Global Health, Epidemiology and Genomics

Review Article

Association of Diabetes with Meningitis Infection Risks: A Systematic Review and Meta-Analysis

Table 2

Study characteristics and the quality score assigned. All columns’ values under disease etiology indicated as “Multiple” represent studies that reported finding both negative and negative grams but did not specify these pathogens. Same for sections indicated “General”.


Study	Country	Study period	Analytic method	Disease etiology	Study design	Quality score	Major etiology	Definition of meningitis

[40]	China	2014-2015	Multivariate and univariate logistic	Multiple	Retrospective	13	General	Meningitis was defined by: (1) organisms cultured from CSF; (2) at least one of these signs without identified cause: Fever (>38°C), headache, stiff neck, meningeal signs, irritability, and if analysis was conducted antemortem, attending physician instituted appropriate antimicrobial therapy, and at least one of the following: (a) Elevated white blood cell count, a rise in protein level in the CSF, and/or attenuated glucose level in CSF, (b) positive antigen test of CSF or blood; and (c) investigative single antibody titer (IgM) or an increase in paired sera (IgG) for pathogen by four-fold

[28]	Taiwan	2002–2010	Conditional logistic regression	C. neoformans meningitis, C. neoformans fungemia	Retrospective cas-control	12	Fungal	Cerebrospinal fluid [CSF]or blood culture positive culture n

[29]	USA	1996–2000	Logistic regression	Coagulase-negative staphylococci, Acinetobacter calcoaceticus, Pseudomonas aeruginosa, Serratia marcescens, Serratia species, Haemophilus influenzae	Retrospective	13	Bacteria	Meningitis was defined through gram stain, CSF culture or both, CSF leukocytosis with elevated protein concentration and reduced glucose level or both. Fever or nuchal rigidity with unknown cause or patients under antibiotic treatment prescribed by a physician.

[41]	Taiwan	2000–2010	Logistic regression	Cryptococcal meningitis	Prospective case-control	11	Fungal	Definition of meningitis: Cryptococcosis (ICD-9 117.5) or cryptococcal meningitis (ICD-9 321.0)

[42]	France	2012–2017	Logistic regression	Invasive meningococcal disease	Case-control	9	Bacteria	Meningitis was defined according to ICD-10 diagnostic code (A39.0 to A39.9) criteria

[4]	Spain	1977–2013	Simple linear regressions	Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes	Observational cohort study	11	Bacteria	Meningitis was defined through the following means: a Positive CSF culture, the occurrence of negative cultures when Gram negative diplococci was found from the CSF stain or when patients showed incidence of severe bacterial meningitis which is medically confirmed

[43]	Denmark	1977–2018	Logistic regression	Meningococcal serogroups B&C	Case-control	13	Bacteria	Positive CSF culture, positive antigen tests, on Gram’s stain of CSF

[44]	Taiwan	2012–2016	Logistic regression	Coagulase-negativeStaphylococcus, Staphylococcus aureus, Streptococcus pneumoniae, Viridans group, streptococci, Enterococcus faecalis, Corynebacterium, Micrococcus luteus, Gemella morbillorum, Klebsiella pneumoniae, Enterobacter aerogenes, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Bacteroides fragilis, Citrobacter freundii, Morganella morganii, Enterobacter cloacae, Cryptococcus neoformans	Retrospective observational	12	Bacteria	Positive organism CSF culture, and at least one of the following signs or symptoms where no other recognized cause was observed: Fever (>38°^C), headache, stiff neck, meningeal signs, cranial nerve signs, or irritability

[31]	Spain	1982–2017	Logistic regression	Neisseria meningitidis, Streptococcus pneumoniae, Listeria monocytogenes, Gram-negative bacilli	Prospective observational cohort study	12	Bacteria	Meningitis was defined as a diagnostic outcome of positive CSF culture and positive antigen tests. Any negative culture was further confirmed through CSF neutrophilic pleocytosis (=>100 neutrophils/cu mm or decreased CSF glucose (defined as CSF/blood glucose ratio <0.40) or elevated CSF proteins >0.5 g/l (for unknown etiology)

[30]	China	Jan-December 2008	Logistic regression	Acinetobacter baumannii, Enterococcus sp, Streptococcus intermedius and Klebsiella pneumonia	Retrospective cohort study	11	Bacteria	Patients had meningitis if they had one of these unknown indications: (Fever >38°c), meningeal signs, elevated white cell count, increased protein, or reduced glucose in the CSF. Organism identified on Gram’s stain of CSF, antigen test, positive blood culture, a prognosis of one antibody titer (IgM) or an elevation in paired sera (IgG) for pathogen by four-fold

[27]	Netherlands	2006–2014	Logistic regression	Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes	Prospective cohort	12	Bacteria	Bacterial meningitis was defined as having a positive cerebrospinal fluid culture, or a mix of positive blood culture without a significant pathogen, or a positive PCR result for streptococcus pneumoniae or neisseria meningitis with at least one cerebrospinal fluid finding predictive bacterial meningitis of a CSF of leukocyte counts >2000 cells/mm³, polymorphonuclear leukocyte count >1180 cells/mm3, glucose level <1.9 mmol/L, protein level >2 g/L, or CSF/blood glucose ratio <0.23

[45]	UK	2007–2017	Multivariate cox models	Neisseria meningitidis	Retrospective observational cohort study	13	Bacteria	Not reported

[46]	USA	1992–1994	Conditional logistic regression	Cryptococcus neoformans	Prospective study	8	Fungal	Positive culture for C. neoformans for any body part; detection of cryptococcal antigen in the blood, cerebrospinal fluid, or urine; or histopathologic findings consistent with cryptococcosis

[47]	Canada	1999-2000	Logistic regression	Staphylococcus aureus, Enterococcus, Streptococcus, Clostridium butyricum, Candida albicans	A population-basedactive-surveillance cohort design	10	Fungal	CSF and blood culture, pleural or synovial fluid, or aseptically obtained deep-tissue aspirates or surgical-tissue samples

[48]	Greece	2006–2008	Multivariate logistic regression, mantel-haenszel test	Acinetobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Enterobacter cloaceae, Proteus mirabilis	Prospective study design	12	Bacteria	CSF culture, signs of: fever, headache, stiff neck, meningeal and cranial nerves signs or irritability (if diagnosis was made antemortem) antimicrobial therapy, increased WBC counts, increased protein level or increased level of glucose in the CSF, organisms seen on Gram stain of CSF; organisms cultured from blood; positive antigen test of CSF, blood, or urine; diagnostic single antibody titer (IgM) or 4-fold increase in paired sera (IgG) for pathogen

[49]	Canada	1997–2001	Logistic regression	Cryptococcus gattii, Cryptococcus neoformans	Case-control study	12	Fungal	CSF and/or blood culture and classification of diseases, 9^th revision (ICD-9), code 117.5 (cryptococcosis)