Microbial Diseases of the Nervous System Notes

Microbial Diseases of the Nervous System

Course Learning Outcomes

• By the end of the lecture, you should be able to:

  • List names of pathogens that cause nervous system infections.

  • Name diseases related to the Central Nervous System (CNS).

  • Explain the transmission of nervous system infections.

  • Discuss the mechanisms to control nervous system infections.

Central Nervous System

• Characteristics:

  • Cerebrospinal fluid (CSF) has low protein content and low immunoglobulin (Ig).

  • No lymphatics; depends on lymphocyte migration to and from the blood circulation.

  • Meninges support and protect the brain and spinal cord.

  • The meninges constitute the blood-brain barrier between blood and the CSF; it inhibits the entry of organisms, many drugs, and toxins.

Meningitis and Meningism

• Meningitis:

  • Inflammation of the meninges.

  • Meninges: 3 protective layers around the brain and spinal cord.

  • Inflammation of the 2 inner layers (leptomeninges).

• Meningism:

  • A group of symptoms and signs accompanying the inflammation.

  • Examples: headache, neck and back stiffness, nausea and vomiting, photophobia.

• Conditions where meningism can occur without meningitis:

  • Small children with high fever.

  • Acute Urinary Tract Infection (UTI).

  • Meningeal malignancies.

  • Triggers: Autoimmune diseases (e.g., lupus), medication, infections.

Meninges

• Dura mater

• Arachnoid

• Pia mater (Leptomeninges)

• Subarachnoid space

• Cerebrospinal fluid (CSF):

  • Watery liquid that cushions impact.

  • Contains nutrients.

• Normal condition:

  • 1 \µL of CSF contains 5 white blood cells.

  • Protein: $15-50 \frac{mg}{dL}$

  • Glucose: $45-100 \frac{mg}{dL}$ (approximately 50% of blood glucose).

  • Total CSF ~ 150mL.

  • 500mL produced every day; excess (350mL) reabsorbed in blood.

• Blood-brain barrier (Blood vessel):

  • Endothelial cells are tightly bound.

  • Only allow certain molecules to pass through.

Pathogenesis of Meningitis

• Bacteria in the bloodstream cross the blood-brain barrier.

• Inflammation occurs in the cerebrospinal fluid.

• White blood cells are present to combat the bacteria.

• Pathogens enter CSF, multiply, and WBCs release cytokines, recruiting more WBCs.

Effects of Meningeal Inflammation

• Increase in cerebrospinal fluid (CSF) protein and cell count.

• Increased entry of water-soluble antibiotics.

• Increased CSF fluid.

• Increased brain pressure.

• Reduced cerebral perfusion pressure.

• Hydrocephalus: accumulation of CSF.

CSF Analysis in Meningitis

• White Blood Cell (WBC) Count:

  • Bacterial: > 100 WBC/\µL

  • Viral: 10-1000 WBC/\µL

  • Fungal: 10-500 WBC/\µL

  • Tuberculosis Meningitis: 50-500 WBC/\µL

• Glucose Concentration:

  • Less than 2/3 or 1/2 of blood glucose.

• Protein Levels:

  • Increase > $50 \frac{mg}{dL}$

Types of Meningitis

• Acute Meningitis:

  • Bacterial and viral infections.

• Severe Meningitis:

  • Fungal infection.

Viral Meningitis

• Examples of pathogens:

  • Enterovirus (Coxsackievirus).

  • HIV.

  • Herpes Simplex Virus Type 2.

  • Mumps.

  • Varicella.

  • Most common.

Enterovirus Meningitis

• Transmission occurs through environmental contamination, such as crowding and poor hygiene.

• Common in children aged 5-14 years old.

• The most common enteroviral meningitis is caused by the Coxsackie virus.

Management of Viral Meningitis

• Analgesic (pain killer) drug – to relieve pain.

• Antiemetics – to reduce nausea and vomiting.

• Bed rest – reduce pain and malaise.

• Antiviral drug – inhibit attachment and entry of the virus into the host cells.

Herpes Simplex Type 2 Meningitis

• Always associated with primary genital herpes simplex infection.

• The meningitis is benign, behaving like an enteroviral infection.

• Mollaret’s meningitis is caused by relapsing attacks of herpes simplex virus.

• It is self-limiting but can persist for weeks.

Bacterial Meningitis

• Examples of pathogens:

  • Neisseria meningitidis (among adults).

  • Streptococcus pneumoniae (among adults).

  • Streptococcus agalactiae (among infants).

  • Haemophilus influenzae (among unvaccinated persons).

  • Listeria monocytogenes.

• The infection causes:

  • High number of neutrophils in CSF.

  • High level of protein.

  • Low glucose level.

Meningococcal Meningitis

• Caused by Neisseria meningitidis.

  • Carried in the nasopharynx.

  • Causes septicemia and meningitis.

  • Has pili for adherence.

  • Possesses lipooligosaccharide (LOS), which alters the permeability of the blood-brain barrier.

  • Can produce IgA protease and capsule.

• Causes morbidity and mortality in children and young adults.

• Is a severe bacteremic disease, causing high mortality.

Prevention and Control of Meningococcal Meningitis

• Immunization: meningococcal vaccines against groups A, C, Y, and W135 strains.

• Education is the key to success.

Haemophilus influenzae Meningitis

• Caused by Haemophilus influenzae type b (Hib).

• The main microbial factors important during infection are:

  • Capsule.

  • Lipopolysaccharide.

  • Pilus.

  • IgA protease.

• Incubation period: 3-4 days.

Prevention and Control of Haemophilus influenzae Meningitis

• Immunization: Hib vaccines are highly effective in infants from 2 months of age.

• All household contacts of patients with Hib should be given treatment (chemoprophylaxis) and vaccination if there is a child under 4 years old.

Pneumococcal Meningitis

• Caused by Streptococcus pneumoniae.

• Gram-positive bacteria.

• Pathogenicity factors:

  • Capsule.

  • Toxins: pneumolysin, neuraminidase.

  • Surface protein A.

  • IgA protease.

  • Hyaluronidase.

• Infection of alveoli.

• Incubation period: 1-2 days.

• Signs and Symptoms: watery diarrhea, impairment of consciousness.

• Prevention & Control: vaccination, education, campaign.

Listerial Meningitis

• Listeriosis is normally associated with infection of pregnant women and neonates.

• Infection in older children or adults in:

  • Immunosuppressed individuals.

  • Those on corticosteroid and anticancer therapy.

• Causative agent: Listeria monocytogenes.

• Microbial factor: Listeriolysin.

• Clinical features: mild gastroenteritis-like illness, purulent meningitis.

• Prevention and control:

  • Practice good hygiene.

  • Adequate reheating of cook-chill and cook-freeze meals.

  • High-risk foods (e.g., cheeses) should not be served to patients or pregnant women.

Encephalitis and Meningoencephalitis

• Encephalitis – inflammation of the brain. Can occur independently of meningitis. If coexists, is known as meningoencephalitis.

• Signs and Symptoms:

  • Mild confusion.

  • Weakness.

  • Loss of control of body movement.

  • Inability to speak.

  • Paralysis of the muscle within or surrounding the eye.

  • Seizure (disturbance in the brain).

List of Pathogens Causing Encephalitis

• Herpes simplex virus type 1

• Arboviruses:

  • Tick-borne encephalitis virus

  • West Nile virus

  • Japanese B encephalitis virus

  • Nipah virus encephalitis

• Rabies virus

Rabies

• A zoonosis caused by the rabies virus.

• Usually causes 100% fatality.

• Bullet-shaped virus with RNA and envelope.

• Commonly affects humans, dogs, raccoons, skunks, foxes, and bats.

Transmission of Rabies

• Bites, scratches, abrasions

• Mucosal exposure

Prevention of Rabies

• Vaccinating pets and killing stray dogs.

• Avoiding contact with stray/wild animals.

• Not touching animal carcasses.

• Vaccine for at-risk persons:

  • Vets, animal handlers

  • Lab workers

  • Cave/wild explorers

  • Forestry workers

  • Travelers in endemic areas

  • Frequent contact with Rabies virus

• Care of bite

• Immediate treatment

• Secure garbage

• Vaccinating pet dogs is essential to control rabies.