Meningitis Review 2024

Meningitis Review - 1/22/2024

• This review covers bacterial, fungal/TB, and viral meningitis, along with tetanus and botulism.

CSF Findings in Meningitis

• Bacterial: Increased opening pressure, increased PMNs, increased protein, decreased sugar
• Fungal/TB: Increased opening pressure, increased lymphocytes, increased protein, decreased sugar
• Viral: Normal/slightly increased opening pressure, increased lymphocytes, normal/slightly increased protein, normal sugar

Bacterial Meningitis, Tetanus, and Botulism

• Bacterial Meningitis:

  • Children (<3 months) and adult meningitis, neonatal meningitis
  • Key causes: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae Type B, Listeria monocytogenes (immunocompromised)
  • Strep agalactiae, E. coli, and Listeria monocytogenes are also causes in neonatal meningitis

• Tetanus:

  • Clostridium tetani

• Botulism:

  • Clostridium botulinum

Bacterial Meningitis Overview

• Newborns/Children Symptoms:

  • Constant crying, poor feeding, sleeping constantly, irritability

• Adult Symptoms:

  • Classic triad: fever, headache, stiff neck.
  • Sensitivity to light, confusion, nausea, vomiting
  • General flu-like symptoms (developing 1-2 days after initial symptoms) may also be present; Petechial rashes

• Diagnosis:

  • Physical exam (Kernig's sign, Brudzinski's sign)
  • CSF analysis (increased polymorphonuclear neutrophils [PMNs], increased protein, decreased glucose)

• Treatment:

  • Empirical treatment—IV vancomycin + ceftriaxone or cefotaxime

Strep pneumoniae

• Leading cause of CNS meningitis
• "Pneumococcal meningitis" = caused by Strep pneumo
• Distinguishing feature: prolonged fever before onset of classic triad (apparent focal infection)
• Virulence factors: polysaccharide capsule, IgA protease, autolysin, pneumolysin

Neisseria meningitidis

• "Meningococcal meningitis"
• Bacteremia can cause septicemia
• Focal infection is often inapparent
• Distinguishing feature: petechial rashes
• Virulence factors—polysaccharide capsule, pili (adherence in nasopharynx), lipooligosaccharide, IgA protease, OpA, OpC.
• Treatment: ceftriaxone or penicillin G

Haemophilus influenzae type b

• "Typeable" = has a capsule
• Apparent focal infection
• Primarily in non-immunized children (1 month to 3 years)
• Prevention: Hib polyribose phosphate vaccine

Strep agalactiae

• Usually transmitted during birth (both baby and mother can get meningitis)
• Virulence factors—Polysaccharide capsule rich in sialic acid, Hemolysin, C5a peptidase

E. coli

• Ferments lactose on MacConkey agar
• Virulent factors: K antigen (main virulence factor for development of neonatal meningitis), O antigen, H antigen
• Meningitis caused by E. coli is transmitted at birth, often with no apparent disease preceding it
• Treatment: Cephalosporins

Listeria monocytogenes

• Foodborne infection (can grow at 4°C)
• Transmission via cell-to-cell transfer or at birth.
• Virulence factors: Internalin, Listeriolysin O, ActA
• Can affect pregnant women and fetus (infection in utero)
• Prevention:
  • Treatment of infants with ampicillin.

Tetanus Overview

• Symptoms:

  • Rigid paralysis: lockjaw (trismus), back spasm, potential respiratory failure due to paralysis of chest muscles

• Treatment:

  • Supportive (ventilation, muscle relaxants) +
  • Human tetanus immune globulin (HTIG) +
  • Antibiotics (metronidazole)

Clostridium tetani

• Virulence factor: tetanospasmin
• Blocks release of inhibitory neurotransmitters (increasing firing rate of motor neurons) causing rigid paralysis.
• Transmission: C. tetani spores inoculated into puncture wounds (e.g. rusty nails)
• Prevention: tetanus vaccine

Botulism Overview

• Symptoms:
  • Flaccid paralysis ("Floppy Baby Syndrome")
  • GI symptoms (foodborne intoxication)
  • Symptoms onset quicker than tetanus
• Treatment:
  • Supportive (ventilation)
  • Antitoxin (equine trivalent) +
  • Antimicrobials (if wound infection is involved)

Clostridium botulinum

• Virulence Factors: Botulinum toxin blocks release of ACH, resulting in no muscle contraction and flaccid paralysis

• Transmission: spores found in soil, surfaces of fruits, and vegetables; Home canning of such as honey

• Prevention or treatment: No current vaccine; no natural immunity

Leprosy - Mycobacterium Leprae

• Obligate aerobe; non-motile, non-spore forming; Acid fast bacillus (Ziehl-Neelsen stain); Lipid cell wall, mycolic acid
• Transmission: via prolonged contact
• Virulence factors: PGL-1 (invasion into Schwann cells); Laminin-binding protein (binding to basal lamina of peripheral nerves)
• Different forms: Tuberculoid and Lepromatous

Leprosy - Lepromatous and Tuberculoid

• Tuberculoid:

  • Cell-mediated response (Th1 and CD8+ T cells)
  • Granuloma formation (little bacilli)
  • Lepromin skin test positive
  • Large, asymmetric, pale, hairless, flattened macules on face, trunks, limbs

• Lepromatous:

  • Poor cell-mediated response
  • Multiple symmetric nodules and plaques—diffuse spread
  • Can cause bone resorption and folding of skin
  • Negative Lepromin skin test

Viral CNS Infections

• Important to note different routes, symptoms and causes of infections.

Important Definitions

• Direct contact: Includes petting, touching, bites, and scratches.
• Indirect contact: Includes places animals live, like chicken coops or aquarium tanks. Plants, soil, etc.
• Vector-borne: Transmittal by ticks, mosquitoes, or fleas.
• Food-borne: Ingesting contaminated animal products (meat, milk, eggs) and plants.
• Sylvatic: Between wild animals involving insect intermediates.
• Urban: When an infection moves from sylvatic cycle to humans—usually via insect, direct contact, or domestic animals.

Rabies

• Negative single-stranded RNA
• Enveloped (glycoprotein surface spikes, phosphoprotein spikes)
• Zoonotic with a sylvatic and urban cycle
• Replication at slow rates to avoid apoptosis
• Fatal

Rabies (Cont.)

• Pathogenesis: Incuation varies. Once in brain, replicates and damages axons, spreads anterograde.
• Clinical illness: Encephalic (furious) or paralytic (20%). Symptoms are severe and consistent that includes confusion, difficulty swallowing, coma/seizures, death.
• Diagnosis: History of exposure, symptoms, post-mortem (Negri bodies in brain tissue).
• Treatment: No effective treatment once symptoms emerge.

Poliovirus

• Positive single-stranded RNA
• Non-enveloped enterovirus
• Transmitted via oral/fecal route
• Most people asymptomatic; some get poliomyelitis; 1% develop major illnesses
• Diagnosis—immunization history, CSF, throat, and stool cultures;
• Prevention: oral vaccine (live, attenuated, some reversion); inactivated vaccine for those immunocompromised

Arboviruses

• Seasonal fluctuations (mosquitoes & ticks)
• Enveloped, positive single-stranded RNA virus
• Transmitted to humans by "bridge" vector (replication starts in cytoplasm-> lytic, destroys cells -> viremia across the CNS (blood); inflammation allows for permeability in brain so viruses can enter).
• Symptoms: may include abrupt fever, chills, weakness, headache, myalgia; diffuse CNS; fever, headache, irritability, nausea, seizures, coma, and death.

Flaviviruses

• Positive enveloped single-stranded RNA
• Incubation period ~1 week
• Spread via "bridge" vectors
• Shares common antigen with EEEV.
• Flaviviruses in US: St. Louis encephalitis, West Nile, Zika virus

St. Louis Encephalitis and West Nile

• St. Louis Encephalitis:
  • Viral saturation of reticuloendothelial system
  • Invasion of CNS causing sudden onset of symptoms (fever, malaise, headache, dizziness, nausea).
  • Symptoms worsen with disorientation, confusion, irritability, tremors, convulsions
  • Death via palliative care in more severe cases.
• West Nile:
  • Transmission by mosquito bites.
  • Migrates to lymph nodes—Blood stream→organs (often the spinal cord).
  • Usually self-limited with mild symptoms (fever, malaise, nausea).
  • More severe forms can involve CNS (severe muscle weakness, flaccid paralysis; stupor/ seizures / coma).

Zika Virus

• Usually mild, self-limiting flu-like disease
• Spread by mosquito bite
• Concerning in pregnant women; causes vertical transmission from mother
• Neuroinvasive (Guillain-Barre and microcephaly)
• Transmission (initial sporadic, increasing urban/suburban spread → vertical transmission across placenta → sexual transmission)
• Diagnosis (RT-PCR and/or IgM antibody)
• Treatment: (none - palliative care) Prevention (Mosquito control and restrict pregnant women travel)

Bunyaviruses

• Single-stranded segmented negative sense RNA virus (LaCrosse virus–California encephalitis)
• Secondary viremia in CNS (symptoms more likely in people <16 years old)
• Neurological sequelae (20% of survivors (often permanent))
• Diagnosis: serum antibody or RT-PCR tests
• Treatment: (none - palliative care) Prevention (Mosquito control)

Polyomaviruses

• Non-enveloped double-stranded DNA
• Common infection in childhood, remains dormant in some people
• Activated when immune systems are weakened. (common in HIV people)
• Causes Progressive Multifocal Leukoencephalopathy
• Includes a range of symptoms like impaired speech, mental issues, paralysis / sensory abnormalities / death
• No prevention

Prions

• Transmissible spongiform encephalopathies (prion diseases).
• Not infectious particles, but rather proteins
• Infectious protein particles form insoluble aggregates
• Proposed mechanism: holes in tissues (sponge-like) during multiplication (H and E)
• Most common: Creutzfeldt-Jakob disease (CJD).

Creutzfeldt-Jakob

• Rapidly progressive neurologic dysfunction
• Myoclonic jerks, visual abnormalities, akinetic mutism
• GSS disease or FFI includes a range of symptoms (ataxia, amyloid deposition, neurofibrillary tangles, insomnia etc).
• Death typically occurs within a year.
• High mortality rate (100%)
• No effective treatment

Fungal Meningitis

• Characteristics:
  • Low glucose
  • High protein
  • Increased opening pressure
  • Increased lymphocytes

Cryptococcus Neoformans

• Asymptomatic in healthy people; opportunistic in HIV patients

• Flu-like symptoms, headaches, fever, disseminated disease (lungs, skin, bones)

• Virulence Factors: Polysaccharide capsule (prevents phagocytosis), phenoloxidase (increased melanin + prevents binding of phagosome to lysosome)

• Characteristics: India Ink and Halo stain, Brain abscesses

• Treatment: Amphotericin + Flucytosine, then Fluconazole, prophylactic <100 CD4

Coccidioides Immitis

• Dimorphic fungi
• Asymptomatic/flu-like symptoms – can disseminate to many body locations (lungs, skin, bones, CNS).
• Transmission: Southwestern USA, spores inhalation
• Characteristics: Spherules of endospores
• Treatment: usually self-limited; fluconazole; amphotericin B (disseminated)

Protozoal Meningitis

• General term for protozoal infections that involve the meninges (protective membranes of the brain and spinal cord)

African Trypanosomiasis (Sleeping sickness)

• T. brucei gambiense: (Western Africa, chronic, human reservoir - infection can last 1 year to death).
• T. brucei rhodesiense: (Eastern Africa, acute, wild animals - infection lasts between 3-6 weeks):
• Transmission: Tsetse fly
• Stages: Chancre; Trypomastigotes in blood (recurrent malaise, lymphadenopathy w/ IgM production. Varying antigens, surface glycoprotein.) Meningitis - headaches; behavior change.

American Trypanosomiasis (Chagas disease)

• Trypanosoma cruzi: Southern US and Argentina
• Transmission: Contact with reduviid (Kissing bug) feces (bite—skin, defecate, enters skin)
• Virulence: Penetrin (invasion of cells), Pore-forming protein, Multiply intracellularly and rupture cell.
• Presentation: Acute chagoma, Romña's sign(eye), heart, brain, liver, spleen. Chronic: cardiomyopathy/arrhythmias, giant esophagus.
• Diagnosis: Motile trypanosomes in body fluid.
• Treatment: Nifurtimox, benznidazole

Naegleria Fowleri

• Amoeba
• Free-living in lakes and swimming pools
• Transmission: Penetration of olfactory neuroepithelium (through nose)
• Presentation: Primary amebic meningoencephalitis: severe headache, vomiting, seizure, coma
• Death: within 10 days
• Diagnosis: Trophozoites in cerebrospinal fluid (CSF)

Acanthamoeba

• Primarily affects immunocompromised individuals
• Transmission: Brackish and saltwater; acquired via swimming or inhalation
• Spread: blood → CNS + lungs + sinuses + skin
• Presentation: subacute or chronic: headache, altered mental status; skin lesions; corneal ulcerations
• Diagnosis: Trophozoites in CSF or brain biopsy/skin scraping (monocytes in CSF)
• Treatment: Self-limiting.

This quiz comprehensively reviews different types of meningitis, including bacterial, fungal/TB, and viral, as well as related conditions like tetanus and botulism. It highlights key CSF findings associated with each type, demographics, and common pathogens linked to bacterial meningitis in various age groups. Test your understanding and retention of critical concepts regarding these infectious diseases.