CNS Infections in Jeddah: Pediatric Pathogen Etiology (2015-2019)

This report investigates the most common pathogen etiologies causing meningitis and encephalitis in pediatric patients suffering from Central Nervous System (CNS) infections in Jeddah, Saudi Arabia, between 2015 and 2019. The study is a retrospective analysis of medical records from Jeddah Regional Laboratory (JRL), examining data from pediatric patients with CNS infections. The research aims to identify prevalent pathogens, understand microbial populations associated with pediatric CNS infections in Jeddah, and potentially aid in the development of rapid and accurate diagnostic tools. The study employs descriptive statistics to summarize patient demographics, epidemiological characteristics, and clinical and laboratory findings, using SPSS for data analysis. The findings are expected to provide valuable insights into the dominant pathogens causing CNS infections in Jeddah, supporting improved clinical management, treatment strategies, and public health measures.

Most common pathogen aetiology causing meningitis and
encephalitis in pediatric suffering from Central Nervous
System (CNS) infections in the city of Jeddah, Saudi Arabia, for
the period 2015- 2019
1

Summary
Central nervous system (CNS) infections amongst children are the common occurrences
worldwide where meningitis being the most dangerous and the most common of such
infections. The infections are mainly caused by pathogens such as bacteria, fungi and
viruses. Incidents such as injuries are also accountable for some of the cases. This study
will attempt to identify the pathogen that is highly responsible for CNS infections in
Jeddah. This will provide key information regarding the prevalence of pathogen,
aetiology of associated CNS infections in pediatric department in Jeddah city, and assist
in the understanding of microbial population associated with pediatric CNS infections in
Jeddah. This might be of valuable help in the development of rapid, accurate, cost-
effective, more reliable diagnostic tools for detection of the pathogen causing CNS
infections in pediatric that may give a clinician a fast answer for proper treatment. This
study will be a retrospective study performed on medical record for all pediatric patients
that had CNS infections from January 2015 – December 2019 at JRL. Descriptive
statistics will be used to summarize the patients’ demographic, epidemiological, clinical
and laboratory characteristics. Statistical software for social sciences (SPSS) will be used
for analysis of exploratory data and for descriptive statistics.
Literature review
2

The central nervous system (CNS) is compromised of the brain and the
spinal cord, which is covered and protected by a triple layer called the
meninges. Central nervous system infections can be defined as
infections that affect the brain (encephalitis), meninges (meningitis)
and the spinal cord (myelitis) or more than one region
(meningoencephalitis). Moreover, it should be noted that the intensity
of the infections could be either acute or chronic. A wide range of
microorganisms can affect the normal functioning of the central
nervous system and cause infections (Beek et al., 2004). These
microorganisms include bacteria, viruses, protozoa and fungus.
(Swanson &Mcgavern, 2015). The general signs and symptoms of CNS
infections include a headache, vomiting, irritability, mental confusion,
photophobia, neck stiffness, nausea, fever, alteration in the level of
consciousness and Coma ( Brown et al., 2018).
Meningitis is defined as an inflammation of the meninges
membrane that leads to the swelling of the layers that covered and
protected the brain and the spinal cord (Beek et al., 2004). This
inflammation is usually occurred due to an infection caused by
bacteria, virus and another microorganism (He et al., 2016). Bacterial
Meningitis has been considered as the fatal CNS infection. It leads to
drastic consequences such as hearing impairment, brain damage,
learning impairment and limb amputation (Masri et al., 2018). Jones
and Winograd, (2018) stated that according to annual estimation of
3

US, 4100-5000 individuals with confirmed bacterial meningitis lead to
approximately 500 deaths every year . He et al. (2016), suggested that
the mortality rate associated with the bacterial meningitis is 6% to
26% in population of Saudi arabia. As mentioned by Jones and
Winograd (2018), the causative agents Haemophilus influenza,
Streptococcus pneumonae and Neisseris meningitides remain the
highest contributor of Bacterial Meningitis in the global population.
Jones and Winograd, (2018), showed causative agent for bacterial
meningitis varies across different age groups of paediatrics as showed
inTable 1. Infection caused by Haemophilus influenza type b and seven
serotypes of Streptococcus pneumoniae has reduced significantly in
pediatrics patient after the introduction of conjugate vaccines (Beek et
al., 2004).
Table. 1
Age-group Causative Agent
New born Streptococcus agalactiae, Escherichia
coli and Listeria monocytogenes
Infants,Children and young adults Neisseria meningitis, Streptococcus
pneumonia, and Haemophilus
influenzae
Source: created by author
4

Fungal meningitis is caused by the transmission of certain types
of the fungus through the blood to the meninges and leads to swelling
of meninges membrane (Dorratoltaj et al., 2017). Fungal meningitis is
usually common in the patients who are infected with HIV that disrupts
the immune system of the body. The common causative agent of
fungal meningitis is Cryptococcus species that equivalent to 70.1%
within the pediatric and the adult patients. Furthermore,
Coccidioidesspp, Candidaspp and Histoplasma species contribute to
approximately 16.4%, 7.6% and 6.0% of the fungal Meningitis in USA
( Jones and Winograd 2018).
CNS viral infections can be either viral meningitis
(asepticmeningitis) or viral encephalitis where viral meningitis occurs
when viruses infect meninges membrane. On the other hand, viral
encephalitis can be defined as a condition that occurs when viruses
directly invade the brain (Swanson &Mcgavern, 2015). The major
causative agents of CNS viral infections are Enteroviruses that has
been targeted children. Other major viral causative agents that cause
CNS infections are Mumps virus, Herpes simplex viruses, Measles
virus, West Nile Virus, Lymphocytic virus St. Louis encephalitis virus,
bunyaviruses, varicella-zoster virus, Epstein Barr virus,
cytomegalovirus, measles and human immunodeficiency virus
(Swanson &Mcgavern, 2015).
5

Cerebrospinal Fluid (CSF) analysis can be defined as a series of
laboratory tests that are performed on a sample of cerebrospinal fluid.
The CSF is produced by specific cells in the Choroid plexus region and
it fills the subarachnoid space (Stone & Hawkins, 2007). The CSF fluid
is regenerated and circulates the nutrients around the brain and spinal
column (Bonadio, 2014).Besides, the fluid is responsible for the
protection of the central nervous system. CSF collected by lumbar
puncture technique where a needle is inserted between lumbar
vertebrae L3 and L4 and using aseptic technique. The analysis of the
CSF sample facilitates analysis of fluid pressure, protein and glucose
level, RBC and WBC count, bacterial and viral profile, cultures and
gram stain (Bonadio, 2014).
A laboratory finding of CSF analysis in case of bacterial, viral and
fungal infections can bedescribed in Table 2 (Seehusen et al., 2003).
Table. 2
Characteristics Bacterial Viral Fungal
Opening pressure Increased Normal Variable
Glucose Low Normal Low
Protein Mild - elevated Normal Elevated
6

Wbcs >1000/mm3 <100/mm3 Variable
Differential polymorphs lymphocytes lymphocytes
Diagnosis is generally carried out through clinical examination,
neuroimaging and laboratory testing that includes culture and Gram
stain in the detection of fungal and bacterial causative agents by
traditional methods (Chadwick et al., 2002). Newer methods have been
identified as effective methods to detect a broad spectrum of
pathogens that cause CNS infections by using molecular techniques
such as polymerase chain PCR (Chadwick et al., 2002).
Despite the regular occurrences of meningitis and encephalitis in
Jeddah, it is considered as one of the most important cities in Saudi
Arabi and because of that Jeddah is a major destination for the
religious pilgrimage (Hajj and Umrah) for people in world. Most
common pathogen aetiology causing meningitis and encephalitis in
pediatric suffering from CNS infection in the city of Jeddah is still
unknown. This is largely because no effort has been made for
documenting and analyzing causes for trends in infection and
designing effective treatment plan in order to help pediatric patients.
Hence, efforts aiming to identify the causal pathogen at an early stage
are extremely important in designing optimal clinical management of
patients who are suffering from CNS infections. Furthermore, this
research will be of significant help in pointing out the most prevalent
7

pathogen causing CNS infections in Jeddah that will go a long way into
helping clinically manage patients suffering from the CNS infections
better. This will reduce costs of acquisition of medicine since it will
ensure that most required intervention is the one that is mostly
invested in. It will also assist researchers for coming up with an
effective treatment for CNS infections since effort will be given for
establishing the dominant symptoms of the most prevalent pathogen
causing the infection. Therefore, a test treatment can be developed,
administered and then monitored to give a clear idea about the one
that is most efficient.
Importance of the study:
This is the first study that will provide key information regarding
the prevalence of pathogen aetiology associated with CNS infections in
pediatric patients in Jeddah city, and help in the understanding of
microbial population associated with pediatric CNS infections in
Jeddah. This might be of valuable help in the development of rapid,
accurate, cost-effective, more reliable diagnostic tools for detection of
the pathogen causing CNS infections in pediatric, which may give a
clinician a fast answer for proper treatment. Moreover, the information
from this study may support the development of new policy for
8

prevention and facilitate epidemiological surveillance and public health
measures.
Aims of the study:
This study aims to identify the most common pathogen etiology
causing meningitis and encephalitis in pediatric patients in the city of
Jeddah by using molecular screening techniques and conventional
techniques.
Specific objectives
The specific objectives of this study will be to:
• To Identify the most common pathogen aetiology causing
meningitis and encephalitis in pediatric patients in the city of Jeddah
by using molecular screening
• Provide supportive information that may be useful in the
development of rapid, accurate, cost-effective, more reliable
diagnostic tools for detection of the pathogen causing CNS infections
in pediatric in Jeddah.
Study design
This study will be a retrospective study performed on medical
record for all pediatric patients that had CNS infections between
January 2010 – December 2014 at Jeddah Regional Laboratory (JRL)
which received all CSF samples from all pediatric hospital in Jeddah .
9

Research question:
What are the most common pathogens causing meningitis and
encephalitis in pediatric patients are suffering from central nervous
system infections in the city of Jeddah, Saudi Arabia, for the period
2015- 2019 ?
Hypotheses:
This is descriptive study and hypothesis is not required.
Subjects and controls
This study will use of all pediatric data collected from January
2015-December 2019 from the medical records of pediatric suffering
from CNS infections at JRL.
The inclusion criteria for study are following:
 All pediatric patients suffering from CNS infections.
 Patients of age 18 years and younger.
 Patients with positive CSF result for viruses or bacteria
byqualitative multiplex Real-Time PCR kits,isolated colony by
conventional methods for bacteria or fungi,abnormal WBC count
of CSF, elevation of CSF protein.
 Patients who are suffering from fever and one or more signs of
meningitis and/ or encephalitis such as severe headache,
photophobia, nausea, vomiting, meningeal signs, altered mental
status, seizures and comma.
Exclusion criteria are following:
10

 repeated result for the same patient (the first result will count)
 Patients with negative pathogen result of PCR and conventional
method, patients older than 18 will be excluded.
This is descriptive study and control not required
Ethical approval will conduct from MOH
Methodology
Descriptive statistics will be used to summarize the patients’
demographic, epidemiological, clinical and laboratory characteristics.
Standard deviation and mean will be described for the continuous
variables with a Gaussian distribution while ranges will be described
for the continuous variables showing skewness in distribution.
Categorical variables will be described by making use of frequencies
and proportions. Statistical software for social sciences (SPSS) will be
used for analysis of exploratory data and for descriptive statistics.
Expected outcomes
This research will be of significant help in pointing out the most
prevalent pathogen causing CNS infections in Jeddah, which will help in
clinically manage patients suffering from the CNS infections better,
and help to understanding of microbial population associated with
pediatric CNS infections in Jeddah. Moreover, the information from this
11

study may support the development of a new policy for prevention and
facilitate epidemiological surveillance and public health measures.
References:
Beek, D. V., Spanjaard, L., &Reitsma, J. B. (2004). Clinical Features and Prognostic
Factors in Adults with Bacterial Meningitis. New England Journal of Medicine,
352(9), 950-950.
Bonadio, W. (2014). Pediatric lumbar puncture and cerebrospinal fluid analysis. The
Journal of emergency medicine, 46(1), 141-150.
Brown, B., Fidell, A., Ingolia, G., Murad, E., & Beckham, J. D. (2018). Defining
diagnostic approaches and outcomes in patients with inflammatory CSF: A
retrospective cohort study. Clinical Neurology and Neurosurgery, 172, 105-111.
12

Chadwick, D., & LEVER, A. (2002). The impact of new diagnostic methodologies in the
management of meningitis in adults at a teaching hospital. Qjm, 95(10), 663-670.
Dorratoltaj, N., O’Dell, M. L., Bordwine, P., Kerkering, T. M., Redican, K. J., & Abbas,
K. M. (2017). Epidemiological Effectiveness and Cost of a Fungal Meningitis
Outbreak Response in New River Valley, Virginia: Local Health Department and
Clinical Perspectives. Disaster Medicine and Public Health Preparedness, 12(01),
38-46.
He, T., Kaplan, S., Kamboj, M., & Tang, Y. W. (2016). Laboratory diagnosis of central
nervous system infection. Current infectious disease reports, 18(11), 35.
Jones, T. W., & Winograd, S. M. (2018). Infectious Meningitis: A Focused Review.
Pediatric Emergency Medicine Reports, 23(5).
Masri, A., Alassaf, A., Khuri-Bulos, N., Zaq, I., Hadidy, A., & Bakri, F. G. (2018).
Recurrent meningitis in children: etiologies, outcome, and lessons to learn. Child's
Nervous System, 1-7.
Seehusen, D. A., Reeves, M. M., &Fomin, D. A. (2003). Cerebrospinal fluid analysis. Am
Fam Physician
Stone, M. J., & Hawkins, C. P. (2007). A medical overview of encephalitis.
Neuropsychological rehabilitation, 17(4-5), 429-449.
Swanson, P. A., &Mcgavern, D. B. (2015). Viral diseases of the central nervous system.
Current Opinion in Virology, 11, 44-54.
13