Chapter 26 - Microbial Diseases of the Nervous System

Central Nervous System (CNS)

brain and spinal cord

Peripheral Nervous System (PNS)

nerves branching out from the brain and spinal cord

Meninges

three protective membranes that surround the brain and spinal cord; dura, arachnoid and pia mater; subarachnoid space contains cerebrospinal fluid (CSF)

Blood-brain barrier

Blood vessels (capillaries) that selectively let certain substances enter the brain tissue and keep other substances out

Meningitis

inflammation of the meninges

Encephalitis

inflammation of the brain

Meningoencephalitis

inflammation of the meninges and brain

Bacterial meningitis

Initial symptoms of fever, headache, and stiff neck

Followed by nausea and vomiting

May progress to convulsions and coma

Diagnosis by Gram stain and latex agglutination of CSF

Less common and more serious than viral infection

Haemophilus influenzae meningitis

Gram-negative aerobic bacteria; normal throat microbiota

Transmission: respiratory route, then enters bloodstream

Pathogenicity due to capsule antigen type b

Occurs mostly in children (6 months to 4 years)

Prevented by the Hib vaccine

Accounts for 45% of bacterial meningitis cases; 6% mortality

Meningococcal meningitis cause

Neisseria meningitidis: aerobic, gram-negative, encapsulated diploccocus; six serotypes associated with disease; carried in nasopharyngeal mucosa; often begins as throat infection and rash leading to bacteremia

Meningococcal meningitis treatment and prevention

Treatment: antibiotics (lowers mortality form 80% to 9-12%)

Prevention: vaccine protects against serotypes A, C, Y, W, and B, but not X

Pneumococcal meningitis

Caused by S. pneumoniae (gram-positive, encapsulated diplococcus)

Seventy percent of people are healthy nasopharyngeal carriers.

Also causes pneumonia and otitis media

Most common in children (1 month to 4 years)

Mortality: 8% in children, 22% in the elderly

Prevented by conjugated vaccine

Diagnosis and treatment of bacterial meningitis

CSF sample from spinal or lumbar tap

Gram-stain will identify causative agent

Latex agglutination test

Broad-spectrum third-generation cephalosporins used before diagnosis

Listeriosis

Caused by Listeria monocytogenes (gram-negative aerobic rod)

Symptoms: usually foodborne and asymptomatic; meningitis more common in the immunocompromised

Can invade the bloodstream, causing sepsis

Reproduces and spreads in phagocytes

Infects pregnant women, crossing the placenta and leading to stillbirth

Tetanus

Caused by Clostridium tetani (gram-positive, endospore-forming, obligate anaerobe)

Grows in deep wounds with anaerobic conditions Tetanospasmin neurotoxin released from dead cells enters CNS and blocks the relaxation pathway in muscles, causing muscle spasms

Death occurs from spasms of respiratory muscles

Tetanus prevention and treatment

-immunization is the best preventative measure (vaccine= inactivated tetanospasmin); booster every 10 years

-thoroughly clean wound, debridement as necessary

-treatment: antibody against tetanospasmin

Botulism

Caused by Clostridium botulinum (gram-positive, endospore-forming, obligate anaerobe)

Intoxication from ingesting the botulinal exotoxin that blocks release of the neurotransmitter acetylcholine, causing flaccid paralysis

Death usually comes from respiratory or cardiac failure.

Botulinal Types

-Type A toxin: Fatality: 60-70%; heat-resistant and proteolytic

-Type B toxin: fatality: 25%

-Type E toxin: produced by organisms in marine and lake sediments; less heat-resistant than other strains

Diagnosed by inoculating immunized mice with patient samples

Infant botulism

C. botulinum growing in the intestines of infants due to a lack of intestinal microbiota

Associated with honey

Wound botulism

growth of C. botulinum in wounds

Botulism treatment and prevention

Treatment with respiratory assistance and antitoxins

Prevented with proper canning and the use of nitrites in foods

Leprosy (Hansen's Disease)

Caused by Mycobacterium leprae (acid-fast rod); grows best at 30°C; generation time of 12 days; Grows in peripheral nerves and skin cells; survives macrophages and invades the myelin sheath

Leprosy stages

Tuberculoid (neural) form: loss of sensation in skin areas

Lepromatous (progressive) form: disfiguring nodules over the body; mucous membranes are affected

Leprosy diagnosis and treatment

Diagnosed with skin biopsy or smear; blood test

Treatment: Dapsone, Rifampin, and Clofazimine for 6-24 months

Poliomyelitis etiology and transmission

Caused by Poliovirus

Transmission: ingestion of contaminated water

Poliomyelitis symptoms

Initial symptoms: sore throat and nausea

Viremia can occur; virus enters CNS and 1% of cases become paralytic; motor nerve cells destroyed and respiratory failure can lead to death

Poliomyelitis prevention

Vaccine for all three stereotypes; cases fell 99% from 1988 to 2000 because of the vaccine

Salk vaccine: inactivated virus, injectable

Sabin vaccine: attenuated virus, oral, lifelong immunity, more effective and cheaper but can occasionally be transmitted

Rabies etiology and transmission

Caused by Lyssavirus: bullet-shaped virus, ssRNA, rapidly mutates

Transmitted by saliva of animal bite, most commonly silver-haired bats in US; can also cross mucous membranes

Rabies symptoms

Initial - muscle spasms of mouth and pharynx; virus multiplies in skeletal muscles, travels through PNS to brain and causes encephalitis; incubation of 30-50 days; Negri bodies in brain stem

Furious (classical) rabies

animals are restless, then highly excitable

Paralytic (dumb or numb) rabies

animals seem unaware of their surroundings; minimally excitable

Rabies Diagnosis and Treatment

Diagnosed from bodily fluids;

Postexposure prophylaxis (PEP): vaccine plus immunoglobulin; human diploid cell vaccine (HDCV); Human rabies immunoglobulin (RIG)

Little effective treatment once symptoms appear, only handful of reported survivors

Lyssavirus Encephalitis

-Clinically indistinguishable from rabies

-Found in countries free of rabies

-Australian bat lyssavirus (ABLV)

-European bat lyssavirus (EBLV)

Arboviral Encephalitis

-Arbovirus; arthropod-borne viruses that belong to several families

-Mosquito vector; higher incidence in summer

-Prevention: Controlling mosquitoes

-Symptoms: range from subclinical to severe

-Diagnosis: ELISA tests (identify IgM antibodies)

Eastern Equine Encephalitis (EEE) and Western Equine Encephalitis (WEE)

Arboviral encephalitis that normally occurs in horses

Thirty percent mortality in humans

Cause brain damage, deafness, and neurological damage

St. Louis Encephalitis (SLE)

Mild arboviral encephalitis

Distributed mostly in the central and eastern United States

Fewer than 1% of the infected show symptoms

California Encephalitis (CE)

Mild and rarely fatal form of arboviral encephalitis common to west coast of US

West Nile virus (WNV)

-Arboviral encephalitis maintained in the bird-mosquito-bird cycle

-Carried by Culex mosquitoes

-Can cause poliolike paralysis and fatal encephalitis

Heartland virus disease

Arboviral encephalitis that can cause neurological problems, thrombocytopenia, and leukopenia

Powassan virus (POW)

Arboviral encephalitis distributed in NE US and Great Lakes region; can cause long-term neurological problems; mortality 10-15%

Japanese encephalitis

Arboviral encephalitis found in Far East and South Asia; 1% show symptoms with 20-30% mortality in symptomatic cases

Zika Virus Disease (ZVD)

Transmission: Aedes spp. mosquitoes, sexual transmission, blood transfusions

Symptoms: 20% show mild symptoms; infection during pregnancy increases risk of microcephaly

Diagnosis: RT-PCR

Prevention: vector control

Cryptococcosis

Caused by Cryptococcus neoformas: soil fungus associated with pigeon and chicken droppings

Transmission: respiratory route through dried contaminated droppings

Symptoms: mild or asymptomatic; in the immunocompromised, it spreads through blood to the CNS resulting in meningitis and mortality of up to 30%

Treatment: amphotericin B and flucytosine

African trypanosomiasis (sleeping sickness)

-Etiology: Trypanosoma brucei gambiense (humans are the only reservoir) andT. b. rhodesiense (reservoir in livestock and wild animals)

-Transmission: from animals to humans by the tsetse fly

Endemic in west and central Africa

-Symptoms: Few early symptoms, followed by fever, headache, and deterioration of the CNS

Parasite evades antibodies through antigenic variation – Difficult for vaccine development

-Treatment: eflornithine: crosses the blood-brain barrier; blocks an enzyme necessary for the parasite

Prevention: elimination of tsetse fly vectors

Primary Amebic Meningoencephalitis (PAM)

Caused by Naegleria fowleri

Protozoan infects nasal mucosa of individuals that swim in natural waters, penetrates the brain, and proliferates as it feeds on brain tissue

Death occurs within days, and the mortality rate is near 100%

Granulomatous amebic encephalitis (GAE)

Caused by Acanthamoeba spp.; Granulomas form around the site of infection, forming multiple lesions around the brain

Balamuthia mandrillaris

Free-living ameba that causes GAE in mammals; very rare but very deadly

Prion

Any of various infectious proteins that are abnormal forms of normal cellular proteins, that proliferate by inducing the normal protein to convert to the abnormal form, and that in mammals include pathogenic forms

PrPc

normal cellular prion protein, on the cell surface

PrPsc

Infectious scrapie protein; accumulates in brain cells, forming spongiform degeneration; chronic and fatal

Transmissible Spongiform Encephalopathies (TSE)

Progressive brain infections caused by unusual pathogens called prions, leading to loss of brain structure and function.

Sheep scrapie

TSE in sheep

Chronic wasting disease

TSE in deer and elk

Creutzfeldt-Jakob disease

TSE in humans

Kuru

TSE in humans that is caused by cannibalism

Bovine Spongiform Encephalopathy (BSE)

disease of cattle ("mad cow disease") that can be transmitted to humans, causing Creutzfeldt-Jakob disease

Variant CJD (vCJD)

Occurs in younger individuals

Some forms of CJD may be inherited

Acute Flaccid Myelitis (AFM)

Symptoms: limb weakness, drooping eyelids, difficulties with swallowing or slurred speech

Possible cause: a nonpolio enterovirus EV-D68

Bell's palsy

Inflammation of nerves that control facial muscles Symptoms: drooping eyelid or mouth

Possible cause: herpes viruses

Chronic Fatigue Syndrome

Diagnostic definition includes persistent, unexplained fatigue that lasts at least 6 months plus other flulike symptoms.

Affects ~800,000 to 2.5 million Americans

Possibly triggered by a variety of infections