A Comparative Study between Children and Adults with Bacterial Neuroinfections

Introduction: Bacterial meningitis is an acute purulent infection of the meninges. There are significant differences in the etiological spectrum, clinical course and outcome of bacterial meningitis in the age groups, and their recognition is important for early diagnosis and adequate therapy. Aim: The study aims to determine the differences in the etiology and clinical presentation of bacterial meningitis between children and adults. Materials and methods: The study included 90 patients (25 children and 65 adults) with bacterial neuroinfection admitted to St George University Hospital, Plovdiv between January 1, 2016 and September 31, 2019. We applied epidemiological and clinical analysis, microbiological and statistical methods. Results: In adults, the most common etiological agent was Streptococcus pneumoniae (20%), followed by Staphylococcus spp . (18.5%), Listeria monocytogenes (12.3%), Streptococcus spp . (3.1%), Haemophilus influenzae (3.1%), Klebsiella pneumoniae (1.5%), and Mycobacterium tuberculosis (1.5%). The etiological structure in children was different: Neisseria meningitidis (20%), Streptococcus pneumoniae (16%), Klebsiella pneumoniae (8%), Enterococcus faecium (8%), Streptococcus salivarius (4%), and Mycobacterium tuberculosis (4%). In 40% of the cases, both children and adults, the causative agent was not identified. Conclusions : Regarding the clinical presentation, a statistical significance between the age groups was found with headache and alterations in consciousness, more commonly seen in adults, while vomiting, ear pain was more common in children ( p <0.05). Concomitant otitis, sinusitis, pneumonia, and sepsis were often observed. The mortality rate was much higher in adults (43%) when compared with children (8%).


AIM
The aim of the study was to establish the differences in the etiology and clinical course of bacterial neuroinfections between children and adults.

MATERIALS AND METHODS
The study included 90 patients with bacterial neuroinfection admitted to St George University Hospital in Plovdiv from January 1, 2016 to September 31, 2019. There were 25 children (up to 17 years of age) and 65 adults (range 18-87 years). The diagnosis was based on the clinical presentation, cerebrospinal fluid (CSF) examination, and microbiological testing.
Only patients with typical CSF abnormalities consistent with bacterial meningitis were included in the study (cell count >100×10 6 /l, protein >1 g/l, CSF/serum glucose ratio ≤0.4) and/or identified etiology by the CSF microbiological analysis.
We used in the study: 1. Epidemiological data about age and sex; 2. Clinical analysis; 3. Microbiological testing included CSF Gram stain and culture. Multiplex PCR for viral and bacterial agents was performed in 28 of the patients with bacterial neuroinfection. It is based on the detection of specific target genes of the most common causative agents by Biofire FilmArray Multiplex PCR (bioMerieux, France). The panel simultaneously identifies the following bacterial pathogens: S. pneumoniae, Streptococcus agalactiae, N. meningitis, L. monocytogenes, H. influenzae, Escherichia coli K1.
4. Statistical analysis: descriptive methods; parametric and non-parametric methods: Fisher's exact test and χ 2 ; Kolmogorov-Smirnov test. The significance level of the null hypothesis is p<0.05. Statistical data analysis was performed using the software product SPSS v.17 (IBM, USA).
The etiological distribution in children and adults differed significantly (χ 2 =23.799; р=0.0001) ( Table 1). Meningococcal meningitis affects only children, and listerial and staphylococcal meningitis -exclusively adults. Adults predominated (76.5%) in the group of pneumococcal meningitis. The ratio is similar for the etiologically unidentified cases of meningitis (72.2% were adults).

The period before hospitalization
Most of the children were admitted to the hospital within the first 3 days of the onset of the symptom (64%). Adult patients were hospitalized later (usually after 4-5 days), and in 21.5% we noticed hospitalisation to be delayed (>7 days from the onset of complaints). However, no significant difference was found between the age groups ( Table  2). Antibiotics were taken by 10 children (40%) and 28 adults (43.1%) prior to performing an initial lumbar puncture, without significant difference (p=0.817).

Clinical features in children and adults
Significant differences between the age groups were found for some clinical symptoms (Table 3). Headache was more frequent in adults, while vomiting was significantly more common in children, as well as otalgia and the presence of angina. Somnolence, sopor, coma, and especially qualitative alterations in consciousness (agitation, bradypsychia, hallucinations) were significantly more common in adults. Only 17.8% of patients had photophobia. The presence of rash (maculopapular, petechial, hemorrhagic), and seizures were more common in children, but without significant difference (p>0.05). Neck stiffness, Kernig, Brudzinski's signs, and focal deficits (paresis, hemiparesis, aphasia) were more common in adults, even without a significant difference (p>0.05) (Table 4).

Comparative assessment based on comorbidities and outcome
We found otitis media, mastoiditis, otomastoiditis, and sinusitis, pneumonia, and sepsis in patients with bacterial meningitis/meningoencephalitis. Sepsis was more com-Folia Medica I 2022 I Vol. 64 I No. 3 mon in adults, even without significant differences between children and adults ( Table 5).
The mortality rate was much higher in adults (43%) than in children (8%). Neurological sequelae (motor deficits and cognitive defects) in survivors were also more common in adults (13.8%) ( Table 6).

DISCUSSION
Streptococcus pneumoniae remains the most common etiologic agent of purulent meningitis in adults, although there has been a reduction in the incidence after the introduction of the pneumococcal vaccines. Unexpectedly high frequency was found for Staphylococcus spp. (18.5%), which according to other studies is quite a rare cause of neuroinfections. [9][10][11] This is probably due to a large number of patients with sepsis, in which staphylococcal meningitis followed. Listeria monocytogenes, which is the third leading cause of bacterial neuroinfections in our patients and according to numerous European studies, will be in-creasingly important in the near future, because of the growing number of people with concomitant oncological and autoimmune diseases and immunosuppression.
Similar to European data [2,12] , the main causative agents of bacterial meningitis in children are Neisseria meningitidis and Streptococcus pneumoniae, but no case of Haemophilus influenzae was observed, in contrast to studies in Poland and Turkey, reporting an incidence of 18%. [13,14] There is still a high incidence of meningitis due to Haemophilus influenzae in countries with incomplete immunization programs such as Iran and Pakistan (12.4%). [15,16] In our study, there is a high proportion of etiologically unidentified neuroinfections (40%). May be due to the fact that a significant proportion of patients were initiated on antibiotic therapy before undergoing a lumbar puncture, that makes it difficult to identify the cause by CSF culture The distribution of patients by gender showed a male prevalence regardless of age. According to other authors, men and women suffer equally often, with insignificant differences. [5,17] Folia Medica I 2022 I Vol. 64 I No. 3  (3); in adults -otitis (4), mastoiditis (4), sinusitis (13)  (2), quadriparesis (2), hemiparesis (4), paraparesis (3); cognitive defects -cognitive slowness (3), neuropsychologic sequelae (2), and epilepsy (1) ache and disturbances in consciousness are more common in adults, while vomiting and ear pain are more typical in children. Because of the high mortality and sequelae in patients with bacterial neuroinfections, rapid clinical recognition and laboratory diagnosis are needed in order to begin adequate treatment as soon as possible.
The analysis of the clinical presentation showed that fever was the most common symptom (96.7%). While vomiting was more prevalent in children (80% vs. 43.1% in adults), the headache was more common in adults (66.2% vs. 40%). Similar data on the main clinical symptoms have been reported by a number of researchers in Europe. [8,13,18,19] Photophobia had an unexpectedly low frequency (17.8%). Our patients had a skin rash in 24% of children and 15.4% of adults. Many authors reported a significantly higher frequency of rash in both children (39-51%) and adults groups (20-26%). [17,[20][21][22] In the observed patients neck stiffness, Kernig and Brudzinski's signs are more widespread in adults. Seizures are more common in children (24%) than in adults (18.5%). These findings correlate with the data of many European authors. [6,[23][24][25] The frequency of cranial nerve palsy in the studied patients (7.8%) was several times lower compared to the data of Van de Beek et al. (28%). [8] The incidence of focal neurological deficit (10%) is also lower when compared to other European studies, reporting 15-34%. [17,20,26] Comorbidities were more common in adults (53.8%) than in children (36%). Weisfelt et al. reported 32.5% for otitis or sinusitis, 15.2% pneumonia, and 13% sepsis, similar to our results. [6,7] The disease prognosis was more favourable for children. The mortality rate was much higher in adults, which is in accordance with the literature. [7,16,17]

CONCLUSIONS
The most common etiological agents of bacterial agents are Streptococcus pneumoniae in adults, and Neisseria meningitidis and Streptococcus pneumoniae in children. Head-