Cuong Chi Ngo1,2,3, Shungo Katoh4,5, Futoshi Hasebe6, Bhim Gopal Dhoubhadel7,8, Tomoko Hiraoka1,9, Sugihiro Hamaguchi10, Anh Thi Kim Le6, Anh Thi Hien Nguyen11, Anh Duc Dang11, Chris Smith7,12, Lay-Myint Yoshida13, Cuong Duy Do3, Thuy Thi Thanh Pham3,14, Koya Ariyoshi15,16. 1. Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. 2. Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 3. Center for Tropical Diseases, Bach Mai Hospital, Hanoi, Vietnam. 4. Department of General Internal Medicine and Clinical Infectious Diseases, Fukushima Medical University, Fukushima, Japan. 5. Department of General Internal Medicine and Infectious Diseases, Kita-Fukushima Medical Center, Fukushima, Japan. 6. Vietnam Research Station, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. 7. School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan. 8. Department of Respiratory Infections, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. 9. Department of General Internal Medicine, Nagasaki Rosai Hospital, Nagasaki, Japan. 10. Department of General Internal Medicine, Fukushima Medical University, Fukushima, Japan. 11. National Institute of Hygiene and Epidemiology, Hanoi, Vietnam. 12. Department of Clinical Research, London School of Hygiene and Tropical Medicine (LSHTM), London, England. 13. Department of Pediatric Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan. 14. The Partnership for Health Advancement in Vietnam (HAIVN), Hanoi, Vietnam. 15. Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. kari@nagasaki-u.ac.jp. 16. School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan. kari@nagasaki-u.ac.jp.
Abstract
BACKGROUND: Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis. METHODS: We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA). RESULTS: Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31-58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2-14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1-212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0-882) was associated with tubercular meningitis. CONCLUSIONS: Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.
BACKGROUND: Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis. METHODS: We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA). RESULTS: Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31-58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2-14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1-212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0-882) was associated with tubercular meningitis. CONCLUSIONS: Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.
Authors: G E Thwaites; T T H Chau; K Stepniewska; N H Phu; L V Chuong; D X Sinh; N J White; C M Parry; J J Farrar Journal: Lancet Date: 2002-10-26 Impact factor: 79.321
Authors: Jorge Parra-Ruiz; V Ramos; C Dueñas; N M Coronado-Álvarez; R Cabo-Magadán; V Portillo-Tuñón; D Vinuesa; L Muñoz-Medina; J Hernández-Quero Journal: Infection Date: 2015-04-14 Impact factor: 3.553
Authors: Walter R Taylor; Kinh Nguyen; Duc Nguyen; Huyen Nguyen; Peter Horby; Ha L Nguyen; Trinh Lien; Giang Tran; Ninh Tran; Ha M Nguyen; Thai Nguyen; Ha H Nguyen; Thanh Nguyen; Giap Tran; Jeremy Farrar; Menno de Jong; Constance Schultsz; Huong Tran; Diep Nguyen; Bich Vu; Hoa Le; Trinh Dao; Trung Nguyen; Heiman Wertheim Journal: PLoS One Date: 2012-08-30 Impact factor: 3.240