Article
Immunology
Jaime Soria, Alfredo Chiappe, Jorge Gallardo, Joseph R. Zunt, Andres G. Lescano
Summary: The impact of treatment initiation timing on mortality was studied in adult hospitalized patients with confirmed tuberculous meningitis. The high mortality rate among these patients was associated with delay in treatment initiation, older age, HIV infection, and higher disease severity at admission.
OPEN FORUM INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Meng Zhang, Jian-Qing He
Summary: The study indicates that genetic variants in the Smurf1 gene region are associated with the risk of tuberculous meningitis, providing important clues for understanding the immunopathogenesis of TBM and potentially identifying targets or genetic markers to guide treatment in patients with TBM.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Public, Environmental & Occupational Health
Abhishek Shridhar, Ravindra Kumar Garg, Imran Rizvi, Mili Jain, Wahid Ali, Hardeep Singh Malhotra, Neeraj Kumar, Praveen Kumar Sharma, Rajesh Verma, Ravi Uniyal, Shweta Pandey
Summary: This study evaluated the proportion of underlying primary immunodeficiency in patients with tuberculous meningitis and its impact on the outcome. The results showed that absolute lymphocyte count and CD4+ T-cell count were lower in tuberculous meningitis cases, and higher serum IgG levels may be associated with a poor outcome.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2022)
Review
Microbiology
Robindra Basu Roy, Sabrina Bakeera-Kitaka, Chishala Chabala, Diana M. Gibb, Julie Huynh, Hilda Mujuru, Naveen Sankhyan, James A. Seddon, Suvasini Sharma, Varinder Singh, Eric Wobudeya, Suzanne T. Anderson
Summary: Children affected by tuberculous meningitis have complex needs that may not be fully addressed within current tuberculosis and meningitis programs. By applying the five pillars outlined in the global roadmap, specific goals and activities can be implemented to defeat TBM in children. Integration between meningitis and TB programs at both the WHO and national levels is crucial for addressing these needs effectively.
Article
Clinical Neurology
Karen du Preez, Helen E. Jenkins, Peter R. Donald, Regan S. Solomons, Stephen M. Graham, H. Simon Schaaf, Jeffrey R. Starke, Anneke C. Hesseling, James A. Seddon
Summary: Tuberculous meningitis (TBM) is a significant cause of illness and death in children with tuberculosis (TB), but there are currently no estimates of the global burden of pediatric TBM. Due to non-specific symptoms and limited diagnostic tests, children with TBM are often diagnosed late or not at all. Even with diagnosis and treatment, 20% of children with TBM still die and survivors often have significant neurological disabilities. Improved surveillance of pediatric TBM is crucial for prevention, early diagnosis, and improved care.
FRONTIERS IN NEUROLOGY
(2022)
Review
Clinical Neurology
Kenneth Ssebambulidde, Jane Gakuru, Jayne Ellis, Fiona V. Cresswell, Nathan C. Bahr
Summary: Diagnosis of TBM remains challenging due to the limitations of current diagnostic methods. A combination of clinical factors and various investigations are utilized for diagnosis. Starting empiric therapy promptly is crucial for good outcomes in many cases.
FRONTIERS IN NEUROLOGY
(2022)
Article
Public, Environmental & Occupational Health
Mailing Huang, Yan Ma, Xinyu Ji, Hui Jiang, Fangchao Liu, Naihui Chu, Qi Li
Summary: This study aimed to identify the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB). A retrospective analysis was conducted on TB patients admitted to Beijing Chest Hospital between January 2012 and December 2019. The study found that being younger than 30, being a farmer, and having disseminated tuberculosis were identified as risk factors for TBM. Screening TB patients with these risk factors could aid in early detection of TBM.
FRONTIERS IN PUBLIC HEALTH
(2023)
Article
Clinical Neurology
Haiko Schurz, Brigitte Glanzmann, Nicholas Bowker, Ronald van Toorn, Regan Solomons, Johan Schoeman, Paul D. van Helden, Craig J. Kinnear, Eileen G. Hoal, Marlo Moeller
Summary: This study investigated the involvement of the host genome in susceptibility to tuberculous meningitis (TBM) using genotyping and sequencing methods. The results suggest that genes NOD2 and CYP4F2 may play important roles in the pathogenesis of TBM, while Centriolar Coiled-Coil Protein 110 (CCP110) may be associated with susceptibility to TBM.
FRONTIERS IN NEUROLOGY
(2022)
Review
Microbiology
Charles M. Manyelo, Regan S. Solomons, Gerhard Walz, Novel N. Cheyou
Summary: Tuberculous meningitis is a devastating form of tuberculosis with limited understanding of its immunology and pathogenesis. Further research is urgently needed to improve disease management and develop new therapeutic approaches.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Microbiology
Navarat Panjasawatwong, Thanaporn Wattanakul, Richard M. Hoglund, Nguyen Duc Bang, Thomas Pouplin, Wichit Nosoongnoen, Vi Nguyen Ngo, Jeremy N. Day, Joel Tarning
Summary: This study investigated the population pharmacokinetics of isoniazid, rifampin, pyrazinamide, and ethambutol in Vietnamese children with TBM, recommended higher rifampin doses to achieve target exposure, and found that low rifampin plasma exposure was associated with an increased risk of neurological disability.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Medicine, General & Internal
Jayantee Kalita, Prakash C. Pandey, Ruchi Shukla, Rudrashish Haldar
Summary: Patients with tuberculous meningitis have prolonged fever response, and the expression of TNF-alpha gene can predict the duration of fever subsidence. Further studies are needed to explore the potential role of TNF-alpha-modifying drugs in tuberculous meningitis.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Infectious Diseases
Marc Weiner, Jon Gelfond, Teresa L. Johnson-Pais, Melissa Engle, John L. Johnson, William C. Whitworth, Erin Bliven-Sizemore, Pheona Nsubuga, Susan E. Dorman, Rada Savic
Summary: Exposure to rifapentine varied with AADAC rs1803155 genotype in black participants, with the G allele associated with lower bactericidal target rifapentine exposure. Other evaluated genes were not associated with rifapentine exposure in both black and non-black participants. Further pharmacogenomic studies are needed to explore the impact of AADAC rs1803155 on rifapentine exposure in different patient populations.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Review
Microbiology
Wen-Feng Cao, Er-Ling Leng, Shi-Min Liu, Yong-Liang Zhou, Chao-Qun Luo, Zheng-Bing Xiang, Wen Cai, Wei Rao, Fan Hu, Ping Zhang, An Wen
Summary: Tuberculous meningitis is the most common and deadly type of central nervous system tuberculosis. Early diagnosis is crucial for patient prognosis, but laboratory diagnosis is challenging. This review summarizes the latest research in microbiological and molecular diagnostics for tuberculous meningitis and discusses issues related to diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Immunology
Juan Zhang, Ming-gui Wang, Jian-Qing He
Summary: This study reveals the association between ALOX5 gene polymorphism and susceptibility to multisystemic tuberculosis in the Chinese Han population.
MICROBIAL PATHOGENESIS
(2023)
Review
Medicine, General & Internal
Juan M. Cubillos-Angulo, Catarina D. Fernandes, Davi N. Araujo, Cristinna A. Carmo, Maria B. Arriaga, Bruno B. Andrade
Summary: Genetic studies have shown the relevance of CD14 and NOD2 gene polymorphisms in association with the risk of diseases caused by Mycobacterium tuberculosis infection. Specific CD14 polymorphisms were found to either increase or decrease the risk of TB disease, while certain NOD2 SNPs were significantly associated with higher risk in the Chinese population. Ethnicity may play a role in the impact of these gene polymorphisms on the risk of Mtb diseases.
SYSTEMATIC REVIEWS
(2021)
Article
Immunology
April C. Pettit, Jason E. Stout, Robert Belknap, Constance A. Benson, Marie Nancy Seraphin, Michael Lauzardo, David J. Horne, Richard S. Garfein, Fernanda Maruri, Christine S. Ho
Summary: Among US-born PLWH, the prevalence of LTBI was low, and TSPOT showed higher specificity and PPV compared to QFT and TST, making it potentially more suitable for testing PLWH with low TB exposure risk and high CD4+ counts.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
T. T. Thanh, C. Casals-Pascual, N. T. H. Ny, N. M. Ngoc, R. Geskus, L. N. T. Nhu, N. T. T. Hong, D. T. Duc, D. D. A. Thu, P. N. Uyen, V. B. Ngoc, L. T. M. Chau, V. X. Quynh, N. H. H. Hanh, N. T. T. Thuong, L. T. Diem, B. T. B. Hanh, V. T. T. Hang, P. K. N. Oanh, R. Fischer, N. H. Phu, H. D. T. Nghia, N. V. V. Chau, N. T. Hoa, B. M. Kessler, G. Thwaites, L. Tan
Summary: The study identified Lipocalin 2 (LCN2) as a sensitive and specific biomarker for discriminating bacterial meningitis from other CNS infections. LCN2 outperformed other CSF markers commonly used in routine care and in combination with CSF leukocytes, glucose, protein, and lactate, it showed the highest diagnostic performance for bacterial meningitis.
CLINICAL MICROBIOLOGY AND INFECTION
(2021)
Article
Biology
Laura Whitworth, Jacob Coxon, Arjan van Laarhoven, Nguyen Thuy Thuong Thuong, Sofiati Dian, Bachti Alisjahbana, Ahmad Rizal Ganiem, Reinout van Crevel, Guy E. Thwaites, Mark Troll, Paul H. Edelstein, Roger Sewell, Lalita Ramakrishnan
Summary: Tuberculous meningitis has high mortality linked to excessive inflammation, and adjunctive anti-inflammatory corticosteroids reduce mortality by only 30%. The LTA4H TT genotype confers survival benefit, particularly in individuals with hyper-inflammatory responses, but this benefit is nullified in the most severe cases with high early mortality.
Article
Infectious Diseases
Jill K. Gersh, Ruanne Barnabas, Daniel Matemo, John Kinuthia, Zachary Feldman, Sylvia M. Lacourse, Jerphason Mecha, Alex J. Warr, Maureen Kamene, David J. Horne
Summary: In Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.
BMC INFECTIOUS DISEASES
(2021)
Article
Microbiology
Amy Oreskovic, Nuttada Panpradist, Diana Marangu, M. William Ngwane, Zanele P. Magcaba, Sindiswa Ngcobo, Zinhle Ngcobo, David J. Horne, Douglas P. K. Wilson, Adrienne E. Shapiro, Paul K. Drain, Barry R. Lutz
Summary: This study aimed to improve the diagnostic sensitivity of TB urine cfDNA by increasing recovery of short fragments during sample preparation. A highly sensitive sequence-specific purification method was developed, which showed high efficiency in capturing short TB cfDNA. In a clinical cohort study in South Africa, the urine cfDNA assay had high sensitivity and specificity for diagnosing active pulmonary TB.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Geriatrics & Gerontology
Isano Hase, Katelynne Gardner Toren, Hitomi Hirano, Kimiko Sakurai, David J. Horne, Takefumi Saito, Masahiro Narita
Summary: A study in Japan found that patients aged 75 years and older with pulmonary TB were more likely to be excluded from PZA in the initial treatment regimen compared to younger patients, which led to higher mortality rates and more frequent adverse events during treatment.
Article
Infectious Diseases
D. A. Black, S. W. McBrien, J. Gersh, B. Ghassemieh, M. Narita, M. J. Pecha, Y. Tan, D. J. Horne
Summary: This study evaluated the risk of TB disease among non-U.S.-born residents in Washington State, USA, and found that the risk was highest within the first year after U.S. entry, and remained elevated for individuals from high-burden countries who had resided in the United States for more than 20 years.
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
(2021)
Review
Infectious Diseases
Ashar Dhana, Yohhei Hamada, Andre P. Kengne, Andrew D. Kerkhoff, Molebogeng X. Rangaka, Tamara Kredo, Annabel Baddeley, Cecily Miller, Satvinder Singh, Yasmeen Hanifa, Alison D. Grant, Katherine Fielding, Dissou Affolabi, Corinne S. Merle, Ablo Prudence Wachinou, Christina Yoon, Adithya Cattamanchi, Christopher J. Hoffmann, Neil Martinson, Eyongetah Tabenyang Mbu, Melissa S. Sander, Taye T. Balcha, Sten Skogmar, Byron W. P. Reeve, Grant Theron, Gcobisa Ndlangalavu, Surbhi Modi, Joseph Cavanaugh, Susan Swindells, Richard E. Chaisson, Faiz Ahmad Khan, Andrea A. Howard, Robin Wood, Swe Swe Thit, Mar Mar Kyi, Josh Hanson, Paul K. Drain, Adrienne E. Shapiro, Tendesayi Kufa, Gavin Churchyard, Duc T. Nguyen, Edward A. Graviss, Stephanie Bjerrum, Isik S. Johansen, Jill K. Gersh, David J. Horne, Sylvia M. LaCourse, Haider Abdulrazzaq Abed Al-Darraji, Adeeba Kamarulzaman, Russell R. Kempker, Nestani Tukvadze, David A. Barr, Graeme Meintjes, Gary Maartens
Summary: C-reactive protein can reduce the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, further research is needed to evaluate the utility of C-reactive protein in outpatients on ART.
LANCET INFECTIOUS DISEASES
(2022)
Article
Immunology
Ethan D. Valinetz, Daniel Matemo, Jill K. Gersh, Lara L. Joudeh, Simon C. Mendelsohn, Thomas J. Scriba, Mark Hatherill, John Kinuthia, Anna Wald, Gerard A. Cangelosi, Ruanne V. Barnabas, Thomas R. Hawn, David J. Horne
Summary: This study examines the association between isoniazid preventive therapy (IPT) or nontuberculous mycobacteria (NTM) sputum culture positivity and tuberculosis (TB) transcriptional signatures in people with HIV. The findings suggest that IPT is associated with significantly lower TB risk scores compared to those who did not receive IPT. These results support further investigation of IPT as a biomarker for TB preventive therapy response.
Article
Immunology
Javeed A. Shah, Alex J. Warr, Andrew D. Graustein, Aparajita Saha, Sarah J. Dunstan, Nguyen T. T. Thuong, Guy E. Thwaites, Maxine Caws, Phan V. K. Thai, Nguyen D. Bang, Tran T. H. Chau, Chiea Chuen Khor, Zheng Li, Martin Hibberd, Xuling Chang, Felicia K. Nguyen, Carlo A. Hernandez, Madison A. Jones, Christopher M. Sassetti, Katherine A. Fitzgerald, Munyaradzi Musvosvi, Anele Gela, Willem A. Hanekom, Mark Hatherill, Thomas J. Scriba, Thomas R. Hawn
Summary: This study identified genetic variations in REL and BHLHE40 that are associated with IL-12 and IL-10 cytokine responses and clinical outcomes of tuberculosis (TB). Understanding the common genetic regulation of intermediate cellular traits provides insights into the mechanisms underlying TB pathogenesis.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Infectious Diseases
Timothy M. Walker, Paolo Miotto, Claudio U. Koser, Philip W. Fowler, Jeff Knaggs, Zamin Iqbal, Martin Hunt, Leonid Chindelevitch, Maha R. Farhat, Daniela Maria Cirillo, Inaki Comas, James Posey, Shaheed V. Omar, Timothy E. A. Peto, Anita Suresh, Swapna Uplekar, Sacha Laurent, Rebecca E. Colman, Carl-Michael Nathanson, Matteo Zignol, Ann Sarah Walker, Derrick W. Crook, Nazir Ismail, Timothy C. Rodwell
Summary: This study aimed to generate a WHO-endorsed catalogue of mutations for drug resistance prediction in Mycobacterium tuberculosis complex (MTBC) and provide a global standard for interpreting molecular information. The research analyzed MTBC isolates from 45 countries and identified mutations associated with resistance to different antituberculosis drugs. The findings can encourage the implementation of molecular diagnostics by national tuberculosis programs.
Article
Biology
Matthew Silcocks, Sarah J. Dunstan
Summary: The Two Layer hypothesis suggests that East Asian population history was shaped by hunter-gatherer groups who migrated via a southern route and were assimilated by agriculturalist migrants from the north. By analyzing the phylogeographic signatures of Mycobacterium tuberculosis (Mtb) and the human Y-chromosome, researchers found that the Y-chromosome lineages associated with the hunter-gatherer groups in East Asia have characteristics consistent with a southern entry route, while the Y-chromosome lineages linked to agriculture development in modern-day China have characteristics incompatible with a southern entry route. This model opens up new research hypotheses for host-pathogen coevolution in East Asia.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Cecilia S. Lindestam Arlehamn, Basilin Benson, Rebecca Kuan, Kimberly A. Dill-McFarland, Glenna J. Peterson, Sinu Paul, Felicia K. Nguyen, Robert H. Gilman, Mayuko Saito, Randy Taplitz, Matthew Arentz, Christopher H. Goss, Moira L. Aitken, David J. Horne, Javeed A. Shah, Alessandro Sette, Thomas R. Hawn
Summary: The immunological mechanisms of susceptibility to nontuberculous mycobacterial disease remain unclear. This study investigated the immune responses to Mycobacterium avium complex (MAC) in individuals with a history of MAC lung disease (MACDZ) to understand the pathogenesis of MAC. The results showed a novel immunologic defect in MACDZ individuals, characterized by impaired MAC-specific immune responses and dysregulation in both innate and adaptive immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Public, Environmental & Occupational Health
James E. Meiring, Mila Shakya, Farhana Khanam, Merryn Voysey, Maile T. Phillips, Susan Tonks, Deus Thindwa, Thomas C. Darton, Sabina Dongol, Abilasha Karkey, K. Zaman, Stephen Baker, Christiane Dolecek, Sarah J. Dunstan, Gordon Dougan, Kathryn E. Holt, Robert S. Heyderman, Firdausi Qadri, Virginia E. Pitzer, Buddha Basnyat, Melita A. Gordon, John Clemens, Andrew J. Pollard
Summary: This study investigated the burden of enteric fever in three urban sites in Africa and Asia, revealing high rates of S Typhi and S Paratyphi infections as well as serious antimicrobial resistance. Multiple intervention strategies are needed to achieve global control of these pathogens as suggested by the study findings.
LANCET GLOBAL HEALTH
(2021)
Review
Medicine, General & Internal
Jerry S. Zifodya, Jonah S. Kreniske, Ian Schiller, Mikashmi Kohli, Nandini Dendukuri, Samuel G. Schumacher, Eleanor A. Ochodo, Frederick Haraka, Alice A. Zwerling, Madhukar Pai, Karen R. Steingart, David J. Horne
Summary: Xpert Ultra shows higher sensitivity but lower specificity compared to Xpert MTB/RIF for pulmonary tuberculosis, especially in smear-negative individuals and those living with HIV. The trade-off between sensitivity and specificity may vary by setting. Additionally, for rifampicin resistance detection, Xpert Ultra and Xpert MTB/RIF have similar sensitivity and specificity, with Xpert Ultra yielding more trace-positive results.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
