factors were associated with VPS complications. CONCLUSION TBM hydrocephalus in HIV-infected children carries a high mortality. Clinicians in high-prevalence settings should have a high suspicion index and institute early treatment.
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Affiliation(s)
- Basil Enicker
- Department of Neurosurgery, Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, Durban, South Africa.
- Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Congella, Durban, 4001, South Africa.
| | - Colleen Aldous
- Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Congella, Durban, 4001, South Africa
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15
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Lequain H, Abramowicz S, Seiller J, Abukhashbah A, Burillon C, Vignot E, Brunet O, Sève P. Immune recovery uveitis in Whipple's disease: an unusual ocular presentation. J Ophthalmic Inflamm Infect 2024; 14:10. [PMID: 38347376 PMCID: PMC10861419 DOI: 10.1186/s12348-024-00390-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 01/27/2024] [Indexed: 02/15/2024] Open
Abstract
PURPOSE To describe an unusual case of Whipple's disease (WD) complicated by uveitis, and subsequent paradoxical worsening after effective antibiotic treatment targeting Tropheryma whipplei (TW). METHODS Case report. RESULTS A 53-year-old male presented with bilateral knee arthritis, weight loss, chronic low-grade fever, and cognitive disorders. He was under treatment with tumor necrosis factor α inhibitors (TNFi) for seronegative spondyloarthritis. Given this unusual clinical presentation, further investigations were performed and revealed blood, saliva, stool, synovial fluid and cerebrospinal fluid positivity for TW, confirming the diagnosis of systemic WD. Ophthalmologic examination revealed bilateral posterior uveitis and an aqueous humor sample confirmed the presence of intraocular TW. TNFi were stopped, and the patient was subsequently treated with adequate antibiotics (ceftriaxone, followed by doxycycline and hydroxychloroquine), and subconjunctival corticosteroid injections. After a transient improvement of the ocular symptoms, he presented a recurrence of posterior segment inflammation, leading to repeated PCR testing for TW which were negative. Therefore, paradoxical worsening of the inflammation in the context of immune recovery uveitis (IRU) was thought to be the culprit. The patient was treated with systemic corticosteroid therapy, allowing for rapid improvement of the ocular findings. CONCLUSIONS This case underlines the possibility of IRU complicating WD. Ophthalmologists, rheumatologists, and internists should be aware of this rare complication, particularly in the context of previous immunosuppressive therapy.
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Affiliation(s)
- Hippolyte Lequain
- Department of Internal Medicine, Croix-Rousse University Hospital, Hospices Civils de Lyon, 103 Grande-Rue de La Croix-Rousse, 69004, Lyon, France
| | - Stéphane Abramowicz
- Department of Internal Medicine, Croix-Rousse University Hospital, Hospices Civils de Lyon, 103 Grande-Rue de La Croix-Rousse, 69004, Lyon, France
| | - Julien Seiller
- Department of Rheumatology, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France
| | - Amro Abukhashbah
- Department of Ophthalmology, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France
- Department of Ophthalmology, King Abdulaziz University, Rabigh, Saudi Arabia
| | - Carole Burillon
- Department of Ophthalmology, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France
| | - Emmanuelle Vignot
- Department of Rheumatology, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France
| | - Olivier Brunet
- Department of Ophthalmology, Edouard Herriot University Hospital, Hospices Civils de Lyon, Lyon, France
| | - Pascal Sève
- Department of Internal Medicine, Croix-Rousse University Hospital, Hospices Civils de Lyon, 103 Grande-Rue de La Croix-Rousse, 69004, Lyon, France.
- Université Claude Bernard Lyon 1, Research On Healthcare Performance (RESHAPE), INSERM U1290, Lyon, France.
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16
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Castilla-Encinas AM, Soto Salas VR, Alvarez-Delgado H, Bocanegra-Becerra JE, Rondan PL. Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome Complicated by Large Bilateral Psoas Abscess: A Case Report. J Int Assoc Provid AIDS Care 2024; 23:23259582241293302. [PMID: 39444327 PMCID: PMC11520005 DOI: 10.1177/23259582241293302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Revised: 08/24/2024] [Accepted: 10/05/2024] [Indexed: 10/25/2024] Open
Abstract
Immune reconstitution inflammatory syndrome is a common manifestation in human immunodeficiency virus (HIV)-positive patients infected with tuberculosis (TB). One of the unusual complications of this condition is the development of psoas abscess. We describe a case of immune reconstitution inflammatory syndrome (IRIS) in a patient with disseminated TB under treatment, HIV-positive with a low CD4 cell count, complicated by bilateral psoas abscess. Our patient presented with fever, abdominal pain, and lymphadenopathy, typical symptoms of TB-IRIS. Diagnosis was confirmed by surgical drainage of the abscess of the right iliac psoas muscle with detection of acid-fast bacteria on Ziehl-Neelsen staining and negative culture of purulent discharge. Treatment with prednisone was started in addition to continuation of antituberculosis therapy and antiretroviral therapy.
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Affiliation(s)
| | | | - Hugo Alvarez-Delgado
- Sociedad Científica de San Fernando, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Jhon E. Bocanegra-Becerra
- Academic Department of Surgery, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Paola L. Rondan
- Universidad Nacional Mayor de San Marcos, Instituto de Medicina Tropical Daniel A. Carrion, Lima, Peru
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17
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Riccardi N, Occhineri S, Vanino E, Antonello RM, Pontarelli A, Saluzzo F, Masini T, Besozzi G, Tadolini M, Codecasa L, on behalf of StopTB Italia. How We Treat Drug-Susceptible Pulmonary Tuberculosis: A Practical Guide for Clinicians. Antibiotics (Basel) 2023; 12:1733. [PMID: 38136767 PMCID: PMC10740448 DOI: 10.3390/antibiotics12121733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Revised: 12/08/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide and pulmonary TB (PTB) is the main variant responsible for fueling transmission of the infection. Effective treatment of drug-susceptible (DS) TB is crucial to avoid the emergence of Mycobacterium tuberculosis-resistant strains. In this narrative review, through a fictional suggestive case of DS PTB, we guide the reader in a step-by-step commentary to provide an updated review of current evidence in the management of TB, from diagnosis to post-treatment follow-up. World Health Organization and Centre for Diseases Control (CDC) guidelines for TB, as well as the updated literature, were used to support this manuscript.
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Affiliation(s)
- Niccolò Riccardi
- StopTB Italia ODV, 20159 Milan, Italy
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, 56124 Pisa, Italy
| | - Sara Occhineri
- StopTB Italia ODV, 20159 Milan, Italy
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Pisana, 56124 Pisa, Italy
| | - Elisa Vanino
- StopTB Italia ODV, 20159 Milan, Italy
- Infectious Diseases Unit, Santa Maria delle Croci Hospital, AUSL Romagna, 48100 Ravenna, Italy
| | | | - Agostina Pontarelli
- StopTB Italia ODV, 20159 Milan, Italy
- Unit of Respiratory Infectious Diseases, Cotugno Hospital, Azienda Ospedaliera dei Colli, 80131 Naples, Italy
| | - Francesca Saluzzo
- StopTB Italia ODV, 20159 Milan, Italy
- Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute, San Raffaele University, 20132 Milan, Italy
| | | | | | - Marina Tadolini
- StopTB Italia ODV, 20159 Milan, Italy
- Infectious Disease Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
- Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy
| | - Luigi Codecasa
- StopTB Italia ODV, 20159 Milan, Italy
- Regional TB Reference Centre, Villa Marelli Institute, ASST Grande Ospedale Metropolitano Niguarda, 20159 Milan, Italy
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18
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Mingjing NO, Casha R, Vella SM, Aquilina N, Fsadni C. Where you least expect it: paradoxical tuberculosis-immune reconstitution inflammatory syndrome and wrist joint tuberculosis as the initial manifestation in a patient who is HIV-seronegative. Br J Hosp Med (Lond) 2023; 84:1-4. [PMID: 38153015 DOI: 10.12968/hmed.2022.0407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2023]
Affiliation(s)
| | - Ramon Casha
- Department of Infectious Diseases and General Medicine, Mater Dei Hospital, Msida, Malta
| | - Sarah M Vella
- Department of Infectious Diseases and General Medicine, Mater Dei Hospital, Msida, Malta
| | | | - Claudia Fsadni
- Department of Infectious Diseases and General Medicine, Mater Dei Hospital, Msida, Malta
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19
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Hashim H. Morbidity and mortality in tuberculosis associated immune reconstitution inflammatory syndrome in children living with HIV: A narrative review. J Clin Tuberc Other Mycobact Dis 2023; 33:100392. [PMID: 37637325 PMCID: PMC10448151 DOI: 10.1016/j.jctube.2023.100392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/29/2023] Open
Abstract
Tuberculosis-associated immune reconstitution syndrome (TB-IRIS) is an increasingly recognized complication of children living with HIV who are receiving treatment for active tuberculosis (TB). The purpose of the study was to appraise available evidence of morbidity and mortality related to TB IRIS among the paediatric population. A non-systematic review of the literature was conducted by retrieving records from Scopus, PubMed and Google Scholar). Four specific research questions assessing the risk factors (age, undernutrition, extrapulmonary TB and degree of immunosuppression) for TB-IRIS were discussed. The search yielded 370 articles, subsequently screened for eligibility according to the inclusion criteria. The majority of the articles were adult studies. Six studies were identified: Three retrospective and three prospective studies. The majority of the studies were conducted in TB/HIV-endemic countries. Only one study addressed mortality due to TB-IRIS as an outcome. A total of 6 mortalities related to TB-IRIS were reported. Advanced immunosuppression is universally agreed as an established risk factor for mortality in TB-IRIS in children. The severe presentation was more common in children with extrapulmonary tuberculosis. There is a paucity of data available on mortality in HIV-infected children with TB-IRIS. Future research is needed to assess the predictive factors of morbidity and mortality in HIV-infected children with TB-IRIS especially in low resource and high endemic countries.
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Affiliation(s)
- Haslina Hashim
- Faculty of Medicine, Universiti Zainal Abidin, Kampus Kota, 20400 Kuala Terengganu, Terengganu, Malaysia
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20
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Chawla R, Singh UB, Kumawat D, Venkatesh P. Presumed ocular tuberculosis - need for caution before considering anti-tubercular therapy. Eye (Lond) 2023; 37:3716-3717. [PMID: 37316712 PMCID: PMC10698026 DOI: 10.1038/s41433-023-02628-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/03/2023] [Accepted: 06/06/2023] [Indexed: 06/16/2023] Open
Affiliation(s)
- Rohan Chawla
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.
| | - Urvashi B Singh
- Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
| | - Devesh Kumawat
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
| | - Pradeep Venkatesh
- Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
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21
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Plate M, Jessurun J, van Besien K. Immune reconstitution inflammatory syndrome in a patient with M.haemophilum infection after allogeneic hematopoietic stem cell transplantation. Leuk Lymphoma 2023; 64:2214-2216. [PMID: 37674433 DOI: 10.1080/10428194.2023.2254875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/27/2023] [Accepted: 08/28/2023] [Indexed: 09/08/2023]
Affiliation(s)
- Markus Plate
- Division of Infectious Diseases, Transplantation-Oncology Infectious Disease Program, Weill Cornell Medical College, New York, NY, USA
| | - Jose Jessurun
- Department of Pathology and Laboratory Medicine, Weill Cornell Medcial College, New York, NY, USA
| | - Koen van Besien
- Division of Hematology/Oncology, Cell Therapy Program, Weill Cornell Medical College, New York, NY, USA
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22
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Sankar P, Mishra BB. Early innate cell interactions with Mycobacterium tuberculosis in protection and pathology of tuberculosis. Front Immunol 2023; 14:1260859. [PMID: 37965344 PMCID: PMC10641450 DOI: 10.3389/fimmu.2023.1260859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 09/26/2023] [Indexed: 11/16/2023] Open
Abstract
Tuberculosis (TB) remains a significant global health challenge, claiming the lives of up to 1.5 million individuals annually. TB is caused by the human pathogen Mycobacterium tuberculosis (Mtb), which primarily infects innate immune cells in the lungs. These immune cells play a critical role in the host defense against Mtb infection, influencing the inflammatory environment in the lungs, and facilitating the development of adaptive immunity. However, Mtb exploits and manipulates innate immune cells, using them as favorable niche for replication. Unfortunately, our understanding of the early interactions between Mtb and innate effector cells remains limited. This review underscores the interactions between Mtb and various innate immune cells, such as macrophages, dendritic cells, granulocytes, NK cells, innate lymphocytes-iNKT and ILCs. In addition, the contribution of alveolar epithelial cell and endothelial cells that constitutes the mucosal barrier in TB immunity will be discussed. Gaining insights into the early cellular basis of immune reactions to Mtb infection is crucial for our understanding of Mtb resistance and disease tolerance mechanisms. We argue that a better understanding of the early host-pathogen interactions could inform on future vaccination approaches and devise intervention strategies.
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Affiliation(s)
| | - Bibhuti Bhusan Mishra
- Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, United States
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23
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Lee S, Yi NJ, Kwak N, Kim H, Hong SY, Lee JM, Hong SK, Choi Y, Lee KW, Suh KS. Immune Reconstitution Inflammatory Syndrome and Drug-Induced Liver Injury During Treatment of Disseminated Tuberculosis in a Liver Transplant Recipient: A Case Report. Transplant Proc 2023; 55:1972-1974. [PMID: 37468353 DOI: 10.1016/j.transproceed.2023.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Accepted: 06/23/2023] [Indexed: 07/21/2023]
Abstract
Studies have shown that tuberculosis (TB) incidence is 20 to 70 times higher in solid organ transplantation recipients. Immunosuppression makes transplant recipients more vulnerable to infection and can interfere with the treatment. Our case report describes a patient who experienced immune reconstitution inflammatory syndrome (IRIS) and drug-induced liver injury (DILI) related to TB medications for disseminated pulmonary and hepatic TB. In addition to anti-TB medication, the patient received a high-dose steroid for IRIS and a change of anti-TB medication to a secondary regimen for DILI. This case illustrates various responses to anti-TB treatment in a liver transplant recipient and the necessity of closely monitoring immune suppression and liver function.
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Affiliation(s)
- Sola Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Nakwon Kwak
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Su Young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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24
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Hashiba T, Sugahara M, Ota Y, Kaseda K, Kashiwagi Y, Nakamura M, Shinohara T, Ikeda M, Okugawa S, Sugimoto K, Sasaki K, Hamasaki Y, Yamada D, Kume H, Moriya K, Nangaku M. Paralytic Ileus during Treatment of Pulmonary and Renal Tuberculosis in a Non-Human Immunodeficiency Virus Patient: An Unusual Presentation of Tuberculosis-immune Reconstitution Inflammatory Syndrome. Intern Med 2023; 62:2559-2564. [PMID: 36642517 PMCID: PMC10518560 DOI: 10.2169/internalmedicine.0898-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 11/29/2022] [Indexed: 01/15/2023] Open
Abstract
Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.
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Affiliation(s)
- Toyohiro Hashiba
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Mai Sugahara
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Yui Ota
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Ken Kaseda
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Yusuke Kashiwagi
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Motonobu Nakamura
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
| | - Takayuki Shinohara
- Department of Infectious Diseases, the University of Tokyo Hospital, Japan
| | - Mahoko Ikeda
- Department of Infectious Diseases, the University of Tokyo Hospital, Japan
| | - Shu Okugawa
- Department of Infectious Diseases, the University of Tokyo Hospital, Japan
| | - Kazuma Sugimoto
- Department of Urology, the University of Tokyo Hospital, Japan
| | - Kenichi Sasaki
- Department of Urology, the University of Tokyo Hospital, Japan
| | - Yoshifumi Hamasaki
- Department of Hemodialysis & Apheresis, the University of Tokyo Hospital, Japan
| | - Daisuke Yamada
- Department of Urology, the University of Tokyo Hospital, Japan
- Department of Hemodialysis & Apheresis, the University of Tokyo Hospital, Japan
| | - Haruki Kume
- Department of Urology, the University of Tokyo Hospital, Japan
| | - Kyoji Moriya
- Department of Infectious Diseases, the University of Tokyo Hospital, Japan
| | - Masaomi Nangaku
- Division of Nephrology and Endocrinology, the University of Tokyo Hospital, Japan
- Department of Hemodialysis & Apheresis, the University of Tokyo Hospital, Japan
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25
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Geteneh A, Andualem H, Belay DM, Kiros M, Biset S. Immune reconstitution inflammatory syndrome, a controversial burden in the East African context: a systematic review and meta-analysis. Front Med (Lausanne) 2023; 10:1192086. [PMID: 37636563 PMCID: PMC10450628 DOI: 10.3389/fmed.2023.1192086] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/18/2023] [Indexed: 08/29/2023] Open
Abstract
Introduction It is well established that starting antiretroviral therapy (ART) increases a patient's life expectancy among HIV-positive individuals. Considering the HIV pandemic, the major concern is initiation of ARTs to the large segment of HIV infected population, not adverse events from immune restoration. The prevalence of HIV-associated immune reconstitution inflammatory syndrome (IRIS) is poorly estimated due to Africa's underdeveloped infrastructure, particularly in Eastern Africa. Therefore, this study compiled data regarding the magnitude and associated factors of IRIS in the context of Eastern Africa. Methods The electronic databases such as Google Scholar, PubMed, Web of Science, and free Google access were searched till 5 June 2021, and the search was lastly updated on 30 June 2022 for studies of interest. The pooled prevalence, and associated factors with a 95% confidence interval were estimated using the random effects model. The I2 and Egger's tests were used for heterogeneity and publication bias assessment, respectively. Results The development of HIV-associated IRIS in Eastern Africa was estimated to be 18.18% (95% CI 13.30-23.06) in the current review. The two most common predictors of IRIS associated with Eastern Africa were the lower pre-ART CD4 T-cell count of 50 cells/μl and the low baseline body mass index level. Therefore, attention should be focused on the early detection and care of HIV-associated IRIS to reduce the morbidity and death caused by IRIS.
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Affiliation(s)
- Alene Geteneh
- Department of Medical Laboratory Science, College of Health Sciences, Woldia University, Woldia, Ethiopia
| | - Henok Andualem
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Demeke Mesfin Belay
- Department of Pediatrics and Child Health Nursing, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
| | - Mulugeta Kiros
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Aksum University, Aksum, Ethiopia
| | - Sirak Biset
- Department of Medical Microbiology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Yang L, Chaves L, Kutscher HL, Karki S, Tamblin M, Kenney P, Reynolds JL. An immunoregulator nanomedicine approach for the treatment of tuberculosis. Front Bioeng Biotechnol 2023; 11:1095926. [PMID: 37304141 PMCID: PMC10249870 DOI: 10.3389/fbioe.2023.1095926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 05/12/2023] [Indexed: 06/13/2023] Open
Abstract
Introduction: A nanoparticle composed of a poly (lactic-co-glycolic acid) (PLGA) core and a chitosan (CS) shell with surface-adsorbed 1,3 β-glucan (β-glucan) was synthesized. The exposure response of CS-PLGA nanoparticles (0.1 mg/mL) with surface-bound β-glucan at 0, 5, 10, 15, 20, or 25 ng or free β-glucan at 5, 10, 15, 20, or 25 ng/mL in macrophage in vitro and in vivo was investigated. Results: In vitro studies demonstrate that gene expression for IL-1β, IL-6, and TNFα increased at 10 and 15 ng surface-bound β-glucan on CS-PLGA nanoparticles (0.1 mg/mL) and at 20 and 25 ng/mL of free β-glucan both at 24 h and 48 h. Secretion of TNFα protein and ROS production increased at 5, 10, 15, and 20 ng surface-bound β-glucan on CS-PLGA nanoparticles and at 20 and 25 ng/mL of free β-glucan at 24 h. Laminarin, a Dectin-1 antagonist, prevented the increase in cytokine gene expression induced by CS-PLGA nanoparticles with surface-bound β-glucan at 10 and 15 ng, indicating a Dectin-1 receptor mechanism. Efficacy studies showed a significant reduction in intracellular accumulation of mycobacterium tuberculosis (Mtb) in monocyte-derived macrophages (MDM) incubated with on CS-PLGA (0.1 mg/ml) nanoparticles with 5, 10, and 15 ng surface-bound β-glucan or with 10 and 15 ng/mL of free β-glucan. β-glucan-CS-PLGA nanoparticles inhibited intracellular Mtb growth more than free β-glucan alone supporting the role of β-glucan-CS-PLGA nanoparticles as stronger adjuvants than free β-glucan. In vivo studies demonstrate that oropharyngeal aspiration (OPA) of CS-PLGA nanoparticles with nanogram concentrations of surface-bound β-glucan or free β-glucan increased TNFα gene expression in alveolar macrophages and TNFα protein secretion in bronchoalveolar lavage supernatants. Discussion: Data also demonstrate no damage to the alveolar epithelium or changes in the murine sepsis score following exposure to β-glucan-CS-PLGA nanoparticles only, indicating safety and feasibility of this nanoparticle adjuvant platform to mice by OPA.
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Affiliation(s)
- Luona Yang
- Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Lee Chaves
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Hilliard L. Kutscher
- Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Shanta Karki
- Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Maria Tamblin
- Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Patrick Kenney
- Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
| | - Jessica L. Reynolds
- Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States
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Sahgal S, Shankaran S, Ansell DA. Immune Reconstitution Inflammatory Syndrome Reaction in Patient on Long-Term Prednisone. Cureus 2023; 15:e38506. [PMID: 37273292 PMCID: PMC10238129 DOI: 10.7759/cureus.38506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/03/2023] [Indexed: 06/06/2023] Open
Abstract
Immune reconstitution inflammatory syndrome (IRIS) can be triggered in many ways. IRIS has been recognized during tuberculosis (TB) therapy, especially in patients newly initiated on antiretroviral therapy for HIV or those taken off immunosuppressives such as tumor necrosis factor-alpha inhibitors. However, there are still many triggers of IRIS that are less understood. This case report describes a patient with scrofula that was concerning for TB reactivation, who then had subsequent IRIS. The patient had been consistently using low-dose long-term prednisone for suppression of his polymyalgia rheumatica. It is suspected that the IRIS reaction could be due to an interaction between rifampin and prednisone causing decreased efficacy of its immunosuppressive effects.
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Affiliation(s)
- Savina Sahgal
- Medical School, Rush University Medical Center, Chicago, USA
| | | | - David A Ansell
- Internal Medicine, Rush University Medical Center, Chicago, USA
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28
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Yakut N, Kutlu NO, Kilinc A, Tinastepe T, Dogan E, Demir F. A case of immunocompetent tuberculosis-associated immune reconstitution inflammatory syndrome treated with a novel strategy-zipper method plasma exchange. J Paediatr Child Health 2023; 59:389-391. [PMID: 36373665 DOI: 10.1111/jpc.16280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 11/16/2022]
Affiliation(s)
- Nurhayat Yakut
- Department of Pediatrics, Division of Pediatric Infectious Diseases, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Nurettin O Kutlu
- Department of Pediatrics, Division of Pediatric Intensive Care, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Arda Kilinc
- Department of Pediatrics, Division of Pediatric Intensive Care, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Tuba Tinastepe
- Department of Pediatrics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Eser Dogan
- Department of Pediatrics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
| | - Firat Demir
- Department of Neurosurgery, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
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29
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Fatimah-Halwani I, Wahab Z, Masnon NA, Wan Hitam WH, Shatriah I, Haron J. Bilateral Optic Perineuritis in Tuberculosis-Immune Reconstitution Inflammatory Syndrome. Cureus 2022; 14:e27600. [PMID: 36059337 PMCID: PMC9435306 DOI: 10.7759/cureus.27600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2022] [Indexed: 11/28/2022] Open
Abstract
Optic perineuritis (OPN) in pulmonary tuberculosis (PTB) patients while on anti-tuberculous treatment is rare. It may occur due to tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS). Visual prognosis is poor if not treated early. We report a rare case of bilateral OPN in an elderly patient on treatment for PTB. A 79-year-old Malay man presented with a painless bilateral blurring of vision for three weeks. He was diagnosed to have PTB and has been on anti-tuberculous treatment for five months. Visual acuity in both eyes was only counting fingers. Optic nerve function tests were significantly reduced bilaterally. Fundoscopy showed bilateral segmental temporal optic disc pallor. Both visual field assessments were constricted. Other infective screenings and tumor markers were negative. Neuro-imaging revealed bilateral OPN involving the intraorbital segment. High-dose intravenous corticosteroid therapy was commenced, followed by slow tapering of oral prednisolone. Anti-tuberculous treatment was continued for a total course of nine months. The left visual acuity improved to 3/60. However, the right eye vision remained poor. His general condition was good.
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30
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Qu C, Xu N, Niu D, Wen S, Yang H, Wang S, Wang G. Case Report: Suspected Case of Brucella-Associated Immune Reconstitution Inflammatory Syndrome. Front Immunol 2022; 13:923341. [PMID: 35935931 PMCID: PMC9353035 DOI: 10.3389/fimmu.2022.923341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/24/2022] [Indexed: 11/22/2022] Open
Abstract
Human brucellosis is one of the most prevalent zoonoses. There are many similarities between the pathogenesis of Mycobacterium tuberculosis (MTB) infection and that of brucellosis. Immune reconstitution inflammatory syndrome (IRIS) may occur during the treatment of MTB infection, but it has not been reported in brucellosis cases thus far. We report the case of a 40-year-old male whose condition initially improved after adequate anti-Brucella therapy. However, 3 weeks later, the patient presented with exacerbation of symptoms and development of a paravertebral abscess. After exclusion of other possible causes of clinical deterioration, immune reconstitution inflammatory syndrome (IRIS) with brucellosis was presumed. After supplementation with anti-Brucella treatment with corticosteroids, the abscess disappeared, and the symptoms completely resolved. Our case suggests that it is necessary to be aware of the possible occurrence of IRIS in patients with brucellosis in clinical practice.
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Affiliation(s)
- Chunmei Qu
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Nannan Xu
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Dehong Niu
- Department of Oncology, the Fifth People’s Hospital of Jinan, Jinan, China
| | - Sai Wen
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Hui Yang
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Shanshan Wang
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Gang Wang
- Department of Infectious Disease, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Gang Wang,
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31
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Christian E, Johnston A. CNS TB-IRIS Following Cessation of Adalimumab in an Adolescent with Crohn’s Disease. Open Forum Infect Dis 2022; 9:ofac367. [PMID: 35949406 PMCID: PMC9356675 DOI: 10.1093/ofid/ofac367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/20/2022] [Indexed: 11/24/2022] Open
Abstract
Immune reconstitution inflammatory syndrome to tuberculosis (TB-IRIS) is an inflammatory response to M. tuberculosis infection that arises following restoration of the immune system and is increasingly recognized as a risk in patients treated with tumor necrosis factor α inhibitors who develop active tuberculosis infection. We present the case of a 19-year-old man treated with adalimumab for Crohn’s disease who presented with disseminated miliary tuberculosis. His treatment course was complicated by central nervous system TB-IRIS following cessation of his immunosuppression. We review the presentation and differential diagnosis of TB-IRIS, as well as risk factors for developing IRIS and the treatment of IRIS in this population.
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Affiliation(s)
- Elizabeth Christian
- Division of Infectious Disease, Boston Children’s Hospital , Boston, MA , USA
- Infectious Disease, Beth Israel Deaconess Medical Center , Boston, MA , USA
| | - Alicia Johnston
- Division of Infectious Disease, Beth Israel Deaconess Medical Center , Boston, MA , USA
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32
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Nakamura S, Muramae N, Fujisawa A, Yasuda N, Okano M, Mori K, Otsui K, Sakaguchi K. Hemophagocytic Syndrome-Like Tuberculosis-Immune Reconstitution Inflammatory Syndrome After the Initiation of Hepatic Tuberculosis Treatment. Cureus 2022; 14:e24644. [PMID: 35663666 PMCID: PMC9156395 DOI: 10.7759/cureus.24644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2022] [Indexed: 11/26/2022] Open
Abstract
A 25-year-old Nepalese woman was referred to our hospital because of fever and intermittent abdominal pain with inguinal lymphadenopathy, which had lasted for several months. A liver biopsy of the positron emission tomography-positive lesion led to a diagnosis of hepatic tuberculosis. After the initiation of antituberculosis treatment, her symptoms resolved. However, 11 days after treatment initiation, chest and back pain, high-grade fever, and vomiting appeared and gradually worsened. She developed anemia and her serum ferritin level was elevated. Hemophagocytic syndrome due to the initial deterioration of tuberculosis was suspected and steroid therapy was initiated with the continuation of the antituberculosis drugs. Thereafter, the patient’s condition improved remarkably.
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33
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Jain M, Vadboncoeur J, Garg SJ, Biswas J. Bacille Calmette-Guérin: An ophthalmic perspective. Surv Ophthalmol 2022; 67:307-320. [PMID: 34343536 PMCID: PMC8325561 DOI: 10.1016/j.survophthal.2021.07.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 07/27/2021] [Accepted: 07/27/2021] [Indexed: 01/20/2023]
Abstract
Vaccines such as bacille Calmette-Guérin (BCG) are known for their heterologous effects mediated through a number of mechanisms, including trained immunity constituted by monocyte-macrophage based innate immunity. Other events such as direct hematogenous spread and induction of autoimmunity are also described. There has been a resurgent interest in harnessing some of the benefits of trained immunity in the management of COVID-19, even as several specific vaccines have been approved. We summarize the current knowledge of ocular effects of BCG. Potential effect of granulomatous inflammation on angiotensin converting enzyme activity and accentuation of cytokine storm that may result in undesirable ocular and systemic effects are also discussed.
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Affiliation(s)
- Manish Jain
- Himalayan Institute of Medical Sciences, Jolly Grant, Dehradun, UK, India
| | - Julie Vadboncoeur
- Department of Ophthalmology, Université de Montréal, Montréal, Uveitis Service, University Ophthalmology Center, Maisonneuve-Rosemont Hospital, Montréal, Canada
| | - Sunir J Garg
- Thomas Jefferson University, Philadelphia, PA USA
| | - Jyotirmay Biswas
- Director of Uveitis & Ocular Pathology Department, Sankara Nethralaya, Chennai, TN, India
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34
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Cerme E, Oztas M, Balkan II, Cetin EA, Ugurlu S. Haemophagocytic lymphohistiocytosis in a patient with familial Mediterranean fever and miliary tuberculosis: a case report. Mod Rheumatol Case Rep 2022; 6:140-144. [PMID: 34549298 DOI: 10.1093/mrcr/rxab026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/02/2021] [Accepted: 08/12/2021] [Indexed: 06/13/2023]
Abstract
Haemophagocytic lymphohistiocytosis (HLH) is a lethal complication of several infections, especially viral origin. Mycobacterium tuberculosis infection can also lead to HLH, yet it is an uncommon trigger. Considering the role of increased cytokines in HLH, autoinflammatory conditions, such as familial Mediterranean fever (FMF), might contribute to its development. Nevertheless, the possible relationship between FMF and HLH has been suggested only in some case reports. We present a case of FMF who admitted to the hospital with consitutional symptoms and chest pain regarding to recurrent pericarditis. On a blood test, pancytopenia and elevated acute phase reactants were seen. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography demonstrated positive FDG uptake sites on both the right and left surrenal glands, the visceral layer of pericard, and reactive lymphadenomegalies at multiple mediastinal regions. Bone marrow biopsy revealed haemophagocytosis. Methylprednisolone treatment was initiated. Despite immunosuppressive treatment, clinical and biochemical parameters deteriorated; thus, a thorax computed tomography was executed. Findings were consistent with miliary tuberculosis infection. M. tuberculosis was detected in blood culture and bronchoalveolar lavage culture material. Also, bone marrow and surrenal biopsy material revealed necrotising caseating granuloma.
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Affiliation(s)
- Emir Cerme
- Department of Internal Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Mert Oztas
- Department of Internal Medicine, Division of Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ilker Inanc Balkan
- Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Esin Aktas Cetin
- Institute of Experimental Medicine (DETAE), Department of Immunology, Istanbul University, Istanbul, Turkey
| | - Serdal Ugurlu
- Department of Internal Medicine, Division of Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey
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35
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A Case of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated Tuberculosis and Hairy Cell Leukaemia after SARS-CoV2 Infection. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12020564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Hemophagocytic Lymphohistiocytosis (HLH) is a rare but life-threatening disease that can occur either as a primary condition or as a consequence of a variety of triggers, including infectious diseases. Here we present a case of secondary HLH triggered by systemic Mycobacterium tuberculosis infection in a 59-year-old immunocompromised Hairy Cell Leukemia and previous SARS-CoV2 infected patient. This case report underlines the role of Etoposide-based chemotherapy in treating the severe inflammation that is the defining factor of HLH, suggesting how, even when such therapy is not effective, it may still give the clinicians time to identify the underlying condition and start the appropriate targeted therapy. Moreover, it gives insight on our decision to treat the underlying haematological condition with a BRAF-targeted therapy rather than purine analog-based chemotherapy to reduce the risk of future severe infections.
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36
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Paradoxical manifestations during tuberculous meningitis treatment among HIV-negative patients: a retrospective descriptive study and literature review. Neurol Sci 2021; 43:2699-2708. [PMID: 34705128 DOI: 10.1007/s10072-021-05693-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/27/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. METHODS Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. RESULTS We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19-49 years old), developed a paradoxical manifestation within 4-14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. CONCLUSIONS This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed.
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Rocco JM, Hammoud DA, Allen CT, Galindo F, Laidlaw E, Sereti I. Trismus and voice change after starting tuberculosis treatment. IDCases 2021; 26:e01307. [PMID: 34692416 PMCID: PMC8517377 DOI: 10.1016/j.idcr.2021.e01307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 11/17/2022] Open
Affiliation(s)
- Joseph M. Rocco
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
- Correspondence to: Infectious Disease, National Institute of Allergy & Infectious Diseases, National Institutes of Health, BG 10 RM 11B17 MSC 1876, 10 Center Dr, Bethesda, MD 20892, USA.
| | - Dima A. Hammoud
- Center for Infectious Diseases Imaging, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
| | - Clint T. Allen
- Translational Tumor Immunology Program, National Institute on Deafness and Other Commination Disorders, National Institutes of Health, Bethesda, MD, USA
| | - Frances Galindo
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Elizabeth Laidlaw
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Irini Sereti
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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38
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Nedkov Gambin M, Vella SM, Vella C, Schembri J. Oesophagomediastinal fistula: a rare complication of tuberculosis. BMJ Case Rep 2021; 14:e242907. [PMID: 34479881 PMCID: PMC8420691 DOI: 10.1136/bcr-2021-242907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/22/2021] [Indexed: 11/04/2022] Open
Abstract
We report a case of a woman from Thailand, living in Malta, who was diagnosed with concomitant tuberculosis (TB) and HIV with depleted CD4 count. Her case was further complicated by the formation of a fistula between the mediastinal lymph nodes and the oesophagus, an unusual finding but for which she had many risk factors. The diagnosis was suspected on CT scan of the thorax and confirmed via upper gastrointestinal endoscopy. Following the commencement of both anti-TB and antiretroviral therapy, she suffered a lapse of immune reconstitution inflammatory syndrome but with aggressive medical management eventually made a full recovery without the need for surgical intervention.
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Affiliation(s)
| | | | - Chantal Vella
- Department of Medicine, Mater Dei Hospital, Msida, Malta
| | - John Schembri
- Department of Medicine, Mater Dei Hospital, Msida, Malta
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39
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Weber MR, Fehr JS, Kuhn FP, Kaelin MB. Approach for tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-negative patient. BMJ Case Rep 2021; 14:14/8/e232639. [PMID: 34404638 PMCID: PMC8375722 DOI: 10.1136/bcr-2019-232639] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott’s disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient’s general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.
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Affiliation(s)
| | - Jan Sven Fehr
- Divison of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Marisa Brigitta Kaelin
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
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40
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Sindgikar SP, Narayanaswamy B, Alexander LM, Kanavu R. Paradoxical immune reconstitution inflammatory syndrome in neurotuberculosis. BMJ Case Rep 2021; 14:e243739. [PMID: 34376417 PMCID: PMC8356154 DOI: 10.1136/bcr-2021-243739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/21/2021] [Indexed: 11/03/2022] Open
Abstract
Tuberculosis (TB) remains the most common infection in developing countries and India contributes the maximum number of cases to the global burden. Primary healthcare physicians across the country face major challenges in diagnosis and treatment of childhood TB. In this context, clinical cases of paradoxical responses to antitubercular therapy seem to be under-reported. We report a case of tubercular meningitis in an adolescent girl who belonged to a remote village. She developed a paradoxical immune response to TB while on anti-TB treatment (ATT). She presented with raised intracranial tension and neurological deficits during the continuation phase of ATT after stopping corticosteroids. The ring-enhancing lesions of tuberculomas in the brain and spine characterised the diagnosis of paradoxical response to TB. Brain biopsy suggested necrotising granulomatous disease and was negative for S100 and CD1a marker, ruling out active TB. Retreatment with a prolonged course of steroids and ATT resulted in the clinical and radiological recovery, though some motor and visual deficits persisted. Clinical risk factors and socioeconomic factors also contributed to the present state of the child.
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Affiliation(s)
- Seema Pavaman Sindgikar
- Pediatric, KS Hegde Medical Academy (KSHEMA), NITTE (Deeemed to be Univeristy), Mangalore, Karntaka, India
| | - Bindu Narayanaswamy
- Pediatric, KS Hegde Medical Academy (KSHEMA), NITTE (Deeemed to be Univeristy), Mangalore, Karntaka, India
| | - Lobo Manuel Alexander
- Neurology, KS Hegde Medical Academy (KSHEMA), NITTE (Deemed to be Univeristy), Mangalore, Karnataka, India
| | - Ramkishore Kanavu
- Radiology, KS Hegde Medical Academy (KSHEMA), NITTE (Deemed to be Univeristy), Mangalore, Karnataka, India
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41
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Masuka JT, Mkhize Z, Pillay S, Mosam A. Concurrent pulmonary tuberculosis and lepromatous leprosy in a newly diagnosed HIV positive patient: a case report. BMC Pulm Med 2021; 21:207. [PMID: 34193098 PMCID: PMC8247149 DOI: 10.1186/s12890-021-01572-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 06/23/2021] [Indexed: 12/01/2022] Open
Abstract
Background The leprosy-tuberculosis (TB) co-infection is rarely reported in recent times. However, this dual comorbidity is associated with high mortality and major morbidity. Unrecognised leprosy-TB co-infection may predispose affected patients to rifampicin monotherapy and subsequent drug resistance. Case presentation A 35 year old migrant, human immunodeficiency virus (HIV) positive male worker presented with 6 month history of symmetric infiltrative nodular plaques of the face and distal, upper extremities. A few days after initial dermatology presentation, a sputum positive pulmonary tuberculosis diagnosis was made at his base hospital. Subsequent dermatology investigations revealed histology confirmed lepromatous leprosy and a weakly reactive rapid plasma reagin test. The presenting clinical features and laboratory results were suggestive of lepromatous leprosy coexisting with pulmonary tuberculosis in an HIV positive patient. Conclusions This case illustrates the occurrence of leprosy with pulmonary tuberculosis in an HIV infected patient and the difficulties in interpreting non-treponemal syphilis tests in these patients. This case also highlights the need for a high index of suspicion for co-infection and the need to exclude PTB prior to initiation of rifampicin containing multi-drug therapy (MDT). Interdisciplinary management and social support are crucial in these patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-021-01572-w.
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Affiliation(s)
- Josiah T Masuka
- Department of Dermatology, Nelson R Mandela School of Medicine, Private Bag X7, Congella, Durban, 4013, South Africa. .,Department of Dermatology, Edendale Hospital, 89 Selby Msimang Rd, Pleissislaer, Pietermaritzburg, 3201, South Africa. .,Harare Central Hospital, PO Box ST14, Southerton, Harare, Zimbabwe.
| | - Zamambo Mkhize
- Department of Dermatology, Nelson R Mandela School of Medicine, Private Bag X7, Congella, Durban, 4013, South Africa.,Department of Dermatology, Edendale Hospital, 89 Selby Msimang Rd, Pleissislaer, Pietermaritzburg, 3201, South Africa
| | - Somasundram Pillay
- Department of Dermatology, Edendale Hospital, 89 Selby Msimang Rd, Pleissislaer, Pietermaritzburg, 3201, South Africa.,Department of Internal Medicine, Nelson R Mandela School of Medicine, Private Bag X7, Congella, Durban, 4013, South Africa
| | - Anisa Mosam
- Department of Dermatology, Nelson R Mandela School of Medicine, Private Bag X7, Congella, Durban, 4013, South Africa
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42
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Abstract
Gastrointestinal (GI) tuberculosis (TB) remains a significant problem worldwide, and may involve the luminal GI tract from oral cavity to perianal area in addition to associated viscera and peritoneum. Although GI TB more commonly affects immunocompromised hosts, it can also occur in immunocompetent people. Diagnosis is difficult because it usually mimics a malignancy or inflammatory bowel disease. A high index of clinical suspicion and appropriate use of combined investigative methods help in early diagnosis, and reduce morbidity and mortality. Anti-TB therapy is the same as for pulmonary disease, and invasive and specialized interventions are reserved for selected complications.
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Affiliation(s)
- Haluk Eraksoy
- Department of Infectious Diseases and Clinical Microbiology, Istanbul Faculty of Medicine, Istanbul University, TR-34093 Istanbul, Turkey.
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43
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Kilgore J, Pelletier J, Becken B, Kenny S, Das S, Parnell L. Miliary tuberculosis in a paediatric patient with psoriasis. BMJ Case Rep 2021; 14:14/3/e237580. [PMID: 33687934 PMCID: PMC7944982 DOI: 10.1136/bcr-2020-237580] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
We present a 16-year-old girl with a history of well-controlled psoriasis, on immunosuppression, who sought evaluation in the emergency department for 4 months of fever, cough and unintentional weight loss. The patient had seen multiple providers who had diagnosed her with community-acquired pneumonia, but she was unimproved after oral antibiotic therapy. On presentation, she was noted to be febrile, tachycardic and chronically ill-appearing. Her chest X-ray showed diffuse opacities and a right upper lobe cavitary lesion concerning for tuberculosis. A subsequent chest CT revealed miliary pulmonary nodules in addition to the cavitary lesion. The patient underwent subsequent brain MRI, which revealed multifocal ring-enhancing nodules consistent with parenchymal involvement. The patient was diagnosed with miliary tuberculosis and improved on quadruple therapy. Though rates of tuberculosis are increasing, rates remain low in children, though special consideration should be given to children who are immunosuppressed.
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Affiliation(s)
- Jacob Kilgore
- Division of Pediatric Infectious Diseases, Duke University Hospital, Durham, North Carolina, USA
| | - Jonathon Pelletier
- Division of Pediatric of Critical Care Medicine, UPMC, Pittsburgh, Pennsylvania, USA
| | - Bradford Becken
- Division of Pediatric Infectious Diseases, Duke University Hospital, Durham, North Carolina, USA
| | - Stephen Kenny
- Department of Pediatrics, King Edward VII Memorial Hospital, Paget, Bermuda
| | - Samrat Das
- Department of Pediatrics, Duke University Hopistal, Durham, North Carolina, USA
| | - Lisa Parnell
- Department of Pediatrics, Duke University Hopistal, Durham, North Carolina, USA
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44
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Latifi Y, Gugelmann R, Rigger J, Preiswerk B, Eriksson U, Eberli FR, Bernheim AM. Effusive-Constrictive Pericarditis due to Immune Reconstitution Inflammatory Syndrome following Tuberculous Pericarditis. CASE 2021; 5:67-72. [PMID: 33644517 PMCID: PMC7887522 DOI: 10.1016/j.case.2020.10.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Tuberculous pericarditis is the most common cause of pericarditis worldwide. Consider the possibility of TB-IRIS in patients with tuberculous pericarditis. Corticosteroids might be necessary, but there are several caveats to consider.
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45
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Lakshmi VP, Abhinandh B, Kunoor A, Mohan T, Sugunan A, Jose J. Paradoxical reaction in lymph node tuberculosis presented as shoulder osteomyelitis. J Pharmacol Pharmacother 2021. [DOI: 10.4103/jpp.jpp_61_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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46
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Tanvi, Aggarwal R. Estimating the impact of antiretroviral therapy on HIV-TB co-infection: Optimal strategy prediction. INT J BIOMATH 2020. [DOI: 10.1142/s1793524521500042] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
In this paper, a nonlinear population model for HIV-TB co-infection has been proposed. The model is incorporated with the effect of early and late initiation of HIV treatment in co-infectives already on TB treatment, on the occurrence of Immune Reconstitution Inflammatory syndrome (IRIS). A 15-dimensional (15D) mathematical model has been developed in this study. We begin with considering constant treatment rates and thereafter, proceed to time-dependent treatment rates for co-infectives as control parameters. The basic reproduction number, a threshold quantity, corresponding to each HIV and TB sub-model has been computed in case of constant controls. With constant values of control parameters, mathematical analysis shows the existence and local stability of the disease-free equilibrium point and the endemic equilibrium point for the model. Together with time-dependent parameters, an optimal control problem is introduced and solved using Pontryagin’s maximum principle with an objective to minimize the number of infectives and disease induced deaths along with the cost of treatment. Numerical simulations are performed to examine the effect of reproduction numbers on control profiles and to identify, the ideal combination of treatment strategies which provides minimum burden on a society. Numerical results imply that if both HIV and TB are endemic in the population, then in order to bring in minimum burden from the co-infection, optimal control efforts must be enforced rather than constant treatment rate.
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Affiliation(s)
- Tanvi
- Department of Mathematics, Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi-110096, India
| | - Rajiv Aggarwal
- Department of Mathematics, Deshbandhu College, University of Delhi, New Delhi-110019, India
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47
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Hajsadeghi S, Iranpour A, Kalantari S, Dashti F. A rare manifestation of extrapulmonary tuberculosis: left ventricular cardiac tuberculoma in an HIV infected male "case report". Cardiovasc Diagn Ther 2020; 10:1341-1344. [PMID: 33224758 DOI: 10.21037/cdt-20-446] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Cardiac tuberculosis (TB) is rare and most commonly manifests itself as tuberculous pericarditis. Involvement of other parts of the heart is unusual and descriptions in the literature are confined to case reports regarding mainly pericardial TB and very few cases of cardiac tuberculoma. Tuberculomas are space occupying lesions most commonly found in the brain of immunocompromised individuals. These space occupying lesions previously described only after autopsies are now more diagnosed with the use of advanced imaging techniques. Herein, we describe a first case of pericardial TB manifesting as left ventricular (LV) cardiac tuberculoma in a 34-year-old human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infected male. Upon presentation the patient complained mainly of progressive dyspnoea over the past month. Primary investigations including chest computed tomography (CT) scan and transthoracic echocardiography (TTE) suggested probable diagnosis of cardiac and pericardial TB which was later confirmed by histopathological modalities. The patient received anti-TB therapy along with surgical subtotal pericardiotomy which resulted in improvement of symptoms, complete resolution of the mass and reduction in the size of pericardial thickening. Although very rare it is crucial to bear in mind the importance of having cardiac tuberculoma as differential diagnosis in patients with a cardiac mass and implement the optimum diagnostic and therapeutic courses.
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Affiliation(s)
- Shokoufeh Hajsadeghi
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Aida Iranpour
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Saeed Kalantari
- Research Center for Antimicrobial Resistance, Iran University of Medical Sciences, Tehran, Iran
| | - Farzad Dashti
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran
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48
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Wong K, Nguyen J, Blair L, Banjanin M, Grewal B, Bowman S, Boyd H, Gerstner G, Cho HJ, Panfilov D, Tam CK, Aguilar D, Venketaraman V. Pathogenesis of Human Immunodeficiency Virus- Mycobacterium tuberculosis Co-Infection. J Clin Med 2020; 9:E3575. [PMID: 33172001 PMCID: PMC7694603 DOI: 10.3390/jcm9113575] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 11/02/2020] [Accepted: 11/04/2020] [Indexed: 02/07/2023] Open
Abstract
Given that infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death amongst individuals living with HIV, understanding the complex mechanisms by which Mtb exacerbates HIV infection may lead to improved treatment options or adjuvant therapies. While it is well-understood how HIV compromises the immune system and leaves the host vulnerable to opportunistic infections such as Mtb, less is known about the interplay of disease once active Mtb is established. This review explores how glutathione (GSH) depletion, T cell exhaustion, granuloma formation, and TNF-α upregulation, as a result of Mtb infection, leads to an increase in HIV disease severity. This review also examines the difficulties of treating coinfected patients and suggests further research on the clinical use of GSH supplementation.
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Affiliation(s)
- Kevin Wong
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - James Nguyen
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Lillie Blair
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Marina Banjanin
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Bunraj Grewal
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Shane Bowman
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Hailey Boyd
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Grant Gerstner
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Hyun Jun Cho
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - David Panfilov
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Cho Ki Tam
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Delaney Aguilar
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
| | - Vishwanath Venketaraman
- College of Osteopathic Medicine of the Pacific-NorthWest, Western University of Health Sciences, Lebanon, OR 97355, USA; (K.W.); (J.N.); (L.B.); (M.B.); (B.G.); (S.B.); (H.B.); (G.G.); (H.J.C.); (D.P.); (C.K.T.); (D.A.)
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA
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49
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Suárez I, Rohr S, Stecher M, Lehmann C, Winter S, Jung N, Priesner V, Berger M, Wyen C, Augustin M, Malin JJ, Fischer J, Horn C, Neuhann F, Püsken M, Plum G, Fätkenheuer G, Rybniker J. Plasma interferon-γ-inducible protein 10 (IP-10) levels correlate with disease severity and paradoxical reactions in extrapulmonary tuberculosis. Infection 2020; 49:437-445. [PMID: 33140838 PMCID: PMC7605464 DOI: 10.1007/s15010-020-01541-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 10/21/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND With 1.5 million deaths worldwide in 2018, tuberculosis (TB) remains a major global public health problem. While pulmonary TB (PTB) is the most common manifestation, the proportion of extrapulmonary TB (EPTB) is increasing in low-burden countries. EPTB is a heterogeneous disease entity posing diagnostic and management challenges due to the lack of reliable biomarkers. In this study, we prospectively evaluated clinical data and treatment response which were correlated with different biomarkers. METHODS The study was conducted at the University Hospital of Cologne. 20 patients with EPTB were enrolled. We analyzed plasma interferon-γ-inducible protein 10 (IP-10) levels in plasma by ELISA for up to 12 months of treatment. In addition, the QuantiFERON®-TB Gold Plus (QFT® Plus) test was performed during the course of treatment. Clinical data were assessed prospectively and correlated with QFT® Plus and IP-10 levels. RESULTS Plasma IP-10 levels were found to be significantly increased (p < 0.001) in patients with extensive disease compared to patients with limited disease (cervical lymph node TB) or healthy controls. In patients with clinically confirmed paradoxical reaction (PR), a further increase of IP-10 was noted. IFN-γ measured by the QFT® Plus test did not decrease significantly during the course of treatment. Of note, in four EPTB patients (20%) without radiographic pulmonary involvement, sputum culture was positive for Mycobacterium tuberculosis. CONCLUSION Our data demonstrate that IP-10 may be a valuable biomarker for estimation of disease severity in EPTB and monitoring of the disease course in extensive forms. However, IP-10 may be less suitable for diagnosis and monitoring of EPTB patients with limited disease. The QFT® Plus test does not appear to be a suitable marker for therapy monitoring. Sputum should be examined in EPTB patients even in case of normal diagnostic imaging of the chest.
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Affiliation(s)
- Isabelle Suárez
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Samuel Rohr
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Melanie Stecher
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Clara Lehmann
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Sandra Winter
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Norma Jung
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Vanessa Priesner
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Melanie Berger
- Department of Pneumology and Critical Care Medicine, Cologne-Merheim Hospital, Kliniken Der Stadt Köln GmbH, Witten/Herdecke University Hospital, Ostmerheimer Strasse 200, 51109, Cologne, Germany
| | - Christoph Wyen
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,Praxis Am Ebertplatz, Cologne, Germany
| | - Max Augustin
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Jakob J Malin
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Julia Fischer
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Carola Horn
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
| | - Florian Neuhann
- Levy Mwanawasa Medical University (LMMU), Lusaka, Zambia.,Institute of Global Health, University Hospital Heidelberg, Heidelberg, Germany.,Municipal Health Authority Cologne, Cologne, Germany
| | - Michael Püsken
- Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Cologne, Germany
| | - Georg Plum
- Institute for Medical Microbiology, Immunology and Hygiene, University Hospital of Cologne, Cologne, Germany
| | - Gerd Fätkenheuer
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany
| | - Jan Rybniker
- Division of Infectious Diseases, Department I of Internal Medicine, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. .,German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany. .,Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
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50
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Quinn CM, Poplin V, Kasibante J, Yuquimpo K, Gakuru J, Cresswell FV, Bahr NC. Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease. Life (Basel) 2020; 10:E262. [PMID: 33138069 PMCID: PMC7693460 DOI: 10.3390/life10110262] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/13/2020] [Accepted: 10/21/2020] [Indexed: 12/14/2022] Open
Abstract
Antiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment. Recently published studies have emphasized the importance of neutrophils and T cell subtypes in TB-IRIS pathogenesis, alongside the recognized role of CD4 T cells and macrophages. Research has also refined our prognostic understanding, revealing how the disease can impact lung function. While corticosteroids remain the only trial-supported therapy for prevention and management of TB-IRIS, increasing interest has been given to biologic therapies directly targeting the immune pathology. TB-IRIS, especially its unmasking form, remains incompletely described and more data is needed to validate biomarkers for diagnosis. Management strategies remain suboptimal, especially in the highly morbid central nervous system (CNS) form of the disease, and further trials are necessary to refine treatment. In this review we will summarize the current understanding of the immunopathogenesis, the presentation of TB-IRIS and the evidence for management recommendations.
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Affiliation(s)
- Carson M. Quinn
- School of Medicine, University of California, San Francisco, CA 94143, USA
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; (J.K.); (J.G.); (F.V.C.)
| | - Victoria Poplin
- Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS 66045, USA; (V.P.); (N.C.B.)
| | - John Kasibante
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; (J.K.); (J.G.); (F.V.C.)
| | - Kyle Yuquimpo
- Department of Medicine, University of Kansas, Kansas City, KS 66045, USA;
| | - Jane Gakuru
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; (J.K.); (J.G.); (F.V.C.)
| | - Fiona V. Cresswell
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; (J.K.); (J.G.); (F.V.C.)
- Clinical Research Department, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
- Medical Research Council, Uganda Virus Research Unit, London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Nathan C. Bahr
- Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS 66045, USA; (V.P.); (N.C.B.)
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