Blood brain barrier

Cells that make up the walls of blood vessels around the
brain allow very few molecules to pass through

Freer passage of ions, sugars, and other metabolites in
other areas of the body

Prohibits most microorganisms from passing into the CNS

Drugs and antibiotics are difficult to introduce into the CNS
when needed

Immune privilege of the CNS

A different or partial immune response when exposed
to immunologic challenge

Functions of the CNS are vital for the life of an
organism and temporary damage from a “normal”
immune response could be detrimental

nervous system defenses

bony structures, blood-brain barrier, microglial cells, and macrophages

no normal biota

Cerebrospinal fluid (CSF)

Fills the subarachnoid space
– Clear, serum like fluid
– Provides nutrition to the CNS
– Provides a liquid cushion for the brain and spinal cord

Meningitis

Inflammation of the meninges

Different microbes cause meningitis, and produce a similar
constellation of syndromes

Noninfectious causes of meningitis exist as well

Serious forms of acute meningitis are caused by
bacteria. Entrance into CNS are facilitation by or co-infection with
respiratory viruses

Suspicion of meningitis

Lumbar puncture to obtain CSF
• Gram stain of CSF
• Culture of CSF
• Begin treatment with broad-spectrum antibiotics with a
shift in treatment after a diagnosis has been confirmed

Signs and Symptoms of Meningitis

Photophobia
– Headache
– Painful or stiff neck
– Fever
– Increased WBC in CSF
– Certain organisms may cause characteristic symptoms

Organisms that can Cause Meningitis

Neisseria meningitidis
• Streptococcus pneumoniae
• Haemophilus influenzae
• Listeria monocytogenes
• Cryptococcus neoformans
• Coccidioides immitis
• Virus

neisseria meningitidis

gram negative diplococci. responsible for 25% of all meningitis cases

transmission: droplet contact

virulence factors: capsule, endotoxin, IgA, protease

prevention: conjugated vaccine; ciprofloxacin, rifampin, or ceftriaxone used to protect contacts

Growth on modified Thayer-Martin (MTM) medium or chocolate agar in high CO2 environment. Oxidase positive.

Ceftriaxone is the first line antibiotic for treatment

Petechiae, meningococcemia, rapid decline

streptococcus pneumoniae

gram positive coccus

Also referred to as the pneumococcus

transmission: droplet contact

virulence factors: capsule, induction of apoptosis, hemolysin and hydrogen peroxide production

Resistant to penicillin, cephalosporins, and macrolide
antibiotics

causes majority of bacterial pneumonias, doesn't cause petechiae

treatment: vancomycin + ceftriaxone or cefotaxime

Haemophilus influenzae

Gram-negative coccobacillus known as "Hib"

Causes one of the most severe forms of meningitis in
humans

transmission: droplet contact

virulence factors: capsule

culture: on chocolate agar

prevention: Hib vaccine, ciprofloxacin, rifampin, or ceftriaxone

treatment: ceftriaxone

Listeria monocytogenes

Gram-positive, ranges in morphology from bacilli to long filaments in palisade formation. Does not produce capsules or endospores. Not fastidious, resistant to cold, heat, salt, pH extremes, and bile. Grows inside host cells, moves directly from an infected cell to an adjacent healthy cell. Transmission from vehicle (food). Prevention: cooking food, avoiding unpasteurized dairy products.

Listeriosis

Mild in healthy adults. Causes meningitis and septicemia in the elderly,
immunocompromised, fetuses, and neonates. Bacterium can cross the placenta and cause premature abortion and fetal death. Associated with contaminated dairy products, poultry, and meat

A 45 year old man presents to his oncologist with a fever, headache and stiff neck. He has been undergoing chemotherapy for the last 4 months for advanced stage colon cancer. A lumbar puncture reveals numerous neutrophils and gram positive coccobacilli with filaments in the palisade formation. What is the disease? What is the causative agent?

Meningitis is the disease, the causative agent is listeria monocytogenes

Cryptococcus neoformans

Fungus that causes more chronic meningitis with a gradual onset of symptoms. Transmission from vehicle (air, dust). Virulence factors are capsule, melanin production. Spherical to ovoid shape with a large capsule. Transmitted in bird droppings. In AIDS patients: fast onset and acute disease. Immediate treatment with amphotericin B and fluconazole.

Coccidioides immitis

Fungi. 25°C: moist white to brown colony with abundant, branching, septate hyphae. 37 - 40°C: parasitic phase, small spherule. Occurs endemically in natural reservoirs. Commonly known as Valley Fever. Treatment: fluconazole or ampthotericin B.

viral meningitis

A wide variety of viruses can cause meningitis. Majority of cases in children. 90% caused by enteroviruses. HSV-2 is sometimes known to cause meningitis. HIV can manifest as meningitis as well. Generally milder than bacterial or fungal meningitis.

Aseptic meningitis

viral meningitis is assumed when a patient shows symptoms of meningitis but no bacteria or fungi are found in CSF.

Neonatal and Infant Meningitis

Usually the result of an infection transmitted by the mother in utero or during passage through the birth canal. As more premature babies survive, rates of neonatal meningitis increase. Mortality rates have significantly declined.

Streptococcus agalactiae

Lancefield group B streptococci. Colonizes 10 – 30% of female genital tracts. Most frequent cause of neonatal meningitis. Treated with IV Penicillin G sometimes supplemented with an aminoglycoside.

Neonatal K1 Escherichia coli

Gram negative. K1 strain second most common cause of neonatal meningitis. Most common in premature babies. 20% mortality rate, brain damage among those who survive. Usually transmitted by the mother’s birth canal

Cronobacter sakazakii

Gram negative. Found mainly in the environment and can survive very dry conditions. Implicated in outbreaks of neonatal and infant meningitis through contaminated powdered infant formula. Mortality rates can reach 40%.

A natural birth, premature infant in the the NICU has a poor prognosis. The child was born 1 month early and currently has a fever and is extremely irritable. Examination of the CSF reveals a gram negative bacillus. What is the disease? What is the causative agent?

Disease: neonatal meningitis

Causative agent: E. Coli

Encephalitis

inflammation of the brain. Because of the close association of the brain and spinal cord, infection of one structure may involve the other.

Amoebas cause meningoencephalitis: Naegleria fowleri and Acanthamoeba

Naegleria fowleri

Amoeba. Amoebas forced into nasal passages utilize the olfactory nerve to enter the brain. Enters the subarachnoid space causing primary amoebic meningoencephalitis (PAM). Cases are rare, but the disease
advances so rapidly that treatment is futile. Treatment with pentamidine or sulfadiazine. Limit warm freshwater or untreated tap water entering nasal passages.

Acanthamoeba

Large, amoeboid trophozoite with spiny pseudopods and a double-walled cyst. Invades broken skin, conjunctiva, lungs, and urogenital epithelia. Causes granulomatous amoebic meningoencephalitis (GAM). Course of infection is lengthier than PAM. 2 – 3% survival rate. Treatment: surgical excision of granulomas; pentamidine.

Acute Encephalitis

Almost always caused by viral infection. Causes behavior changes or confusion, decreased consciousness and seizures, and symptoms of meningitis. Treatment is usually with acyclovir.

Arboviruses

Viruses transmitted by arthropod vectors. Clustered in the tropics and subtropics. Periodic epidemics in temperate zones. Most vectors feed on the blood of hosts. Peak incidence usually during the late spring and early
fall. Warm blooded hosts maintain the infection during cold and dry seasons. Millions of infections per year, thousands die. No satisfactory treatment for most arboviral infections.

Eastern equine, LaCrosse, St. Louis, Western equine, West nile, Venezuelan encephalitis's

Western Equine Encephalitis

Arbovirus. Occurs sporadically in the western US and Canada. Appears first in horses and later in humans. Mosquito vector emerges in the early summer. Extremely dangerous to infants and small children. Case fatality rate 3 – 7%.

Eastern Equine Encephalitis

Endemic to an area along the eastern coast of North America and Canada. Sporadic with occasional epidemics in humans and horses. High periods of rainfall favor mosquito populations, leading to increased incidence. Cases first appear in horses and caged birds. Vaccine exists and its use is strongly urged to eliminate the virus from its reservoir. Case fatality rate can reach 70%

California Encephalitis

Most often caused by California serotype viruses. Children are primary targets and exhibit mild, transient symptoms. Fatalities are rare.

California strain: Occurs occasionally in the western US and has little impact on humans

LaCrosse strain: Widely distributed in the eastern US and Canada and prevalent cause of viral encephalitis in North America.

St. Louis Encephalitis

Very common viral encephalitis. Cases occur in North and South America. Epidemics in the US occur in the Midwest and South. Asymptomatic infection is common. Peak activity occurs in the spring and summer.

An 8 year old boy from Maine is brought to the emergency room by his parents with complaints of fever, headache, stiff neck, malaise, nausea and vomiting that began 2 days ago. The boy appears disoriented and confused and has a seizure in the emergency department. Two weeks earlier in August, the patient had been on a summer camping trip in a rural wooded area of the county. The county health department has been trying to control the mosquito population in the area. What is the disease? What is the causative agent?

Disease: Encephalitis

Causative Agent: La Cross Virus

Herpes Simplex Virus

Herpes Simplex types I and II can cause encephalitis in newborns born to HSV-positive mothers. Virus is disseminated and progress is poor. Most common modes of transmission: vertical or reactivation of latent virus.

Subacute Encephalitis

Symptoms take longer to show up and are less striking. Toxoplasma, persistent measles infection, prions

Toxoplasma gondii

Flagellated parasite. Vehicle (meat) or fecal-oral. People with a history of this are more likely to display thrill-seeking behaviors and have slower reaction times. Primary reservoir is felines, both wild and domestic. Usually asymptomatic. Sore throat, lymph node enlargement, low grade fever. Chronic or subacute encephalitis in patients with immune suppression. 33% chance of the mother transmitting the infection to the fetus.

Measles Virus: Subacute Sclerosing Panencephalitis

“Slow virus infection”. Symptoms appear years after an initial measles episode. Caused by direct viral invasion of neural tissue. Unclear what factors lead to persistence of the virus in some people.

Prions

Proteinaceous infectious particles. Contain no genetic material. Cause transmissible spongiform encephalopathies. Creutzfeldt-Jacob disease (CJD). Gerstmann-Strussler-Scheinker disease. Kuru. Fatal familial insomnia. Scrapie in sheep and goats. Bovine spongiform encephalopathy (BSE). Normal protein in the brain (PRPC) is transformed into a prion protein (PRPSC). Altered protein spontaneously converts other PRPC
proteins into PRPSC proteins. Accumulation of PRPSC proteins cause plaques and spongiform damage in the brain.

Rabies

Slow, progressive zoonotic disease characterized by fatal encephalitis.

Furious rabies: Agitation, disorientation, seizures, twitching. Hydrophobia.

Dumb rabies: Patient is paralyzed, disoriented, stuporous

Both forms progress to a coma phase. Death results from cardiac or respiratory arrest

Rhabdoviridae lyssavirus, enveloped RNA virus

Polio

Acute enteroviral infection of the spinal cord. Can cause neuromuscular
paralysis. Fever, headache, nausea, sore throat, myalgia. Neurotropic: infiltrates the anterior horn of the motor neurons of the spinal cord. Also attacks the spinal ganglia, cranial nerves, and motor nuclei.

Polio sequelae

Paralytic disease: various degrees of flaccid paralysis of the muscles of the legs, abdomen, back, intercostals, diaphragm, pectoral girdle, and bladder
Bulbar poliomyelitis: brain stem, medulla, and cranial nerves are affected Post-polio syndrome: progressive muscle deterioration in 25 – 50% of patients decades after the initial infection

Tetanus

Clostridium tetani. Common resident of soil and GI tracts of animals. Gram-positive, endospore-forming rod.

Tetanospasmin

Binds to target sites on peripheral motor neurons on the spinal cord, brain, and sympathetic nervous system
Blocks inhibition of muscle contraction, causing muscles to contract uncontrollably, resulting in spastic paralysis
Death results from paralysis of respiratory muscles and respiratory arrest

Botulism

Intoxication: caused by an exotoxin. Associated with eating poorly preserved foods. Toxin travels from the bloodstream to the neuromuscular junctions of skeletal muscles. Prevents the release of
acetylcholine, resulting in flaccid paralysis. Utilized by doctors to treat
uncontrolled muscle spasms, migraine headaches, and other conditions.

African Sleeping Sickness

Trypanosoma brucei. Hemoflagellate: lives on the blood and tissues of the human host. Transmitted by the tsetse fly: T. brucei gambiense or T. brucei rhodesiense. Intermittent fever, enlarged spleen, swollen lymph
nodes, joint pain. Personality and behavioral changes. Lassitude and sleep disturbances. Uncontrollable sleepiness during the day,
sleeplessness at night. Muscle tremors, shuffling gait, slurred speech,
seizures, local paralysis. Death results from coma, secondary infections, and heart damage.