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Bergeron A, Mikulska M, De Greef J, Bondeelle L, Franquet T, Herrmann JL, Lange C, Spriet I, Akova M, Donnelly JP, Maertens J, Maschmeyer G, Rovira M, Goletti D, de la Camara R, Maertens J, De Greef J, Slavin M, Spriet I, Hubacek P, Bergeron A, Cordonnier C, Kanerva J, Herbrecht R, Herrmann JL, Lanternier F, Bondeelle L, Robin C, Einsele H, Lehrnbecher T, Groll A, Maschmeyer G, Lange C, von Lilienfeld-Toal M, Pana D, Roilides E, Kassa C, Averbuch D, Engelhard D, Cesaro S, Mikulska M, Pagano L, Castagnola E, Compagno F, Goletti D, Mesini A, Donnelly PJ, Styczynski J, Botelho de Sousa A, Aljurf M, de la Camara R, Navarro D, Rovira M, Franquet T, Garcia-Vidal C, Ljungman P, Paukssen K, Ammann R, Lamoth F, Hirsch H, Ritz N, Akova M, Ceesay M, Warris A, Chemaly R. Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia. THE LANCET. INFECTIOUS DISEASES 2022; 22:e359-e369. [PMID: 35636446 DOI: 10.1016/s1473-3099(22)00227-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 03/27/2022] [Accepted: 03/29/2022] [Indexed: 10/18/2022]
Abstract
Mycobacterial infections, both tuberculosis and nontuberculous, are more common in patients with haematological malignancies and haematopoietic stem cell transplant recipients than in the general population-although these infections remain rare. Mycobacterial infections pose both diagnostic and therapeutic challenges. The management of mycobacterial infections is particularly complicated for patients in haematology because of the many drug-drug interactions between antimycobacterial drugs and haematological and immunosuppressive treatments. The management of mycobacterial infections must also consider the effect of delaying haematological management. We surveyed the management practices for latent tuberculosis infection (LTBI) in haematology centres in Europe. We then conducted a meticulous review of the literature on the epidemiology, diagnosis, and management of LTBI, tuberculosis, and nontuberculous mycobacterial infections among patients in haematology, and we formulated clinical guidelines according to standardised European Conference on Infections in Leukaemia (ECIL) methods. In this Review, we summarise the available literature and the recommendations of ECIL 8 for managing mycobacterial infections in patients with haematological malignancies.
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Affiliation(s)
- Anne Bergeron
- Division of Pulmonology, Geneva University Hospitals, Geneva, Switzerland; University of Paris, ECSTRRA Team, Inserm, Paris, France.
| | - Malgorzata Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; San Martino Polyclinic Hospital, Genoa, Italy
| | - Julien De Greef
- Division of Internal Medicine and Infectious Diseases, Saint-Luc University Clinics, Catholic University of Louvain, Brussels, Belgium
| | - Louise Bondeelle
- Division of Pulmonology, Saint Louis Hospital, APHP, University of Paris, Paris, France
| | - Tomas Franquet
- Department of Radiology, Sant Pau Hospital, Autonomous University of Barcelona, Barcelona, Spain
| | - Jean-Louis Herrmann
- Microbiology Department, Raymond Poincaré Hospital, GHU Paris-Saclay, Paris, France; Division of Infection and Inflammation, Paris-Saclay University, UVSQ, Inserm, Paris, France
| | - Christoph Lange
- Division of Clinical Infectious Diseases, Research Center Borstel, Borstel, Germany; German Center for Infection Research (DZIF), TTU Tuberculosis, Borstel, Germany; Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany; Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA
| | - Isabel Spriet
- Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, University of Leuven, Leuven, Belgium
| | - Murat Akova
- Department of Medicine, Section of Infectious Diseases, Hacettepe University Medical School, Ankara, Turkey
| | | | - Johan Maertens
- Department of Haematology, University Hospitals Leuven, University of Leuven, Leuven, Belgium
| | - Georg Maschmeyer
- Department of Haematology, Oncology, and Palliative Care, Ernst von Bergmann Clinic, Potsdam, Germany
| | - Montserrat Rovira
- BMT Unit, Haematology Department, Hospital Clinic, IDIBAPS and Josep Carreras Foundation, Barcelona, Spain
| | - Delia Goletti
- Translational Research Unit, Department of Epidemiology and Preclinical Research, Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy
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Czech MM, Dioverti MV, Karaba AH, Jain T, Talluru SM, Sunshine JC, Kang J, Parrish N, Kates OS. Disseminated Tuberculosis With an Atypical Cutaneous Manifestation in a Hematopoietic Cell Transplant Patient in the Early Posttransplant Period: Case Report and Review of the Literature. Open Forum Infect Dis 2022; 9:ofac643. [PMID: 36570971 PMCID: PMC9772869 DOI: 10.1093/ofid/ofac643] [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] [Accepted: 11/28/2022] [Indexed: 11/30/2022] Open
Abstract
We describe an unusual case of posttransplant tuberculosis reactivation in a man who underwent allogeneic hematopoietic cell transplant. Concomitant with disseminated adenovirus infection, reactivation of tuberculosis manifested as disseminated, nonfollicular pustules on day +49. Skin biopsy was obtained on day +50. Initial histopathologic evaluation did not suggest mycobacterial infection, but tissue stain showed acid-fast organisms, which were subsequently identified as Mycobacterium tuberculosis. Shortly after the cutaneous presentation of tuberculosis, the patient died on day +52. Our case is among a paucity of reports describing tuberculosis reactivation in hematopoietic cell transplant patients in the early posttransplant period. It highlights the difficulty of diagnosing contemporaneous systemic infections, and it presents a rare and atypical cutaneous manifestation of tuberculosis in a hematopoietic cell transplant patient. Our case and review of the literature emphasize the need for further research to elucidate risk factors associated with early posttransplant reactivation of tuberculosis, and the importance of remaining vigilant for active tuberculosis in hematopoietic cell transplant patients with epidemiologic risk factors.
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Affiliation(s)
- Mary M Czech
- Correspondence: Mary M. Czech, MD, MS, National Institutes of Health, 10 Center Drive, Building 10, Room 2C146, Bethesda, MD 20892 ()
| | - Maria Veronica Dioverti
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Andrew H Karaba
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Tania Jain
- Division of Hematologic Malignancies, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sai M Talluru
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joel C Sunshine
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA,Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jun Kang
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Nikki Parrish
- Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Mert D, Ozer M, Merdin A, İskender G, Uncu Ulu B, Kizil Çakar M, Dal MS, Altuntaş F, Ertek M. Latent tuberculosis in adult hematopoietic stem cell transplantation recipients: Clinical experience from a previously endemic population. Medicine (Baltimore) 2022; 101:e31786. [PMID: 36401428 PMCID: PMC9678539 DOI: 10.1097/md.0000000000031786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Hematopoietic stem cell transplantation (HSCT) recipients may be at an elevated risk of developing active tuberculosis infection due to suppression in the cellular immune system. Herein, we aimed to evaluate the prevalence of latent tuberculosis and active tuberculosis in patients with allogeneic and autologous HSCT. In this cohort, data were obtained retrospectively from patients' records. The patients who were followed up in the bone marrow transplantation unit of the University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital between January 2016 and December 2019 were screened for the study. And the HSCT recipients who had tuberculin skin test and/or QuantiFERON-TB gold (QFT-GIT) test results were included in the study. A total of 361 patients were included in the study, 227 patients had autologous HSCT, and 134 patients had allogeneic HSCT. QFT-GIT was performed in 10 patients with allogeneic HSCT, and it was found positive in only 1 patient. Tuberculin skin test ≥5 mm was accepted as positive and was accepted to have latent tuberculosis, and it was positive in 18.2% (41) of the patients with autologous HSCT and was positive in 21.6% (29) of the patients with allogeneic HSCT. There was no significant difference between the 2 groups (P = .429). Isoniazid (INH) prophylaxis was started in 16.7% of patients with autologous HSCT and 22.4% of patients with allogeneic HSCT. During follow-up, active tuberculosis did not develop in any patients in both groups. There was no statistically significant difference found between allogeneic and autologous HSCT recipients regarding the prevalence of latent tuberculosis. Active tuberculosis infection did not develop in any of the patients who started INH prophylaxis. INH prophylaxis seems to be very efficient in preventing the reactivation of latent tuberculosis in patients going through allogeneic HSCT and/or autologous HSCT.
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Affiliation(s)
- Duygu Mert
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
- *Correspondence: Duygu Mert, University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Mehmet Akif Ersoy mah, Vatan cad., No: 91, Yenimahalle/Ankara 06200, Turkey (e-mail: )
| | - Muhammet Ozer
- Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - Alparslan Merdin
- University of Health Sciences Ankara Gülhane Education and Research Hospital, Department of Hematology, Ankara, Turkey
| | - Gülşen İskender
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
| | - Bahar Uncu Ulu
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Merih Kizil Çakar
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Mehmet Sinan Dal
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Fevzi Altuntaş
- University of Health Sciences Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Hematology & Bone Marrow Transplantation, Ankara, Turkey
| | - Mustafa Ertek
- University of Health Sciences Dr Abdurrahman Yurtaslan Ankara Oncology Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey
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Tuberculosis in allogeneic haematopoietic stem cell transplantation: so many unresolved questions! Bone Marrow Transplant 2021; 56:2050-2051. [PMID: 34145415 DOI: 10.1038/s41409-021-01381-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 05/25/2021] [Accepted: 06/10/2021] [Indexed: 02/05/2023]
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Riccardi N, Villa S, Canetti D, Giacomelli A, Taramasso L, Martini M, Di Biagio A, Bragazzi NL, Brigo F, Sotgiu G, Besozzi G, Codecasa L. Missed opportunities in tb clinical practice: How to bend the curve? A medical, social, economic and ethical point of view. Tuberculosis (Edinb) 2020; 126:102041. [PMID: 33385833 DOI: 10.1016/j.tube.2020.102041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/10/2020] [Accepted: 12/10/2020] [Indexed: 10/22/2022]
Affiliation(s)
- Niccolò Riccardi
- StopTB Italia Onlus, Milan, Italy; Department of Infectious - Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Simone Villa
- StopTB Italia Onlus, Milan, Italy; Centre for Multidisciplinary Research in Health Science, University of Milan, Milan, Italy
| | - Diana Canetti
- StopTB Italia Onlus, Milan, Italy; Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Giacomelli
- StopTB Italia Onlus, Milan, Italy; Department of Biomedical and Clinical Sciences DIBIC L. Sacco, University of Milan, Milan, Italy
| | - Lucia Taramasso
- Infectious Diseases Clinic, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | | | - Antonio Di Biagio
- StopTB Italia Onlus, Milan, Italy; Infectious Diseases Clinic, Ospedale Policlinico San Martino - IRCCS, Genoa, Italy
| | | | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Merano, Italy
| | - Giovanni Sotgiu
- StopTB Italia Onlus, Milan, Italy; Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | | | - Luigi Codecasa
- StopTB Italia Onlus, Milan, Italy; Regional TB Reference Centre, Istituto Villa Marelli, Niguarda Hospital, Milan, Italy
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Zeng QZ, Zhang YY, Wu YJ, Zhang ZY, Zhang JN, Fu HX, Wang JZ, Wang FR, Yan CH, Mo XD, Wang Y, Chen YH, Chang YJ, Xu LP, Liu KY, Huang XJ, Zhang XH. Frequency, Risk Factors, and Outcome of Active Tuberculosis following Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2020; 26:1203-1209. [DOI: 10.1016/j.bbmt.2020.02.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 02/15/2020] [Accepted: 02/16/2020] [Indexed: 12/16/2022]
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Mamishi S, Pourakbari B, Moradzadeh M, van Leeuwen WB, Mahmoudi S. Prevalence of active tuberculosis infection in transplant recipients: A systematic review and meta-analysis. Microb Pathog 2019; 139:103894. [PMID: 31805320 DOI: 10.1016/j.micpath.2019.103894] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 11/24/2019] [Accepted: 11/25/2019] [Indexed: 10/25/2022]
Abstract
INTRODUCTION Tuberculosis (TB) is considered as a serious complication of organ transplant; therefore, the detection and appropriate treatment of active TB infection is highly recommended for the reduction of mortality in the future. The aim of this review was to conduct a systematic review and meta-analysis assessing the prevalence of active TB infection in transplant recipients (TRs). MATERIAL AND METHODS Electronic databases, including MEDLINE (via PubMed), SCOPUS and Web of Science were searched up to December 24, 2017. The prevalence of active TB was estimated using the random effects meta-analysis. Heterogeneity was evaluated by subgroup analysis. Data were analyzed by STATA version 14. RESULTS The pooled prevalence of post-transplant active TB was estimated 3% [95% CI: 2-3]. The pooled prevalence of active TB in different transplant forms was as follows: renal,3% [95% CI: 2-4]; stem cell transplant (SCT), 1% [95% CI: 0-3]; lung, 4% [95% CI: 2-6]; heart, 3% [95% CI: 2-4]; liver, 1% [95% CI: 1], and hematopoietic stem cell transplant (HSCT), 2% [95% CI: 1-3]. The prevalence of different clinical presentations of TB was as follows: pulmonary TB (59%; 95% CI: 54-65), extra pulmonary TB (27%; 95% CI: 21-33), disseminated TB (15%; 95% CI: 12-19) and miliary TB (8%; 95% CI: 4-13). The pooled prevalence of different diagnostic tests was as follows: chest X-ray, 57% [95% CI, 46-67]; culture, 56% [95% CI, 45-68]; smear, 49% [95% CI, 40-58]; PCR, 43% [95% CI, 40-58]; histology, 26% [95% CI, 20-32], and tuberculin skin test, 19% [95% CI, 10-28]. CONCLUSION A high suspicion level for TB, the early diagnosis and the prompt initiation of therapy could increase the survival rates among SOT patients. Overall, renal and lung TRs appear to have a higher predisposition for acquiring TB than other type of recipients. Monitoring of the high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection among TRs especially in endemic areas.
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Affiliation(s)
- Setareh Mamishi
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran; Department of Infectious Diseases, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Pourakbari
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Mina Moradzadeh
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran
| | - Willem B van Leeuwen
- Department of Innovative Molecular Diagnostics, University of Applied Sciences Leiden, Leiden, the Netherlands
| | - Shima Mahmoudi
- Pediatric Infectious Disease Research Center, Tehran University of Medical Science, Tehran, Iran.
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Anastasopoulou A, Ziogas DC, Samarkos M, Kirkwood JM, Gogas H. Reactivation of tuberculosis in cancer patients following administration of immune checkpoint inhibitors: current evidence and clinical practice recommendations. J Immunother Cancer 2019; 7:239. [PMID: 31484550 PMCID: PMC6727332 DOI: 10.1186/s40425-019-0717-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Accepted: 08/23/2019] [Indexed: 12/18/2022] Open
Abstract
Immune checkpoint inhibitors (ICBs) have revolutionized cancer treatment producing remarkable and durable responses for a range of malignancies. However, the additional modulation of immune response by ICBs may rarely cause immune-related infectious complications, including re-activation of latent tuberculosis infection (LTBC) with detrimental effects on those patients’ outcome. Here, we present two “real-world” melanoma cases that were treated in our department with blockade of PD-1/PD-L1 and developed active Mycobacterium tuberculosis (MTB) during immunotherapy. In view of these cases, we review the literature for ICB-associated MTB reactivation and discuss our considerations about the possible interactions of immunotherapy and the underlying co-existent mycobacterial infection. Based on the current evidence from preclinical findings prior to this experience, we raise questions regarding cancer patients who are at higher risk for developing MTB infection, whether ICB-treated patients should be considered immunocompromised, and how they should be managed for latent and/or active tuberculosis. Aside from the well-established clinical benefit of immunotherapy, the blockade of PD-1/PD-L1 axis may concurrently disrupt the immune control of specific opportunistic infections such as tuberculosis that should be carefully and expectantly managed in order to avoid compromising the outcome of cancer treatment and the affected patient’s survival.
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Affiliation(s)
- Amalia Anastasopoulou
- First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11527, Athens, Greece
| | - Dimitrios C Ziogas
- First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11527, Athens, Greece
| | - Michael Samarkos
- First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11527, Athens, Greece
| | - John M Kirkwood
- Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA
| | - Helen Gogas
- First Department of Medicine, Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, 11527, Athens, Greece.
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Abad CLR, Razonable RR. An update on Mycobacterium tuberculosis infection after hematopoietic stem cell transplantation in adults. Clin Transplant 2018; 32:e13430. [PMID: 30347465 DOI: 10.1111/ctr.13430] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 10/15/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Mycobacterium tuberculosis (TB) is common worldwide, but is rarely reported after hematopoietic transplantation (HSCT). We reviewed all TB cases among HSCT since 2010 to provide an update on its epidemiology, clinical presentation, management and outcome. METHODS Several databases were reviewed from January 1, 2010 to June 30, 2018 using key words tuberculosis and hematopoietic transplantation. RESULTS The 47 cases of TB were reported during the study period. The highest TB frequency was reported from India (2.9%), with a median frequency of 2% (range, 0.18%-2.9%). The majority were recipients of allogeneic transplants (45/47, 95.7%). Pulmonary TB was the most common clinical presentation (20/47, 42.6%). The median time to clinical presentation was 4.6 (range, 3-12.9) and 2.4 (range, 0.6-5) months, based on cohort data and case reports, respectively. Fever was reported in 87.5% (14/16) of patients. First-line quadruple drug therapy was frequently used (29/35, 82.9%), with a median length of 12 and 9 months for cohorts and case reports, respectively. All-cause and attributable mortality was 27.6% (13/47), and 8.5% (4/47), respectively. CONCLUSIONS Mycobacterium tuberculosis presents early after HSCT, most commonly as fever. A high index of suspicion is needed for early diagnosis and treatment, to prevent TB-attributable mortality.
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Affiliation(s)
- Cybele Lara R Abad
- Section of Infectious Diseases, Department of Medicine, University of the Philippines Manila, UP-Philippine General Hospital, Manila, Philippines
| | - Raymund R Razonable
- Division of Infectious Diseases, Department of Medicine, The William J Von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
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Hasan T, Au E, Chen S, Tong A, Wong G. Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines. BMJ Open 2018; 8:e022445. [PMID: 30209157 PMCID: PMC6144320 DOI: 10.1136/bmjopen-2018-022445] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Revised: 07/15/2018] [Accepted: 07/25/2018] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE Immunosuppressed individuals are at a high risk of latent tuberculosis infection (LTBI) and clinical practice guidelines for the screening and management of LTBI in at-risk patients have been developed. We assessed the scope, quality and consistency of clinical practice guidelines on screening for LTBI and the prevention of tuberculosis infection (TB) in high-risk patient populations. DESIGN We conducted a systematic review of clinical practice guidelines. Methodological quality of these guidelines was assessed using the Appraisal of Guidelines for Research and Education (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations. DATA SOURCES Electronic databases (MEDLINE, EMBASE, PsycINFO) and guideline registries were searched from inception to December 2017. RESULTS Thirty-eight guidelines were included. Nineteen focused on patients receiving medical immunosuppression, seven on transplantation, three on patients with HIV and nine were generalised across all at risk populations. Most guidelines (n=32, 84%) used a systematic approach to identify and appraise the evidence. The methodological quality of the guidelines varied with the overall mean AGREE II scores ranging from 35% to 80%. Guidelines performed poorly in terms of editorial independence (average score 35%, range 0%-92%); however, most were robust in defining their scope and purpose (average score 80%, range 56%-100%). Guidelines recommended either or both the tuberculin skin test and the interferon gamma release assay for screening. Treatment of LTBI with isoniazid was consistently recommended. CONCLUSION Clinical practice guidelines on LTBI vary in quality and scope. The recommendations for screening varied across guidelines, while recommendations for treatment were largely consistent. Improving the consistency and quality of guidelines may help to optimise the screening and management of LTBI for improved patient outcomes.
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Affiliation(s)
- Tasnim Hasan
- Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia
| | - Eric Au
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
| | - Sharon Chen
- Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, New South Wales, Australia
- School of Medicine, The University of Sydney, Sydney, New South Wales, Australia
| | - Allison Tong
- Centre for Kidney Research, The Children’s Hospital, Westmead, New South Wales, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Germaine Wong
- Centre for Transplant and Renal Research, Westmead Hospital, Westmead, New South Wales, Australia
- Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia
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Akı ŞZ, Sucak GT, Tunçcan ÖG, Köktürk N, Şenol E. The incidence of tuberculosis infection in hematopoietic stem cell transplantation recipients: A retrospective cohort study from a center in Turkey. Transpl Infect Dis 2018; 20:e12912. [DOI: 10.1111/tid.12912] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 01/23/2018] [Accepted: 03/25/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Şahika Zeynep Akı
- Departments of Hematology; Faculty of Medicine; Gazi University; Ankara Turkey
| | - Gülsan Türköz Sucak
- Departments of Hematology; Faculty of Medicine; Gazi University; Ankara Turkey
| | - Özlem Güzel Tunçcan
- Departments of Infectious Disease; Faculty of Medicine; Gazi University; Ankara Turkey
| | - Nurdan Köktürk
- Departments of Pulmonary Disease; Faculty of Medicine; Gazi University; Ankara Turkey
| | - Esin Şenol
- Departments of Infectious Disease; Faculty of Medicine; Gazi University; Ankara Turkey
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Abstract
Mycobacterium tuberculosis is a major opportunistic pathogen in transplant recipients. Compared to that in the general population, the frequency of tuberculosis (TB) is 10 to 40 times higher in hematopoietic stem cell transplant (HSCT) recipients and 20 to 74 times higher in solid-organ transplant (SOT) recipients. Transplant recipients with TB are also more likely to develop disseminated disease, have longer time to definitive diagnosis, require more invasive diagnostic procedures, and experience greater anti-TB treatment-related toxicity than the general population. Specific risk factors for TB in SOT recipients include previous exposure to M. tuberculosis (positive tuberculin skin tests and/or residual TB lesions in pretransplant chest X ray) and the intensity of immunosuppression (use of antilymphocyte antibodies, type of basal immunosuppression, and intensification of immunosuppressive therapy for allograft rejection). Risk factors in HSCT recipients are allogeneic transplantation from an unrelated donor; chronic graft-versus-host disease treated with corticosteroids; unrelated or mismatched allograft; pretransplant conditioning using total body irradiation, busulfan, or cyclophosphamide; and type and stage of primary hematological disorder. Transplant recipients with evidence of prior exposure to M. tuberculosis should receive treatment appropriate for latent TB infection. Optimal management of active TB disease is particularly challenging due to significant drug interactions between the anti-TB agents and the immunosuppressive therapy. In this chapter, we address the epidemiology, clinical presentation, diagnostic considerations, and management strategies for TB in SOT and HSCT recipients.
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Lee HJ, Lee DG, Choi SM, Park SH, Cho SY, Choi JK, Kim SH, Choi JH, Yoo JH, Cho BS, Eom KS, Lee S, Kim YJ, Kim HJ, Min CK, Kim DW, Lee JW, Min WS, Jung JI. The demanding attention of tuberculosis in allogeneic hematopoietic stem cell transplantation recipients: High incidence compared with general population. PLoS One 2017; 12:e0173250. [PMID: 28278166 PMCID: PMC5344370 DOI: 10.1371/journal.pone.0173250] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 02/17/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. METHODS From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. RESULTS TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49-886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59-14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. CONCLUSION Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed.
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Affiliation(s)
- Hyo-Jin Lee
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Gun Lee
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- * E-mail:
| | - Su-Mi Choi
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sun Hee Park
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Sung-Yeon Cho
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jae-Ki Choi
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Si-Hyun Kim
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung-Hyun Choi
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin-Hong Yoo
- Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Byung-Sik Cho
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Seong Eom
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seok Lee
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yoo-Jin Kim
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hee-Je Kim
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Chang-Ki Min
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Dong-Wook Kim
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong-Wook Lee
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Woo-Sung Min
- The Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Im Jung
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Young JAH, Weisdorf DJ. Infections in Recipients of Hematopoietic Stem Cell Transplants. MANDELL, DOUGLAS, AND BENNETT'S PRINCIPLES AND PRACTICE OF INFECTIOUS DISEASES 2015. [PMCID: PMC7152282 DOI: 10.1016/b978-1-4557-4801-3.00312-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Al-Anazi KA, Al-Jasser AM, Alsaleh K. Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation. Front Oncol 2014; 4:231. [PMID: 25207262 PMCID: PMC4144006 DOI: 10.3389/fonc.2014.00231] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 08/11/2014] [Indexed: 12/11/2022] Open
Abstract
Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10-40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between <1 and 16% and varies considerably according to the type of transplant and the geographical location. Approximately 80% of M. tuberculosis infections in stem cell transplant recipients have been reported in patients receiving allografts. Several risk factors predispose to M. tuberculosis infections in recipients of hematopoietic stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies in addition to the transplant procedure and its own complications. These infections can develop as early as day 11 and as late as day 3337 post-transplant. The course may become rapidly progressive and the patient may develop life-threatening complications. The diagnosis of M. tuberculosis infections in stem cell transplant recipients is usually made on clinical grounds, cultures obtained from clinical specimens, tissues biopsies in addition to serology and molecular tests. Unfortunately, a definitive diagnosis of M. tuberculosis infections in these patients may occasionally be difficult to be established. However, M. tuberculosis infections in transplant recipients usually respond well to treatment with anti-tuberculosis agents provided the diagnosis is made early. A high index of suspicion should be maintained in recipients of stem cell transplantation living in endemic areas and presenting with compatible clinical and radiological manifestations. High mortality rates are associated with infections caused by multidrug-resistant strains, miliary or disseminated infections, and delayed initiation of therapy. In recipients of hematopoietic stem cell transplantation, isoniazid prophylaxis has specific indications and bacillus Calmette-Guerin vaccination is contraindicated as it may lead to disseminated infection. The finding that M. tuberculosis may maintain long-term intracellular viability in human bone marrow-derived mesenchymal stem cells complicates the development of effective vaccines and strategies to eliminate tuberculosis. However, the introduction of linezolid, cellular immunotherapy, and immunomodulation in addition to autologous mesenchymal stem cell transplantation will ultimately have a positive impact on the overall management of infections caused by M. tuberculosis.
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Affiliation(s)
- Khalid Ahmed Al-Anazi
- Section of Adult Hematology and Oncology, Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
| | | | - Khalid Alsaleh
- Section of Adult Hematology and Oncology, Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia
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García-Elorriaga G, Rey-Pineda GD. Tuberculosis and hematopoietic stem cell transplant: Review of a difficult and often underestimated problem. World J Clin Infect Dis 2013; 3:70-78. [DOI: 10.5495/wjcid.v3.i4.70] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Revised: 08/10/2013] [Accepted: 10/16/2013] [Indexed: 02/06/2023] Open
Abstract
Recipients of solid organ transplants (SOT) and stem cell transplants (SCT) constitute a group of patients at risk for tuberculosis (TB) development. The prevalence of active TB in patients undergoing SOT is higher than in patients undergoing SCT, probably due to the shorter period of immunosuppression in the latter. We reviewed the importance of SCT in individuals with hematological malignancies. Most TB cases occur in transplant patients by reactivation of latent infection after immunosuppression, most often within the first year after transplant, leading to graft loss and in some cases, death. Relevant variables to assess the risk of TB infection in a transplant recipient include the donor’s and recipient’s medical histories, imaging results, microbiology and tuberculin skin test (TST) and interferon-gamma release assays (IGRA). TST is routinely performed in the donor and recipient before transplantation. If TST is > 5 mm in the recipient or > 10 mm in the donor, it is necessary to exclude active TB (pulmonary and renal). Chemoprophylaxis is recommended in TST (+) recipients and in recipients with recent seroconversion, in donors with a history of untreated TB or in contact with an individual with active TB, if radiological images are suspicious and the IGRA is (+). The drug of choice is isoniazid. These topics are herewith reviewed.
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17
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Tuberculosis in hematopoietic stem cell transplant recipients. Mediterr J Hematol Infect Dis 2013; 5:e2013061. [PMID: 24363876 PMCID: PMC3867227 DOI: 10.4084/mjhid.2013.061] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 10/16/2013] [Indexed: 01/25/2023] Open
Abstract
Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50% and is higher in allogeneic HSCT than in autologous. There is no consensus regarding the screening with tuberculin skin test or QuantiFERON-TB gold, primary prophylaxis for latent TB, and whether the epidemiologic query should be emphasized in developing countries with high prevalence of TB.
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18
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Abstract
PURPOSE OF REVIEW Hematopoietic stem cell as well as solid-organ transplantation is being carried out with increasing frequency throughout the world. Lower respiratory tract infections (LRTIs) remain a common life-threatening complication faced by the transplant recipients. The purpose of this review is to provide up-to-date information on pulmonary infections among the transplant recipients, especially emphasizing the endemicity of microorganisms, epidemiology, work-up of infections, and principles of their management. RECENT FINDINGS A lower respiratory tract infection such as pneumonia is the most frequent of all the infections and is associated with high morbidity and mortality. Factors increasing the risk of pulmonary infections include surgical techniques, immune status, chemoradiotherapy, alloimmune mechanisms between the host and the graft, and the environment. A high degree of suspicion, computed tomography (CT) scan of the chest, and flexible bronchoscopy are required in most to establish the diagnosis. SUMMARY Proper management of LRTI in transplant recipients requires a high degree of suspicion, thorough knowledge of the epidemiology and endemicity of the suspected organisms, CT scan of the chest, and expertise at bronchoscopy. Utmost teamwork among transplant physicians, infectious disease specialist, and bronchoscopist is essential.
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19
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Moon SM, Lee SO, Choi SH, Kim YS, Woo JH, Yoon DH, Suh C, Kim DY, Lee JH, Lee JH, Lee KH, Kim SH. Comparison of the QuantiFERON-TB Gold In-Tube test with the tuberculin skin test for detecting latent tuberculosis infection prior to hematopoietic stem cell transplantation. Transpl Infect Dis 2012; 15:104-9. [PMID: 22823749 DOI: 10.1111/j.1399-3062.2012.00765.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2011] [Revised: 01/25/2012] [Accepted: 05/16/2012] [Indexed: 02/04/2023]
Abstract
A total of 244 patients including 100 (41%) autologous hematopoietic stem cell transplant (HCT) recipients and 144 (59%) allogeneic HCT recipients were enrolled over a 28-month period. During the study period, no prophylaxis for latent tuberculosis (TB) infection was administrated. Of these, 201 (82%) had Bacillus Calmette-Guérin (BCG) scars or prior histories of BCG vaccination. The tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube (QFT-GIT) test were performed simultaneously in all 244 patients. TST indurations were ≥ 5 mm in 39 of these patients (15%), and in 25 (10%) indurations were ≥ 10 mm. In addition, 40 (16%) had positive QFT-GIT outcomes, and 34 (14%) indeterminate outcomes. If the 34 patients with indeterminate QFT-GIT results were excluded from the overall agreement analysis, the agreement between the TST results (induration size ≥ 5 mm) and the QFT-GIT results in the 210 patients with clear QFT results was poor (κ = 0.08, 95% confidence interval [CI] -0.06 to 0.24), as it was for the patients with indurations ≥ 10 mm (κ = 0.15, 95% CI -0.004 to 0.31). During follow up, 2 patients developed TB after HCT. The incidence of TB in the patients with positive QFT-GIT outcomes was 2.80 per 100 person-years (95% CI 0.07-15.81), whereas among those with positive TST (≥ 5 mm) results, it was 0 per 100 person-years (95% CI 0-8.00). However, this finding should be cautiously interpreted because of the relatively short follow up and the fact that the sample size of the study cohort did not have adequate power. In conclusion, our data show that, although the frequencies of positive outcomes in the 2 TB screening tests were similar, the overall agreement between the TST and the QFT-GIT test was poor, regardless of BCG vaccination history.
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Affiliation(s)
- S M Moon
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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20
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Machado CM, Martins TC, Colturato I, Leite MS, Simione AJ, Souza MPD, Mauad MA, Colturato VR. Epidemiology of neglected tropical diseases in transplant recipients: review of the literature and experience of a Brazilian HSCT center. Rev Inst Med Trop Sao Paulo 2009; 51:309-24. [DOI: 10.1590/s0036-46652009000600002] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Accepted: 08/27/2009] [Indexed: 02/06/2023] Open
Abstract
The rising success rate of solid organ (SOT) and haematopoietic stem cell transplantation (HSCT) and modern immunosuppression make transplants the first therapeutic option for many diseases affecting a considerable number of people worldwide. Consequently, developing countries have also grown their transplant programs and have started to face the impact of neglected tropical diseases (NTDs) in transplant recipients. We reviewed the literature data on the epidemiology of NTDs with greatest disease burden, which have affected transplant recipients in developing countries or may represent a threat to transplant recipients living in other regions. Tuberculosis, Leprosy, Chagas disease, Malaria, Leishmaniasis, Dengue, Yellow fever and Measles are the topics included in this review. In addition, we retrospectively revised the experience concerning the management of NTDs at the HSCT program of Amaral Carvalho Foundation, a public transplant program of the state of São Paulo, Brazil.
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Russo RL, Dulley FL, Suganuma L, França IL, Yasuda MAS, Costa SF. Tuberculosis in hematopoietic stem cell transplant patients: case report and review of the literature. Int J Infect Dis 2009; 14 Suppl 3:e187-91. [PMID: 19819176 DOI: 10.1016/j.ijid.2009.08.001] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Revised: 08/12/2009] [Accepted: 08/16/2009] [Indexed: 02/08/2023] Open
Abstract
The literature describing tuberculosis (TB) in hematopoietic stem cell transplant (HSCT) recipients is scant, even in countries where TB is common. We describe a case of pulmonary TB in a patient who underwent HSCT and review the English language literature on this subject. An extensive PubMed and Ovid search was undertaken for the period January 1980 to March 2009; the search terms used were 'Mycobacterium tuberculosis' or 'tuberculosis', in combination with 'hematopoietic stem cell transplantation' or 'bone marrow transplantation'. The patient in the present case report underwent allogeneic transplantation and developed TB 8 days after his HSCT. The patient had received vaccination against TB in childhood. During the year prior to the HSCT he had had contact with a relative who had pulmonary TB. On day 3 of anti-TB treatment he developed pericarditis. The patient received anti-TB treatment for 6 months without major problems. From the literature review, we found 34 related studies, 25 on the clinical manifestations of TB. Most of the reports were from Asia (48%), and the incidence of TB varied from 0.0014% in the USA to 16% in Pakistan. TB occurred at between +21 and +1410 days post-HSCT (257.2 days the median), and the lung was the organ most frequently involved. Mortality varied from 0% to 50% and was higher in allogeneic HSCT. There is no consensus regarding screening with the tuberculin skin test or primary prophylaxis for latent TB, and further research into this is necessary in developing countries with a high prevalence of TB.
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Affiliation(s)
- Rachel Leite Russo
- Department of Infectious and Parasitic Diseases, Faculty of Medicine, University of São Paulo, Brazil
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22
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Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JAH, Boeckh MJ, Boeckh MA. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15:1143-238. [PMID: 19747629 PMCID: PMC3103296 DOI: 10.1016/j.bbmt.2009.06.019] [Citation(s) in RCA: 1195] [Impact Index Per Article: 74.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2009] [Accepted: 06/23/2009] [Indexed: 02/07/2023]
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Infections caused by mycobacterium tuberculosis in patients with hematological disorders and in recipients of hematopoietic stem cell transplant, a twelve year retrospective study. Ann Clin Microbiol Antimicrob 2007; 6:16. [PMID: 18021401 PMCID: PMC2200647 DOI: 10.1186/1476-0711-6-16] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2007] [Accepted: 11/16/2007] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Tuberculous infections in patients with hematological disorders and hematopoietic stem cell transplant vary in incidence, complications and response to treatment. METHODS AND MATERIALS A retrospective study of patients with various benign and malignant hematological disorders and recipients of hematopoietic stem cell transplant who were treated at Riyadh Armed Forces Hospital, Saudi Arabia between January 1991 and December 2002 and who developed tuberculous infections was conducted. RESULTS Tuberculous infections occurred in eighteen patients with hematological disorders and hematopoietic stem cell transplant. The main associated factors were: reduced immunity due to the primary hematological disorder, age more than 50 years and the administration of cytotoxic chemotherapy, steroids or radiotherapy. These infections frequently involved the lungs and predominantly occurred in males and in patients with chronic myeloproliferative disorders, myelodysplastic syndrome and acute myeloid leukemia. In patients treated with intravenous cytotoxic chemotherapy, tuberculous infections tended to occur earlier and also tended to be more disseminated compared to infections occurring in patients treated with oral chemotherapy. Anti-tuberculous treatment was given to 16 patients and it was successful in 15 of these patients. CONCLUSION Tuberculous infections cause significant morbidity and mortality in patients with various hematological disorders and in recipients of hematopoietic stem cell transplant. The early administration of anti-tuberculous therapy and compliance with drug treatment are associated with successful outcomes while delayed management, drug resistance and the presence of miliary infections are associated with poor prognosis and high mortality rates.
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Safdar A, Rodriguez GH, De Lima MJ, Petropoulos D, Chemaly RF, Worth LL, Shpall EJ, Rolston KVI, Raad II, Chan KW, Champlin RE. Infections in 100 cord blood transplantations: spectrum of early and late posttransplant infections in adult and pediatric patients 1996-2005. Medicine (Baltimore) 2007; 86:324-333. [PMID: 18004177 DOI: 10.1097/md.0b013e31815c52b0] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Cord blood-derived stem cells are successfully used in the treatment of cancer and congenital disorders in children. This alternative source of stem cells is also explored for adult cancer patients with limited donor options. However, delayed engraftment, prolonged neutropenia, secondary graft loss, and graft-versus-host disease (GVHD) in recipients of cord blood transplantation (CBT) make opportunistic infections a serious concern. We evaluated the spectrum of infections in adults and children undergoing CBT at our National Cancer Institute-designated comprehensive cancer center. The infection incidence rate ratio (total infection episodes/days at risk [survival after CBT] x 100) was 2.4 times higher in 35 adult patients than in 62 children, especially in adults with neutropenia (3 x higher) and GVHD (1.9 x higher). Ninety-two percent of fungal infection episodes occurred within 100 days after transplantation; half of these infections occurred in the first 30 days after CBT. Most bacterial infections (80%) were also diagnosed in the first 100 days, whereas late (>100 d) post-CBT cytomegalovirus and varicella zoster virus infections occurred only in children with chronic GVHD. Multivariate analysis showed that resolution of lymphocytopenia (> or =1000 cells/microL) (hazard ratio [HR] 0.71; p < 0.0001) and successful engraftment (HR 0.20; p < 0.0001) were associated with a low risk of serious infection. Children (HR 0.36; p < 0.0002) with sustained engraftment (HR 0.39; p < 0.004) and those with cancer in remission (HR 0.47; p < 0.007) were less likely to die from infection. More effective measures for surveillance and prevention of late cytomegalovirus and varicella zoster virus infections in children with CBT and chronic GVHD are needed.
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Affiliation(s)
- Amar Safdar
- From Departments of Infectious Diseases, Infection Control, and Employee Health (AS, GHR, RFC, KVIR, IIR), Stem Cell Transplantation and Cellular Therapy (MJDL, EJS, REC), and Pediatrics (DP, LLW, KWC), M. D. Anderson Cancer Center, Houston, Texas
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Collaco JM, Gower WA, Mogayzel PJ. Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: overview, diagnostic considerations, and infectious complications. Pediatr Blood Cancer 2007; 49:117-26. [PMID: 17029246 DOI: 10.1002/pbc.21061] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Pulmonary complications are among the most common and serious sequelae seen in hematopoietic stem cell transplantation (HSCT) recipients. This two-part review addresses the incidence and impact of pulmonary complications in pediatric HSCT patients. In this first part we review the available data for the use of diagnostic modalities in this population, including flexible bronchoscopy with bronchoalveolar lavage (BAL) and open lung biopsy (OLB). We also review the many infectious pulmonary complications that may occur in pediatric HSCT recipients, utilizing the traditional chronologic divisions of neutropenic phase (0-30 days following HSCT), early phase (30-100 days), and late phase (>100 days).
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MESH Headings
- Anti-Infective Agents/therapeutic use
- Antineoplastic Agents/adverse effects
- Biopsy
- Bronchoalveolar Lavage Fluid
- Bronchoscopy
- Child
- Child, Preschool
- Hematopoietic Stem Cell Transplantation
- Humans
- Immunocompromised Host
- Incidence
- Infant
- Lung Diseases/diagnosis
- Lung Diseases/etiology
- Lung Diseases, Fungal/diagnosis
- Lung Diseases, Fungal/drug therapy
- Lung Diseases, Fungal/epidemiology
- Lung Diseases, Fungal/etiology
- Lung Diseases, Fungal/microbiology
- Neoplasms/complications
- Neoplasms/surgery
- Neutropenia/etiology
- Pneumonia/diagnosis
- Pneumonia/drug therapy
- Pneumonia/epidemiology
- Pneumonia/etiology
- Pneumonia, Bacterial/diagnosis
- Pneumonia, Bacterial/drug therapy
- Pneumonia, Bacterial/epidemiology
- Pneumonia, Bacterial/etiology
- Pneumonia, Bacterial/microbiology
- Pneumonia, Viral/diagnosis
- Pneumonia, Viral/drug therapy
- Pneumonia, Viral/epidemiology
- Pneumonia, Viral/etiology
- Pneumonia, Viral/virology
- Postoperative Complications/diagnosis
- Postoperative Complications/drug therapy
- Postoperative Complications/epidemiology
- Postoperative Complications/etiology
- Postoperative Period
- Time Factors
- Tomography, X-Ray Computed
- Transplantation Conditioning/adverse effects
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Affiliation(s)
- J Michael Collaco
- Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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Tavil B, Gulhan B, Ozcelik U, Cetin M, Tezcan I, Tuncer M, Uckan D. Tuberculin skin test positivity in pediatric allogeneic BMT recipients and donors in Turkey. Pediatr Transplant 2007; 11:414-8. [PMID: 17493222 DOI: 10.1111/j.1399-3046.2007.00679.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The preliminary study was performed to determine the frequency of tuberculin skin test (TST) positivity among 26 patients and their donors screened by TST to investigate whether tuberculin positivity of a recipient or donor influenced the rate of tuberculosis disease, transplant-related events, and to evaluate the effectiveness of isoniazide (INAH) prophylaxis administered to those with positive TST. The frequency of TST positivity was 23% (n = 6) among recipients and also 23% (n = 6) among donors. Two recipients and five donors with positive TST received INAH prophylaxis for six months. Our use of INAH prophylaxis in transplant patients was very conservative because of the risk of drug interaction. The transplantation procedure was not postponed for either recipient or donor TST positivity. Despite the high frequency of tuberculosis in our country, we have not detected any case of tuberculosis in our center, either among the purified protein derivative-screened (n = 26) or non-screened (n = 128) patients except for disseminated tuberculosis infection because of BCG vaccination in two patients with severe combined immunodeficiency. In conclusion, TST positivity in either recipient or donor may not be a contraindication for bone marrow transplantation and the procedure may not be postponed. Pretransplantation TST screening may be needed in countries where tuberculosis is common in the general population.
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Affiliation(s)
- Betul Tavil
- Pediatric Hematology Unit, Hacettepe University School of Medicine, Ankara, Turkey
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Abstract
Paediatric haematopoietic cell transplantation has experienced significant advances in the last few decades. However, pulmonary complications are an important limitation to the efficacy of this intervention, contributing to post-transplantation morbidity and mortality. Such complications persist even in experienced centres and occur in adult and paediatric recipients. This review identifies the paediatric pulmonary complications that are commonly seen following haematopoietic cell transplantation and addresses both infectious and non-infectious aetiologies and their clinical manifestations, evaluation, and potential therapy. Ultimately, improvement in outcomes will require attention to immunosuppression as well as traditional diagnostic procedures and treatment. This article aims to review the current state of pulmonary complications post-transplantation, to examine the impact of our recent advances and changes in treatment, and to identify potential future therapies and hypothesise what role these might have on long-term survival.
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Naqvi R, Akhtar S, Noor H, Saeed T, Bhatti S, Sheikh R, Ahmed E, Akhtar F, Naqvi A, Rizvi A. Efficacy of Isoniazid Prophylaxis in Renal Allograft Recipients. Transplant Proc 2006; 38:2057-8. [PMID: 16979998 DOI: 10.1016/j.transproceed.2006.06.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.
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Affiliation(s)
- R Naqvi
- Sindh Institute of Urology and Transplantation (SIUT), Civil Hospital, Karachi 74200, Pakistan.
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George B, Mathews V, Viswabandya A, Srivastava A, Chandy M. Infections in children undergoing allogeneic bone marrow transplantation in India. Pediatr Transplant 2006; 10:48-54. [PMID: 16499587 DOI: 10.1111/j.1399-3046.2005.00397.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We studied the clinical profile of infections among 221 pediatric patients who underwent 230 allogeneic transplants between 1986 and June 2004. All patients developed febrile neutropenia. There were 283 documented infections, which included bacterial (36.9%), viral (45.7%), fungal (11.1%) and other infections (6.3%) including tuberculosis. Bacterial and fungal infections were more common in the first 30 days following BMT, while viral infections were more common >30 days after BMT. Bacterial pathogens were predominantly gram-negative organisms (72.7%), when compared with gram-positive organisms (27.3%). Common gram-negative organisms included NFGNB, Pseudomonas, Escherichia coli and Klebsiella while coagulase negative Staphylococci was the main gram-positive organism. Bacteremia (61.2%) was the main source positive cultures and was mainly because of gram-negative organisms (81%), predominantly NFGNB and Pseudomonas. Exactly 103/221(43.7%) transplants had 128 documented viral infections commonly because of Cytomegalovirus, Herpes group of viruses and transfusion related hepatitis. Thirty of 221 (13.5%) of transplants had 30 documented fungal infections with the majority being because of aspergillus (90%). Tuberculosis was seen in 1.7% of transplants while catheter infections were seen in 21 patients (9.1%). Infection related mortality was seen in 12% predominantly because of CMV or fungal infections. A sub group analysis (pre-1998 vs. post-1998) revealed higher incidences of gram-negative infections, bacteremia and bacterial infection related mortality in the pre-1998 era when compared with the recent times. The profile and mortality of infections in this series from India is not significantly different from reports from the West.
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Affiliation(s)
- Biju George
- Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India.
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Akan H, Arslan O, Akan OA. Tuberculosis in stem cell transplant patients. J Hosp Infect 2006; 62:421-6. [PMID: 16413085 DOI: 10.1016/j.jhin.2005.09.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2005] [Accepted: 09/23/2005] [Indexed: 02/06/2023]
Abstract
Tuberculosis (TB) is an increasing health problem, and patients undergoing stem cell transplantation (SCT) are at high risk of acquiring TB. Following a review of the medical literature, this article reports the current situation of TB in SCT patients. A PubMed search was undertaken using the keywords 'tuberculosis', 'stem cell transplantation' and 'bone marrow transplantation', and cases with meaningful data for analysis were included. The medical literature contains relatively few data on TB and SCT. Although there is a risk of TB in allogeneic SCT patients, this is less than in solid organ transplant patients, and the risk in autologous SCT patients is similar to the risk in the general population. The incidence of TB in SCT patients is proportional to the incidence of TB in the general population. Evidence favouring TB prophylaxis is not well established. While allogeneic transplantation carries a risk of TB, this is not true for autologous transplantation. Prophylaxis can only be an option for selected patients or countries with high rates of TB.
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Affiliation(s)
- H Akan
- Department of Haematology, Faculty of Medicine, Ankara University, Ankara, Turkey.
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Erdstein AA, Daas P, Bradstock KF, Robinson T, Hertzberg MS. Tuberculosis in allogeneic stem cell transplant recipients: still a problem in the 21st century. Transpl Infect Dis 2004; 6:142-6. [PMID: 15762931 DOI: 10.1111/j.1399-3062.2004.00068.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Allogeneic stem cell transplant (ASCT) recipients have severely impaired cell-mediated immunity as a result of their conditioning regimen, immunosuppressive therapy, and graft-versus-host disease (GVHD). Accordingly, they are susceptible to bacterial, viral, and fungal infections. Mycobacterial infections can also occur in these patients, although the incidence is not high, even in countries where tuberculosis (TB) is common. We describe four patients from our hospital who developed pulmonary T tuberculous infection in the post-transplant period over a 3-year period. During that time a total of 127 patients have undergone an ASCT, representing an incidence of TB of 2.3%. The pretransplant diagnosis was acute myeloid leukemia in three patients and chronic myeloid leukemia in one case. All four patients were treated with a combination of cyclosporine and corticosteroids for acute and/or chronic GVHD. Three of the four patients were born outside Australia, each from an area where TB is endemic. Two patients died within 2 weeks of the commencement of antituberculous therapy, the third is alive and well, and the fourth died of multi-organ failure and sepsis after 4 months in hospital. A higher index of suspicion of previous TB exposure and infection is required in the assessment of ASCT recipients, particularly in those born in areas where TB is common or endemic.
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Affiliation(s)
- A A Erdstein
- Department of Thoracic Medicine, Westmead Hospital and University of Sydney, Westmead, New South Wales, Australia
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34
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Recognition of Misdiagnosed Tuberculosis in a Bone Marrow Transplant Recipient Leads to Identification of "Pseudotuberculosis" Due to Laboratory Contamination. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2004. [DOI: 10.1097/01.idc.0000144899.20580.4d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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George B, Mathews V, Srivastava A, Chandy M. Infections among allogeneic bone marrow transplant recipients in India. Bone Marrow Transplant 2004; 33:311-5. [PMID: 14647246 DOI: 10.1038/sj.bmt.1704347] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
SUMMARY Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT) despite prophylaxis, use of growth factors and newer antimicrobial drugs. We report the clinical profile of infections among 297 patients who underwent 304 allogeneic transplants between 1986 and December 2001. All patients developed febrile neutropenia. There were 415 documented infections among 304 transplants. This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram-negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%), Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major source of positive cultures was blood (53.7%) followed by urine (25.5%) and sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral infections. The common viral infections were due to cytomegalovirus, herpes group of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had 66 documented fungal infections. Common fungi included Aspergillus species (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in 2.3% of the transplants. Catheter infections were suspected or documented in 7.8% of the transplants (24/304). The incidence of infections in this series from developing countries is not significantly different from reports from the West. Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347 Published online 1 December 2003
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Affiliation(s)
- B George
- Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India.
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Sayarlioglu M, Inanc M, Kamali S, Cefle A, Karaman O, Gul A, Ocal L, Aral O, Konice M. Tuberculosis in Turkish patients with systemic lupus erythematosus: increased frequency of extrapulmonary localization. Lupus 2004; 13:274-8. [PMID: 15176665 DOI: 10.1191/0961203303lu529xx] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
The objective was to investigate the frequency and characteristics of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE). We reviewed the charts of 556 patients with SLE who were followed up between 1978 and 2001 in our lupus clinic. Patients who developed TB after the diagnosis of SLE were identified (SLE/TB+). Ninety-six consecutive patients with SLE who did not develop TB during the follow-up were evaluated as a control group (SLE/TB-). Clinical, laboratory and management characteristics of these two groups of patients were recorded according to a predefined protocol, and compared. Of the 556 patients evaluated, 20 patients (3.6%) with TB were identified. Nine of the 20 patients (45%) had extrapulmonary TB (vertebral involvement in three patients, meningeal in two, and joint and soft tissue in four). Arthritis and renal involvement were significantly high in the SLE/TB+ group (P = 0.045, P = 0.009, respectively). The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone were significantly higher in the SLE/TB+ group compared to the SLE/TB- group (27 +/- 22 g versus 16 +/- 16 g, 24 +/- 45 mg versus 11 +/- 8.5 mg, respectively). In conclusion, we found an increased frequency of TB infection and a high prevalence of extrapulmonary TB in a large cohort of SLE patients. The mean daily dose of prednisolone before the diagnosis of TB and the cumulative dose of prednisolone, which possibly related to disease severity, were important determinants for the increased risk of TB in these patients with SLE.
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Affiliation(s)
- M Sayarlioglu
- Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
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Yoo JH, Lee DG, Choi SM, Choi JH, Park YH, Kim YJ, Kim HJ, Lee S, Kim DW, Lee JW, Min WS, Shin WS, Kim CC. Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea. Bone Marrow Transplant 2004; 34:497-504. [PMID: 15286689 DOI: 10.1038/sj.bmt.1704636] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
We reviewed 242 allogeneic hematopoietic stem cell transplantation (HSCT) recipients retrospectively over a 2-year period (January 1998-December 1999) in order to analyze the characteristics and assess the outcomes of infectious complications in patients after HSCT in Korea. Bacteria were the major pathogens before engraftment, and viral and fungal infections predominated during the post-engraftment period. Varicella zoster virus was the most common viral pathogen after engraftment. Cytomegalovirus disease occurred mainly in the late-recovery phase. The frequency of mold infection was higher than that of yeast. There was a relatively high incidence of tuberculosis (3.0%) and Pneumocystis carinii pneumonia (6.5%). One case of death by measles confirmed by autopsy was also noted. Overall, cumulative mortality was 43% (104/242), and 59.6% of these deaths (62/104) were infection-related. Allogeneic HSCT recipients from unrelated donors were prone to infectious complication and higher mortality than those from matched sibling (17/39 (43.6%) vs 45/203 (22.2%), respectively; P<0.01; odd ratio 2.5; 95% confidence interval 1.2-5.1). As infection was the main post-HSCT complication in our data, more attention should be given to the management of infections in HSCT recipients.
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Affiliation(s)
- J-H Yoo
- Department of Internal Medicine, The Catholic Hematopoietic Stem Cell Transplantion Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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39
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Au WY, Cheng VCC, Ho PL, Yuen KY, Hung I, Ma SY, Lie AKW, Liang R, Kwong YL. Nontuberculous mycobacterial infections in Chinese hematopoietic stem cell transplantation recipients. Bone Marrow Transplant 2003; 32:709-14. [PMID: 13130319 DOI: 10.1038/sj.bmt.1704210] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Between 1995 and 2002, nine cases of nontuberculous mycobacterium (NTM) were isolated from 462 allogeneic stem cell transplant (SCT) recipients (1.9%), and none from 139 autologous cases. They included three cases each of Mycobacterium fortuitum and M. chelonae, and single cases of M. scrofalaceum, M. gordonnae and M. avium complex. Seven cases were respiratory, including five cases requiring treatment, and two involved infected catheters and vascular conduits. Compared with nine cases of mycobacterium tuberculosis (MTB) isolated in the same period, NTM isolation occurred later after HSCT and involved more unrelated donors. Important risk factors for NTM infection included significant aGVHD (P=0.043), leukemia relapse (P=0.022), MUD and mismatch SCT (P<0.001) and existence of BO (P<0.001). Coinfection with aspergillus was common. Invasive NTM disease required prolonged antimicrobial treatment in five cases due to M. fortuitum and M. chelonae. With better MTB prophylaxis, intensive immunosuppression and better awareness, NTM has become an emerging threat in oriental allogeneic HSCT recipients. The cutoff between colonization and infection, and the threshold for starting treatment is unclear. NTM isolation is a marker for severe immunosuppression and poor prognosis. When there is doubt over species identity or extent of infection, broad-spectrum cover may be prudent.
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Affiliation(s)
- W Y Au
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
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40
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Weinstock DM, Feinstein MB, Sepkowitz KA, Jakubowski A. High rates of infection and colonization by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2003; 31:1015-21. [PMID: 12774053 DOI: 10.1038/sj.bmt.1704043] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Nontuberculous mycobacteria (NTM) are essentially ubiquitous and can infect both immunocompetent and immunocompromised hosts. However, NTM infection is surprisingly uncommon in reports from allogeneic hematopoietic stem cell transplant (alloSCT) centers that do not routinely perform allograft T-cell depletion. We reviewed medical records for all adult patients who underwent alloSCT at our center between January 1993 and December 2001. American Thoracic Society and Centers for Disease Control and Prevention guidelines Were used to define definite, probable, and possible NTM infection. Of 571 patients, 36 of 372 (9.7%) T-cell depleted and 14 of 199 (7.0%) conventional alloSCT recipients (P=0.26) had a positive culture for NTM after alloSCT. Of the 50 patients with NTM infection, 16 had definite infection and 34 had probable or possible infection. Rates of NTM infection were 5 to 20-fold higher than rates reported by other centers. Of the 16 definite infections, nine were caused by Mycobacterium haemophilum. Two patients had disseminated M. avium complex (MAC) infection and one had a vascular catheter infected by MAC. Three patients died from complications of NTM infection. Patients with probable or possible NTM infection had markedly different epidemiology, risk factors, site and species of NTM infection, and prognosis than patients with definite NTM infection.
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Affiliation(s)
- D M Weinstock
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
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Abstract
Although one third of the world's population is infected with tuberculosis (TB), TB in blood and marrow transplant (BMT) recipients is relatively less well studied, as the incidence of TB is relatively low in developed countries with BMT units. Since the report of the first two cases in 1983, 52 cases of TB complicating BMT have been reported in the English literature from BMT centers in ten different countries. Not unexpectedly, the two largest series were reported from areas with a high incidence of TB in the general population, with about 45 cases per 10(5) inhabitants per year in Spain and about 100 cases per 10(5) inhabitants per year in Hong Kong respectively. The overall frequency of occurrence of TB in BMT recipients was 0.4% (52 cases among 13 881 BMT recipients), with a male:female ratio of 11:9 and median age of 33 (range 7-57). The incidence of TB in the general population is a major predictor of a higher frequency of occurrence in BMT recipients. Moreover, allogeneic transplantation, graft-versus-host disease, and total body irradiation were found to be risk factors associated with TB. Among the 48 cases in whom the time of manifestation were reported, only one case manifested during the neutropenic period (day 11). On the other hand, 11 cases (23%) manifest after engraftment but before day 100, and 36 (75%) manifest after day 100. The most important aspect towards making the diagnosis is a high index of suspicion, as TB occurred in relatively low frequencies especially in developed countries, and the clinical patterns usually mimic other more common infectious and non-infectious complications after BMT. As the incidence of drug resistant TB is increasing, we prefer to treat our patients for at least one year (as compared with six months in immunocompetent hosts) with four drugs in the first six months and two or three drugs for another six months. In those patients who could not tolerate oral medication, we used an intravenous regimen of rifampicin, ciprofloxacin, and amikacin until oral therapy could be instituted. The absence of relapse after termination of treatment in our patients suggested that secondary prophylaxis would not be necessary as long as immune function has been restored. With the rising incidence of TB in countries that previously enjoyed a very low prevalence of TB, attributed to the growing population of HIV-infected subjects with TB, and the changing patterns of population migration, it is important to bear a high index of suspicion of Mycobacterium tuberculosis as a pathogen in BMT recipients.
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Affiliation(s)
- K Y Yuen
- Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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Affiliation(s)
- C Liatsos
- Liver Transplantation and Hepatobiliary Medicine, Royal Free Hospital, Hampstead, London, UK
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