Acute bacterial meningitis in Iran: Systematic review and meta-analysis Hamidreza Houri1☯‡, Ali Pormohammad1☯‡*, Seyed Mohammad Riahi2,3, Mohammad Javad Nasiri1, Fatemeh Fallah1, Hossein Dabiri1, Ramin Pouriran4 1 Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2 Department of Epidemiology, Birjand University of Medical Sciences, Birjand, Iran, 3 Department of Epidemiology, Faculty of Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 4 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran ☯ These authors contributed equally to this work. ‡ These authors are co-first authors. * [email protected]

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OPEN ACCESS Citation: Houri H, Pormohammad A, Riahi SM, Nasiri MJ, Fallah F, Dabiri H, et al. (2017) Acute bacterial meningitis in Iran: Systematic review and meta-analysis. PLoS ONE 12(2): e0169617. doi:10.1371/journal.pone.0169617 Editor: Ray Borrow, Public Health England, UNITED KINGDOM

Abstract Introduction Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial therapy. Accurate data has not been available regarding the epidemiology of bacterial meningitis particularly in developing countries, yet. Indeed, the present systematic review provides a comprehensive data analysis on the prevalence and epidemiology of bacterial meningitis in Iran.

Methods We systematically reviewed articles from 1994 to 2015. The reports which contained the prevalence and etiology of acute bacterial meningitis by valid clinical and laboratory diagnosis were comprised in the present study.

Received: August 26, 2016 Accepted: December 20, 2016 Published: February 7, 2017 Copyright: © 2017 Houri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information file. Funding: The authors received no specific funding for this work.

Results Our analysis indicated that Streptococcus pneumoniae (30% [I2 = 56% p < 0.01]), Haemophilus influenza type b (15% [I2 = 82.75% p < 0.001]), coagulase negative staphylococci (CoNS) (14% [I2 = 60.5% p < 0.06]), and Neisseria meningitidis (13% [I2 = 74.16% p < 0.001]) were the most common cause of acute bacterial meningitis among meningitis cases in Iran. Notably, high frequency rates of nosocomial meningitis pathogens were detected in the present analysis.

Conclusions It was magnificently attained that the majority of cases for bacterial meningitis in Iran could be avertable by public immunization schemes and by preventive care to inhibit the broadening of hospital acquired pathogens.

Competing interests: The authors have declared that no competing interests exist.

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Introduction Infectious meningitis includes viral, bacterial, fungal, and parasitic meningitis which have been considered as severe and potentially fatal pathogens, caused 422,900 deaths and according to the statistic in 2010 approximately 2628,000 patients with disabling sequelae [1]. In the meantime, acute bacterial meningitis (ABM) has been perceived as a common life threatening infection, especially in neonates and infants [2]. Even though, the introduction of broad-spectrum of antibiotics have made bacterial meningitis curable; nonetheless, the mortality and morbidity rate of this life threatening pathogens remains ostensibly high. Whereas, endemic bacterial meningitis residues relatively an infrequent illness in developed countries, the probability of occurrence of endemic and epidemic bacterial meningitis in undeveloped countries accumulates as the major infection [3]. As a matter of fact, ABM continues to be a principal reason of death among neonates in developing countries. Apparently, it seems that this disease debris’s the fourth leading cause of disability in these parts of the globe [4, 5]. Diagnosis of ABM is based on the combination of typical clinical symptoms and the consequent of laboratory tests which indicates the inflammatory response in cerebrospinal fluid (CSF); indeed, demonstrates the specific causative bacterial agent (Gram’s stain, culture, antigen assay and molecular detection) [6]. Three major pathogens have been detected for manifestation of ABM which are listed as follows: Streptococcus pneumonia (pneumococcus), Haemophilus influenzae type b (Hib), and Neisseria meningitidis (meningococcus). Transparently, they have been responsible for 118.400, 83.000, and 75.000 deaths, respectively worldwide [7, 8]. According to the above evidence analysis, a wide range of bacteria can cause ABM. Limpidly, group B Streptococci (GBS) or Streptococcus agalactiae is one of the primary causes of neonatal bacterial meningitis in premature and term infants up to 3 months in many developing countries [9]. The other transpicuous deliberated bacterial strains which apparently could cause bacterial meningitis are Enterobacteriaceae spp., principally Escherichia coli K1 and Klebsiella pneumoniae that can be quite fatal. Moreover, Listeria monocytogenes has been rarely responsible for bacterial meningitis in newborns and infants, especially during zoonotic outbreaks [10, 11]. Translucently, It is essential to state that according to the previous repots, the prevalence and etiologies of ABM vary in each geographical area [12]. To the best of our knowledge, there is no sufficient data regarding the epidemiology of bacterial meningitis in Iran. Allegedly due to the lack of a routine vaccination program against meningeal pathogens; such as, pneumococci in Iran, ABM is considered as a public health hazard with high rate of morbidity, mortality, and tremendous cost burden for the health care providers [13]. Consequently, since there was no accurate estimate of the burden of ABM in Iran, the present systematic study was conducted to provide useful insights concerning the prevalence and epidemiology of the ABM in Iran. Systematic review and meta-analysis according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement were used (S1 Table) [14].

Materials and methods Search strategies From January 1, 1994 to May 1, 2015, the entire studies addressing meningitis infections in Iran were collected from world-wide databases including Medline (via PubMed), Web of Science, Embase, and Iranian national databases. Presumably, the search was carried out in both English and Farsi, distinctly and the research was restricted solely to original articles. The following search terms containing Medical Subject Headings (MESH) or keywords in text, title, or abstract were used with the help of Boolean operators (“and” or “or”): ‘‘bacterial”, ‘‘meningitis” and ‘‘Iran”. In addition to English articles, all relevant papers in national databases;

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included Scientific Information Database ( and Magiran (, were utilized with similar search strategy and Farsi keywords. The reference and citation lists for the regain papers were searched by this phenomenal strategy and with any selected additional study.

Inclusion and exclusion criteria Apparently, the entire original articles presenting cross-sectional studies on the prevalence and etiology of ABM in patients with suspected meningitis in Iran were considered. Diagnosis of meningitis in the included studies were performed by abnormal CSF findings, including: increased polymorphonuclear leukocytes counts, protein concentration more than 100 mg/dl and hypoglycorrhachia, and CSF culture as the gold standard method for detecting and identifying meningeal isolates [15]. Evidently, numerous studies were excluded from the analysis because of the following reasons: articles which only focused on individual etiological agent for meningitis; article which only considered sub-acute or chronic meningitis, those which only considered individual groups of patients such as HIV positive or immunocompromised patients, surveys which contained other infectious meningitis besides bacterial infections; such as, viral, fungal, and those papers which did not utilize the mentioned methods above; furthermore, reviews and systematic review articles, case reports, and articles which were only available in abstract form were excluded.

Data extraction and definitions Data were extracted using an extraction form independently and in duplicate by 2 investigators. The following data were extracted from the chosen articles: the first author’s name, the year of the study, the year of publication, the mean age, the location of the studies, the number of cases participated, the method of conducting surveys, the source of samples, sample size, and the prevalence of ABM. The studies identified by the search strategy and were reviewed for eligibility based on title and abstract by two authors. Differences in data extraction between investigators were resolved by consensus.

Quality assessment Perspicuously, the quality assessment of inquiries were accompanied by two reviewers independently according to the Critical Appraisal Checklist recommended by the Joanna Briggs Institute [16]; moreover, the disagreements were resolved by consensus. The checklist composed of ten questions in which the reviewers answered the questions for the chosen studies based on an individual basis. The ‘Yes’ answer for each question got a point; indeed, the scores ranged from zero to ten. Apparently, the studies which obtained more than 60% were included in the present inquiry.

Meta-analysis The statistical analysis was carried out by Stata (version13) software. The point estimates of the effect size, the prevalence of bacterial meningitis, and its 95% confidence interval (95% CI) were estimated peculiarly for each study. Random effects models were used to estimate pooled effect. In this regard, the heterogeneity among studies were tested by Cochran’s Q-statistic I2 squared and Galbraith graph. In order to estimate pooled effect, we utilized metaprop command rather than metan in Stata software. For installing, the command needs to be connected to the internet and then typing ssc install metaprop in Stata. We used ftt cimethod (score) or Freeman-Tukey transformation procedures for collecting binomial data. Contrary to metan

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command, Stata automatically omits studies which their proportion were 0 or 1, transparently, this method does not make the mentioned problem; eventually, plot confidence in forest intervals always were in the range of 0–1 [17–19]. The P-value, 0.05 was considered significant.

Results Characteristics of included studies Translucently, a total of 314 reports were screened for the analysis of patients with ABM. Out of these studies 18 met the inclusion pellucid criteria (Fig 1). Characteristics of the selected articles are summarized in Table 1. In fact, 16 studies that were included in the analysis were in English and the rest were in Farsi. Overall, 1078 culture positive samples were analyzed in the included inquiries. Geographic location of the reports comprised east to west and north to south part of Iran; indeed, the majority of patients were coming from central part of Iran. The main diagnostic method in all included studies was the isolation and culture of the pathogen

Fig 1. Flow diagram of literature search and study selection. doi:10.1371/journal.pone.0169617.g001

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Table 1. Characteristics of studies included in the meta-analysis. Study

Published time

Enrollment time

Sampling area

Mean age

No. of culture positive

Attarpour et al. [30]




61±40.2 months


Ataee et al. [31]




16–70 years


Qurbanalizadegan et al. [32]




Acute bacterial meningitis in Iran: Systematic review and meta-analysis.

Bacterial meningitis persists in being a substantial cause of high mortality and severe neurological morbidity, despite the advances in antimicrobial ...
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