Common Pathogens Causing Meningitis And Encephalitis In Pediatric Patients In Jeddah, Saudi Arabia (2015-2019)

Literature Review

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. 

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 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). 

Common Pathogens Causing CNS Infections

Table. 1

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).

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 

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 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. 

Diagnosis of CNS Infections

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 prevention and facilitate epidemiological surveillance and public health measures.

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.

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 . 

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:

• 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 

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.

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 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.

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.

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