|
1
|
Hara M, Yashiro T, Yashiro Y. Delayed diagnosis of pulmonary tuberculosis with pleuritis due to ampicillin/sulbactam: A case report. World J Clin Cases 2025; 13:104083. [DOI: 10.12998/wjcc.v13.i19.104083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/06/2025] [Accepted: 02/24/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Tuberculosis (TB) remains a global health concern despite decreasing incidence. Delayed TB diagnosis can exacerbate patient outcomes and lead to broader public health issues such as mass infections. Differentiation between TB and bacterial pneumonia is often complicated by variable clinical and radiological manifestations of TB, leading to diagnostic delays.
CASE SUMMARY An 89-year-old, Japanese male patient with a history of diabetes mellitus, hypertension, and hypothyroidism presented with right-sided chest pain. Based on the elevated inflammatory response, right pleural effusion, and infiltrating shadow in the lung field, the diagnosis of right pleurisy was made and the antibiotic, ampicillin/sulbactam, was administered. The patient’s condition, inflammatory reaction, and right pleural effusion temporarily improved. However, persistent low-grade fever and malaise prompted further evaluation, revealing repeated right pleural effusion and inflammatory response. A right thoracentesis was performed; the patient was diagnosed with tuberculous pleurisy as a result of exudative effusion with lymphocyte predominance, elevated adenosine deaminase levels, and positive Mycobacterium TB polymerase chain reaction test. Anti-TB treatment, including isoniazid, rifampicin, and ethambutol was initiated, leading to significant clinical improvement. The patient successfully completed a 12-month course of TB therapy without recurrence or deterioration.
CONCLUSION There are cases of TB wherein temporary improvement apparently could be shown through treatment with antimicrobial agents other than anti-TB drugs, necessitating careful evaluation in atypical cases of bacterial pneumonia.
Collapse
Affiliation(s)
- Munechika Hara
- Department of Internal Medicine, Fujimi-Kogen Hospital, Fujimi-Kogen Medical Center, Nagano 399-0214, Japan
| | - Toshitsugu Yashiro
- Department of Internal Medicine, Fujimi-Kogen Hospital, Fujimi-Kogen Medical Center, Nagano 399-0214, Japan
| | - Yasuaki Yashiro
- Department of Internal Medicine, Fujimi-Kogen Hospital, Fujimi-Kogen Medical Center, Nagano 399-0214, Japan
| |
Collapse
|
|
2
|
Ye L, Cao Y, Fu Y, Tian C, Cao Q. Crohn's Disease With Latent Tuberculosis Infection or Intestinal Tuberculosis: Rapid Discrimination by Targeted Next-Generation Sequencing. Aliment Pharmacol Ther 2025; 61:1218-1225. [PMID: 39905821 PMCID: PMC11908111 DOI: 10.1111/apt.18522] [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: 09/15/2024] [Revised: 10/15/2024] [Accepted: 01/16/2025] [Indexed: 02/06/2025]
Abstract
BACKGROUND Discriminating Crohn's disease (CD) with latent tuberculosis infection (LTBI) from intestinal tuberculosis (ITB) in tuberculosis-endemic regions remains challenging. AIM To assess whether targeted next-generation sequencing (tNGS) could be an efficient method for ITB diagnosis and discrimination from CD with LTBI. METHODS The study was conducted prospectively from September 2020 until December 2023. We recruited patients with undetermined intestinal ulcers and positive interferon-gamma release assay. We compared tNGS (using fresh biopsy tissue samples from ulcer bases) to pathological detection of caseous necrotising granuloma, acid-fast bacillus (AFB) staining, tuberculosis polymerase chain reaction (TB-PCR) for diagnostic efficiency. ITB was diagnosed based on cure by anti-tuberculosis therapy and comprehensive clinical evaluation. RESULTS Of the 100 patients included, 66 had ITB and 34 had CD with LTBI. The sensitivity, specificity, positive predictive value and negative predictive value of tNGS for ITB were 83% (72%-91%), 100% (87%-100%), 100% (92%-100%) and 76% (60%-87%), respectively. TNGS had significantly higher diagnostic sensitivity than AFB staining [15% (4%-39%), p < 0.05], TB-PCR [22% (12%-36%), p < 0.05] and detection of caseous necrotising granulomas [17% (9%-28%), p < 0.05]. The models combining multiclinical factors increased sensitivity (97% vs. 83%) than tNGS alone. No patients with CD and LTBI had positive tNGS. CONCLUSIONS TNGS using fresh biopsy tissue from ulcer bases is highly sensitive and specific, with superiority over other traditional diagnostic methods for ITB detection. TNGS could facilitate rapid diagnosis of ITB and discrimination from CD with LTBI, particularly in high TB-endemic countries.
Collapse
Affiliation(s)
- Lingna Ye
- Department of Gastroenterology, Qiantang Branch of Sir Run Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhouChina
| | - Yushu Cao
- Department of Gastroenterology, Sir Run Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhouChina
| | - Yujuan Fu
- Department of Pathology, Sir Run Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhouChina
| | - Chuwen Tian
- Department of Gastroenterology, Sir Run Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhouChina
| | - Qian Cao
- Department of Gastroenterology, Sir Run Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhouChina
| |
Collapse
|
|
3
|
Sato R, Takasaka N, Hosaka Y, Fukuda T, Shinfuku K, Takatsuka M, Hasegawa T, Yamada M, Yamanaka Y, Ryu K, Ishikawa T, Araya J. Association between the extent of intrapulmonary spread on chest CT and false-negative results of T-SPOT.TB in pulmonary tuberculosis: a retrospective study. BMC Infect Dis 2025; 25:391. [PMID: 40114064 PMCID: PMC11927247 DOI: 10.1186/s12879-025-10777-x] [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: 03/02/2024] [Accepted: 03/10/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND The T-SPOT.TB assay is widely used for the adjunctive diagnosis of tuberculosis (TB). However, clinicians often encounter false-negative T-SPOT.TB results. The extent of TB spread may influence host immune functions, which can influence the results of the T-SPOT.TB test. However, few previous reports have investigated the association between radiologic pulmonary tuberculosis (PTB) severity and T-SPOT.TB test results. METHODS We retrospectively investigated patients with culture-confirmed pulmonary TB (PTB) at the Jikei University Daisan Hospital between September 2016 and December 2021. We aimed to clarify the association of PTB severity, according to computed tomography (CT), with the false-negative results of the T-SPOT.TB test. RESULTS Among 193 patients with PTB, 43 (22.3%) had false-negative T-SPOT.TB results. High rates of false-negative results were noted for 7/18 (38.9%) patients with PTB spread in two lung segments (mild PTB) and 16/39 (41.0%) patients with PTB spread in 19 lung segments (severe PTB). Multivariate logistic regression analysis showed that mild or severe PTB (odds ratio [OR]: 3.23; 95% confidence interval [CI]: 1.46-7.13; P = 0.004) and lymphopenia (OR: 3.33; 95% CI: 1.20-9.26; P = 0.02) were statistically significant risk factors for false-negative results. CONCLUSIONS Mild or severe intrapulmonary lesions on chest CT might be associated with the false-negative results of the T-SPOT.TB assay. Additionally, estimating the intrapulmonary spread of PTB using chest CT could serve as a useful supplementary tool in diagnosing patients with PTB who receive false-negative results on the T-SPOT.TB test.
Collapse
Affiliation(s)
- Ryo Sato
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Naoki Takasaka
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan.
| | - Yusuke Hosaka
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Taiki Fukuda
- Department of Radiology, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Kyota Shinfuku
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Makiko Takatsuka
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Tsukasa Hasegawa
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Masami Yamada
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Yumie Yamanaka
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Kai Ryu
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Takeo Ishikawa
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University Daisan Hospital, 4-11-1 Izumihoncho, Komae, Tokyo, 201-8601, Japan
| | - Jun Araya
- Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
4
|
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. [PMID: 40104936 DOI: 10.1111/imj.70017] [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: 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.
Collapse
Affiliation(s)
- Hayden Zhang
- Infectious Diseases Department, Blacktown Hospital, Blacktown, New South Wales, Australia
- School of Medicine, Western Sydney University, Blacktown, New South Wales, Australia
| | - Tasnim Hasan
- Infectious Diseases Department, Blacktown Hospital, Blacktown, New South Wales, Australia
- Faculty of Health and Medicine, University of Sydney, Sydney, New South Wales, Australia
| | - Ravindra Dotel
- Infectious Diseases Department, Blacktown Hospital, Blacktown, New South Wales, Australia
| | - Evan Ulbricht
- NSW Tuberculosis Program, Health Protection New South Wales, Sydney, New South Wales, Australia
| | - Nicole Gilroy
- Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, New South Wales, Australia
| | - Susan Maddocks
- Faculty of Health and Medicine, University of Sydney, Sydney, New South Wales, Australia
- Centre for Infectious Diseases and Microbiology, Westmead Hospital, Sydney, New South Wales, Australia
| |
Collapse
|
|
5
|
Eisenhut M, Shah S, Kaba O, Kara M, Sütçü M, Song KH, Kim HB, Wang M. Sensitivity of Immunodiagnostic Tests in Localized Versus Disseminated Tuberculosis-A Systematic Review of Individual Patient Data. Trop Med Infect Dis 2025; 10:70. [PMID: 40137824 PMCID: PMC11946558 DOI: 10.3390/tropicalmed10030070] [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: 01/21/2025] [Revised: 02/27/2025] [Accepted: 03/05/2025] [Indexed: 03/29/2025] Open
Abstract
Our objective was to perform a systematic review of individual patient data comparing immunodiagnostic test sensitivity in patients with localized versus disseminated tuberculosis who are from high- and less-than-high-income countries. In a systematic review of individual patient data, we compared IGRA results and characteristics of patients with disseminated tuberculosis with IGRA results and characteristics of patients with localized tuberculosis. Data were extracted from Pubmed, EMBASE and the Cochrane Library, analyzed and presented following the PRISMA-IPD and STROBE statements. We identified 52 patients with localized and 105 with disseminated tuberculosis. Immunodiagnostic tests in localized tuberculosis from high-income countries were positive in 88.8% and in 67.3% of patients with disseminated tuberculosis (p = 0.034). In patients from less-than-high-income countries, the sensitivity of immunodiagnostic tests was not significantly lower with disseminated tuberculosis. Patients with disseminated tuberculosis were significantly younger and had a higher rate of microbiological confirmation. Multivariate logistic regression analysis revealed that rate of microbiological confirmation was associated with a negative IGRA. Disseminated tuberculosis may be associated with a reduced sensitivity of IGRA in high-income countries and this may be related to a higher bacterial load with a negative IGRA.
Collapse
Affiliation(s)
- Michael Eisenhut
- Paediatric Department, Luton & Dunstable University Hospital, Lewsey Road, Luton LU40DZ, UK
| | - Shagun Shah
- Paediatric Department, Luton & Dunstable University Hospital, Lewsey Road, Luton LU40DZ, UK
| | - Ozge Kaba
- Pediatric Infectious Diseases Department, Başakşehir Çam and Sakura City Hospital, 34480 Istanbul, Turkey;
| | - Manolya Kara
- Department of Pediatric Infectious Diseases, School of Medicine, Yeditepe University, 34728 Istanbul, Turkey
| | - Murat Sütçü
- Department of Pediatric Infectious Diseases, School of Medicine, İstinye University, Bahçeşehir Liv Training and Education Hospital, 34010 Istanbul, Turkey
| | - Kyoung-Ho Song
- Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea
| | - Hong Bin Kim
- Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea
| | - Maoshui Wang
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan 250013, China
| |
Collapse
|
|
6
|
Wang MS, Li-Hunnam J, Chen YL, Gilmour B, Alene KA, Zhang YA, Nicol MP. Conversion or Reversion of Interferon γ Release Assays for Mycobacterium tuberculosis Infection: A Systematic Review and Meta-analysis. Clin Infect Dis 2025; 80:168-179. [PMID: 38954503 DOI: 10.1093/cid/ciae357] [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: 02/29/2024] [Revised: 06/05/2024] [Accepted: 06/28/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Interferon γ release assays (IGRAs) are widely used for diagnosis of latent tuberculosis infection. However, with repeated testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and participant characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% confidence interval [CI], 6.1%-8.5%) or 22.8% (20.1%-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (95% CI, 35.7%-56.4%) or 19.6% (9.2%-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [95% CI, .1%-3.5%]). IGRA results in the borderline-positive or borderline-negative range were associated with increased risk of conversion or reversion (pooled odds ratio [OR] for conversion, 4.15 [95% CI, 3.00-5.30]; pooled OR for reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (OR, 0.70 [95% CI, .56-.84]), cigarette smoking with decreased risk of reversion (0.44 [.06-.82]), and female sex with decreased risk of either conversion or reversion (OR for conversion, 0.66 [.58-.75]; OR for reversion, 0.46 [.31-.61]). CONCLUSIONS IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis-preventive treatment. Retesting of people with indeterminate results is probably not indicated, because indeterminate results seldom revert to positive.
Collapse
Affiliation(s)
- Mao-Shui Wang
- Department of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, China
| | - Jarrod Li-Hunnam
- School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| | - Ya-Li Chen
- Department of Lab Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, China
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, China
| | - Beth Gilmour
- Faculty of Health Sciences, School of Population Health, Curtin University, Perth, WA, Australia
- Geospatial and Tuberculosis Research Team, Telethon Kids Institute, Perth, WA, Australia
| | - Kefyalew Addis Alene
- Faculty of Health Sciences, School of Population Health, Curtin University, Perth, WA, Australia
- Geospatial and Tuberculosis Research Team, Telethon Kids Institute, Perth, WA, Australia
| | - Yan-An Zhang
- Shandong Key Laboratory of Infectious Respiratory Disease, Jinan, China
- Department of Cardiovascular Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, China
| | - Mark P Nicol
- Marshall Centre, Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia
| |
Collapse
|
|
7
|
Arriaga MB, Amorim G, Figueiredo MC, Staats C, Kritski AL, Cordeiro-Santos M, Rolla VC, Andrade BB, Sterling TR. Effect of Smoking on Longitudinal Interferon γ Release Assay Results Among Close Contacts of People with Pulmonary Tuberculosis. J Infect Dis 2025; 231:103-108. [PMID: 38820119 PMCID: PMC11793032 DOI: 10.1093/infdis/jiae285] [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: 01/27/2024] [Revised: 05/21/2024] [Accepted: 05/29/2024] [Indexed: 06/02/2024] Open
Abstract
Diagnosis of Mycobacterium tuberculosis infection in close contacts is critical for tuberculosis control. Smoking is a risk factor for M. tuberculosis infection and tuberculosis disease but its effect on longitudinal interferon γ release assay (IGRA) results remains unknown. We conducted a multisite prospective study in Brazil between 2015 and 2019, among close contacts of adults with culture-confirmed pulmonary tuberculosis. IGRA was performed at baseline, at month 6 if results were negative at baseline, and at months 24-30 after enrollment. IGRA results were categorized as IGRA positive (maintained from baseline to the last visit), IGRA conversion (from negative to positive at any time), IGRA reversion (from positive to negative at any time), and IGRA negative (maintained from baseline to the last visit). Associations between IGRA results and smoking status at baseline (current/former vs never) in contacts were evaluated using propensity score-adjusted logistic regression models. Estimated propensity score was used as a covariate in models, which regressed the outcome (IGRA positive, IGRA conversion, IGRA reversion) on smoking status. Of 430 close contacts, 89 (21%) were IGRA positive, 30 (7%) were converters, 30 (7%) were reverters and 22 were indeterminate. Smoking frequency was 26 (29%) among IGRA-positive contacts, 7 (23%) in converters, and 3 (10%) in reverters. Smoking in contacts was associated with lower odds of IGRA reversion (adjusted odds ratio, 0.16 [95% confidence interval, .03-.70]). We did not detect associations between smoking and IGRA positive or IGRA conversion. Our findings highlight the importance of smoking on longitudinal IGRA results. This has implications for clinical care and clinical trials in which IGRA status is monitored or used as an outcome.
Collapse
Affiliation(s)
- María B Arriaga
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Gustavo Amorim
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Marina C Figueiredo
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Cody Staats
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Afrânio L Kritski
- Programa Acadêmico de Tuberculose, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marcelo Cordeiro-Santos
- Faculdade de Medicina, Fundação Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Brazil
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil
- Faculdade de Medicina, Universidade Nilton Lins, Manaus, Brazil
| | - Valeria C Rolla
- Laboratório de Pesquisa Clínica em Micobacterioses, Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil
| | - Bruno B Andrade
- Laboratório de Pesquisa Clínica e Translacional, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil
- Curso de Medicina, Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil
- Instituto de Pesquisa Clínica e Translacional, Faculdade de Tecnologia e Ciências, Salvador, Brazil
- Faculdade de Medicina, Univerdidade Federal da Bahia, Salvador, Brazil
| | - Timothy R Sterling
- Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
- Curso de Medicina, Universidade Salvador, Salvador, Brazil
| |
Collapse
|
|
8
|
Capoferri G, Ghielmetti G, Glatz B, Mutke MR, Tzankov A, Stephan R, Keller PM, Labhardt ND. Disseminated, fatal reactivation of bovine tuberculosis in a patient treated with adalimumab: a case report and review of the literature. Infection 2025; 53:481-487. [PMID: 39143434 PMCID: PMC11825525 DOI: 10.1007/s15010-024-02364-0] [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: 06/02/2024] [Accepted: 07/25/2024] [Indexed: 08/16/2024]
Abstract
PURPOSE Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported. CASE PRESENTATION/RESULTS We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection. CONCLUSION This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation.
Collapse
Affiliation(s)
- Gioele Capoferri
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
| | - Giovanni Ghielmetti
- Section of Veterinary Bacteriology, Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Bettina Glatz
- Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Markus R Mutke
- Department of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Alexandar Tzankov
- Institute of Pathology and Medical Genetics, University Hospital Basel, Basel, Switzerland
| | - Roger Stephan
- Section of Veterinary Bacteriology, Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Peter M Keller
- Division of Clinical Bacteriology and Mycology, University Hospital of Basel, Basel, Switzerland
| | - Niklaus D Labhardt
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
- Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
| |
Collapse
|
|
9
|
He Y, Shen L, Du J, Cao X, Zhang B, Wang D, Feng B, Li Z, Di Y, Huang J, Guo T, Liang J, Yan J, Liu Z, Jin Q, Duan W, Xin H, Gao L. Agreement between Mycobacterium tuberculosis antigen-based skin test and interferon-gamma release assay in elderly individuals aged ≥65 years in China. Clin Microbiol Infect 2025; 31:290.e1-290.e3. [PMID: 39454755 DOI: 10.1016/j.cmi.2024.10.016] [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: 08/01/2024] [Revised: 10/12/2024] [Accepted: 10/19/2024] [Indexed: 10/28/2024]
Abstract
OBJECTIVES To determine the agreement of Mycobacterium tuberculosis (MTB) antigen-based skin test (TBST) with interferon-gamma release assay (IGRA) in the elderly individuals aged ≥65 years beyond instruction for use in China. METHODS Based on the baseline survey of a randomized controlled trial with the objective of exploring suitable regimens for tuberculosis(TB) preventive treatment, MTB infection was tested using TBST and IGRA in parallel in rural residents aged 50-70 years using a cross-sectional study design. RESULTS A total of 21 219 participants with both TBST and IGRA results were included in this analysis. The concordance between TBST and IGRA was 89.4% (95% CI, 89.0-89.8%) with a kappa coefficient of 0.61 (95% CI, 0.60-0.62). In those aged ≥65 years, the concordance was 86.5% (95% CI, 85.6-87.4%) with a kappa coefficient of 0.55 (95% CI, 0.52-0.58). 21.2% (35/165) of the participants with indeterminate IGRA results were TBST positive, and nine of them were aged ≥65 years. DISCUSSION The consistent agreement between TBST and IGRA in individuals aged ≥65 years suggests that TBST has the potential to be used in the elderly with age beyond instruction for use in China. The respective diagnostic performance of each test will be analysed when the longitudinal data on incident TB is obtained in the future.
Collapse
Affiliation(s)
- Yijun He
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Lingyu Shen
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Jiang Du
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Xuefang Cao
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Bin Zhang
- Center for Diseases Control and Prevention of Zhongmu, Zhengzhou, People's Republic of China
| | - Dakuan Wang
- Center for Diseases Control and Prevention of Zhongmu, Zhengzhou, People's Republic of China
| | - Boxuan Feng
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Zihan Li
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Yuanzhi Di
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Juanjuan Huang
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Tonglei Guo
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Jianguo Liang
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Jiaoxia Yan
- Center for Diseases Control and Prevention of Zhongmu, Zhengzhou, People's Republic of China
| | - Zisen Liu
- Center for Diseases Control and Prevention of Zhongmu, Zhengzhou, People's Republic of China
| | - Qi Jin
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Weitao Duan
- Center for Diseases Control and Prevention of Zhongmu, Zhengzhou, People's Republic of China
| | - Henan Xin
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Lei Gao
- NHC Key Laboratory of Systems Biology of Pathogens, National Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
| |
Collapse
|
|
10
|
Yao F, Zhang R, Lin Q, Xu H, Li W, Ou M, Huang Y, Li G, Xu Y, Song J, Zhang G. Plasma immune profiling combined with machine learning contributes to diagnosis and prognosis of active pulmonary tuberculosis. Emerg Microbes Infect 2024; 13:2370399. [PMID: 38888093 PMCID: PMC11225635 DOI: 10.1080/22221751.2024.2370399] [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: 02/02/2024] [Accepted: 06/16/2024] [Indexed: 06/20/2024]
Abstract
Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89-0.99, with a sensitivity of 82-93% at a specificity of 88-92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.
Collapse
Affiliation(s)
- Fusheng Yao
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| | - Ruiqi Zhang
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| | - Qiao Lin
- The Baoan People's Hospital of Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
| | - Hui Xu
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| | - Wei Li
- Zhuhai ICXIVD Biotechnology Co., Ltd, iCarbonX, Zhuhai, People’s Republic of China
| | - Min Ou
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| | - Yiting Huang
- Zhuhai ICXIVD Biotechnology Co., Ltd, iCarbonX, Zhuhai, People’s Republic of China
| | - Guobao Li
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| | - Yuzhong Xu
- The Baoan People's Hospital of Shenzhen, The Second Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
| | - Jiaping Song
- Zhuhai ICXIVD Biotechnology Co., Ltd, iCarbonX, Zhuhai, People’s Republic of China
| | - Guoliang Zhang
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China
| |
Collapse
|
|
11
|
Bonde Christiansen S, Ainsworth MA. The role of chest X-rays when screening for latent tuberculosis infection in patients with inflammatory bowel disease before starting biologic treatment. Scand J Gastroenterol 2024; 59:918-924. [PMID: 38907722 DOI: 10.1080/00365521.2024.2368248] [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: 01/13/2024] [Revised: 06/05/2024] [Accepted: 06/10/2024] [Indexed: 06/24/2024]
Abstract
BACKGROUND Guidelines generally recommend a combination of immunological assays and chest X-ray imaging (CXR) when screening for latent tuberculosis infection (LTBI) prior to biologic treatment in inflammatory bowel disease (IBD). OBJECTIVE To investigate whether CXR identify patients with suspected LTBI/TB who were not identified with QuantiFERON tests (QFT) when screening for LTBI/TB before starting biologic treatment in IBD patients. METHODS Single-center, retrospective cohort study of patients with inflammatory bowel disease who had a QFT and a CXR prior to initiation of biologic treatment in a 5-year period (October 1st, 2017 to September 30th, 2022). RESULTS 520 patients (56% female, mean age 40.1 years) were included. The majority had none or few risk factors for TB (as reflected by the demographic characteristics) but some risk factors for having false negative QFT results (concurrent glucocorticoid treatment and inflammatory activity). QFT results were positive in 8 patients (1.5%), inconclusive in 18 (3.5%) and negative in 494 (95.0%). Only 1 patient (0.19%) had CXR findings suspicious of LTBI. This patient also had a positive QFT and was subsequently diagnosed with active TB. All patients with negative or inconclusive QFT had CXR without any findings suggesting LTBI/TB. One patient developed active TB after having initiated biologic treatment in spite of having negative QFT and a normal CXR at screening. CONCLUSION In a population with low risk of TB, the benefits of supplementing the QFT with a CXR are limited and are unlikely to outweigh the cost in both patient test-burden, radioactive exposure, and economic resources.
Collapse
Affiliation(s)
| | - Mark Andrew Ainsworth
- Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark
| |
Collapse
|
|
12
|
Matsuura H, Higo H, Kuribayashi T, Tamaoki A, Nakasuka T, Uno M, Makimoto G, Ninomiya K, Fujii M, Rai K, Ichihara E, Hotta K, Miyahara N, Tabata M, Maeda Y, Kiura K, Ohashi K. Concomitant osimertinib and antituberculosis therapy in an elderly patient with EGFR-mutated lung cancer and pulmonary tuberculosis: A case report. Thorac Cancer 2024; 15:1390-1394. [PMID: 38698706 PMCID: PMC11168902 DOI: 10.1111/1759-7714.15324] [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: 01/26/2024] [Revised: 04/14/2024] [Accepted: 04/18/2024] [Indexed: 05/05/2024] Open
Abstract
The concurrent incidence of lung cancer and tuberculosis is expected to escalate due to the projected growth in the older population. Combination therapy with osimertinib and antituberculosis drugs has not been well-established. We report a case of successful treatment involving the concomitant administration of osimertinib and antituberculosis drugs in an older patient, an 89-year-old female, diagnosed with epidermal growth factor receptor (EGFR)-mutant lung cancer and pulmonary tuberculosis. Accumulating evidence is warranted to develop an optimal treatment strategy for patients with lung cancer and tuberculosis.
Collapse
Affiliation(s)
- Hiroaki Matsuura
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Hisao Higo
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | | | - Akihiko Tamaoki
- Okayama Health Foundation Hospital, Okayama Health FoundationOkayamaJapan
| | - Takamasa Nakasuka
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Mari Uno
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Go Makimoto
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Kiichiro Ninomiya
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Masanori Fujii
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Kammei Rai
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Eiki Ichihara
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Katsuyuki Hotta
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Nobuaki Miyahara
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Masahiro Tabata
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Yoshinobu Maeda
- Department of Hematology, Oncology and Respiratory MedicineOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Katsuyuki Kiura
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| | - Kadoaki Ohashi
- Department of Respiratory MedicineOkayama University HospitalOkayamaJapan
| |
Collapse
|
|
13
|
Martineau AR, Chandran S, Palukani W, Garrido P, Mayito J, Reece ST, Tiwari D. Toward a molecular microbial blood test for tuberculosis infection. Int J Infect Dis 2024; 141S:106988. [PMID: 38417613 DOI: 10.1016/j.ijid.2024.106988] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 02/22/2024] [Accepted: 02/23/2024] [Indexed: 03/01/2024] Open
Abstract
The World Health Organization's aim to end the global tuberculosis (TB) epidemic by 2050 cannot be achieved without taking measures to identify people with asymptomatic Mycobacterium tuberculosis (Mtb) infection and offer them an intervention to reduce the risk of disease progression, such as preventive antimicrobial therapy. Implementation of this strategy is limited by the fact that existing tests for Mtb infection, which use immunosensitization to Mtb-specific antigens as a proxy for infection, have low positive predictive value for progression to TB. A blood test that detects Mtb deoxyribonucleic acid (DNA) could allow preventive therapy to be targeted at individuals with microbiological evidence of persistent infection. In this review, we summarize recent advances in the development of molecular microbial blood tests for Mtb infection and discuss potential explanations for discordance between their results and those of immunodiagnostic tests in adults with recent exposure to an infectious index case. We also present a roadmap for further development of molecular microbial blood tests for Mtb infection, and highlight the potential for research in this area to provide novel insights into the biology of Mtb infection and yield new tools to support efforts to control the global TB epidemic.
Collapse
Affiliation(s)
- Adrian R Martineau
- Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, United Kingdom.
| | - Shruthi Chandran
- Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Winnie Palukani
- Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Patricia Garrido
- Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Jonathan Mayito
- Infectious Diseases Institute, Makerere University, Kampala, Uganda
| | - Stephen T Reece
- Infectious Diseases and Vaccines, Kymab, Babraham Research Campus, Cambridge, United Kingdom
| | - Divya Tiwari
- Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, United Kingdom
| |
Collapse
|
|
14
|
Bruzzone F, Plebani M, Koryllou A, Perreau M, Guex-Crosier Y. The Importance of QuantiFERON Gold Plus Test for the Diagnosis of Presumed Ocular Tuberculosis. Klin Monbl Augenheilkd 2024; 241:432-434. [PMID: 38653273 PMCID: PMC11038820 DOI: 10.1055/a-2244-6657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 11/20/2023] [Indexed: 04/25/2024]
Affiliation(s)
- Francesca Bruzzone
- Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Switzerland
| | - Margherita Plebani
- Pediatric Infectious Diseases and Vaccinology Unit, Department Women-Mother-Child, Lausanne University Hospital, CHUV, Lausanne, Switzerland
| | - Aikaterini Koryllou
- Unit of Pediatric Rheumatology, Immunology and Allergology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Matthieu Perreau
- Division of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland
| | - Yan Guex-Crosier
- Ophthalmology, Jules-Gonin Eye Hospital, University of Lausanne, Switzerland
| |
Collapse
|
|
15
|
Ren W, Ma Z, Li Q, Liu R, Ma L, Yao C, Shang Y, Zhang X, Gao M, Li S, Pang Y. Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection. Front Immunol 2024; 15:1359555. [PMID: 38510248 PMCID: PMC10950995 DOI: 10.3389/fimmu.2024.1359555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 02/23/2024] [Indexed: 03/22/2024] Open
Abstract
Background Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals. Methods Participants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples. Results A total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance. Conclusion The MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.
Collapse
Affiliation(s)
- Weicong Ren
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Zichun Ma
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Qiang Li
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Rongmei Liu
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Liping Ma
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Cong Yao
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Yuanyuan Shang
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Xuxia Zhang
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Mengqiu Gao
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Shanshan Li
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Yu Pang
- Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| |
Collapse
|
|
16
|
Mi J, Liu Y, Xue Y, Sun W, Liang Y, Liang J, An H, Wu X. The changes and its significance of peripheral blood NK cells in patients with tuberculous meningitis. Front Microbiol 2024; 15:1344162. [PMID: 38486698 PMCID: PMC10937341 DOI: 10.3389/fmicb.2024.1344162] [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: 11/25/2023] [Accepted: 02/01/2024] [Indexed: 03/17/2024] Open
Abstract
Objective Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients. Methods We conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023. Results The absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p < 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (p < 0.05), and slightly higher than that in NSTB group (36.0%) (p > 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (-) group, and antibody (+) group were lower than that in simple TBM group, etiology (-) group, IGRA (+) group, and antibody (-) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p < 0.05). The counts of CD3+ T, CD4+ T, and B cells in the etiology (+) group were significantly lower than those in the etiology (-) group (p < 0.05). Conclusion The absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.
Collapse
Affiliation(s)
- Jie Mi
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Yinping Liu
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Yong Xue
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Wenna Sun
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Yan Liang
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Jianqin Liang
- Department of Tuberculosis, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Huiru An
- Department of Tuberculosis, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| | - Xueqiong Wu
- Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis Research, Senior Department of Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China
| |
Collapse
|
|
17
|
Delarbre D, Junca-Laplace C, Otto MP, Antoine C, Defuentes G. Disseminated tuberculosis after anti-TNF alpha treatment: Do not blindly trust the IGRA test. ENFERMEDADES INFECCIOSAS Y MICROBIOLOGIA CLINICA (ENGLISH ED.) 2024; 42:98-101. [PMID: 37919203 DOI: 10.1016/j.eimce.2023.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 06/03/2023] [Indexed: 11/04/2023]
Abstract
INTRODUCTION Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism. METHODS We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis. RESULTS The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient's history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis. CONCLUSION Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.
Collapse
Affiliation(s)
- David Delarbre
- Division of Internal Medicine, Military Teaching Hospital Sainte-Anne, 2, Boulevard Sainte-Anne, Toulon Cedex 9, France.
| | - Camille Junca-Laplace
- Radiology Department, Military Teaching Hospital Sainte-Anne, 2, Boulevard Sainte-Anne, Toulon Cedex 9, France
| | - Marie-Pierre Otto
- Microbiology Department, Military Teaching Hospital Sainte-Anne, 2, Boulevard Sainte-Anne, Toulon Cedex 9, France
| | - Carole Antoine
- Division of Internal Medicine, Military Teaching Hospital Sainte-Anne, 2, Boulevard Sainte-Anne, Toulon Cedex 9, France
| | - Gilles Defuentes
- Division of Internal Medicine, Military Teaching Hospital Sainte-Anne, 2, Boulevard Sainte-Anne, Toulon Cedex 9, France
| |
Collapse
|
|
18
|
Masiá M, de la Rica A, Fernández-González M, García JA, Padilla S, García-Abellán J, Botella Á, Mascarell P, Gutiérrez F. Integrating SARS-CoV-2-specific interferon-γ release assay testing in the evaluation of patients hospitalized with COVID-19. Microbiol Spectr 2023; 11:e0241923. [PMID: 37855635 PMCID: PMC10715100 DOI: 10.1128/spectrum.02419-23] [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: 06/08/2023] [Accepted: 09/06/2023] [Indexed: 10/20/2023] Open
Abstract
IMPORTANCE The cellular immune response is essential in the protection against severe disease in patients with established SARS-CoV-2 infection. The novelty of this study lies in the evaluation of the overall performance of a standardized assay to measure cellular immune response, the SARS-CoV-2-specific interferon-γ release assay (IGRA), in hospitalized patients with severe COVID-19. The SARS-CoV-2 IGRA was shown to accurately classify patients based on disease severity and prognosis, and the study revealed that test performance was not affected by the SARS-CoV-2 variant or control tube results. We identified an assay cut-off point with a high negative predictive value against mortality. The SARS-CoV-2 IGRA in patients hospitalized for COVID-19 may be a useful tool to assess cellular immunity and adopt targeted therapeutic and preventive measures.
Collapse
Affiliation(s)
- Mar Masiá
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Clinical Medicine Department, Universidad Miguel Hernández, San Juan de Alicante, Spain
| | - Alba de la Rica
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- Microbiology Service, Hospital General Universitario de Elche, Alicant, Spain
| | - Marta Fernández-González
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - José Alberto García
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
| | - Sergio Padilla
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Clinical Medicine Department, Universidad Miguel Hernández, San Juan de Alicante, Spain
| | - Javier García-Abellán
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Clinical Medicine Department, Universidad Miguel Hernández, San Juan de Alicante, Spain
| | - Ángela Botella
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
| | - Paula Mascarell
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
| | - Félix Gutiérrez
- Infectious Diseases Unit, Hospital General Universitario de Elche, Alicant, Spain
- CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain
- Clinical Medicine Department, Universidad Miguel Hernández, San Juan de Alicante, Spain
| |
Collapse
|
|
19
|
Toriu C, Tsubota K, Usui Y, Goto H. Resuming anti-TNF therapy after development of miliary tuberculosis in Behcet's disease-related uveitis: a case report. J Ophthalmic Inflamm Infect 2023; 13:52. [PMID: 38017191 PMCID: PMC10684474 DOI: 10.1186/s12348-023-00375-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 11/23/2023] [Indexed: 11/30/2023] Open
Abstract
PURPOSE There is no consensus concerning restarting anti-tumour necrosis factor (TNF)-α therapy for uveitis after treatment for active tuberculosis (TB). We report a case of Behcet disease (BD) in which treatment with TNF inhibitor was successfully resumed after treatment for miliary TB. CASE REPORT A 48-year-old Japanese male was treated for uveitis of unknown aetiology in the left eye at a general ophthalmology clinic. He was referred to Department of Ophthalmology, Tokyo Medical University Hospital because of macula oedema (ME) not responding to prednisolone (PSL) 20 mg. BD was diagnosed based on fluorescein angiographic findings of diffuse retinal vasculitis characteristic of BD, recurrent oral aphthous ulcer, erythema nodosum-like rash in his legs, and HLA-A26 positivity. After a screening test, adalimumab (ADA) was started as steroid-sparing therapy. Eight months after starting ADA, the patient was diagnosed with miliary TB. ADA and PSL were discontinued immediately due to TB. Anti-TB treatment was completed after 6 months based on clinical improvement, although T-SPOT.TB was still positive. Infliximab with isoniazid was started due to relapse of ME, worsened vitreous haze, and worsened visual acuity in his left eye. Subsequently, his ocular symptoms subsided and there was no relapse of TB. CONCLUSION This case suggests that in patients with BD who have discontinued anti-TNF therapy due to miliary TB, restarting anti-TNF therapy may be a therapeutic option after TB has been treated appropriately with careful monitoring for relapse.
Collapse
Affiliation(s)
- Chika Toriu
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Kinya Tsubota
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan.
| | - Yoshihiko Usui
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| | - Hiroshi Goto
- Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan
| |
Collapse
|
|
20
|
Chen K, Jiang F, Zhou Q, Dong X, He T, Li Y, Luo Z, Duan W, Yang H. Latent tuberculosis infection in myasthenia gravis patients on immunosuppressive therapy: high incidence yet moderate reactivation rate. Ann Med 2023; 55:2282182. [PMID: 38375813 PMCID: PMC10812855 DOI: 10.1080/07853890.2023.2282182] [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: 07/17/2023] [Accepted: 11/03/2023] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Immunosuppressive therapies (ISTs) are mainstays for management of myasthenia gravis (MG). Meanwhile, latent tuberculosis infection (LTBI) is common in the setting of high-burden countries. However, the prevalence of LTBI among MG patients and whether receiving ISTs for MG would aggravate LTBI reactivation remain unknown. METHODS We retrospectively analyzed the frequency of LTBI via interferon-gamma release assay (IGRA) positivity among hospitalized MG patients from both rural and urban areas in a tertiary hospital, and those receiving ISTs were followed up to investigate the reactivation risk of LTBI. RESULTS A total of 300 MG patients with determinate IGRA results were enrolled, where the frequency of LTBI was 35.0%. Male (OR = 1.910, 95% CI: 1.181-3.089, p = .008) and elderly (OR = 1.044, 95% CI: 1.027-1.061, p < .001) patients were prone to LTBI. Of those with LTBI, 78 individuals on ISTs were successfully followed up for a median duration of 18.3 (8.5-24.0) months, of which 25 (32.1%) received anti-tuberculosis (TB) treatments. The rate of various degrees of adverse events was 82.1% over the course of the follow-up, but was not different between individuals with and without therapies against TB (χ2 < 0.001, p > .999). Only 1 patient eventually reported lymph node and intestinal TB, with the incidence rate of LTBI reactivation preliminarily estimated to be 0.81 per 100 person years. CONCLUSION The frequency of LTBI is high in our MG cohort, especially among those with advanced age and males. However, receiving immunosuppressives seems not to increase the risk of LTBI reactivation. LTBI screening is strongly recommended for all MG patients ready to receive ISTs, while preventive anti-TB chemotherapy should be prescribed after weighing potential benefits against the risk of side effects in those with LTBI. In-depth investigation is still entailed to further verify these findings due to the limitation of the retrospective single-center design of our study.
Collapse
Affiliation(s)
- Kangzhi Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Fei Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Qian Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Xiaohua Dong
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Ting He
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Zhaohui Luo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Weiwei Duan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Huan Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
21
|
Zeeb M, Tepekule B, Kusejko K, Reiber C, Kälin M, Bartl L, Notter J, Furrer H, Hoffmann M, Hirsch HH, Calmy A, Cavassini M, Labhardt ND, Bernasconi E, Braun DL, Günthard HF, Kouyos RD, Nemeth J. Understanding the Decline of Incident, Active Tuberculosis in People With Human Immunodeficiency Virus in Switzerland. Clin Infect Dis 2023; 77:1303-1311. [PMID: 37257071 PMCID: PMC10640694 DOI: 10.1093/cid/ciad330] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 05/03/2023] [Accepted: 05/26/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear. METHODS We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures. RESULTS In 21 528 PWH, LTBI prevalence declined from 15.1% in 2001% to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (hazard ratio [HR] 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease. CONCLUSIONS TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need.
Collapse
Affiliation(s)
- Marius Zeeb
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Burcu Tepekule
- Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, USA
| | - Katharina Kusejko
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Claudine Reiber
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Marisa Kälin
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Lena Bartl
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| | - Julia Notter
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St Gallen, St. Gallen, Switzerland
| | - Hansjakob Furrer
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Matthias Hoffmann
- Clinic for Infectious Diseases, Cantonal Hospital Olten, Olten, Switzerland
| | - Hans H Hirsch
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland
- Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland
- Department Biomedicine, Transplantation and Clinical Virology, University of Basel, Basel, Switzerland
| | - Alexandra Calmy
- HIV/AIDS Unit, Division of Infectious Diseases, University Hospital Geneva, University of Geneva, Geneva, Switzerland
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Matthias Cavassini
- Division of Infectious Diseases, University Hospital Lausanne, University of Lausanne, Lausanne, Switzerland
| | - Niklaus D Labhardt
- Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Enos Bernasconi
- Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Division of Infectious Diseases, Ente Ospedaliero Cantonale Lugano, University of Geneva and University of Southern Switzerland, Lugano, Switzerland
| | - Dominique L Braun
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Huldrych F Günthard
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Roger D Kouyos
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
- Institute of Medical Virology, University of Zurich, Zurich, Switzerland
| | - Johannes Nemeth
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland
| |
Collapse
|
|
22
|
Louie JK, Agraz-Lara R, Romo L, Deiterich C, Xing C, Graves S. Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA. Emerg Infect Dis 2023; 29:1651-1654. [PMID: 37486210 PMCID: PMC10370851 DOI: 10.3201/eid2908.230347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023] Open
Abstract
Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.
Collapse
|
|
23
|
Liu L, Wu G, Wang J, Peng L, Xu X, Cai L. Smoking is a Factor in Discordance Between QuantiFERONTB Gold Assay and Tuberculosis Etiology: Especially in Older Patients. Infect Drug Resist 2023; 16:3443-3451. [PMID: 37283941 PMCID: PMC10241176 DOI: 10.2147/idr.s412473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/25/2023] [Indexed: 06/08/2023] Open
Abstract
Purpose Exploring whether smoking is an influencing factor for the inconsistency between QuantiFERONTB Gold assay (QFT-GIT) and tuberculosis etiology. Patients and Methods The clinical data of patients who were confirmed positive for Mycobacterium tuberculosis (MTB) after undergoing QFT-GIT testing from September 2017 to August 2021 were retrospectively analyzed. Chi-square and rank-sum tests were used to compare the differences in characteristics between smokers and non-smokers. Logistic regression was used to adjust for confounding factors affecting smoking. Propensity score matching (PSM) was used to verify the above conclusions again. Results Positive results of tuberculosis etiology were adopted as the standard, the incidence of inconsistent results between QFT-GIT and tuberculosis etiology was 8.90% (108/1213), of which the false negative rate was 6.27% (76/1213) and the indeterminate rate was 2.64% (32/1213). In the overall population, the smokers had a lower level of basal IFN-γ (Z=-2.079, P=0.038). Among 382 elderly (≥65 years old) patients, the smokers had lower levels of antigen-stimulated IFN-γ (Z=-2.838, P=0.005). After performing BOX-COX transformation on all non-normally distributed data, logistic stepwise regression was used to adjust confounding factors. The results showed that smoking was an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiology results (OR=1.69, P=0.020). Using PSM for 1:2 matching, the results showed that smoking was still an independent risk factor for the inconsistent results of QFT-GIT and tuberculosis etiology (OR= 1.95, P=0.019). Age-stratified analysis showed that smoking was an independent risk factor in discordance between QFT-GIT and tuberculosis etiology in patients aged ≥65 years (OR=2.40, P=0.005), but not in patients aged <65 years (P > 0.05). Conclusion Smoking can reduce the body's IFN-γ release ability, and smoking (especially the elderly) is an influencing factor for the inconsistency between QFT-GIT and tuberculosis etiological results.
Collapse
Affiliation(s)
- Libin Liu
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| | - Guihua Wu
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| | - Jing Wang
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| | - Lijun Peng
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| | - Xiaoqun Xu
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| | - Long Cai
- Centre of Laboratory Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China
- Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China
| |
Collapse
|
|
24
|
Della Torre A, Di Francesco P, Montanelli GA, Bolis M, Comelli A, Ferrarese M, Croci GA, Tobaldini E. An unusual case of pleural effusion. Intern Emerg Med 2023; 18:1127-1131. [PMID: 36890333 DOI: 10.1007/s11739-023-03236-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 02/17/2023] [Indexed: 03/10/2023]
Abstract
CASE PRESENTATION A 63-year-old man presented with fever, thoracalgia, weight loss, diffuse lymphadenopathy, and a massive pleural effusion. Extensive laboratory and radiologic investigations for possible autoimmune, infectious, hematologic, and neoplastic conditions all resulted negative. A lymph node biopsy showed a granulomatous necrotizing lymphadenitis, suspicious for tuberculosis. Although mycobacterium tuberculosis (MT) was never isolated and tuberculin skin test resulted negative, diagnosis of extrapulmonary tuberculosis was made and anti-tubercular therapy was started. Despite the strict adherence to 5 months of treatment, he returned to the emergency ward complaining of fever, chest pain and pleural effusion; total-body CT and PET scans demonstrated a progression of new disseminated nodular consolidations. DIAGNOSTIC WORK-UP Microscopic and cultural search for MT and other micro-organisms resulted again negative on urine, stool, blood, pleural fluid, and spinal lesion biopsy. We therefore started considering alternative diagnosis for necrotizing granulomatosis, including multidrug-resistant tuberculosis, Wegener granulomatosis, Churg Strauss syndrome, necrobiotic nodules of rheumatoid arthritis, lymphomatoid granulomatosis and Necrotizing Sarcoid Granulomatosis (NSG). Having already rejected other autoimmune, hematological, and neoplastic disorders, NSG resulted the most consistent hypothesis. With an expert we thus re-examined histological specimens that were suggestive for an atypical presentation of sarcoidosis. Steroid therapy was initiated, achieving symptoms improvement. DISCUSSION Sarcoidosis is a rare condition that can be challenging to diagnose, due to its variability in clinical presentation, often mimicking alternative conditions like disseminated tuberculosis. A high degree of suspicion and an experienced lab in anatomical pathology are essential for final diagnosis.
Collapse
Affiliation(s)
- Alice Della Torre
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy
| | - Pietro Di Francesco
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
| | - Gaia Annalisa Montanelli
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
| | - Matteo Bolis
- Infectious Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
| | - Agnese Comelli
- Infectious Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
| | - Maurizio Ferrarese
- Regional TB Reference Centre, Villa Marelli Institute and Laboratory/ASST GOM Niguarda, 20122, Milan, Italy
| | - Giorgio Alberto Croci
- Division of Pathology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy
| | - Eleonora Tobaldini
- Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.
- Department of Clinical Sciences and Community Health, University of Milan, 20122, Milan, Italy.
| |
Collapse
|
|
25
|
Valeyre D, Brauner M, Bernaudin JF, Carbonnelle E, Duchemann B, Rotenberg C, Berger I, Martin A, Nunes H, Naccache JM, Jeny F. Differential diagnosis of pulmonary sarcoidosis: a review. Front Med (Lausanne) 2023; 10:1150751. [PMID: 37250639 PMCID: PMC10213276 DOI: 10.3389/fmed.2023.1150751] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/24/2023] [Indexed: 05/31/2023] Open
Abstract
Diagnosing pulmonary sarcoidosis raises challenges due to both the absence of a specific diagnostic criterion and the varied presentations capable of mimicking many other conditions. The aim of this review is to help non-sarcoidosis experts establish optimal differential-diagnosis strategies tailored to each situation. Alternative granulomatous diseases that must be ruled out include infections (notably tuberculosis, nontuberculous mycobacterial infections, and histoplasmosis), chronic beryllium disease, hypersensitivity pneumonitis, granulomatous talcosis, drug-induced granulomatosis (notably due to TNF-a antagonists, immune checkpoint inhibitors, targeted therapies, and interferons), immune deficiencies, genetic disorders (Blau syndrome), Crohn's disease, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and malignancy-associated granulomatosis. Ruling out lymphoproliferative disorders may also be very challenging before obtaining typical biopsy specimen. The first step is an assessment of epidemiological factors, notably the incidence of sarcoidosis and of alternative diagnoses; exposure to risk factors (e.g., infectious, occupational, and environmental agents); and exposure to drugs taken for therapeutic or recreational purposes. The clinical history, physical examination and, above all, chest computed tomography indicate which differential diagnoses are most likely, thereby guiding the choice of subsequent investigations (e.g., microbiological investigations, lymphocyte proliferation tests with metals, autoantibody assays, and genetic tests). The goal is to rule out all diagnoses other than sarcoidosis that are consistent with the clinical situation. Chest computed tomography findings, from common to rare and from typical to atypical, are described for sarcoidosis and the alternatives. The pathology of granulomas and associated lesions is discussed and diagnostically helpful stains specified. In some patients, the definite diagnosis may require the continuous gathering of information during follow-up. Diseases that often closely mimic sarcoidosis include chronic beryllium disease and drug-induced granulomatosis. Tuberculosis rarely resembles sarcoidosis but is a leading differential diagnosis in regions of high tuberculosis endemicity.
Collapse
Affiliation(s)
- Dominique Valeyre
- Pulmonology Department, Groupe Hospitalier Paris Saint Joseph, Paris, France
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
| | - Michel Brauner
- Radiology Department, Avicenne University Hospital, Bobigny, France
| | - Jean-François Bernaudin
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
- Faculté de Médecine, Sorbonne University Paris, Paris, France
| | | | - Boris Duchemann
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
- Thoracic and Oncology Department, Avicenne University Hospital, Bobigny, France
| | - Cécile Rotenberg
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
- Pulmonology Department, Avicenne University Hospital, Bobigny, France
| | - Ingrid Berger
- Pulmonology Department, Groupe Hospitalier Paris Saint Joseph, Paris, France
| | - Antoine Martin
- Pathology Department, Avicenne University Hospital, Bobigny, France
| | - Hilario Nunes
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
- Pulmonology Department, Avicenne University Hospital, Bobigny, France
| | - Jean-Marc Naccache
- Pulmonology Department, Groupe Hospitalier Paris Saint Joseph, Paris, France
| | - Florence Jeny
- INSERM UMR 1272, Sorbonne University Paris-Nord, Paris, France
- Pulmonology Department, Avicenne University Hospital, Bobigny, France
| |
Collapse
|
|
26
|
Chin KL, Anibarro L, Sarmiento ME, Acosta A. Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection. Trop Med Infect Dis 2023; 8:tropicalmed8020089. [PMID: 36828505 PMCID: PMC9960903 DOI: 10.3390/tropicalmed8020089] [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: 12/13/2022] [Revised: 01/20/2023] [Accepted: 01/23/2023] [Indexed: 02/03/2023] Open
Abstract
Globally, it is estimated that one-quarter of the world's population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5-10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.
Collapse
Affiliation(s)
- Kai Ling Chin
- Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia
- Borneo Medical and Health Research Centre, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu 88400, Malaysia
- Correspondence: (K.L.C.); (L.A.); (A.A.)
| | - Luis Anibarro
- Tuberculosis Unit, Infectious Diseases and Internal Medicine Department, Complexo Hospitalario Universitario de Pontevedra, 36071 Pontevedra, Spain
- Immunology Research Group, Galicia Sur Health Research Institute (IIS-GS), 36312 Vigo, Spain
- Correspondence: (K.L.C.); (L.A.); (A.A.)
| | - Maria E. Sarmiento
- School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Malaysia
| | - Armando Acosta
- School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian 16150, Malaysia
- Correspondence: (K.L.C.); (L.A.); (A.A.)
| |
Collapse
|
|
27
|
Salles I, Travassos P, Spener-Gomes R, Loch AP, Saraceni V, Lauria L, Cavalcante S, Garcia de Oliveira J, Brito de Souza A, Guimarães Costa A, Sakabe S, Schiavon Nogueira R, Chaisson LH, Cohn S, Jamal LF, Valdez Ramalho Madruga J, Cordeiro-Santos M, Castro B, Portella Ferreira D, Hoffmann CJ, Golub JE, Durovni B, Kerrigan D. Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0001251. [PMID: 36962892 PMCID: PMC10021802 DOI: 10.1371/journal.pgph.0001251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 12/06/2022] [Indexed: 01/05/2023]
Abstract
Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.
Collapse
Affiliation(s)
- Isadora Salles
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | | | - Renata Spener-Gomes
- Gerência de Micobacteriologia, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil
- Universidade Federal do Amazonas, Manaus, Brazil
| | - Ana Paula Loch
- Centro de Referência e Treinamento DST/Aids, Secretaria de Estado da Saúde de São Paulo, São Paulo, Brazil
| | | | - Lilian Lauria
- Secretaria Municipal de Saúde, Rio de Janeiro, Brazil
| | - Solange Cavalcante
- Secretaria Municipal de Saúde, Rio de Janeiro, Brazil
- Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil
| | | | - Alexandra Brito de Souza
- Gerência de Micobacteriologia, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
| | - Allyson Guimarães Costa
- Gerência de Micobacteriologia, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Escola de Enfermagem de Manaus, Universidade Federal do Amazonas, Manaus, Brazil
| | - Sumire Sakabe
- Centro de Referência e Treinamento DST/Aids, Secretaria de Estado da Saúde de São Paulo, São Paulo, Brazil
| | - Roberta Schiavon Nogueira
- Centro de Referência e Treinamento DST/Aids, Secretaria de Estado da Saúde de São Paulo, São Paulo, Brazil
| | - Lelia H. Chaisson
- Division of Infectious Diseases, Department of Medicine, University of Illinois at Chicago, Chicago, Illinos, United States of America
| | - Silvia Cohn
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Leda Fatima Jamal
- Centro de Referência e Treinamento DST/Aids, Secretaria de Estado da Saúde de São Paulo, São Paulo, Brazil
| | | | - Marcelo Cordeiro-Santos
- Gerência de Micobacteriologia, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas, Manaus, Brazil
| | | | | | - Christopher J. Hoffmann
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Jonathan E. Golub
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
| | - Betina Durovni
- Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil
- Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Deanna Kerrigan
- Department of Prevention and Community Health, Milken Institute School of Public Health, Washington, District of Columbia, United States of America
| |
Collapse
|
|
28
|
Sudcharoen A, Ruchikajorndech G, Srisajjakul S, Pongpaibul A, Ngamskulrungroj P, Tulyaprawat O, Limsrivilai J. Clinical characteristics and diagnosis of intestinal tuberculosis in clinical practice at Thailand's largest national tertiary referral center: An 11-year retrospective review. PLoS One 2023; 18:e0282392. [PMID: 37053242 PMCID: PMC10101504 DOI: 10.1371/journal.pone.0282392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 02/12/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Diagnosing intestinal tuberculosis (ITB) is challenging due to the low diagnostic sensitivity of current methods. This study aimed to assess the clinical characteristics and diagnosis of ITB at our tertiary referral center, and to explore improved methods of ITB diagnosis. METHODS This retrospective study included 177 patients diagnosed with ITB at Siriraj Hospital (Bangkok, Thailand) during 2009-2020. RESULTS The mean age was 49 years, 55.4% were male, and 42.9% were immunocompromised. Most diagnoses (108/177) were made via colonoscopy; 12 patients required more than one colonoscopy. Among those, the sensitivity of tissue acid-fast bacilli (AFB), presence of caseous necrosis, polymerase chain reaction (PCR), and culture was 40.7%, 13.9%, 25.7%, and 53.4%, respectively. Among patients with negative tissue histopathology, 4 (3.7%) and 13 (12.0%) were ITB positive on tissue PCR and culture, respectively. The overall sensitivity when all diagnostic methods were used was 63%. Seventy-six patients had stool tests for mycobacteria. The overall sensitivity of stool tests was 75.0%. However, when analyzing the 31 patients who underwent both endoscopy and stool testing, the sensitivity of stool testing when using tissue biopsy as a reference was 45.8%. Combining stool testing and tissue biopsy did not significantly increase the sensitivity compared to tissue biopsy alone (83.9% vs. 77.4%, respectively). CONCLUSION Despite the availability of PCR and culture for TB, the overall diagnostic sensitivity was found to be low. The sensitivity increased when the tests were used in combination. Repeated colonoscopy may be beneficial. Adding stool mycobacteria tests did not significantly increase the diagnostic yield if endoscopy was performed, but it could be beneficial if endoscopy is unfeasible.
Collapse
Affiliation(s)
- Asawin Sudcharoen
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Srinakarinwirot University, Nakhon Nayok, Thailand
| | - Gahwin Ruchikajorndech
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sitthipong Srisajjakul
- Department of Radiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Ananya Pongpaibul
- Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Popchai Ngamskulrungroj
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Orawan Tulyaprawat
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Julajak Limsrivilai
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| |
Collapse
|
|
29
|
Mayito J, Martineau AR, Tiwari D, Nakiyingi L, Kateete DP, Reece ST, Biraro IA. Determinants of QuantiFERON Plus-diagnosed tuberculosis infection in adult Ugandan TB contacts: A cross-sectional study. PLoS One 2023; 18:e0281559. [PMID: 36972254 PMCID: PMC10042355 DOI: 10.1371/journal.pone.0281559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 01/26/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND The tuberculin skin test is commonly used to diagnose latent tuberculosis infection (LTBI) in resource-limited settings, but its specificity is limited by factors including cross-reactivity with BCG vaccine and environmental mycobacteria. Interferon-gamma release assays (IGRA) overcome this problem by detecting M. tuberculosis complex-specific responses, but studies to determine risk factors for IGRA-positivity in high TB burden settings are lacking. METHODS We conducted a cross-sectional study to determine factors associated with a positive IGRA by employing the QuantiFERON-TB® Gold-plus (QFT Plus) assay in a cohort of asymptomatic adult TB contacts in Kampala, Uganda. Multivariate logistic regression analysis with forward stepwise logit function was employed to identify independent correlates of QFT Plus-positivity. RESULTS Of the 202 participants enrolled, 129/202 (64%) were female, 173/202 (86%) had a BCG scar, and 67/202 (33%) were HIV-infected. Overall, 105/192 (54%, 95% CI 0.48-0.62) participants had a positive QFT Plus result. Increased risk of QFT-Plus positivity was independently associated with casual employment/unemployment vs. non-casual employment (adjusted odds ratio (aOR) 2.18, 95% CI 1.01-4.72), a family vs. non-family relation to the index patient (aOR 2.87, 95% CI 1.33-6.18), living in the same vs. a different house as the index (aOR 3.05, 95% CI 1.28-7.29), a higher body mass index (BMI) (aOR per additional kg/m2 1.09, 95% CI 1.00-1.18) and tobacco smoking vs. not (aOR 2.94, 95% CI 1.00-8.60). HIV infection was not associated with QFT-Plus positivity (aOR 0.91, 95% CI 0.42-1.96). CONCLUSION Interferon Gamma Release Assay positivity in this study population was lower than previously estimated. Tobacco smoking and BMI were determinants of IGRA positivity that were previously unappreciated.
Collapse
Affiliation(s)
- Jonathan Mayito
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
- Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - Adrian R Martineau
- Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Divya Tiwari
- Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Lydia Nakiyingi
- Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda
- Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - David P Kateete
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Stephen T Reece
- School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Irene Andia Biraro
- Department of Internal Medicine, Makerere University College of Health Sciences, Kampala, Uganda
- MRC/UVRI & LSHTM Uganda Research Unit, Entebbe, Uganda
| |
Collapse
|
|
30
|
Tungsattayathitthan U, Boonsopon S, Tesavibul N, Dharakul T, Choopong P. Interferon-gamma release assays in tuberculous uveitis: a comprehensive review. Int J Ophthalmol 2022; 15:1520-1528. [PMID: 36124199 DOI: 10.18240/ijo.2022.09.16] [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: 10/23/2021] [Accepted: 07/19/2022] [Indexed: 12/11/2022] Open
Abstract
Tuberculous uveitis (TBU) comprises a broad clinical spectrum of ocular manifestations, making its diagnosis challenging. Ophthalmologists usually require evidence from investigations to confirm or support a clinical diagnosis of TBU. Since direct isolation of the causative organism from ocular specimens has limitations owing to the small volume of the ocular specimens, resultant test positivities are low in yield. Immunodiagnostic tests, including the tuberculin skin test and interferon-gamma release assays (IGRAs), can help support a clinical diagnosis of TBU. Unlike the tuberculin skin test, IGRAs are in vitro tests that require a single visit and are not affected by prior Bacillus Calmette-Guerin vaccination. Currently, available IGRAs consist of different techniques and interpretation methods. Moreover, newer generations have been developed to improve the sensitivity and ability to detect active tuberculosis. This narrative review collates salient practice points as a reference for general ophthalmologists, such as evidence for the utilization of IGRAs in patients with suspected TBU, and summarizes basic knowledge and details of clinical applications of these tests in a clinical setting.
Collapse
Affiliation(s)
- Usanee Tungsattayathitthan
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Sutasinee Boonsopon
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Nattaporn Tesavibul
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Tararaj Dharakul
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Pitipol Choopong
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| |
Collapse
|
|
31
|
Li Q, Ren W, Yuan J, Guo H, Shang Y, Wang W, Pan J, Gao M, Pang Y. Significant difference in Th1/Th2 paradigm induced by tuberculosis-specific antigens between IGRA-positive and IGRA-negative patients. Front Immunol 2022; 13:904308. [PMID: 36119060 PMCID: PMC9471257 DOI: 10.3389/fimmu.2022.904308] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 08/04/2022] [Indexed: 11/13/2022] Open
Abstract
False negative interferon-γ release assay (IGRA) results constitute the major dilemma for the diagnosis of tuberculosis (TB) infections. Herein, we conducted a cohort study to compare the host immunological response to TB-specific antigens between active TB patients with positive and negative IGRA results and control groups. A total of 274 laboratory-confirmed TB patients were included in our analysis, consisting of 221 were IGRA positive and 53 were IGRA negative. Patients with the elderly were identified as an independent risk factor for negative IGRA results. In addition, the elevated level of IL-4 and the decreased levels of IFN-γ, IL-2, IL-6, IL-1β, and IL-12 in IGRA negative TB relative to IGRA positive TB group, demonstrating a significant difference in Th1/Th2 paradigm between two groups. The IFN-γ&IL-2 based assay could correctly identify 247 out of 307 MTB-infected individuals [271 TB patients and 36 individuals with latent TB infection (LTBI)], demonstrating a sensitivity of 80.5%. Then the IFN-γ and IL-4 were applied to distinguish healthy control and IGRA-negative group. When using the stepwise algorithm, the sensitivity for detecting Mycobacterium tuberculosis (MTB) infections was significantly increased from 80.5% to 89.6%. Additionally, patients with negative IGRA results had a conversion to culture-negative status longer than those with positive IGRA results. In conclusion, a stepwise algorithm outperforms IGRA assays to accurately identify MTB infections by the combination IFN-γ, IL-2, and IL-4. Further study is needed to evaluate the accuracy of our diagnostic algorithm in the LTBI population.
Collapse
Affiliation(s)
- Qiang Li
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Weicong Ren
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Jinfeng Yuan
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Haiping Guo
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Yuanyuan Shang
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Wei Wang
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
| | - Junhua Pan
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
- *Correspondence: Junhua Pan, ; Mengqiu Gao, ; Yu Pang,
| | - Mengqiu Gao
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
- *Correspondence: Junhua Pan, ; Mengqiu Gao, ; Yu Pang,
| | - Yu Pang
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, China
- *Correspondence: Junhua Pan, ; Mengqiu Gao, ; Yu Pang,
| |
Collapse
|
|
32
|
Wu IL, Chitnis AS, Jaganath D. A narrative review of tuberculosis in the United States among persons aged 65 years and older. J Clin Tuberc Other Mycobact Dis 2022; 28:100321. [PMID: 35757390 PMCID: PMC9213239 DOI: 10.1016/j.jctube.2022.100321] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 06/06/2022] [Accepted: 06/10/2022] [Indexed: 11/04/2022] Open
Abstract
Tuberculosis (TB) is a preventable infectious disease that confers significant morbidity, mortality, and psychosocial challenges. As TB incidence in the United States (U.S.) decreased from 9.7/100,000 to 2.2/100,000 from 1993 to 2020, the proportion of cases occurring among adults aged 65 and older increased. We conducted a review of published literature in the U.S. and other similar low-TB-burden settings to characterize the epidemiology and unique diagnostic challenges of TB in older adults. This narrative review also provides an overview of treatment characteristics, outcomes, and research gaps in this patient population. Older adults had a 30% higher likelihood of delayed TB diagnosis, with contributing factors such as acid-fast bacilli sputum smear-negative disease (56%) and non-classical clinical presentation. At least 90% of TB cases among older adults resulted from reactivation of latent TB infection (LTBI), but guidance around when to screen and treat LTBI in these patients is lacking. In addition, routine TB testing methods such as interferon-gamma release assays were two times more likely to have false-negative results among older adults. Advanced age was also often accompanied by complex comorbidities and impaired drug metabolism, increasing the risk of treatment failure (23%) and death (19%). A greater understanding of the unique factors of TB among older adults will inform clinical and public health efforts to improve outcomes in this complex patient population and TB control in the U.S.
Collapse
Affiliation(s)
- Iris L Wu
- School of Public Health, University of California, Berkeley, Berkeley, CA, United States.,School of Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Amit S Chitnis
- Tuberculosis Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, CA, United States
| | - Devan Jaganath
- Division of Pediatric Infectious Diseases, University of California, San Francisco, San Francisco, CA, United States.,Center for Tuberculosis, University of California, San Francisco, CA, United States
| |
Collapse
|
|
33
|
Yamatani I, Komiya K, Shuto H, Yamanaka M, Yamasue M, Yoshikawa H, Hiramatsu K, Kadota JI. Correlation between tuberculosis-specific interferon-γ release assay and intrathoracic calcification: A cross-sectional study. PLoS One 2022; 17:e0270785. [PMID: 35793290 PMCID: PMC9258869 DOI: 10.1371/journal.pone.0270785] [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: 04/16/2022] [Accepted: 06/20/2022] [Indexed: 11/25/2022] Open
Abstract
Background Although persistent tuberculosis (TB) infection is known to cause calcification in the lungs, the relationship between intrathoracic calcification and the results of the interferon-γ release assay (IGRA) has not been fully elucidated. This study aimed to assess the association between intrathoracic calcification and IGRA results. Methods We retrospectively included consecutive patients who concurrently underwent chest X-ray, chest computed tomography (CT), and an IGRA. Patients with a current diagnosis of active TB or treatment history of active TB or latent tuberculosis infection (LTBI) were excluded. The association between calcification according to the chest X-ray or CT and IGRA results were analyzed using binomial logistic regression. Results This study included 574 patients, and 38 (7%) patients had a positive IGRA result. Patients with a positive result were significantly older and had a higher proportion of comorbidities, and history of tuberculosis exposure compared to those with a negative result. Calcification of the lung field and mediastinal lymph nodes according to chest CT was more frequently observed in patients with a positive IGRA result, whereas no significant difference was observed concerning the proportion of lung field calcification on chest X-ray between patients with positive and negative IGRA results. In multivariate analysis, calcification of mediastinal lymph nodes alone (adjusted odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.76–8.26) and the combination of lung field and mediastinal lymph node calcification (adjusted OR = 4.12, 95% CI = 1.51–11.76) on chest CT was independently associated with positive IGRA results. Conclusions The finding of mediastinal lymph node calcification, with or without lung field calcification, on chest CT was associated with positive IGRA results independent of TB exposure history. Previous TB infection including eliminated TB infection and LTBI can be suspected when calcified lymph nodes in are observed the mediastinum on chest CT.
Collapse
Affiliation(s)
- Izumi Yamatani
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Kosaku Komiya
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
- * E-mail:
| | - Hisayuki Shuto
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Marimu Yamanaka
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Mari Yamasue
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Hiroki Yoshikawa
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Kazufumi Hiramatsu
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| | - Jun-ichi Kadota
- Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan
| |
Collapse
|
|
34
|
Shah T, Shah Z, Yasmeen N, Baloch Z, Xia X. Pathogenesis of SARS-CoV-2 and Mycobacterium tuberculosis Coinfection. Front Immunol 2022; 13:909011. [PMID: 35784278 PMCID: PMC9246416 DOI: 10.3389/fimmu.2022.909011] [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: 03/31/2022] [Accepted: 05/23/2022] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is an infectious disease that poses severe threats to global public health and significant economic losses. The COVID-19 global burden is rapidly increasing, with over 246.53 million COVID-19 cases and 49.97 million deaths reported in the WHO 2021 report. People with compromised immunity, such as tuberculosis (TB) patients, are highly exposed to severe COVID-19. Both COVID-19 and TB diseases spread primarily through respiratory droplets from an infected person to a healthy person, which may cause pneumonia and cytokine storms, leading to severe respiratory disorders. The COVID-19-TB coinfection could be fatal, exacerbating the current COVID-19 pandemic apart from cellular immune deficiency, coagulation activation, myocardial infarction, and other organ dysfunction. This study aimed to assess the pathogenesis of SARS-CoV-2-Mycobacterium tuberculosis coinfections. We provide a brief overview of COVID19-TB coinfection and discuss SARS-CoV-2 host cellular receptors and pathogenesis. In addition, we discuss M. tuberculosis host cellular receptors and pathogenesis. Moreover, we highlight the impact of SARS-CoV-2 on TB patients and the pathological pathways that connect SARS-CoV-2 and M. tuberculosis infection. Further, we discuss the impact of BCG vaccination on SARS-CoV-2 cases coinfected with M. tuberculosis, as well as the diagnostic challenges associated with the coinfection.
Collapse
Affiliation(s)
- Taif Shah
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| | - Zahir Shah
- College of Veterinary Sciences, The University of Agriculture Peshawar, Peshawar, Pakistan
| | - Nafeesa Yasmeen
- College of Veterinary Medicine, South China Agricultural University, Guangzhou, China
| | - Zulqarnain Baloch
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
| |
Collapse
|
|
35
|
Diagnostic accuracy of interferon-gamma release assays for diagnosis of smear-negative pulmonary tuberculosis: a systematic review and meta-analysis. BMC Pulm Med 2022; 22:219. [PMID: 35668411 PMCID: PMC9169405 DOI: 10.1186/s12890-022-02013-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 05/31/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Introduction
The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes.
Methods
We performed a comprehensive search from each databases’ inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included.
Results
Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71–0.82), specificity of 0.70 (95% CI 0.58–0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51–14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80–3.80), negative LR of 0.33 (95% CI 0.25–0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77–0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71–0.78), specificity of 0.71 (95% CI 0.49–0.86), DOR of 6.96 (95% CI 2.31–20.98), positive LR of 2.53 (95% CI 1.26–5.07), negative LR of 0.36 (95% CI 0.24–0.55), and AUROC of 0.77 (95% CI 0.73–0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden.
Conclusion
IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability.
Registry: PROSPERO: CRD42021274653.
Collapse
|
|
36
|
Jo HH, Kim EY, Jung JT, Kwon JG, Kim ES, Lee HS, Lee YJ, Kim KO, Jang BI. Value of Fecal Calprotectin Measurement During the Initial Period of Therapeutic Anti-Tubercular Trial. Clin Endosc 2021; 55:256-262. [PMID: 34736314 PMCID: PMC8996000 DOI: 10.5946/ce.2021.061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 07/11/2021] [Indexed: 11/14/2022] Open
Abstract
Background/Aims The diagnosis of intestinal tuberculosis (ITB) is often challenging. Therapeutic anti-tubercular trial (TATT) is sometimes used for the diagnosis of ITB. We aimed to evaluate the changing pattern of fecal calprotectin (FC) levels during TATT in patients with ITB.
Methods A retrospective review was performed on the data of 39 patients who underwent TATT between September 2015 and November 2018 in five university hospitals in Daegu, South Korea. The analysis was performed for 33 patients with serial FC measurement reports.
Results The mean age of the participants was 48.8 years. The final diagnosis of ITB was confirmed in 30 patients based on complete mucosal healing on follow-up colonoscopy performed after 2 months of TATT. Before starting TATT, the mean FC level of the ITB patients was 170.2 μg/g (range, 11.5-646.5). It dropped to 25.4 μg/g (range, 11.5-75.3) and then 23.3 μg/g (range, 11.5-172.2) after one and two months of TATT, respectively. The difference in mean FC before and one month after TATT was statistically significant (p<0.001), and FC levels decreased to below 100 μg/g in all patients after one month of TATT.
Conclusions All ITB patients showed FC decline after only 1 month of TATT, and this finding correlated with complete mucosal healing in the follow-up colonoscopy after 2 months of TATT.
Collapse
Affiliation(s)
- Hyeong Ho Jo
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Eun Young Kim
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Jin Tae Jung
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Hyun Seok Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Yoo Jin Lee
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Kyeong Ok Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Byung Ik Jang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | | |
Collapse
|
|
37
|
Fukushima K, Kubo T, Akagi K, Miyashita R, Kondo A, Ehara N, Takazono T, Sakamoto N, Mukae H. Clinical evaluation of QuantiFERON®-TB Gold Plus directly compared with QuantiFERON®-TB Gold In-Tube and T-Spot®.TB for active pulmonary tuberculosis in the elderly. J Infect Chemother 2021; 27:1716-1722. [PMID: 34412981 DOI: 10.1016/j.jiac.2021.08.016] [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: 06/01/2021] [Revised: 07/16/2021] [Accepted: 08/11/2021] [Indexed: 01/30/2023]
Abstract
BACKGROUND Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly. METHODS Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured. RESULTS A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p < 0.00001). All three IGRAs exhibited the same specificity (100%), as assessed using blood samples from healthy, low TB-risk individuals (n = 118; median age: 39, IQR; 32-47 years). Positivity in 43 active TB patients with CD4 T-cell counts <200/μL, 39 of whom were ≥80 years of age, was as follows: QFT-Plus, 83.7%; QFT-GIT, 74.4%; and T-SPOT, 58.1%. The difference between TB2-TB1 of the QFT-Plus assay was statistically correlated with CD8 but not CD4 T-cell counts in blood (r = 0.193, p = 0.0298). CONCLUSIONS QFT-Plus showed high performance in the detection of TB infection in patients irrespective of their advanced age (≥80 years) or lower CD4 counts. QFT-Plus can be useful for the diagnosis of TB infection in all patients, including those who are elderly and/or immunocompromised.
Collapse
Affiliation(s)
- Kiyoyasu Fukushima
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Toru Kubo
- Department of Laboratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Kazumasa Akagi
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Ritsuko Miyashita
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Akira Kondo
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Naomi Ehara
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya Tarami-cho, Isahaya City, Nagasaki, 859-0497, Japan.
| | - Takahiro Takazono
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
| | - Noriho Sakamoto
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
| |
Collapse
|
|
38
|
Guo J, Li Q, Zhang X, Yao C, Liu R, Pang Y, Gao M. Increased Expression of IL-10 in Peripheral Blood Mononuclear Cells Correlates with Negative Interferon-γ Release Assay Results in Culture-Confirmed Tuberculosis Patients. Infect Drug Resist 2021; 14:3135-3143. [PMID: 34413657 PMCID: PMC8370592 DOI: 10.2147/idr.s314084] [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: 04/09/2021] [Accepted: 07/01/2021] [Indexed: 11/25/2022] Open
Abstract
Introduction Interferon-γ release assays (IGRAs) can have high false-negative rates for active tuberculosis (TB) cases. Here we investigated factors, including potential anti-inflammatory mechanisms, that contributed to false-negative IGRA results. Methods We established two cohorts. In the first cohort, we reviewed IGRA results for confirmed TB cases diagnosed in our hospital in 2018. Cases with false-negative IGRA results were analysed to identify factors contributing to false-negative results. In the second cohort, we prospectively studied IL-10 expression levels in peripheral blood mononuclear cells (PBMCs) of IGRAs-positive and IGRAs-negative TB cases after antigenic stimulation to correlate IL-10 expression with IGRAs results. Results Of 1232 culture-confirmed TB cases, 1124 produced true-positive IGRA results and 108 had false-negative IGRA results. Multivariate logistic regression analysis identified glucocorticoid use and extrapulmonary TB as independent risk factors for false-negative IGRA results. Notably, IL-10 expression of the IGRA-negative group was significantly up-regulated as compared to that of the IGRA-positive group. The average cell supernatant IL-10 concentration of the IGRA-negative group was 4.77 pg/mL, a value that was statistically greater than the IGRA-positive group concentration (1.47 pg/mL, P = 0.007). After PBMCs pretreatment with BRD6989 (to enhance IL-10 secretion), average IFN-γ concentrations in cell supernatants from the IGRA-positive group significantly decreased from 59.73 pg/mL to 33.79 pg/mL (P = 0.011). By contrast, addition of AS101 (to inhibit IL-10 secretion) to false-negative group PBMCs led to an increase of average IFN-γ concentration in cell supernatants from 19.01 pg/mL to 45.10 pg/mL (P = 0.030), a result that was inversely correlated with IL-10 concentration. Conclusion Our data demonstrate that increased IL-10 secretion by PBMCs is inversely correlated with IGRA assay results in culture-confirmed TB patients. Glucocorticoids use and extrapulmonary TB are significantly associated with false-negative IGRA results. Combination testing to measure IL-10 secretion and IFN-γ release is recommended to improve IGRAs specificity.
Collapse
Affiliation(s)
- Jidong Guo
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China.,Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Qiang Li
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Xuxia Zhang
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Cong Yao
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Rongmei Liu
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Yu Pang
- Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Mengqiu Gao
- Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| |
Collapse
|
|
39
|
Mitchell JL, Stanley P, McDonald K, Burr P, Rhodes SG, Gunn-Moore DA, Hope JC. Diagnostic accuracy of the interferon-gamma release assay (IGRA) for cases of feline mycobacteriosis. Prev Vet Med 2021; 193:105409. [PMID: 34126470 DOI: 10.1016/j.prevetmed.2021.105409] [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: 03/15/2021] [Revised: 05/22/2021] [Accepted: 06/06/2021] [Indexed: 10/21/2022]
Abstract
The aim of this study was to evaluate the sensitivity and specificity of the interferon-gamma release assay (IGRA) for diagnosing infections with members of the Mycobacterium (M.) tuberculosis-complex (MTBC) and non-tuberculous mycobacteria (NTM) in domestic cats, and to generate defined feline-specific cut-off values using receiver operating characteristic (ROC) curve analysis to improve test performance. Records of 594 cats that had been tested by IGRA were explored to identify individuals that had a culture and/or polymerase chain reaction (PCR)-confirmed case of mycobacterial disease, and those that had a final diagnosis of non-mycobacterial disease. A total of 117 cats - 80 with mycobacterial disease and 37 diagnosed with a condition other than mycobacteriosis - were identified for further detailed analysis. This population was used to estimate test sensitivity and specificity, as well as likelihood ratios for the IGRA to correctly identify a cat with or without mycobacterial disease. Agreement between IGRA results and culture/PCR using current and proposed new cut-off values was also determined. ROC analysis of defined confirmed infected and non-mycobacterial disease control cats allowed an adjustment of current test cut-offs that increased the overall test sensitivity for MTBC infections from 83.1 % (95 % confidence interval [CI]: 71.5-90.5 %) to 90.2 % (95 % CI: 80.2-95.4%), and M. bovis infection from 43 % (95 % CI: 28.2-60.7%) to 68 % (95 % CI: 51.4-82.1%) while maintaining high test specificity (100 % in both cases). Overall agreement between IGRA results and culture/PCR, while recognising that neither culture nor PCR tests have perfect sensitivity, improved from weak (κ = 0.57) to moderate (κ = 0.71) using new proposed IGRA test cut-off values. Application of these results, based upon the statistical analysis of accumulated test data, can improve the diagnostic performance of the feline IGRA, particularly for identifying infections with M. bovis, without compromising specificity.
Collapse
Affiliation(s)
- Jordan L Mitchell
- The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom.
| | - Paul Stanley
- The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom
| | - Kieran McDonald
- Biobest Laboratories Ltd, 6 Charles Darwin House, Edinburgh Technopole, Milton Bridge, Near Penicuik, EH26 0PY, United Kingdom
| | - Paul Burr
- Biobest Laboratories Ltd, 6 Charles Darwin House, Edinburgh Technopole, Milton Bridge, Near Penicuik, EH26 0PY, United Kingdom
| | - Shelley G Rhodes
- Animal & Plant Health Agency, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, United Kingdom
| | - Danièlle A Gunn-Moore
- The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom
| | - Jayne C Hope
- The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom
| |
Collapse
|
|
40
|
Keshavan A, McAnena L, Acheson JF, Booth H, Plant GT, Khaleeli Z. Bilateral optic neuritis as a first presentation of lymph node tuberculosis. Pract Neurol 2021; 22:51-54. [PMID: 34321330 DOI: 10.1136/practneurol-2021-003086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2021] [Indexed: 11/04/2022]
Abstract
Tuberculosis (TB) may affect the nervous system in many ways. We describe an immunocompetent teenage girl with lymph node TB who had first presented with bilateral optic neuritis. Detailed history identified features inconsistent with immune-mediated optic neuritis. Several unusual features prompted further investigation, including transient visual obscurations without raised intracranial pressure, prominent disc swelling and absence of laboratory findings to support an immune-mediated cause. Whole body PET/MR imaging identified widespread mediastinal and supraclavicular lymphadenopathy. Despite no known TB contacts, a negative interferon gamma release assay and a normal chest X-ray, a targeted lymph node biopsy confirmed TB.
Collapse
Affiliation(s)
- Ashvini Keshavan
- Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK .,Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, UK
| | - Lisa McAnena
- Department of Neuro-ophthalmology, Moorfields Eye Hospital City Road Campus, London, UK
| | - James F Acheson
- Department of Neuro-ophthalmology, Moorfields Eye Hospital City Road Campus, London, UK
| | - Helen Booth
- North Central London Tuberculosis Service, Whittington Health NHS Trust, London, UK.,Department of Respiratory Medicine, University College London Hospitals NHS Foundation Trust, London, UK
| | - Gordon T Plant
- Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, UK
| | - Zhaleh Khaleeli
- Department of Neuro-ophthalmology, National Hospital for Neurology and Neurosurgery, London, UK.,Department of Neuroinflammation, National Hospital fro Neurology and Neurosurgery, London, UK
| |
Collapse
|
|
41
|
Murakami S, Usui R, Nakahara Y, Kondo T, Kato T, Saito H. Readministration of Pembrolizumab after Treatment of Tuberculosis Activated by Initial Pembrolizumab Therapy. Intern Med 2021; 60:1743-1746. [PMID: 33390489 PMCID: PMC8222114 DOI: 10.2169/internalmedicine.6002-20] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Increasing the T-cell immune response to Mycobacterium tuberculosis with an anti-programmed cell death 1 (anti-PD-1) antibody may ultimately have detrimental effects. We present the case of a patient with advanced non-small cell lung cancer who developed active tuberculosis (TB) after initial treatment with pembrolizumab, an anti-PD-1 antibody. Pembrolizumab was resumed after completing anti-TB treatment, and no relapse of TB was observed clinically or radiologically. Checkpoint inhibitor-related pneumonitis (CIP) is first suspected when a pulmonary shadow presents during treatment with an anti-PD-1 antibody. It is sometimes difficult to diagnose CIP using computed tomographic images alone. Careful testing, including bacterial examinations and bronchoscopic biopsy, should be performed.
Collapse
Affiliation(s)
| | - Ryou Usui
- Department of Thoracic Oncology, Kanagawa Cancer Center
| | | | - Tetsuro Kondo
- Department of Thoracic Oncology, Kanagawa Cancer Center
| | - Terufumi Kato
- Department of Thoracic Oncology, Kanagawa Cancer Center
| | | |
Collapse
|
|
42
|
Jia D, Li H, Xu Y. Awareness and Mental Health of Male Drug Addicts With Tuberculosis During the COVID-19 Pandemic. Front Psychiatry 2021; 12:697508. [PMID: 34483992 PMCID: PMC8416263 DOI: 10.3389/fpsyt.2021.697508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 07/09/2021] [Indexed: 11/21/2022] Open
Abstract
Introduction: At present, the COVID-19 pandemic remains the most pressing global health issue. Given the significant amount of public awareness, the infection rate and rehabilitation efforts are governed not only by the compliance of transmission mitigation strategies but also by the understanding of coexisting diseases and COVID-19 in patients with chronic infectious diseases. The main goal of this study was to evaluate the differences in demographics, as well as awareness, risk perception, and emotional reactions, among imprisoned drug addicts with and without tuberculosis (TB) regarding their perceptions of and feelings toward the COVID-19 pandemic. The secondary goal of the study was also to measure how the psychological health and nutritional indices of the drug addicts with TB changed during their ongoing rehabilitation. Methods: A total of 265 male drug addicts, 45 of which were positive for TB and another 220 who were negative, were selected as subjects from a mandatory detoxification and rehabilitation center (MDRC). Data were collected through a combination of questionnaires (questions regarding COVID-19 awareness, emotional knowledge and responses, and SCL-90 tests), anthropometric examination, and laboratory blood tests, with which inferential and descriptive statistical analyses were performed. Results: During a period of 1 week in early 2021, the differences in the accuracy of the responses from the questions probing the awareness of COVID-19 symptoms, transmission, susceptible populations, what kind of mask should be worn, and preventive measures between TB addicts to non-TB addicts were 11.11 vs. 60.45%, 57.78 vs. 77.27%, 66.67 vs. 78.64%, 97.98 vs. 97.73%, and 93.33 vs. 65.91%, respectively. In the risk perception and emotional reaction sections of the questionnaire, there was a significant difference in the responses to "What you were more worried about was?" (p < 0.001) and "Alteration in your mood since the outbreak?" (p = 0.002) between the two cohorts. In the section assessing the 10 dimensions of the SCL-90 scale, there were significant differences between the TB addicts and the Chinese norm. In addition, the BMI (21.06 ± 2.65 kg/m2) and total serum protein (77.14 ± 6.12 g/L) levels of the TB addicts were normal, but the serum hemoglobin (117.02 ± 4.97 g/L) and albumin (42.08 ± 1.81 g/L) levels were significantly lower in the TB addicts compared to the norm (p < 0.001). Conclusion: The COVID-19 pandemic we are facing is both an epidemiologic and a psychological crisis. However, while the COVID-19 epidemic will eventually disappear (or become manageable, similar to the flu), the TB epidemic may still persist. To avoid the deleterious consequences of multiple simultaneous epidemics, complementary response measures to COVID-19 and TB can help curb the exacerbation of both situations and, therefore, save lives. Imprisoned drug addicts, especially those with TB, can master relevant knowledge on COVID-19.
Collapse
Affiliation(s)
- Dongming Jia
- The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.,Zhejiang Police Vocational College, Hangzhou, China
| | - Hai Li
- Qiongshan Mandatory Detoxification and Rehabilitation Center, Haikou, China
| | - Yuming Xu
- The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China
| |
Collapse
|
|
43
|
Posterior mediastinal nodule diagnosed as a tuberculous granuloma infiltrating into the aorta. Gen Thorac Cardiovasc Surg 2020; 69:572-576. [PMID: 33006751 DOI: 10.1007/s11748-020-01499-9] [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: 07/11/2020] [Accepted: 09/21/2020] [Indexed: 10/23/2022]
Abstract
Although tuberculous infection rarely results in aortic aneurysm formation or rupture, its precursor lesion has never been identified in cases with tuberculosis. We incidentally encountered a case of a posterior mediastinal nodule with concomitant chest computed tomography (CT) findings of multiple pulmonary micronodular shadows. Since an enlargement of the mediastinal nodule was retrospectively apparent, we considered the lesion as malignant. Enhanced CT showed luminal irregularity in the descending aorta, located adjacent to the nodule, in addition to the disappearance of the fat plane between the lesion and the aorta. We successfully resected the nodule with the aorta under partial cardiopulmonary bypass. Based on the pathological and postoperative bacterial findings, the nodule was diagnosed as a tuberculous granuloma infiltrating into the medial layer of the aorta.
Collapse
|
|
44
|
Tuberculosis and COVID-19: Lessons from the Past Viral Outbreaks and Possible Future Outcomes. Can Respir J 2020; 2020:1401053. [PMID: 32934758 PMCID: PMC7479474 DOI: 10.1155/2020/1401053] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 07/29/2020] [Accepted: 08/28/2020] [Indexed: 01/08/2023] Open
Abstract
Background The threat of contagious infectious diseases is constantly evolving as demographic explosion, travel globalization, and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results The PubMed electronic database was systematically searched for relevant articles linking TB, influenza, and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (focusing on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from past outbreaks (other coronaviruses) and influenza pandemic/seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their lethal synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead. The trial is registered with NCT04327206, NCT01829490, and NCT04121494.
Collapse
|
|
45
|
Tuberculosis sepsis after tocilizumab treatment. Clin Microbiol Infect 2020; 26:1493-1494. [PMID: 32512231 PMCID: PMC7274085 DOI: 10.1016/j.cmi.2020.05.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/20/2020] [Accepted: 05/25/2020] [Indexed: 01/09/2023]
|
|
46
|
Kim HJ, Ryu S, Choi SH, Seo H, Yoo SS, Lee SY, Cha SI, Park JY, Kim CH, Lee J. Comparison of biochemical parameters and chemokine levels in pleural fluid between patients with anergic and non-anergic tuberculous pleural effusion. Tuberculosis (Edinb) 2020; 123:101940. [PMID: 32452425 DOI: 10.1016/j.tube.2020.101940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Revised: 02/20/2020] [Accepted: 04/22/2020] [Indexed: 01/10/2023]
Abstract
Pleural fluid (PF) immune response in anergic tuberculous pleural effusion (TPE) patients is poorly understood. This study aimed to compare PF biochemical parameters and chemokine levels between anergic and non-anergic TPE patients. Chemokine arrays, cytokine measurements, and flow cytometry were performed in 58 patients (TPE [non-anergic (n = 32) and anergic (n = 10)] and malignant pleural effusion (MPE) [n = 16]). PF adenosine deaminase 2 (ADA2) levels were significantly lower in anergic TPE patients than in non-anergic TPE patients (p = 0.048). Among the 40 chemokines tested, PF CCL27 levels were significantly higher in anergic TPE patients than in non-anergic TPE and MPE patients (p < 0.001). The percentage of CD4+CCR10+T cells in PF was higher in anergic TPE patients than in non-anergic TPE and MPE patients (p = 0.001). We reported here that CCL27/CCR10 interactions might contribute to pathophysiology in anergic TPE. PF CCL27 and CD4+CCR10+T cells may help in diagnosing TPE in patients with moderate elevation of PF ADA levels.
Collapse
Affiliation(s)
- Ha-Jeong Kim
- Department of Physiology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Tumor Heterogeneity and Network (THEN) Research Center, Kyungpook National University, School of Medicine, Daegu, South Korea; Kyungpook National University Bio-Medical Research Institute, Daegu, South Korea
| | - Suyeon Ryu
- Department of Physiology, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program, Tumor Heterogeneity and Network (THEN) Research Center, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Sun Ha Choi
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Hyewon Seo
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Seung Soo Yoo
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Shin Yup Lee
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Seung Ick Cha
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Jae Yong Park
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea
| | - Chang Ho Kim
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea.
| | - Jaehee Lee
- Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea; Kyungpook National University Bio-Medical Research Institute, Daegu, South Korea.
| |
Collapse
|