Epidemiology of central nervous system infectious diseases: a meta-analysis and systematic review with implications for neurosurgeons worldwide

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OBJECTIVE

Central nervous system (CNS) infections cause significant morbidity and mortality and often require neurosurgical intervention for proper diagnosis and treatment. However, neither the international burden of CNS infection, nor the current capacity of the neurosurgical workforce to treat these diseases is well characterized. The objective of this study was to elucidate the global incidence of surgically relevant CNS infection, highlighting geographic areas for targeted improvement in neurosurgical capacity.

METHODS

A systematic literature review and meta-analysis were performed to capture studies published between 1990 and 2016. PubMed, EMBASE, and Cochrane databases were searched using variations of terms relating to CNS infection and epidemiology (incidence, prevalence, burden, case fatality, etc.). To deliver a geographic breakdown of disease, results were pooled using the random-effects model and stratified by WHO region and national income status for the different CNS infection types.

RESULTS

The search yielded 10,906 studies, 154 of which were used in the final qualitative analysis. A meta-analysis was performed to compute disease incidence by using data extracted from 71 of the 154 studies. The remaining 83 studies were excluded from the quantitative analysis because they did not report incidence. A total of 508,078 cases of CNS infections across all studies were included, with a total sample size of 130,681,681 individuals. Mean patient age was 35.8 years (range: newborn to 95 years), and the male/female ratio was 1:1.74. Among the 71 studies with incidence data, 39 were based in high-income countries, 25 in middle-income countries, and 7 in low-income countries. The pooled incidence of studied CNS infections was consistently highest in low-income countries, followed by middle- and then high-income countries. Regarding WHO regions, Africa had the highest pooled incidence of bacterial meningitis (65 cases/100,000 people), neurocysticercosis (650/100,000), and tuberculous spondylodiscitis (55/100,000), whereas Southeast Asia had the highest pooled incidence of intracranial abscess (49/100,000), and Europe had the highest pooled incidence of nontuberculous vertebral spondylodiscitis (5/100,000). Overall, few articles reported data on deaths associated with infection. The limited case fatality data revealed the highest case fatality for tuberculous meningitis/spondylodiscitis (21.1%) and the lowest for neurocysticercosis (5.5%). In all five disease categories, funnel plots assessing for publication bias were asymmetrical and suggested that the results may underestimate the incidence of disease.

CONCLUSIONS

This systematic review and meta-analysis approximates the global incidence of neurosurgically relevant infectious diseases. These results underscore the disproportionate burden of CNS infections in the developing world, where there is a tremendous demand to provide training and resources for high-quality neurosurgical care.

ABBREVIATIONS AFR = African Region; AMR-L = Region of the Americas–Latin America; AMR-US/Can = Region of the Americas–United States/Canada; BM = bacterial meningitis; CNS = central nervous system; EMR = Eastern Mediterranean Region; EUR = European Region; HIC = high-income country; HIV = human immunodeficiency virus; LIC = low-income country; LMICs = low- and middle-income countries; MIC = middle-income country; NCC = neurocysticercosis; SEAR = Southeast Asia Region; TB = tuberculosis; WPR = Western Pacific Region.

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Article Information

Correspondence Faith Robertson: Harvard Medical School, Boston, MA. faith_robertson@hms.harvard.edu.

F.C.R. and J.R.L. contributed equally to this work and share first authorship.

INCLUDE WHEN CITING Published online June 15, 2018; DOI: 10.3171/2017.10.JNS17359.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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Figures

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    PRISMA diagram summarizing the search process. From a total of 10,906 studies, 154 were incorporated into the review, with 71 in the quantitative analysis.

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    Global incidence and burden of CNS infection. For the five CNS infection types studied, the combined incidence (A) and global burden (B) of CNS infection are depicted, as are proportions of infection by pathology (C). Publications on cerebral malaria, cryptococcal meningitis, unspecified CNS infections, and HIV-related CNS infections were not included since those are primarily medically managed disease entities with less relevance for neurosurgical intervention. Map reproduced with permission from OpenStreetMap Contributors, CC BY-SA 2.0 (http://www.openstreetmap.org/copyright). Figure is available in color online only.

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    Forest plot demonstrating distribution of overall incidence of BM by WHO region. Twenty-two studies on BM were included, and data were analyzed according to WHO region. Overall incidence was highest in Africa and lowest in AMR-US/Can. Solid squares represent the point estimate of each study, and the diamonds represent the pooled estimate of the incidence for each subgroup. The width of the diamond denotes 95% CIs. The size of the solid squares is proportional to the weight of the study. ES = effect size. Figure is available in color online only.

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    Forest plot demonstrating distribution of overall incidence of BM by World Bank income level. Twenty-two studies on BM were included, and data were analyzed according to LIC, MIC, and HIC World Bank indication. Figure is available in color online only.

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    Forest plot demonstrating distribution of overall incidence of NCC by WHO region. Neurocysticercosis was the most reported individual disease in publications of CNS infections worldwide (27 of 71 included in the final statistical analysis). Overall incidence was highest in AFR and lowest in EMR. Solid squares represent the point estimate of each study, and the diamonds represent the pooled estimate of the incidence for each subgroup. The width of the diamond denotes 95% CIs. The size of the solid squares is proportional to the weight of the study. Figure is available in color online only.

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    Forest plot demonstrating distribution of overall incidence NCC by World Bank income level. Twenty-seven studies regarding NCC were analyzed according to LIC, MIC, and HIC World Bank indication. Solid squares represent the point estimate of each study, and the diamonds represent the pooled estimate of the incidence for each subgroup. The width of the diamond denotes 95% CIs. The size of the solid squares is proportional to the weight of the study. Figure is available in color online only.

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