MICR 201 Microbiology for Health Related Sciences Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 24: Infections of the central nervous system

Why is this chapter important? Infections that affect the central nervous system (CNS) can be catastrophic and potentially lethal. Neurons do not regenerate, hence loss of neurons due to infection leads to permanent damage.

MENINGITIS, ENCEPHALITIS, BRAIN ABSCESS IN GENERAL Map for chapter 24 MENINGITIS, ENCEPHALITIS, BRAIN ABSCESS IN GENERAL

The human nervous system

Anatomy of the CNS CNS has two major parts Brain Spinal cord Both surrounded by three layers of connective tissue – meninges. Cerebrospinal fluid is found in the subarachnoid space. The brain and spinal cord are protected from the body by the blood-brain barrier. Protects against infectious disease Some pathogens can pass through the blood- brain barrier

Effects of edema on the brain Inflammation is one of the first and most formidable responses. Always causes swelling No room for swelling in the CNS. Danger of brain herniation Normal Edema

Effects of infection on brain function Infection can also affect proper brain function through: Acidosis Hypoxia Destruction of neurons Effects of infection can be profound and irreversible. Blood-brain barrier can make it difficult to treat CNS infections.

Spread of microorganisms into the brain Skull or backbone fractures Medical procedures Along peripheral nerves Rabies virus, Herpes simplex virus Blood or lymph Infection originates from another body site Neisseria meningitidis, Streptococcus pneumoniae Must cross blood-brain barrier (capillaries)

The meninges and cerebrospinal fluid (CSF) CSF is obtained by lumbar puncture Used for diagnoses of meningitis and other CNS disorders Never refrigerate CSF for culture

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Main types of infections of the nervous system Meningitis Inflammation of meninges Headaches, stiff neck, light sensitivity, vomiting Encephalitis Inflammation of the brain Mental disturbance, altered consciousness, seizures Abscess Focal symptoms depending on the location of the abscess Often polymicrobial, anaerobes, amoeba

Bacterial meningitis Fever, headache, stiff neck, light sensitivity Followed by nausea and vomiting May progress to convulsions and coma Bacterial meningitis can be severe and cause: Brain damage Hearing loss Learning disability Diagnostics with CSF Neutrophil exudate Low glucose Latex agglutination for selected microorganisms Culture Important to know type of bacterium Antibiotic therapy can prevent its spread. Cephalosporines Streptococcus pneumoniae Haemophilus influenzae Neisseria meningitidis Listeria monocytogenes Escherichia coli Streptococcus agalactiae newborns

Waterhouse-Friderichsen Syndrome Neisseria meningitidis sepsis Septic Shock and bleeding into adrenal gland Petechial skin lesions (bleeding into skin) Death within 12 – 48 hours

Viral meningitis Most common cause of aseptic meningitis Lymphocytic pleocytosis in CSF Viral meningitis is generally less severe: Fever less elevated Usually resolves without treatment. 90% of cases caused by enterovirus Also herpesvirus and mumps virus.

Fungal meningitis: Cryptococcus neoformans Soil fungus associated with pigeon and chicken dropping (soil enriched for growth of fungus) Transmitted by the respiratory route; spreads through blood to the CNS Capsule Mortality up to 30% AIDS patients Treatment: amphotericin B and flucytosine

Encephalitis Infection of the brain Fever, head aches, chills and altered consciousness Abnormal EEG, MRI

Viral encephalitis Western and Eastern equine Virus, West Nile Virus Edema in right temporal lobe Most common is arboviral encephalitis (transmitted by arthropods) Western and Eastern equine Virus, West Nile Virus Seasonal occurrence Subclinical to severe symptoms including death Herpes Virus 2 encephalitis 33 y old female patient presented with agitation, confusion, mutism, and fever

Amoeba meningoencephalitis Free living amoeba found in fresh water Infection during swimming Entry via nasal mucosa and ascension into brain via olfactory nerve Naegleri fowleri infection has near 100% fatality rate Acantamoeba infection has better prognosis

Brain abscess Cerebellar abscess in CT

Tetanus Many bacteria cause meningitis. Increased cranial pressure and inflammation Tetanus and botulism infections affect the CNS in different ways. Produce exotoxins with an affinity for CNS tissue Antibiotic therapy is ineffective once the exotoxin has been produced.

Specific diseases of the central nervous System Tetanus Poliomyelitis Rabies Trypansomiasis Prion diseases (Chapter 8)

Tetanus Tetanus is caused by Clostridium tetani. Gram-positive Anaerobic Rod shaped Produces terminal endospores Commonly found in soil Spores enter tissue and germinate Vegetative bacteria produce a neurotoxin call tetanospasmin or tetanus toxin

Tetanus toxin Toxin enters the presynaptic terminals of the lower motor neurons. From there, it gets into the CNS. Toxin acts at the anterior horn cells in the spinal cord. Blocks postsynaptic inhibition of the spinal motor reflexes Produces spasmodic contraction of the muscles Occur locally at first May extend up and down the spinal cord

Tetanus Incubation period can vary between 4 days and several weeks. The shorter the incubation period, the more severe the infection. Tetanus leads to systemic muscle spasms. Masseter muscle of the jaw usually first to be affected. Mouth cannot be opened (sometimes called lockjaw) Muscles for respiration and swallowing can eventually be compromised. Severe cases can suffer from opisthotonus (head and heels move toward each other) Death results from exhaustion and respiratory failure. Mortality for untreated tetanus is 15 - 60%.

Tetanus ophistotonus

Tetanus treatment Antibiotics are not effective once toxin is produced. Neutralization of the toxin with human tetanus immunoglobulin is important. Additional supportive measures are: Maintenance of a dark, quiet environment Sedation Provision of an adequate airway for breathing Vaccination with toxoid

Rabies Transmitted by animal bite Virus multiplies in skeletal muscles, then brain cells causing encephalitis Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia, saliva overproduction Develops into acute fatal encephalitis Furious rabies: animals are restless then highly excitable Paralytic rabies: animals seem unaware of surroundings Pre-exposure prophylaxis: Vaccine Post-exposure treatment: Vaccine + immune globulin

Rabies infection pathway

Polio Condition first known as infantile paralysis Risk of paralysis actually increases with age. Essentially nonexistent in most modern countries There is an effective vaccine. Still a major problem in developing countries. Virus is an enterovirus with an affinity for the CNS. Normally crosses the blood-brain barrier Can also use axons or the perineural sheath of the peripheral nervous system Motor neurons are particularly vulnerable.

Polio Various levels of neuronal destruction cause: Necrosis of neural tissue Infiltration by mononuclear cells, primarily lymphocytes 90% of poliomyelitis infections are very mild and subclinical. Three types of polio infection: Abortive poliomyelitis Nonparalytic poliomyelitis (aseptic meningitis) Paralytic poliomyelitis

Paralytic poliomyelitis Occurs in 2% of persons infected Characterized by asymmetric flaccid paralysis Extent varies from case to case Temporarily damaged neurons can regain function Recovery can take six months Paralysis persisting after this period is permanent

Polio vaccines Polio vaccine essentially wiped out this infection. Two types of vaccine: Inactive form – developed by Jonas Salk Live attenuated form – developed by Albert Sabin

Success of poliomyelitis vaccination

Trypanosomiasis Protozoa Transmitted by tsetse fly Undulating membrane Live in body fluids Escape immune system by changing a surface protein (encoded by ~ 1000 different genes) Enter brain and cause encephalitis Sleeping disease Fatal within 2- 3 years if left untreated http://www.cdc.gov/parasites/sleepingsickness/

Chapter 24 key concepts Central nervous system infections can be very dangerous and require immediate and aggressive therapy. The central nervous system has a blood–brain barrier to prevent access of blood borne pathogens. Pathogens that can move from the blood to the cerebrospinal fluid cause meningitis. Most central nervous system infections result from bacteremia or viremia. Many viruses have an affinity for the central nervous system.

Chapter 24 key concepts Viral infection of the central nervous system can be acute or persistent. Acute viral CNS infections include rabies, polio, and encephalitis. Persistent viral infections include measles and rubella. Prions cause persistent central nervous system infections. Fungal infections of the central nervous system are primarily opportunistic and occur in immunocompromised individuals. Parasitic infections of the central nervous system are usually caused by free-living amebas.

Final Examination – Wednesday, June 12, 2013 10:45am – 1:15pm Lecture, Chapter End Self Study Questions 100 Multiple Choice Questions: 2 points each x 100 = 200 points ~65%: Chapters 14-26 ~35%: Chapters 1-13 Please bring Scantron and No. 2 pencil

CORRECTION – Chapter Question Chapter 22 Infections of the Digestive System 1. The most common source of gastrointestinal infection in the developed world is A. Salmonella B. Shigella C. Escherichia D. Campylobacter E. Staphylococcus aureus Correct answer is D. Campylobacter