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What are most common pathogen etiology causing meningitis and encephalitis in pediatric suffering from central nervous system infections?

Global Incidence and Prevalence of CNS Infection

According to Scheld et al. (2014), central nervous system infections can be defined as infections that affect the brain and the spinal region of the human body. A wide range of microorganisms affect the normal functioning of the central nervous system and cause infections. These microorganisms include, bacteria, viruses and parasites. Additionally, a special class of microorganism known as the prion has been reported to damage the normal functioning of the brain. It should be noted in this regard that infection within the central nervous system can either lead to meningitis, encephalitis or meningoencephalitis which could either be acute or chronic (Teasdale & Jennet, 1974)

According to He et al. (2016), CNS infections are classified on the basis of their anatomic localization. Encephalitis, Meningitis, formation of brain abscess and myelitis has been reported to be the most common forms of CNS infection. Bacterial Meningitis has been considered as the most fatal CNS infection that leads to approximately 500 deaths every year in US. The mortality rate associated with the disease is 6% to 26% (He et al., 2016).

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. According to Jones and Winograd (2018), it has been mentioned that fungal meningitis caused by Cryptococcus species is equivalent to 70.1% within the paediatric and the adult patients account. Further, Coccidioides sp, Candida sp. And Histoplasma species contribute to approximately 16.4%, 7.6% and 6.0% of the fungal Meningitis within USA.

Bacterial meningitis has been reported to be a severe form of meningitis that elicits serious effect on the normal functioning of the brain. It leads to drastic consequences such as hearing impairment, brain damage, learning impairment and limb amputation (Masri et al., 2018). It is usually caused by the bacteria Neisseria meningitides (Stone & Hawkins, 2007). The causative agent for Meningitis varies across different age groups (Hacochen et al., 2013):

Age-group

Causative Agent

New born

Streptococci, E.coli and Listeria monocytogenes

Infants

Neisseria meningitis, Streptococcus pneumonia, Haemophilus influenzae

Children

N.meningitidis, S. pneumoniae

Adults

S.pneumoniae, N.meningitidis and Mycobacteria

Bacterial meningitis has been reported to be contagious and spreads through the exchange of respiratory fluids and throats secretions (Hase et al., 2014). The incidence of bacterial meningitis has been reported to be 0.6-4 per 100,000 individuals in the adults across developed countries (Jones & Winograd, 2018). It should further be noted that the prevalence rate is estimated to be ten times higher in different parts of the world. The most common causative agents of bacterial encephalitis that cause 85% of the infections has been recorded to be S.pneumoniae and N.meningitis (Abbas et al., 2016). Infection caused by Haemophilus influenza type b and seven serotypes of streptococcus pneumoniae has reduced significantly in paediatrics after the introduction of conjugate vaccines (Heydeman & Klein, 2000).

The signs and symptoms for bacterial meningitis include the following (Kumar, 2005) :

  • Nausea and vomiting tendency
  • Pertinent fever
  • Pain in muscular joint
  • Pertinent headache and stiffness of neck
  • Manifestation of rashes
  • Feeling of numbness and coldness in hand or feet and mottled skin

The signs and symptoms for bacterial encephalitis include similar symptoms as that of bacterial meningitis. However, severe cases are marked by speech and hearing impairment, double vision. Hallucinations and personality changes. Other symptoms also include, memory loss, seizures, partial paralysis of the limbs and impaired intellectual ability (Hosseininasab et al.,2011).

Bacterial Diseases

Cerebrospinal Fluid Analysis can be defined as a series of laboratory tests that is performed on a sample of cerebrospinal fluid. The CSF is produced by the Choroid plexus region of the brain and the fluid is reabsorbed to the bloodstream. The fluid is regenerated at brief intervals and circulates the nutrients around the brain and spinal column (Seehusen et al., 2003). Also, the fluid is responsible for the protection of the brain and the spinal column. The CSF lumbar puncture is performed by the collection of the CSF sample through spinal tapping. The analysis of the sample facilitates analysis of fluid pressure, protein and glucose level, RBC and WBC content, bacterial and viral profile and detection of invasive antigen (Seehusen et al., 2003). The sample is collected from the lower back area through a needle. It is extremely important for the patient to lay completely motionless so as to avoid incorrect placement of the needle. The patient is generally made to sit with a curled spine so as to make space in between the bones present at the lower back. The procedure takes place in a span of thirty minutes and the procedure is directed by fluoroscopy that helps the physician in placing the needle between the two vertebrae (Bonadio, 2014). It should be noted in this context that the pressure inside the brain is maintained using a manometer (Tamune et al., 2014). After the collection of the sample, the punctured site a bandage is applied at the punctured site and the patient is made to lie down for an hour to reduce risks of side-effects such as headaches or trauma (Seehusen et al., 2003).

The CSF characteristics in case of bacterial, viral and fungal infections can be enlisted as under (Chadwick, 2002):

Characteristics

Bacterial

Viral

Fungal

Opening pressure

Glucose

Protein

Rbcs

Wbcs

Difference

Appearance

increased

Low

Elevated

Few

>200

PMNs

Turbid

Normal or elevated

Normal

Normal

Negligible

<200

Mono

Clear

Normal or elevated

Low

High

Negligible

<50

Mono

Turbid

Viral meningitis can be listed as a less severe form of meningitis that causes inflammation of the tissue that surrounds the brain and the spinal cord (Hosseininasab et al., 2011). The major causative agent of viral encephalitis has been reported to be Non-polio eneteroviruses. Other major viral causative agents that cause meningitis are Mumps virus, Herpes virus, Measles virus, West Nile Virus, Influenza virus and Lymphocytic virus (De Ory et al., 2013). Meningitis is common in children aged 5 years and below (Hacohen et al., 2013). Also, individuals who have recently undergone an organ transplantation, bone marrow transplantation or chemotherapy and possess a weakened immune system are susceptible to develop meningitis. The mode of transmission of the viral agent is through coughing or sneezing.  

On the other hand, viral encephalitis can be defines as a condition that occurs on account of inflammation within the brain. It is commonly characterized by the infectious viral agents that include the category of enteroviruses. The virus typically invades the human body and multiplies within the brain. On identifying the antigen the body elicits an immune response that leads to inflammation of the brain. The disease has been associated with permanent brain damage and has been reported to affect children below 5 years and adults above 55 years of age. The virus can usually spread through exchange of respiratory fluid or consumption of contaminated food items and beverage (Stone & Hawkins, 2007). Also, the viral agent can spread through vectors that include infected insects and recurrent activity of dormant viral infection. The symptoms of viral meningitis are similar to that of bacterial meningitis but of lower intensity. The onset of viral meningitis is generally marked by a viral infection that proceeds to assume the form of acute or chronic viral meningitis.

Signs and Symptoms

The signs and symptoms of viral encephalitis include the following (Stone & Hawkins, 2007):

  • Amnesia
  • Partial or complete paralysis
  • Photophobia
  • Elevated temperature
  • Stiffness within the neck and back region
  • General malaise

Fungal meningitis is caused by the transmission of fungus through the blood to the spinal cord. The common causative agent of fungal meningitis is Cryptococcus (Abbas et al.,2016). It is usually common in individuals who are affected with HIV or Cancer that disrupts the immune system of the body. The disease is spread by the transmission of a fungus from the brain to the spinal cord (Chen et al., 2014). Fungal meningitis is also characterized by the intake of medications that include Prednisone which is administered after organ transplantation as anti-TNF medications (Heydeman & Klein, 2000).

Bacterial meningitis has been linked to a mortality rate of about 5-10% in the paediatric group across the globe. The case of recurrent meningitis in children was recorded to be 39% (Jones & Winograd, 2018). Studies reveal that the incidence of carriage prevalence significantly increases throughout childhood ranging from 4.5% in infants to 27.3% in children aged 5 years. Also, population studies has revealed 80.69 cases per 100,000 individuals to be affected with bacterial meningitis who are younger than 2 months in age (He et al.,2016).

Diagnosis is generally carried out through clinical examination, neuroimaging and laboratory testing that includes biochemical tests and assays. Cell culture and direct virus antigen detection are traditional methods (Chadwick, 2002). Newer methods such as investigation of CSF for cells, protein and glucose, nucleic acid amplification tests and polymerase chain PCR have been identified as effective methods to detect a broad spectrum of antigens (Thomson & Bertram, 2001).

References:

Abbas, K. M., Dorratoltaj, N., O’Dell, M. L., Bordwine, P., Kerkering, T. M., & Redican, K. J. (2016). Clinical response, outbreak investigation, and epidemiology of the fungal meningitis epidemic in the United States: systematic review. Disaster medicine and public health preparedness, 10(1), 145-151.

Bonadio, W. (2014). Pediatric lumbar puncture and cerebrospinal fluid analysis. The Journal of emergency medicine, 46(1), 141-150.

Chadwick, D. (2002). The impact of new diagnostic methodologies in the management of meningitis in adults at a teacching hospital

Chen, C., Zhang, B., Yu, S., Sun, F., Ruan, Q., Zhang, W., ... & Chen, S. (2014). The incidence and risk factors of meningitis after major craniotomy in China: a retrospective cohort study. PLoS one, 9(7), e101961.

De Ory, F., Avellón, A., Echevarría, J. E., Sánchez?Seco, M. P., Trallero, G., Cabrerizo, M., ... & Pena, M. J. (2013). Viral infections of the central nervous system in Spain: a prospective study. Journal of medical virology, 85(3), 554-562.

Hacohen, Y., Wright, S., Waters, P., Agrawal, S., Carr, L., Cross, H., ... & Hedderly, T. (2013). Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. Journal of Neurology, Neurosurgery & Psychiatry, 84(7), 748-755.

Hase, R., Hosokawa, N., Yaegashi, M., & Muranaka, K. (2014). Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: a case report and review of the literature. Canadian Journal of Infectious Diseases and Medical Microbiology, 25(5), 249-251.

He, T., Kaplan, S., Kamboj, M., & Tang, Y. W. (2016). Laboratory diagnosis of central nervous system infection. Current infectious disease reports, 18(11), 35.

Heydeman, R. S., & Klein, N. J. (2000). Emergency management of meningitis

Hosseininasab, A., Alborzi, A., Ziyaeyan, M., Jamalidoust, M., Moeini, M., Pouladfar, G., ... & Kadivar, M. R. (2011). Viral etiology of aseptic meningitis among children in southern Iran. Journal of medical virology, 83(5), 884-888.

Jones, T. W., & Winograd, S. M. (2018). Infectious Meningitis: A Focused Review. Pediatric Emergency Medicine Reports, 23(5).

Kumar, R. (2005). Aseptic meningitis: diagnosis and management. The Indian Journal of Pediatrics, 72(1), 57-63.

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.

Scheld, M. W., Whitley, R. J., & Marra, C. M. (Eds.). (2014). Infections of the central nervous system. Lippincott Williams & Wilkins.

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.

Tamune, H., Takeya, H., Suzuki, W., Tagashira, Y., Kuki, T., Honda, H., & Nakamura, M. (2014). Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis. The American journal of emergency medicine, 32(3), 263-266.

Teasdale , G., & Jennet, B. (1974). Assessment of coma and impaired consciousness. A practical scale. Lancet

Thomson, R. B., & Bertram, H. (2001). Laboratory diagnosis of central nervous system infections. Infectious Disease Clinics, 15(4), 1047-1071.

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