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Winichakoon P, Watcharasaksilp K, Butphet S, Wongworapat K, Pantip C, Khamnoi P, Supparatpinyo K, Salee P. Sequential testing with Xpert MTB/RIF assay for diagnosis of tuberculous meningitis in Maharaj Nakorn Chiang Mai University Hospital. Sci Rep 2025; 15:3675. [PMID: 39881189 PMCID: PMC11779814 DOI: 10.1038/s41598-025-87739-5] [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: 06/18/2024] [Accepted: 01/21/2025] [Indexed: 01/31/2025] Open
Abstract
Early diagnosis and appropriate treatment are essential for reducing morbidity and mortality in tuberculous meningitis (TBM). This study aimed to evaluate the diagnostic performance of the Xpert MTB/RIF assay for the diagnosis of TBM in patients with subacute lymphocytic meningitis. This cross-sectional study included 65 cerebrospinal fluid (CSF) specimens from patients at Maharaj Nakorn Chiang Mai University Hospital, Thailand, between January 2015 and March 2016. Mycobacteria growth indicator tube (MGIT) culture was used as the reference standard. Sensitivity, specificity, and agreement between Xpert MTB/RIF and MGIT culture were calculated. Sequential testing using a TBM score, followed by Xpert MTB/RIF was also analyzed. Xpert MTB/RIF demonstrated 83.33% sensitivity (95% CI 57.19-98.22) and 96.23% specificity (95% CI 87.02-99.54). Agreement between Xpert MTB/RIF and MGIT culture was 93.85% (p < 0.001), with a kappa score of 0.80 (95% CI 0.60-0.99). Sequential testing with a TBM score cut-off of 6, followed by Xpert MTB/RIF improved specificity from 96.23 to 97.15%. The Xpert MTB/RIF assay is a rapid and valuable tool for detecting Mycobacterium tuberculosis in centrifuged CSF specimens. A diagnostic algorithm incorporating the TBM score enhances performance, balancing sensitivity and specificity, and could improve patient outcomes in resource-limited settings.
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Affiliation(s)
- Poramed Winichakoon
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 110 Intavaroros Rd., Muaeng, Chiang Mai, 50200, Thailand
| | - Kanokwan Watcharasaksilp
- Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Sunisa Butphet
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Kanlaya Wongworapat
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Chansom Pantip
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Phadungkiat Khamnoi
- Microbiology Section, Diagnostic Laboratory, Maharaj Nakorn Chiang Mai University Hospital, Chiang Mai, Thailand
| | - Khuanchai Supparatpinyo
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 110 Intavaroros Rd., Muaeng, Chiang Mai, 50200, Thailand
- Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
| | - Parichat Salee
- Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 110 Intavaroros Rd., Muaeng, Chiang Mai, 50200, Thailand.
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Chen X, Wei J, Zhang M, Su B, Ren M, Cai M, Zhang Y, Zhang T. Prevalence, incidence, and case fatality of tuberculous meningitis in adults living with HIV: a systematic review and meta-analysis. BMC Public Health 2024; 24:2145. [PMID: 39112980 PMCID: PMC11308199 DOI: 10.1186/s12889-024-19683-4] [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: 03/12/2024] [Accepted: 08/02/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND Tuberculous meningitis (TBM) emerges as a grave complication of tuberculosis in people living with HIV (PLWH). The diagnosis and treatment of TBM pose significant challenges, leading to elevated mortality rates. To comprehensively grasp the epidemiological landscape of TBM in PLWH, a systematic review and meta-analysis were meticulously undertaken. METHODS We performed a comprehensive search in PubMed, Embase, and Web of Science from database inception to September 19th, 2023, with no limitations on the publication type. The search terms were HIV/AIDS terms (AIDS OR HIV OR PLWH) and TBM-related terms (tuberculous meningitis OR TBM). Studies included in this meta-analysis evaluated the incidence of TBM among PLWH, or we were able to calculate the incidence of TBM among PLWH from the research. RESULTS The analysis revealed that the prevalence of TBM among PLWH was 13.6% (95% CI: 6.6-25.9%), with an incidence rate of 1.5 cases per 1000 persons per year. The case fatality rate was found to be 38.1% (95% CI: 24.3-54.1%). No significant publication bias was observed. Meta-regression analysis identified the proportion of females and finance situation as factors influencing the outcomes. CONCLUSIONS Our study highlights TBM as a prevalent opportunistic infection that targets the central nervous system in PLWH. The elevated case fatality rate is especially prominent among PLWH in impoverished regions, underscores the pressing necessity for enhanced management strategies for PLWH suffering from TBM. TRIAL REGISTRATION PROSPERO; No: CRD42022338586.
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Affiliation(s)
- Xue Chen
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China
- Beijing Youan Hospital, Beijing Institute of Hepatology, Capital Medical University, Beijing, 100069, China
| | - Jiaqi Wei
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China
| | - Mei Zhang
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China
| | - Bin Su
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China
| | - Meixin Ren
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China
| | - Miaotian Cai
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China
| | - Yulin Zhang
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, China.
- Beijing Research Center for Respiratory Infectious Diseases, Beijing, 100069, China.
| | - Tong Zhang
- Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Beijing Key Laboratory for HIV/AIDS Research, Capital Medical University, Beijing, 100069, China.
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Ma Q, Chen J, Kong X, Zeng Y, Chen Z, Liu H, Liu L, Lu S, Wang X. Interactions between CNS and immune cells in tuberculous meningitis. Front Immunol 2024; 15:1326859. [PMID: 38361935 PMCID: PMC10867975 DOI: 10.3389/fimmu.2024.1326859] [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: 10/24/2023] [Accepted: 01/10/2024] [Indexed: 02/17/2024] Open
Abstract
The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells, monocytes, and the barrier systems within the brain. Recently, advances in the immune cells in the CNS provided new insights to understand the development of tuberculous meningitis (TBM), which is the predominant form of Mycobacterium tuberculosis (M.tb) infection in the CNS and accompanied with high mortality and disability. The development of the CNS requires the protection of immune cells, including macrophages and microglia, during embryogenesis to ensure the accurate development of the CNS and immune response following pathogenic invasion. In this review, we summarize the current understanding on the CNS immune cells during the initiation and development of the TBM. We also explore the interactions of immune cells with the CNS in TBM. In the future, the combination of modern techniques should be applied to explore the role of immune cells of CNS in TBM.
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Affiliation(s)
| | | | | | | | | | | | | | - Shuihua Lu
- National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China
| | - Xiaomin Wang
- National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong, China
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Quaresma M, Paulino M, Oliveira A, Nunes A. Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment. Cureus 2024; 16:e52715. [PMID: 38260110 PMCID: PMC10801818 DOI: 10.7759/cureus.52715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/17/2024] [Indexed: 01/24/2024] Open
Abstract
Tuberculosis (TB) remains a global health challenge. Although pulmonary TB is the most frequent presentation, extrapulmonary involvement can occur, especially in immunocompromised patients. HIV-positive individuals are particularly vulnerable to opportunistic infections, such as TB, and CNS involvement is more prevalent in these patients, often leading to a poorer prognosis. CNS TB management is challenging due to nonspecific symptoms and delayed diagnosis, contributing to high mortality. It can manifest diffusely as tuberculous meningitis (TBM), localized as tuberculoma or tuberculous abscess, or as extradural and intradural spinal infections. TBM is the primary CNS manifestation, bearing significant morbidity and mortality, and rarely complicates with involvement of the spinal cord, termed tuberculous myelitis, which is associated with an unfavorable prognosis. A 61-year-old male, smoker with a history of substance abuse, undergoing seven months of antiretroviral therapy (ART) for HIV-1, presented with a two-day history of altered consciousness, sphincter incontinence, and fever. He also reported headaches, dizziness, and sleep disturbances over the past months. The examination revealed fever, asthenia, prostration, disorientation, neck rigidity, and bilateral lower limb weakness. Initial tests indicated lymphopenia, hyponatremia, and a slightly elevated C-reactive protein. Cranial CT showed no abnormalities. Lumbar puncture yielded abnormal cerebrospinal fluid (CSF), xanthochromic, hyperproteinorrheic (2316 g/L), hypoglycorrhagic (24mg/dl), with pleocytosis predominantly of mononuclear cells (98%). Compared to the values prior to ART treatment, the patient had a decreased HIV-1 viral (44 copies/ml) load but also a decreased CD4+ cell count (43 cells/mm3). Given the patient's rapid clinical deterioration, immunosuppression history, and a positive interferon-gamma release assay (IGRA) prior to ART, treatment with antituberculous drugs and dexamethasone was started at admission. Subsequently, Mycobacterium tuberculosis was identified through polymerase chain reaction (PCR) of the CSF. Cranial and spinal MRI revealed leptomeningeal enhancement from C2-C3 to the cauda equina, consistent with meningitis, without intracranial extension, and findings suggestive of myelitis, without evidence of tuberculomas or spinal cord osseous involvement. One week after treatment, the recovery of higher neurological functions became evident. Improvement in lower limb motor deficits had a delayed trajectory, with marginal progress observed at discharge. After an eight-week incubation, CSF mycobacterial culture analysis yielded negative results. This case discusses the importance of early suspicion and intervention in CNS infection prognosis. Attention to signs and symptoms beyond the most frequent ones is crucial, particularly in immunocompromised individuals like HIV patients. Identifying CSF features in different CNS infections and group-specific particulars facilitates the prompt initiation of treatment. Additionally, in co-infected patients (HIV and CNS TB), considering factors such as ART duration, CD4+ cell count, and viral load is important, in influencing the disease's incidence, course, and prognosis.
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Affiliation(s)
- Marta Quaresma
- Internal Medicine Department, Hospital Vila Franca Xira, Vila Franca Xira, PRT
| | - Madalena Paulino
- Internal Medicine Department, Hospital de São José, Centro Hospitalar Universitário de Lisboa Central, Lisboa, PRT
| | - Ana Oliveira
- Internal Medicine Department, Hospital Vila Franca Xira, Vila Franca Xira, PRT
| | - Ana Nunes
- Internal Medicine Department, Hospital Vila Franca Xira, Vila Franca Xira, PRT
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Loghin II, Vâță A, Miftode EG, Cobaschi M, Rusu ȘA, Silvaș G, Frăsinariu OE, Dorobăț CM. Characteristics of Tuberculous Meningitis in HIV-Positive Patients from Northeast Romania. Clin Pract 2023; 13:1488-1500. [PMID: 38131680 PMCID: PMC10742667 DOI: 10.3390/clinpract13060131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/10/2023] [Accepted: 11/14/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND AND OBJECTIVES One of the most severe forms of extrapulmonary tuberculosis (EPTB) is tuberculous meningitis (TBM), which is linked to significant morbidity and high mortality. It is well recognized that human immunodeficiency virus (HIV)-positive people are more likely to develop EPTB, including TBM, especially if they have severe immunodeficiencies. We aim to highlight the profile and the characteristics of TBM in HIV-infected patients. MATERIAL AND METHODS We conducted a retrospective clinical study based on hospital medical records of patients diagnosed with HIV/AIDS (acquired immunodeficiency syndrome) and TBM in Northeast Romania, hospitalized at "St. Parascheva" Clinical Hospital of Infectious Diseases of Iasi from 1 January 2010 to 1 December 2022. RESULTS From a total number of 1692 patients on record in our center, 195 had a HIV-tuberculosis (TB) coinfection, and 19 cases were HIV-TBM coinfected. Six cases were newly HIV-diagnosed late presenters, and thirteen patients' names were already found in the center's records with deficient immunological viral status (median CD4 lymphocyte level 47/mm3). The average age in the study group was 27 years old. The clinical manifestations and cerebrospinal fluid (CSF) variables were typical in most cases, despite the severe immunodepression of the patients. The Thwaites scoring system correctly identified 89.5% of the patients. The median admission period was 18 days; the lethality rate was 31.6%, despite access to ART and anti-TB drugs, and was associated with a more severe immunosuppression. No rifampicin resistance was detected. CONCLUSIONS TBM appeared in a minority of our HIV cohort and affected severely immunodepressed patients; the clinical and CSF variables had a typical aspect in most cases, and the Thwaites scoring system performed well for this type of patient. The lethality rate was high and was correlated with a more severe immunodepression.
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Affiliation(s)
- Isabela Ioana Loghin
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.L.); (A.V.); (E.G.M.)
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
| | - Andrei Vâță
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.L.); (A.V.); (E.G.M.)
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
| | - Egidia Gabriela Miftode
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.L.); (A.V.); (E.G.M.)
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
| | - Mihaela Cobaschi
- Faculty of Medicine/Clinical II Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- National Institute of Infectious Diseases “Prof. Dr. Matei Balș”, 021105 Bucharest, Romania
| | - Șerban Alin Rusu
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
| | - George Silvaș
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
| | - Otilia Elena Frăsinariu
- Department of Infectious Diseases, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (I.I.L.); (A.V.); (E.G.M.)
- Emergency Clinical Hospital for Children “St. Maria”, 700309 Iasi, Romania
| | - Carmen Mihaela Dorobăț
- Department of Infectious Diseases, “St. Parascheva” Clinical Hospital of Infectious Diseases, 700116 Iasi, Romania; (Ș.A.R.); (G.S.); (C.M.D.)
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Lin H, Teng S, Wang Z, Liu QY. Congenital tuberculosis with tuberculous meningitis and situs inversus totalis: A case report. World J Clin Cases 2022; 10:5495-5501. [PMID: 35812650 PMCID: PMC9210909 DOI: 10.12998/wjcc.v10.i16.5495] [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: 12/21/2021] [Revised: 01/30/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Congenital tuberculosis (TB), tuberculous meningitis, and situs inversus totalis are rare diseases. We here report a patient who simultaneously suffered from these three rare diseases. There is currently no such report in the literature. Congenital TB is easily misdiagnosed and has a high case fatality rate. Timely anti-TB treatment is required.
CASE SUMMARY A 19-day-old male newborn was admitted to hospital due to a fever for 6 h. His blood tests and chest X-rays suggested infection, and he was initially considered to have neonatal pneumonia and sepsis. He did not respond to conventional anti-infective treatment. Finally, Mycobacterium tuberculosis was found in sputum lavage fluid on the 10th day after admission. In addition, the mother's tuberculin skin test was positive, with an induration of 22 mm, and her pelvic computed tomography scan suggested the possibility of tuberculous pelvic inflammatory disease. The child was diagnosed with congenital TB and immediately managed with anti-TB therapy and symptomatic supportive treatment. However, the infant's condition gradually worsened and he developed severe tuberculous pneumonia and tuberculous meningitis, and eventually died of respiratory failure.
CONCLUSION If conventional anti-infective treatment is ineffective in neonatal pneumonia, anti-TB treatment should be considered.
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Affiliation(s)
- Hu Lin
- Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Shuang Teng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610036, Sichuan Province, China
| | - Zhong Wang
- Department of Radiology, Mianyang Central Hospital, Mianyang 621000, Sichuan Province, China
| | - Qi-Yu Liu
- Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
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Dodd PJ, Osman M, Cresswell FV, Stadelman AM, Lan NH, Thuong NTT, Muzyamba M, Glaser L, Dlamini SS, Seddon JA. The global burden of tuberculous meningitis in adults: A modelling study. PLOS GLOBAL PUBLIC HEALTH 2021; 1:e0000069. [PMID: 36962116 PMCID: PMC10021871 DOI: 10.1371/journal.pgph.0000069] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/15/2021] [Indexed: 11/19/2022]
Abstract
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis. The incidence and mortality of TBM is unknown due to diagnostic challenges and limited disaggregated reporting of treated TBM by existing surveillance systems. We aimed to estimate the incidence and mortality of TBM in adults (15+ years) globally. Using national surveillance data from Brazil, South Africa, the United Kingdom, the United States of America, and Vietnam, we estimated the fraction of reported tuberculosis that is TBM, and the case fatality ratios for treated TBM in each of these countries. We adjusted these estimates according to findings from a systematic review and meta-analysis and applied them to World Health Organization tuberculosis notifications and estimates to model the global TBM incidence and mortality. Assuming the case detection ratio (CDR) for TBM was the same as all TB, we estimated that in 2019, 164,000 (95% UI; 129,000-199,000) adults developed TBM globally; 23% were among people living with HIV. Almost 60% of incident TBM occurred in males and 20% were in adults 25-34 years old. 70% of global TBM incidence occurred in Southeast Asia and Africa. We estimated that 78,200 (95% UI; 52,300-104,000) adults died of TBM in 2019, representing 48% of incident TBM. TBM case fatality in those treated was on average 27%. Sensitivity analysis assuming improved detection of TBM compared to other forms of TB (CDR odds ratio of 2) reduced estimated global mortality to 54,900 (95% UI; 32,200-77,700); assuming instead worse detection for TBM (CDR odds ratio of 0.5) increased estimated mortality to 125,000 (95% UI; 88,800-161,000). Our results highlight the need for improved routine TBM monitoring, especially in high burden countries. Reducing TBM incidence and mortality will be necessary to achieve the End TB Strategy targets.
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Affiliation(s)
- Peter J Dodd
- School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom
| | - Muhammad Osman
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa
| | - Fiona V Cresswell
- London School of Hygiene and Tropical Medicine, London, United Kingdom
- Infectious Diseases Institute, Kampala, Uganda
- MRC-UVRI-LSHTM Uganda Research Unit, Entebbe, Uganda
| | - Anna M Stadelman
- School of Public Health, University of Minnesota, Minneapolis, MN, United States of America
| | | | - Nguyen Thuy Thuong Thuong
- Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
- Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Morris Muzyamba
- Tuberculosis Section, National Infection Service, Public Health England, London, United Kingdom
| | - Lisa Glaser
- Tuberculosis Section, National Infection Service, Public Health England, London, United Kingdom
| | - Sicelo S Dlamini
- Research Information Monitoring, Evaluation, and Surveillance, National Tuberculosis Control and Management Cluster, National Department of Health, Pretoria, South Africa
| | - James A Seddon
- Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Stellenbosch University, Stellenbosch, South Africa
- Department of Infectious Diseases, Imperial College London, London, United Kingdom
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Hernandez AV, de Laurentis L, Souza I, Pessanha M, Thota P, Roman YM, Barboza-Meca J, Boulware DR, Vidal JE. Diagnostic accuracy of Xpert MTB/RIF for tuberculous meningitis: systematic review and meta-analysis. Trop Med Int Health 2020; 26:122-132. [PMID: 33164243 DOI: 10.1111/tmi.13525] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE This systematic review evaluated the diagnostic accuracy of Xpert MTB/RIF to detect tuberculous meningitis (TBM). METHODS PubMed and five other databases were systematically searched through March 2019. All studies evaluating diagnostic accuracy of Xpert MTB/RIF on cerebrospinal fluid (CSF) samples were included. Reference standards were definitive or definite plus probable TBM. The quality of studies was assessed by the QUADAS-2 tool. We performed bivariate random-effects meta-analysis and calculated summary diagnostic statistics. RESULTS We identified 30 studies (n = 3972 participants), including 5 cohort studies and 25 cross-sectional studies. Reference standards were definite TB (n = 28 studies) or definite plus probable TBM (n = 6 studies). The pooled Xpert MTB/RIF sensitivity was 85% (95% CI, 70-93%), and specificity was 98% (95% CI, 97-99%) with a negative likelihood ratio of 0.15 (95% CI, 0.04-0.27) for definite TBM. For probable TBM cases, pooled sensitivity was 81% (95% CI, 66-90%), and specificity was 99% (95% CI, 97-99%). For both reference standard types, meta-analyses showed a C-statistic area under the curve of 0.98. The QUADAS-2 tool revealed low risk of bias as well as low concerns regarding applicability. Methodological heterogeneity was high among studies. CONCLUSIONS Xpert MTB/RIF showed high accuracy for TBM diagnosis, but a negative Xpert MTB/RIF test does not rule out TBM. Repeat Xpert testing may be necessary. In clinical practice, Xpert MTB/RIF adds speed and sensitivity when compared to classic TBM diagnostic methods or previous commercial nucleic acid amplification techniques. More studies and better strategies for rapidly confirming a diagnosis of TBM in children are urgently needed.
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Affiliation(s)
- Adrian V Hernandez
- University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT, USA.,Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru
| | - Laryssa de Laurentis
- Department of Infectious Diseases, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil
| | - Isadora Souza
- Department of Infectious Diseases, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil
| | - Marcelo Pessanha
- Department of Infectious Diseases, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil
| | | | - Yuani M Roman
- University of Connecticut/Hartford Hospital Evidence-based Practice Center, Hartford, CT, USA
| | - Joshuan Barboza-Meca
- Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru
| | - David R Boulware
- Department of Medcine, University of Minnesota, Minneapolis, MN, USA
| | - Jose E Vidal
- Department of Neurology, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil.,Department of Infectious Diseases, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Sun JM, Wang C, Jin DQ, Deng F. Fatal congenital tuberculosis owing to late diagnosis of maternal tuberculosis: case report and review of congenital tuberculosis in China. Paediatr Int Child Health 2020; 40:194-198. [PMID: 32195623 DOI: 10.1080/20469047.2020.1743932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Congenital tuberculosis (TB) is rare and the prognosis is poor if not detected early. The diagnosis is often delayed owing to non-specific clinical presentation, misdiagnosis and undiagnosed maternal TB during pregnancy. A 12-day-old girl presented with a 5-day history of fever, cough, poor feeding and respiratory distress. Her mother had a cough and fever at 30 weeks gestation which was managed empirically as community-acquired pneumonia without a TB workup. Immediately postpartum, her mother developed a high fever and shortness of breath and required admission to the intensive care unit. The infant was separated from her mother after delivery. The infant's chest radiograph showed bilateral miliary nodules. Thoracic and abdominal computed tomography (CT) showed multiple enlarged lymph nodes and congenital TB was suspected. Early morning gastric aspirate and sputum (obtained through a suction tube) were positive for acid-fast bacilli on smear microscopy and subsequently Mycobacterium tuberculosis was cultured from both specimens. Lumbar puncture was performed and cerebrospinal fluid (CSF) was compatible with TB meningitis. TB-polymerase chain reaction (TB-PCR) was positive. Her mother was diagnosed with miliary TB on postpartum day 17. Both were given anti-TB chemotherapy. Unfortunately, despite the treatment, the infant died from multiple organ dysfunction syndrome (MODS) caused by congenital TB at the age of 14 days. This case highlights the importance of screening pregnant women for TB in regions where it is highly prevalent. A high index of suspicion of maternal and congenital TB is critical to early diagnosis, especially in such regions.
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Affiliation(s)
- Jing-Min Sun
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University , Anhui, China
| | - Chang Wang
- Department of Radiology, Anhui Province Children's Hospital , Anhui, China
| | - Dan-Qun Jin
- Department of Pediatrics, Anhui Province Children's Hospital , Anhui, China
| | - Fang Deng
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University , Anhui, China
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HIV Associated Risk Factors for Ischemic Stroke and Future Perspectives. Int J Mol Sci 2020; 21:ijms21155306. [PMID: 32722629 PMCID: PMC7432359 DOI: 10.3390/ijms21155306] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 07/11/2020] [Accepted: 07/22/2020] [Indexed: 12/12/2022] Open
Abstract
Although retroviral therapy (ART) has changed the HIV infection from a fatal event to a chronic disease, treated HIV patients demonstrate high prevalence of HIV associated comorbidities including cardio/cerebrovascular diseases. The incidence of stroke in HIV infected subjects is three times higher than that of uninfected controls. Several clinical and postmortem studies have documented the higher incidence of ischemic stroke in HIV infected patients. The etiology of stroke in HIV infected patients remains unknown; however, several factors such as coagulopathies, opportunistic infections, vascular abnormalities, atherosclerosis and diabetes can contribute to the pathogenesis of stroke. In addition, chronic administration of ART contributes to the increased risk of stroke in HIV infected patients. Concurrently, experimental studies in murine model of ischemic stroke demonstrated that HIV infection worsens stroke outcome, increases blood brain barrier permeability and increases neuroinflammation. Additionally, residual HIV viral proteins, such as Trans-Activator of Transcription, glycoprotein 120 and Negative regulatory factor, contribute to the pathogenesis. This review presents comprehensive information detailing the risk factors contributing to ischemic stroke in HIV infected patients. It also outlines experimental evidence demonstrating the impact of HIV infection on stroke outcomes, in addition to possible novel therapeutic approaches to improve these outcomes.
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Diaz-Arias LA, Pardo CA, Probasco JC. Infectious Encephalitis in the Neurocritical Care Unit. Curr Treat Options Neurol 2020. [DOI: 10.1007/s11940-020-00623-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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12
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Robertson KR, Oladeji B, Jiang H, Kumwenda J, Supparatpinyo K, Campbell TB, Hakim J, Tripathy S, Hosseinipour MC, Marra CM, Kumarasamy N, Evans S, Vecchio A, La Rosa A, Santos B, Silva MT, Montano S, Kanyama C, Firnhaber C, Price R, Marcus C, Berzins B, Masih R, Lalloo U, Sanne I, Yosief S, Walawander A, Nair A, Sacktor N, Hall C. Human Immunodeficiency Virus Type 1 and Tuberculosis Coinfection in Multinational, Resource-limited Settings: Increased Neurological Dysfunction. Clin Infect Dis 2019; 68:1739-1746. [PMID: 30137250 PMCID: PMC6495021 DOI: 10.1093/cid/ciy718] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 08/17/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)-infected participants in resource-limited settings treated with 3 World Health Organization-recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes. METHODS Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance. RESULTS Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/μL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity. CONCLUSIONS TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life. CLINICAL TRIALS REGISTRATION NCT00096824.
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Affiliation(s)
- Kevin R Robertson
- AIDS Neurological Center, Neurology, University of North Carolina, Chapel Hill
| | | | - Hongyu Jiang
- Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | | | | | | | | | | | | | | | | | - Scott Evans
- Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | | | | | | | | | | | | | | | | | - Cheryl Marcus
- AIDS Neurological Center, Neurology, University of North Carolina, Chapel Hill
| | | | - Reena Masih
- Social Scientific Systems, Silver Springs, Maryland
| | | | | | - Sarah Yosief
- AIDS Neurological Center, Neurology, University of North Carolina, Chapel Hill
| | - Ann Walawander
- Frontier Science & Technology Research Foundation, Buffalo, New York
| | - Aspara Nair
- Frontier Science & Technology Research Foundation, Buffalo, New York
| | | | - Colin Hall
- AIDS Neurological Center, Neurology, University of North Carolina, Chapel Hill
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Abstract
The epidemiology of spinal cord disease in human immunodeficiency virus (HIV) infection is largely unknown due to a paucity of data since combination antiretroviral therapy (cART). HIV mediates spinal cord injury indirectly, by immune modulation, degeneration, or associated infections and neoplasms. The pathologies vary and range from cytotoxic necrosis to demyelination and vasculitis. Control of HIV determines the differential for all neurologic presentations in infected individuals. Primary HIV-associated acute transverse myelitis, an acute inflammatory condition with pathologic similarities to HIV encephalitis, arises in early infection and at seroconversion. In contrast, HIV vacuolar myelopathy and opportunistic infections predominate in uncontrolled disease. There is systemic immune dysregulation as early as primary infection due to initial depletion of gut-associated lymphoid tissue CD4 cells and allowance of microbial translocation across the gut that never fully recovers throughout the course of HIV infection, regardless of how well controlled. The subsequent proinflammatory state may contribute to spinal cord diseases observed even after cART initiation. This chapter will highlight an array of spinal cord pathologies classified by stage of HIV infection and immune status.
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Affiliation(s)
- Seth N Levin
- Department of Neurology, Massachusetts General Hospital, Boston, MA, United States; Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States
| | - Jennifer L Lyons
- Department of Neurology, Brigham and Women's Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States.
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Abstract
Childhood tuberculosis (TB) has a high incidence and prevalence in developing countries like India with tubercular meningitis (TBM) being the most common cause of death. Most cases of TBM are diagnosed late when despite adequate therapy; morbidity and mortality continue to remain high. This review aims to provide a pragmatic approach at dealing with cases of tubercular meningitis in children including clinical features, laboratory and radiological criteria, treatment options and prognostic implications. The objective of this review is to assist in early identification, proper investigation and timely treatment of TBM in children in order to reduce neurological morbidity and mortality associated with it.
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Affiliation(s)
- Roosy Aulakh
- Department of Paediatrics, Government Medical College and Hospital, Chandigarh, India
| | - Sanya Chopra
- Department of Paediatrics, Government Medical College and Hospital, Chandigarh, India
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Kozko VM, Bondarenko AV, Gavrylov AV, Shevchenko OS, Gargin VV. Pathomorphological peculiarities of tuberculous meningoencephalitis associated with HIV infection. Interv Med Appl Sci 2017; 9:144-149. [PMID: 29201438 PMCID: PMC5700704 DOI: 10.1556/1646.9.2017.31] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background and aims One of the most severe manifestation displays of tuberculosis (TB) generalization is meningitis/meningoencephalitis. The purpose of this work was to improve the diagnostic efficiency of TB central nervous system (CNS) affection in human immunodeficiency virus (HIV)-infected persons. Materials and methods Meninges and cerebral tissues, taken from died patients, who were HIV-infected and dead from TB of CNS affection, were investigated histologically. Results and discussion Our examination showed that clinical course of the pathologic process loses the peculiarity of TB-undulating character, and changes in tissues have monomorphism that appears in the presence of the same type of granulomas with a few Pirogov–Langhans cells. Alterative reactions with formation of the large fields of caseous necrosis, necrotic focuses, areas of infiltration with polymorphic cellular elements went out on the first plan in the disorder of cerebrum in patients with the terminal stage of HIV infection. The tendency to decrease in inflammatory–proliferative processes was observed, which is confirmed by the presence of the poorly expressed cellular reaction on the peripheries of focuses of caseous necrosis. Conclusion Morphologic features of tuberculous meningoencephalitis in HIV-infected patients are the presence of edema, gliosis, trombovasculitis, small focal hemorrhage, tuberculous granuloma formation with a small number of Pirogov–Langhans cells, and the prevalence of alterative–exudative reactions.
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Affiliation(s)
- Volodymyr M Kozko
- Department of Infectious Diseases, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Andriy V Bondarenko
- Department of Infectious Diseases, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Anatoliy V Gavrylov
- Department of Infectious Diseases, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Olga S Shevchenko
- Department of Infectious Diseases, Kharkiv National Medical University, Kharkiv, Ukraine
| | - Vitalii V Gargin
- Department of Infectious Diseases, Kharkiv National Medical University, Kharkiv, Ukraine
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16
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Naidoo J, Mahomed N, Moodley H. A systemic review of tuberculosis with HIV coinfection in children. Pediatr Radiol 2017; 47:1269-1276. [PMID: 29052773 DOI: 10.1007/s00247-017-3895-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 04/04/2017] [Accepted: 05/04/2017] [Indexed: 12/19/2022]
Abstract
The epidemiology of tuberculosis is adversely impacted by the human immunodeficiency virus (HIV) coinfection. HIV-infected patients are more prone to opportunistic infections, most commonly tuberculosis, and the risk of death in coinfected patients is higher than in those without HIV. Due to the impaired cellular immunity and reduced immunological response in HIV-infected patients, the classic imaging features of tuberculosis usually seen in patients without HIV may present differently. The aim of this review article is to highlight the imaging features that may assist in the diagnosis of tuberculosis in patients with HIV coinfection.
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Affiliation(s)
- Jaishree Naidoo
- Department of Radiology, University of the Witwatersrand, Johannesburg, 2000, South Africa.
| | - Nasreen Mahomed
- Department of Radiology, University of the Witwatersrand, Johannesburg, 2000, South Africa
| | - Halvani Moodley
- Department of Radiology, University of the Witwatersrand, Johannesburg, 2000, South Africa
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Mandal N, Anand PK, Gautam S, Das S, Hussain T. Diagnosis and treatment of paediatric tuberculosis: An insight review. Crit Rev Microbiol 2017; 43:466-480. [PMID: 28502224 DOI: 10.1080/1040841x.2016.1262813] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Tuberculosis (TB) is a major public health problem, invading all age groups world-wide. It is an opportunistic infection affecting the individuals alone or with co-infections. Childhood TB is a neglected aspect and a significant health problem in epidemic areas. It constitutes more than 20% of TB incidence. Pediatric TB exists in the shadow of adult TB. The clinicians concentrate on pulmonary manifestation of TB, whereas it is a major problem in both pulmonary and extra-pulmonary infections. The rate of infection with this disease is mostly associated with poverty, social disruption and human immunodeficiency virus (HIV) infection. The diagnosis of extra-pulmonary TB (EPTB) is more difficult than pulmonary TB (PTB). Delayed diagnosis and executive treatment contribute to increase in the mortality rate in endemic areas. This article provides the evidence-based simple and safe screening method, indicating rapid, highly sensitive and specific diagnostic tests for pulmonary and EPTB in children. The most important aspect of treatment is the correct course of anti-tubercular drugs. This review serves the purpose of quick reference for microbiologists, epidemiologists, academicians, students and researchers. It provides guidance regarding early diagnosis and treatment accuracy of pediatric TB.
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Affiliation(s)
| | | | - Subhash Gautam
- b National Institute of Medical Statistics , New Delhi , India
| | - Shritam Das
- c Division of NCDs, Regional Medical Research Centre , Bhubaneswar , India
| | - Tahziba Hussain
- d Regional Medical Research Centre (ICMR) , Bhubaneswar , India
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Graf EH, Farquharson MV, Cárdenas AM. Comparative evaluation of the FilmArray meningitis/encephalitis molecular panel in a pediatric population. Diagn Microbiol Infect Dis 2016; 87:92-94. [PMID: 27771208 DOI: 10.1016/j.diagmicrobio.2016.09.022] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 08/29/2016] [Accepted: 09/28/2016] [Indexed: 11/16/2022]
Abstract
We compared an FDA cleared molecular meningitis/encephalitis panel to lab developed viral PCRs and bacterial culture. Of the 67 viral PCR or bacterial culture-positive samples, 92.5% were positive for the same target by the panel. Of the 66 negative samples tested, no targets were detected by the panel, for an agreement of 96.2%.
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Affiliation(s)
- Erin H Graf
- University of Pennsylvania, Department of Pathology and Laboratory Medicine, 3400 Spruce Street, Philadelphia, PA 19104; Children's Hospital of Philadelphia, Infectious Disease Diagnostics Laboratory, 3401 Civic Center Boulevard, Philadelphia, PA 19104
| | - Maria Victoria Farquharson
- Children's Hospital of Philadelphia, Infectious Disease Diagnostics Laboratory, 3401 Civic Center Boulevard, Philadelphia, PA 19104
| | - Ana María Cárdenas
- University of Pennsylvania, Department of Pathology and Laboratory Medicine, 3400 Spruce Street, Philadelphia, PA 19104; Children's Hospital of Philadelphia, Infectious Disease Diagnostics Laboratory, 3401 Civic Center Boulevard, Philadelphia, PA 19104.
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Yu N, Zhang QQ, Zhang K, Xie Y, Zhu HQ, Lin XJ, Di Q. Comparative study of CD4 and CD45RO T cells and CD20 B cells in cerebrospinal fluid of syphilitic meningitis and tuberculous meningitis patients. APMIS 2016; 124:764-9. [PMID: 27467195 DOI: 10.1111/apm.12572] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 05/30/2016] [Indexed: 12/11/2022]
Abstract
This study was to investigate the differences of lymphocyte in the cerebrospinal fluid (CSF) of patients with syphilis meningitis (SM) and tuberculous meningitis (TBM) for new diagnostic insights. Totally, 79 cases of SM and 45 cases of TBM were enrolled. In the CSF, the CD4, CD45RO or CD20 positive lymphocytes were detected by immunohistochemistry. The proportion of CD4 T cells in the CSF lymphocytes in patients with SM was significantly higher than that in patients with TBM (p < 0.05). After medical therapy, there was a significantly decline trend of the CD4 T-cell proportion in both groups (p < 0.05). The proportion of CD45RO T cells in CSF lymphocytes of patients with SM was less than that of patients with TBM (p < 0.05). After medical therapy, the positive ratio of CD45RO T cells was increased in the CSF of both group patients (p < 0.05). The proportion of CD20B cells in the CSF lymphocytes was not obviously different between the two groups during every stage. In conclusion, there are strong differences of CD4 and CD45RO T-cell ratio, but not the CD20 B cells in the meningitis. CD4 and CD45RO T cells in CSF are a useful complement in differentially diagnosing SM and TBM; it contributes to further understand the pathogenesis and prognosis of SM and TBM.
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Affiliation(s)
- Nian Yu
- Department of Neurology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Qiao-Quan Zhang
- Department of Pathology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Kang Zhang
- Department of Neurology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Yuan Xie
- Department of Pathology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Hai-Qing Zhu
- Department of Pathology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Xing-Jian Lin
- Department of Neurology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
| | - Qing Di
- Department of Neurology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, Nanjing, China
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van Veen KEB, Brouwer MC, van der Ende A, van de Beek D. Bacterial meningitis in patients with HIV: A population-based prospective study. J Infect 2016; 72:362-8. [PMID: 26774622 DOI: 10.1016/j.jinf.2016.01.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 12/22/2015] [Accepted: 01/07/2016] [Indexed: 12/23/2022]
Abstract
OBJECTIVE We studied occurrence, disease course, and prognosis of community-acquired bacterial meningitis in HIV-infected adults in the Netherlands. METHODS We performed a nationwide, prospective cohort study. Patients over 16 years old with bacterial meningitis were included. Data on patient history, symptoms and signs on admission, laboratory findings, radiologic examination, treatment, and outcome were collected prospectively. For HIV-positive patients additional information was collected retrospectively. RESULTS From March 2006 to December 2013, 1354 episodes of community-acquired meningitis were included in the cohort. Thirteen patients were HIV-infected (1.0%). The annual incidence of bacterial meningitis was 8.3-fold higher (95%CI 4.6-15.1, P < 0.001) among HIV-infected patients as compared to the general population (10.79 [95%CI 5.97-19.48] vs 1.29 [95%CI 1.22-1.37] per 100.000 patients per year). Predisposing factors (other than HIV), clinical symptoms and signs, ancillary investigations, causative organisms and outcome were comparable between HIV-infected and patients without HIV infection. CONCLUSIONS HIV-infected patients in the Netherlands have a 8.3-fold higher risk for bacterial meningitis as compared to the general population despite cART therapy. Clinical presentation and outcome of patients with acute bacterial meningitis with and without HIV are similar.
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Affiliation(s)
- Kiril E B van Veen
- Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands
| | - Matthijs C Brouwer
- Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Arie van der Ende
- The Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Diederik van de Beek
- Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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22
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Abstract
Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications.
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Affiliation(s)
- Kelly J. Baldwin
- Department of Neurology, Geisinger Medical Center, Danville, PA, USA
| | - Joseph R. Zunt
- Department of Neurology and Global Health, Harborview Medical Center, University of Washington School of Medicine, Seattle, WA, USA
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Rai D, Garg RK, Mahdi AA, Jain A, Verma R, Tripathi AK, Singh MK, Malhotra HS, Singh GP, Ahmad MK. Cerebrospinal fluid cytokines and matrix metalloproteinases in human immunodeficiency seropositive and seronegative patients of tuberculous meningitis. Ann Indian Acad Neurol 2014; 17:171-8. [PMID: 25024567 PMCID: PMC4090842 DOI: 10.4103/0972-2327.132617] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 12/03/2013] [Accepted: 12/06/2013] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Some important clinical differences exist between human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients. Alterations in the cerebrospinal fluid (CSF) cytokines and matrix metalloproteinase have been noted in tuberculous meningitis. In HIV-infected patients, the immunopathogenesis is expected to be different. MATERIALS AND METHODS In this study, 64 patients of tuberculous meningitis (28 HIV seropositive and 36 seronegative) were included. The patients were followed up for six months. Cerebrospinal fluid (CSF) samples of tuberculous meningitis patients and 20 controls were subjected to tissue necrosis factor (TNF)-α, interleukin (IL)-1β, interferon (IFN)-γ, IL-10, matrix metalloproteinase (MMP)-2, and MMP-9 estimations. The levels were correlated with the patients' baseline clinical characteristics, CSF parameters, neuroimaging findings, and the outcome. The outcome was assessed and modified with the Barthel index. RESULTS The CSF cytokines and MMP levels were significantly elevated in tuberculous meningitis when compared with the controls. There was no significant difference seen between HIV seropositive and seronegative tuberculous meningitis, except for the IL-1β level, which was significantly lower in the HIV-infected patients. The cytokine and MMP levels did not correlate with the baseline clinical characteristics, disease severity, cerebrospinal fluid characteristics, neuroimaging findings, and outcome. CONCLUSION In conclusion, HIV infection did not affect a majority of the CSF cytokines and MMP levels in tuberculous meningitis except for IL-1β level. None of the estimated inflammatory parameters correlated with the outcome.
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Affiliation(s)
- Dheeraj Rai
- Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Ravindra Kumar Garg
- Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Abbas Ali Mahdi
- Department of Biochemistry, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Amita Jain
- Department of Microbiology, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Rajesh Verma
- Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
| | | | - Maneesh Kumar Singh
- Department of Neurology, King George Medical University, Lucknow, Uttar Pradesh, India
| | | | - Gyan Prakash Singh
- Department of Anesthesia, King George Medical University, Lucknow, Uttar Pradesh, India
| | - Mohammad Kaleem Ahmad
- Department of Biochemistry, King George Medical University, Lucknow, Uttar Pradesh, India
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Luma HN, Tchaleu BCN, Ngahane BHM, Temfack E, Doualla MS, Halle MP, Joko HA, Koulla-Shiro S. Tuberculous meningitis: presentation, diagnosis and outcome in hiv-infected patients at the douala general hospital, cameroon: a cross sectional study. AIDS Res Ther 2013; 10:16. [PMID: 23758832 PMCID: PMC3686666 DOI: 10.1186/1742-6405-10-16] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2013] [Accepted: 06/06/2013] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION Tuberculous meningitis (TBM) the most fatal presentation of tuberculosis (TB) especially in HIV-infected patients is a real diagnostic and therapeutic challenge worldwide. In Cameroon where HIV and TB are amongst the leading public health problems, the magnitude of TBM has not been defined. Therefore, the objective of this cross sectional study was to describe the presentation and in-hospital outcome of TBM among HIV patients in Douala as well as its diagnostic difficulties. METHODS We did a clinical case note analysis of all HIV-1 infected patients treated for TBM in the Internal medicine unit of the Douala General Hospital, between January 1st 2004 and December 31st 2009. The diagnosis of TBM was made using clinical, laboratory [cerebrospinal fluid (CSF) analysis] and/or brain computerised tomographic (CT) scan features. RESULTS During the study period, 8% (54/672) of HIV-infected patients had TBM. Their mean age was 40.3 ± 12.7 years. The main presenting complaint was headache in 74.1% (40/54) of patients. Their median CD4 cell count was 16 cells/mm3 (IQR: 10 - 34). CSF analysis showed median protein levels of 1.7 g/l (IQR: 1.3 - 2.2), median glucose level of 0.4 g/l (IQR: 0.3 - 0.5) and median white cell count (WCC) count of 21 cells/ml (IQR: 12 - 45) of which mononuclear cells were predominant in 74% of CSF. Acid fast bacilli were found in 1.9% (1/54) of CSF samples. On CT scan hydrocephalus was the main finding in 70.6% (24/34) of patients. In hospital case fatality was 79.6% (43/54). CONCLUSION TBM is a common complication in HIV-infected patients in Douala with high case fatality. Its presumptive diagnosis reposes mostly on CSF analysis, so clinicians caring for HIV patients should not hesitate to do lumbar taps in the presence of symptoms of central nervous system disease.
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Abstract
PURPOSE OF REVIEW This article describes the background, clinical presentation, diagnosis, and treatment of selected etiologies of subacute and chronic meningitis. Key diagnostic considerations when evaluating a patient presenting with chronic inflammation of the CNS are discussed, and several specific infectious, neoplastic, and autoimmune etiologies are reviewed in detail. RECENT FINDINGS With recent advancement in serologic and CSF diagnostic testing, specific infectious, neoplastic, or autoimmune etiologies of chronic meningitis can be identified. Eliminating previous diagnostic uncertainty of chronic inflammation in the CNS has led to rapid and specific treatment regimens that ultimately improve patient outcomes. Recent advances in imaging have also aided clinicians in both their diagnostic approach and the detection of inflammatory complications such as hydrocephalus, hemorrhage, and ischemic stroke. SUMMARY Meningitis is defined as inflammation involving the meninges of the brain and spinal cord. Meningitis can be categorized as acute, subacute, or chronic based on duration of inflammation. This article focuses on the most common causes of subacute and chronic meningitis. Chronic meningitis is commonly defined as inflammation evolving during weeks to months without resolution of CSF abnormalities. Determining the time course of meningitis is important for creating a differential diagnosis. Most organisms causing acute meningitis rarely persist more than a few weeks. Although numerous etiologies of subacute and chronic meningitis have been identified, this article focuses on the most common etiologies: (1) infectious, (2) autoimmune, and (3) neoplastic.
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Affiliation(s)
- Joseph R Zunt
- Harborview Medical Center, 325 Ninth Ave, Room 3EH70, Box 359775, Seattle, WA 98104, USA.
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Abstract
Central nervous system (CNS) infections—i.e., infections involving the brain (cerebrum and cerebellum), spinal cord, optic nerves, and their covering membranes—are medical emergencies that are associated with substantial morbidity, mortality, or long-term sequelae that may have catastrophic implications for the quality of life of affected individuals. Acute CNS infections that warrant neurointensive care (ICU) admission fall broadly into three categories—meningitis, encephalitis, and abscesses—and generally result from blood-borne spread of the respective microorganisms. Other causes of CNS infections include head trauma resulting in fractures at the base of the skull or the cribriform plate that can lead to an opening between the CNS and the sinuses, mastoid, the middle ear, or the nasopharynx. Extrinsic contamination of the CNS can occur intraoperatively during neurosurgical procedures. Also, implanted medical devices or adjunct hardware (e.g., shunts, ventriculostomies, or external drainage tubes) and congenital malformations (e.g., spina bifida or sinus tracts) can become colonized and serve as sources or foci of infection. Viruses, such as rabies, herpes simplex virus, or polioviruses, can spread to the CNS via intraneural pathways resulting in encephalitis. If infection occurs at sites (e.g., middle ear or mastoid) contiguous with the CNS, infection may spread directly into the CNS causing brain abscesses; alternatively, the organism may reach the CNS indirectly via venous drainage or the sheaths of cranial and spinal nerves. Abscesses also may become localized in the subdural or epidural spaces. Meningitis results if bacteria spread directly from an abscess to the subarachnoid space. CNS abscesses may be a result of pyogenic meningitis or from septic emboli associated with endocarditis, lung abscess, or other serious purulent infections. Breaches of the blood–brain barrier (BBB) can result in CNS infections. Causes of such breaches include damage (e.g., microhemorrhage or necrosis of surrounding tissue) to the BBB; mechanical obstruction of microvessels by parasitized red blood cells, leukocytes, or platelets; overproduction of cytokines that degrade tight junction proteins; or microbe-specific interactions with the BBB that facilitate transcellular passage of the microorganism. The microorganisms that cause CNS infections include a wide range of bacteria, mycobacteria, yeasts, fungi, viruses, spirochaetes (e.g., neurosyphilis), and parasites (e.g., cerebral malaria and strongyloidiasis). The clinical picture of the various infections can be nonspecific or characterized by distinct, recognizable clinical syndromes. At some juncture, individuals with severe acute CNS infections require critical care management that warrants neuro-ICU admission. The implications for CNS infections are serious and complex and include the increased human and material resources necessary to manage very sick patients, the difficulties in triaging patients with vague or mild symptoms, and ascertaining the precise cause and degree of CNS involvement at the time of admission to the neuro-ICU. This chapter addresses a wide range of severe CNS infections that are better managed in the neuro-ICU. Topics covered include the medical epidemiology of the respective CNS infection; discussions of the relevant neuroanatomy and blood supply (essential for understanding the pathogenesis of CNS infections) and pathophysiology; symptoms and signs; diagnostic procedures, including essential neuroimaging studies; therapeutic options, including empirical therapy where indicated; and the perennial issue of the utility and effectiveness of steroid therapy for certain CNS infections. Finally, therapeutic options and alternatives are discussed, including the choices of antimicrobial agents best able to cross the BBB, supportive therapy, and prognosis.
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Affiliation(s)
- A Joseph Layon
- Pulmonary and Critical Care Medicine, Geisinger Health System, Danville, Pennsylvania USA
| | - Andrea Gabrielli
- Departments of Anesthesiology & Surgery, University of Florida College of Medicine, Gainesville, Florida USA
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Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat 2011; 2011:798764. [PMID: 22567269 PMCID: PMC3335590 DOI: 10.1155/2011/798764] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2011] [Revised: 11/16/2011] [Accepted: 11/18/2011] [Indexed: 01/01/2023] Open
Abstract
Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis (TB) and has very high morbidity and mortality. TBM is typically a subacute disease with symptoms that may persist for weeks before diagnosis. Characteristic cerebrospinal fluid (CSF) findings of TBM include a lymphocytic-predominant pleiocytosis, elevated protein, and low glucose. CSF acid-fast smear and culture have relatively low sensitivity but yield is increased with multiple, large volume samples. Nucleic acid amplification of the CSF by PCR is highly specific but suboptimal sensitivity precludes ruling out TBM with a negative test. Treatment for TBM should be initiated as soon as clinical suspicion is supported by initial CSF studies. Empiric treatment should include at least four first-line drugs, preferably isoniazid, rifampin, pyrazinamide, and streptomycin or ethambutol; the role of fluoroquinolones remains to be determined. Adjunctive treatment with corticosteroids has been shown to improve mortality with TBM. In HIV-positive individuals with TBM, important treatment considerations include drug interactions, development of immune reconstitution inflammatory syndrome, unclear benefit of adjunctive corticosteroids, and higher rates of drug-resistant TB. Testing the efficacy of second-line and new anti-TB drugs in animal models of experimental TBM is needed to help determine the optimal regimen for drug-resistant TB.
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