Introduction influenzae, Enterobacter spp., N. meningitidis, and B.


Introduction

Meningitis
is an acute inflammatory disease which impacts membranes surrounding the
central nervous system (brain and spinal cord) and is relatively a common and
potentially severe infection in childhood 1-3. Meningitis is
generally classified into bacterial and aseptic meningitis 3.

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Aseptic
meningitis is a clinical syndrome in which cultures for routine bacterial
pathogens are negative. Viral infections are the most common cause of aseptic
meningitis 4,5. Acute
meningitis in children is mainly aseptic and does not require antibiotic
treatment, is rarely life-threatening or requires hospitalization (unless
comorbidity or illness severity dictate otherwise) and full recovery is
achieved quickly1 3 6.

Although bacterial meningitis has a considerably
lower incidence rate than viral/aseptic meningitis 7, it
is still known as one of the most dangerous infectious diseases. The mortality and
disabling neurological sequelae from septic meningitis among children are
significant 8,9. So, rapid diagnosis of bacterial meningitis and its
differentiation from aseptic meningitis should be done to allow early
initiation of therapy for children at risk of having the disease without over
treating low-risk children 8-10.

 Epidemiological studies have been conducted to
determine the prevalence and incidence of bacterial meningitis among children
in different parts of Iran, including the study that was reported by Ghotaslou
et al.(2015). This systematic review showed that in 23 years, among 18,163 cases
that were studied, 1,074 cases met the criteria for bacterial meningitis in 23
papers. Overall, the most common agent associated with bacterial meningitis was
S. pneumoniae followed by H. influenzae, Enterobacter spp., N. meningitidis,
and B. streptococcus group.11

In another study
that was conducted by Mosavi Jarrahi et al(2009), the average incidence of
meningitis for all children under the age of 15 years was 12.8 and 6.6 cases
per 100,000 population for men and women, respectively, in Tehran metropolis
between1999 and 2005.12

Another
interesting cross-sectional study that was carried out by Motamedifar et al in 2015 with the aim of determining the
etiological agents and pattern of bacterial meningitis Shiraz Namazi Hospital
showed that out of
2229 suspected meningitis cases, 255 (11.4%) were detected as positive culture.
Most of the isolates were Gram-positive cocci, which 116 (45.5%) were Staphylococcus
epidermidis, and 20 (7.8%) identified as Streptococcus spp.
Among Gram-negative isolates, Escherichia coli and Acinetobacter spp.,
each with 19 isolates (5.9%), were predominant. 13

Studies have also been conducted in other countries
of the world, including a Cohort study in Canada in 2017 by Ouchenir et al that
included infants <90 days of age with bacterial meningitis at 7 pediatric tertiary care hospitals. There were 113 patients diagnosed with proven meningitis (n = 63) or suspected meningitis (n = 50) presented at median 19 days of age, with 63 patients (56%) presenting a diagnosis from home. Predominant pathogens were Escherichia coli (n = 37; 33%) and group B streptococcus (n = 35; 31%) 14. The vast majority of patients with acute meningitis are administered broad-spectral antibiotics targeting acute bacterial meningitis while awaiting results of definitive CSF bacterial cultures 15. Since laboratory results are normally prepared within 24 to 72 hours, distinguishing bacterial from aseptic meningitis is often difficult at the time of admission 16. Failure to diagnose and accurately differentiate bacterial meningitis leads to devastating attack rates and growing drug resistance among causative bacteria, leading to treatment failures 17. on the hand, in the absence of acute bacterial meningitis, this practice may enhance the local frequency of antibiotic resistance, cause adverse antibiotic effects, and high medical cost 18. One of the other problems with differentiating bacterial and viral meningitis is a negative cerebrospinal fluid (CSF) Gram stain and culture that is a diagnostic and therapeutic challenge 19,20. Because of the uncertainty in the diagnosis and the criticality of the situation, most patients are admitted to the hospital and treated empirically with intravenous antibiotic therapy, even though only a small minority have bacterial meningitis 21. One of the important issues in diagnosing this disease is the clinical presentations. the clinical symptoms and laboratory tests including CSF parameters could be overlapping in bacterial and viral/aseptic meningitis. The constellation of symptoms of fever, nuchal rigidity, and changes in mental status, a well-known triad of meningitis, was observed in only 44% of patients with bacterial meningitis 22. Also, fever, headache, vomiting, and neck stiffness were significantly more in aseptic meningitis children in some studies; While convulsion, consciousness change, fontanelle bulging, and desaturation were more objective and were significantly more in bacterial group 23. Thus, relying solely on the clinical history and physical examination of patients suspected of having bacterial meningitis could be misleading 24. Most important diagnostic study for patients with possible meningitis is lumbar puncture with CSF analysis.25 Till now, the gold standard for the diagnosis of bacterial meningitis and distinguishing it from aseptic meningitis has been CSF which requires considerable time to prepare its result.26 Fortunately, several diagnostic methods have been developed to diagnose viral or aseptic meningitis, the most important being reverse transcriptase PCR, which is increasingly being used as the incidence of aseptic meningitis rises and its use may reduce the hospital related cost by rapid diagnosis and earlier discharge from the hospital.27 Serum biomarkers such as C-reactive protein (CRP) and lactate also have some roles in differentiating bacterial meningitis from other meningitis. Gram stain, culture, glucose and cell count of cerebrospinal fluid (CSF) provide evidence to assist the clinical diagnosis.28-30 Unfortunately, no single clinical symptom or laboratory test has differentiated acute bacterial meningitis from aseptic meningitis with 100% sensitivity and high specificity.31 A combination of test results, however, may permit an accurate prediction of the likelihood of bacterial versus viral meningitis.32 In a retrospective chart review of 129 child hospitalized as meningitis in a polish hospital, that mostly admit patients with low vaccination coverage, parameters including C-reactive protein, D-dimers, fibrinogen, glucose level, and leukocyte level, and in cerebrospinal fluid, protein, glucose, and leukocyte concentrations were analyzed for discriminating between bacterial and aseptic meningitis. Results showed that among 65 diagnosed with bacterial meningitis and 64 with aseptic meningitis all measured parameters were significantly different between two groups (p < 0.000001). 33 Therefore, this study is designed with the aim of developing a model that uses clinical, laboratory and radiological manifestations by considering geographical and epidemiological location of Fars province as well as vaccination status of the most common etiological agents causing meningitis in children. The results of this study will help pediatricians to quickly and accurately diagnose and differentiate bacterial meningitis in a more accurate and timely manner, and prevent unnecessary antibiotic treatment of viral infections as much as possible in order to decrease the costs of admission, antibiotic treatment and resistance. It can also reduce unwanted psychological complications caused by hospitalization of children at this critical age.  

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