HTHSCI 2HH3 - Central Nervous System Infections

meningitis

inflammation of the meninges; both infectious and non-infectious causes

encephalitis

inflammatory process of the brain; involves whole brain; infectious and non-infectious causes

brain abscess

focal intracerebral infection (within the brain); focal area of necrosis within the brain, surrounded by a membrane and inflamed tissue

blood-brain barrier

• capillaries limit access to CSF and brain tissue

• limits toxin and pathogen access

• makes pharmacotherapy a challenge

host risk factors

• absence of normal flora; no microbial antagonism

• low amounts of local macrophages, antibodies and complement

• inflammation increases permeability of blood-brain barrier facilitating entry of both immune cells and pathogens

portals of infection

trauma to skin, bones and meninges, surgery, peripheral neurons, respiratory system and GI system (bacteremia)

bacteremia

bacteria/infection in the bloodstream

acute bacterial meningitis

bacterial infection and a medical emergency, symptom duration < 2 weeks, patients are seriously ill

aseptic meningitis

associated with viral and fungal infections, adverse drug reactions, autoimmune disorders, and cancers, symptom duration of more than 2 weeks; variable severity of symptoms

pathophysiology of clinical findings in meningitis

systemic infection, meningeal inflammation, cerebral vasculitis, elevated intracranial pressure

systemic infection

fever, myalgia (muscle pain), rash

meningeal inflammation

neck stiffness, Brudzinski’s sign, Kernig’s sign, jolt accentuation of headache

cerebral vasculitis

seizures

elevated intracranial pressure

headache, nausea and vomiting, change in mental status, neurologic symptoms, seizures

diagnosis of meningitis

patient history (international travel), signs & symptoms, physical exam, diagnostic imaging, lab tests - blood and CSF (chemistry & culture)

signs & symptoms of meningitis

• Fever, nuchal rigidity (stiff neck), rash, Brudzinski & Kernig signs, jolt accentuation of headache, Glasgow coma scale (GCS), chills, headache, lethargy, lack of appetite, nausea & vomiting, altered mental state, seizure and focal neurological deficits (changes in movement, sensation, hearing, swallowing, speech, vision)

• 95% of patients with meningitis exhibit 2 of the following - fever, headache, nuchal rigidity, confusion/altered mental state

classic clinical triad of meningitis

• fever, headache, nuchal rigidity (stiff neck)

• absence of all three rules out meningitis with 99% certainty

nuchal rigidity exam

Inability to flex neck forward due to rigidity of the neck muscles; if flexion of the neck is painful, and full range of motion is present, nuchal rigidity is considered absent

Brudzinski’s sign

flexing the neck which involves movement of the chin downward, causes the knees and hips to flex; passive neck flexion in supine position leads to flexion of knees and hips

Kernig’s sign

extension of knee with patient supine and hip flexed at 90 degrees results in resistance or pain

jolt accentuation of headache

accentuation (worsening) of headache with active horizontal head turning at a frequency of 2-3 turns per second

CSF analysis

lumbar puncture for CSF analysis is required for all clients with suspected case of meningitis, only thing that can rule out or confirm a meningitis diagnosis

CSF analysis bacterial meningitis

• lumbar puncture opening pressure is higher in cases of bacterial meningitis

• Low CSF glucose levels (< 2.5 mmol/L or < 40% of serum glucose)

• High CSF protein levels (> 0.45 g/L)

• CSF pleocytosis (500 – 20,000 WBC/mm3); >80% neutrophils

• Gram stain & culture

CSF analysis viral meningitis

• Normal CSF glucose levels

• Normal to mildly increased CSF protein levels

• CSF WBC elevated (10 – 1000 WBC/mm3); mainly lymphocytes and monocytes

Why are CSF glucose levels low in cases of bacterial meningitis

glucose transport from the blood into the CSF is impaired; inflammation of the meninges leads to decreased glucose receptor expression

bacterial pathogens causing meningitis

Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B Streptococcus

viruses causing meningitis

Enteroviruses (Coxsackie B), Herpes Simplex Virus

pneumococcal meningitis

• Causative organism of meningitis in all age groups

  • ~75% colonized with S. pneumoniae (gram-positive) in nasopharynx

• Bacteremia associated with pneumococcal pneumonia in most cases

• Transmission via respiratory droplets

  • Infectious period: 1-3 days prior to onset of clinical symptoms until pathogen is no longer present in nasal and oral discharge (24hrs post targeted antibiotic therapy)

• Case fatality rate of ~26%

• ~40% of survivors left with permanent neurological deficit (e.g., hearing loss)

pneumococcal meningitis public health implications

• All cases of pneumococcal meningitis must be reported to public health

• No droplet precautions necessary; routine precautions only

• No chemoprophylaxis for close contacts

pneumococcal meningitis immunizations

• Routine infant immunization with conjugate vaccine: Pneu-C-15 or Pneu-C-20

• Adult immunization with conjugate vaccine: Pneu-C-20

  • All Individuals ≥ 65 years of age

  • Individuals at increased risk for invasive pneumococcal disease ≥ 2 years of age

neisseria meningitidis

• Attachment; fimbriae, capsule penetration; invasins

• Evasion of host defenses; capsule

• Tissue damage - gram negative pathogen; Lipid A (endotoxin)

• Meningitis - subarachnoid inflammation, cerebral vasculitis, increased BBB permeability

• causes meningococcal meningitis

meningococcal meningitis

• Affects mainly children, adolescents & young adults - large social groups

  • Serogroups A, B, C, Y and W-135 most common in Canada

  • ~10% of individuals are colonized with N. meningitidis in nasopharynx

• Endotoxin production (Lipid A)

  • Chills, fever, weakness, generalized aches, petechial rash (non-blanching)

  • Endotoxic shock & disseminated intravascular coagulation

• Transmitted via respiratory droplets - drop precautions required

  • Infectious period: 7 days prior to onset of symptoms until pathogen no longer present in nasal or oral discharge (24hrs post targeted antibiotic therapy)

• Case fatality rate (with treatment) ~ 10%

• ~ 20% of survivors exhibit permanent neurological or physical deficit

meningococcal meningitis public health implications

• All cases of must be reported to public health

• All suspected or possible cases of meningococcal meningitis should be placed in droplet precautions for 24 hours post targeted antibiotic therapy

• Special attention to those who are in “close contact” of a patient within 7 days before the disease onset, regardless of their vaccination status

Who are considered close contacts?

• Household contacts of a patient

• Children and staff in childcare and nursery school facilities

• Persons who share sleeping arrangements with the patient (e.g., residences)

• Persons who have direct contamination of their nose or mouth with the oral/nasal secretions of a case (e.g., kissing on the mouth, shared cigarettes and bottles)

• Health care workers who have had intensive unprotected contact (without wearing a mask) with infected patients (e.g., intubating, resuscitating or closely examining the oropharynx)

• Airline passengers sitting immediately on either side of the case (but not across the aisle) when the total time spent aboard the aircraft was at least 8 hours

meningococcal meningitis immunizations

• Vaccination recommended to control outbreaks, for patients with increased susceptibility to meningococcal disease, and for travelers

• Men-C-C; Serogroup C only (2 months – 11 years of age)

• Men-C-ACYW; Serogroups A, C, Y, W-135 (Grade 7)

• Bexsero: Serogroup B only (2 months – 25 years of age)

• Close contacts should be immunized and receive chemoprophylaxis

• Chemoprophylaxis

  • Rifampin (PO) or ceftriaxone (IM); all ages

  • Ciprofloxacin (PO) >18 years of age

haemophilus influenzae public health implications

• Prior to 1986, H. influenzae was the leading cause of Gram-negative bacterial meningitis. By 1994, the number of cases of H. influenzae meningitis dropped by 94% with a case fatality rate of 6%

• All cases must be reported to public health

• Transmitted via respiratory droplets

  • Suspected or possible cases of H. influenzae meningitis; droplet precautions 24hrs post targeted antibiotic therapy

• Close contacts should receive chemoprophylaxis (rifampin) & immunization

listeriosis

• GI infection caused by listeria monocytogenes

• Transmission: Ingestion of contaminated foods (soft cheeses, refrigerated unpasteurized foods, deli meats) and poor hand hygiene

• Associated with extremes of age and immunodeficiency - pregnant people, newborns, frail elderly

• Gram-positive bacillus; case fatality rate with treatment ~15%

• Routine precautions required

• Avoid unpasteurized foods and deli meats when pregnant or at extremes of age

streptococcus agalactiae group B streptococcus (GBS)

• Approximately 30% of Canadian women and people with a vagina are colonized with GBS

• 40-70% of these patients will transmit GBS during vaginal delivery

• 1-3% of neonates will develop a GBS infection

• Swab (vagina & rectum) of pregnant clients at 35 - 37 weeks gestation

GBS risk factors

• GBS positive, premature labour, elevated temperature, UTI caused by GBS, membrane rupture >18 hours

• If GBS positive, antibiotics at time of labour or membrane rupture

• IV antibiotics (2 doses; 4 hours apart), last dose ≥ 2 hours prior to delivery ▪ Or neonatal blood cultures (@ 24 and 48 hours), or antibiotic prophylaxis

incidence of meningitis in north america

• streptococcus pneumoniae - older age, most common

• neisseria meningitidis - young people

• listeria monocytogenes - extremes of age - very young or old

• GBS - babies

• haemophilus influenzae - uncommon for all age groups

bacterial antibiotic therapy for bacterial meningitis

• administered after lumbar puncture or after blood cultures

• empiric antibiotic therapy directed at likely pathogens; must be able to cross blood brain barrier

• targeted antibiotic therapy once pathogen is confirmed, and susceptibility tests results are reviewed

general treatment regimen for bacterial meningitis

• Dexamethasone co-administered with antibiotic therapy; decreases risk of death; no increase in adverse events

• Supportive measures; antipyretics, fluids & electrolytes, nutritional support

viral meningitis

• causes less acute illness with less systemic severity compared to bacterial meningitis

• treatment involves supportive therapy

causes of viral meningitis

enteroviruses (Coxsackie B, Echovirus), Herpes Simplex Virus (HSV)

enteroviruses

• Responsible for ~85% of viral meningitis cases in Canada

• Mode of transmission: Direct contact & fecal-oral route, most common in summer and fall

• Self-limited illness in most patients (e.g., those that are immunocompetent)

  • Duration of illness typically 7 - 10 days

summary of meningitis

• Bacterial meningitis is a MEDICAL EMERGENCY requiring prompt diagnosis and treatment

• Prompt collection/transport of CSF to microbiology laboratory, and initiation of empiric antibiotic therapy makes the difference between life & death

• Patients require close monitoring for signs of deterioration or complication

• Practice appropriate infection control measures

• With appropriate antibiotic therapy, mortality rate and sequelae associated with bacterial meningitis remains significant

• Approximately 1 in 5 survivors of bacterial meningitis have permanent neurological or physical deficits

  • Hearing and vision loss, difficulties with speech, language, memory, and communication, seizures, scarring, limb weakness, and limb amputations after sepsis

meningoencephalitis

overlapping syndrome of meningitis and encephalitis

encephalitis cause considerations

Season, geography, prevalence of disease in the local community, travel history, recreational activities, occupational exposure, insect contact, animal contact, vaccination history, and immune status of the patient; viral encephalitis most common with bacterial, fungal and protozoal causes also observed

encephalitis clinical findings

changes in cognitive function and awareness (LOC, confusion, disorientation, seizures), focal neurological deficits

classic clinical triad of encephalitis

fever, headache, altered level of consciousness (LOC)

encephalitis CSF lab findings

increased protein, increased lymphocytes and normal glucose for viral encephalitis, cultures, CSF analysis, serology

viral encephalitis initial sites of infection

• viruses most commonly access the brain via the bloodstream

• respiratory tract - measles, mumps, varicella

• GI tract - poliovirus, enterovirus

• Genital tract - HSV

• Subcutaneous tissues - west nile virus

why is viral encephalitis more serious than viral meningitis?

encephalitis is associated with higher intracranial pressures

HSV and viral encephalitis

• Most common cause of infection-related encephalitis

• Focal temporal lobe symptoms most common

  • Visual field cut, hemiparesis, aphasia

• Acyclovir reduces overall mortality to 28% at 18 months post treatment

  • Patients should be treated presumptively for HSV encephalitis until an alternate pathogen is detected

  • Otherwise, supportive therapy; corticosteroids in some cases - no cure for HSV

• Prognostic factors include age, duration of symptoms and Glasgow Coma Scale measurement at time of treatment

west nile virus and viral encephalitis

• Normally, WNV causes mild symptoms within three to seven days of infection

• Incidence is seasonal, with peaks corresponding to times of the year when adult mosquitoes are active

• Those > 50 years of age and older are at increased risk of poor outcomes and more severe disease

• Diagnosed by positive laboratory test for WNV antibodies in CSF

• Treatment is supportive: possible hospitalization, administration of intravenous fluids, respiratory support (ventilator), prevention of secondary infections

• Symptoms include headache, fever, stiff neck, body aches, muscle weakness

brain abscess clinical findings

Increased intracranial pressure, seizures and focal neurological deficits most common clinical presentation; abscess can rupture into the ventricular system leading to a sudden worsening of clinical presentation

brain abscess diagnosis

• brain imaging (MRI) is used; looks like a hypo-dense centre with a peripherally uniform ring of enhancement following injection of contrast material

• MRI guided aspiration establishes microbiologic diagnosis and can reduce intracranial pressure

• immunocompromised individuals most at risk of getting a brain abscess

brain abscess treatment

• Surgical removal of abscess

  • Infection can be treated without surgery, if pathogen is identified and abscess diameter is less than 2.5 cm

  • Surgical intervention will also reduce intracranial pressure

• Empiric therapy

  • Antimicrobial therapy directed at suspected organisms

    • Empiric therapy should be narrowed in spectrum when culture results from aspirate (if collected) or abscess is available

• Corticosteroid Therapy

  • Appropriate in cases of increased intracranial pressure or significant edema