MICR 201 Microbiology for Health Related Sciences

1. Lecture 13: Microbial diseases of the skin and eyes Edith Porter, M.D. MICR 201 Microbiology for Health Related Sciences

2. Lecture outline • Structure of the nervous system • Main types of infections of the nervous system • Infections of the central nervous system • Infections of the peripheral nervous system • General and specific diseases of the nervous system • Bacterial diseases • Fungal diseases • Parasitic diseases • Prion diseases

3. The human nervous system

4. CSF is obtained by lumbar puncture Used for diagnostics of meningitis and other CNS disorders Never refrigerate CSF for culture The meningesand cerebrospinal fluid (CSF)

5. http://doctorgrasshopper.files.wordpress.com/2010/01/lots-of-lumbar-puncture-pics.jpghttp://doctorgrasshopper.files.wordpress.com/2010/01/lots-of-lumbar-puncture-pics.jpg

6. Spread of microorganisms into the brain • Skull or backbone fractures • Medical procedures • Along peripheral nerves • Blood or lymph • Must cross blood-brain barrier (capillaries)

7. Effects of edema on the brain • Increased intracranial pressure • Never remove cerebrospinal by lumbar puncture in these patients • Biochemical abnormalities • Neural tissue necrosis with loss of function

8. 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

9. Meningitis Note the turbid appearance of the meninges and yellowish liquid accumulation

10. Bacterial Meningitis • Fever, headache, stiff neck, light sensitivity • Followed by nausea and vomiting • May progress to convulsions and coma • Diagnostics with CSF • Neutrophil exsudate • Low glucose • Latex agglutination for selected microorganisms • Culture • Treated with cephalosporins (broad spectrum antibiotic)

11. Bacterial Meningitis • Streptococcus pneumoniae • Haemophilus influenzae • Neisseria meningitidis • Listeria monocytogenes • In newborns: • Group B streptococci • From vaginal flora • Transmitted during birth • Prophylactic ampicillin treatment i.v. of mother during birth if mother tests positive for Group B streptococci

12. Haemophilusinfluenzaemeningitis • Occurs mostly in children (6 months to 4 years) • Gram-negative aerobic bacteria, normal microbiota in nasooropharynx (throat ) • Pathogenic factor: capsule type b • Prevented by Hib vaccine

13. Neisseriaor meningococcal meningitis • N. meningitidis • Gram-negative aerobic cocci, capsule • 10% of people are healthy nasopharyngeal carriers • Begins as throat infection, rash (doesn’t fade when pressed) • Serotype B and Y is most common in the U.S. • Vaccine against some serotypes (but not B) is available

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

15. Listeriamonocytogenesmeningitis • Gram-positive rods • Symptomatic in immunocompromised • Intrauterine infections with abortion or stillbirth • Pregnant woman asymptomatic or only very mild disease • Proliferates at 4°C • Intracellular survival and cell to cell spread

16. Viral meningitis • Most common cause of aseptic meningitis • Lymphocyticpleocytosis in CSF • Most commonly enteroviruses • Fever less elevated • Better prognosis

17. Fungal meningitis: Cryptococcus neoformans • Soil fungus associated with pigeon and chicken dropping • Transmitted by the respiratory route; spreads through blood to the CNS • Capsule • Mortality up to 30% • AIDS patients • Treatment: amphotericin B and flucytosine

18. Encephalitis • Infection of the brain • Fever, head aches, chills and alteredconsciousness • Abnormal EEG, MRI

19. Viral encephalitis Edema in right temporal lobe • Arboviral (transmitted by arthropods) • Most common • Seasonal occurrence • Subclinical to severe symptoms including death • Herpes Virus 2 encephalitis 33 y old female patient presented with agitation, confusion, mutism, and fever

20. 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 hasd near 100% fatality rate • Acantamoeba infection has better prognosis

21. Brain abscess Cerebellar abscess in CT

22. Clinical Case Two hours after the onset of fever and malaise, a 15-year-old boy began to have tachycardia and tachypnea and became unconscious. He was taken to the intensive care unit, where he was found to be in septic shock (pulse, 180; blood pressure, 70/45 mm Hg; temperature, 40.2°C; and partial-thromboplastin time, 90 seconds). He had bullous lesions about the elbow and confluent petechial and purpuric lesions on his face, arms, and legs (Panel A). His hands and feet were cool and cyanotic. He had no signs of meningeal irritation. He was intubated, placed on cardiopulmonary support, and given large doses of catecholamines. A single dose of dexamethasone (3 mg per kilogram of body weight) was given immediately, and treatment with penicillin G (16 million IU per square meter of body-surface area) was started. Meanwhile, the petechiae spread rapidly, and four hours later peripheral pulses could not be detected in the arms or legs. Therapy with fresh-frozen plasma and heparin was also begun. Although the treatment led to resolution of the sepsis syndrome, local intravascular lysis with streptokinase failed to prevent severe ischemia-induced damage to the patient’s hands (Panel B) and feet (Panel C). Seven digits and both forefeet had to be amputated. After reconstructive surgery with free flaps, the patient was able to walk with orthopedic shoes and could use his remaining fingers in a pincer-like grip. N Engl J Med, Vol. 344, No. 18 May 3, 2001;www.nejm.org

23. Specific diseases of the nervous System • Tetanus • Botulism • Leprosy • Poliomyelitis • Rabies • Trypansomiasis • Prion diseases

24. Tetanus • Clostridium tetani • Gram-positive, endospore-forming, obligate anaerobe • Intoxication due to tetanus toxin • Tetanospasmin, a neurotoxin, blocks relaxation pathway in muscles causing contractions • Treatment • Supportive care and antitoxin • Prevention: • Vaccination • Wound cleaning

25. Tetanus

26. Botulism • Clostridium botulinum • Gram-positive, endospore-forming, obligate anaerobe • Intoxication due to ingesting botulinum toxin (dose: 0.001 mg/kg)  food poisoning • Botulinum toxin blocks release of neurotransmitter causing flaccid paralysis • Treatment • Supportive care and antitoxin • Prevention: • Proper canning • Nitrites prevent endospore germination in sausages • No honey for very young children! http://www.moondragon.org/obgyn/graphics/hypotonia.jpg

27. Funeral of an Oregon family wiped out by botulism • Home-canned string beans • 12 deaths (2 funerals held at a different location)

28. Diagnosis of botulism • Decontaminate and inject suspicious material into laboratory mice • Follow fate of mice over next 72 hours

29. Leprosy (Hansen’s disease) • Mycobacterium leprae • 12 day generation time • Survival in macrophages • Spread in the myelin sheaths of peripheral nerves

30. Poliomyelitis • Poliovirus • Transmitted by ingestion • Initial symptoms: sore throat and nausea • Viremia may occur; if persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases • Prevention is by vaccination (enhanced-inactivated polio vaccine)

31. Success of poliomyelitis vaccination

32. Rabies virus • 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 • 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

33. Rabies infection pathway

34. Reported cases of rabies in animals

35. 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/

36. Priondiseases • Transmissible Spongiform Encephalopathies • Sheep scrapie • Creutzfeldt-Jakob disease • Kuru • Bovine spongiform encephalopathy • Proteinaceous infectious particle • Transmitted by ingestion or transplant or inherited • Chronic, fatal within months – a few years

37. Transmissible spongiform encephalopathies Normal Spongiform encephalitis Neurological Damage Fibrillar deposit

38. Important to remember • The CNS is covered by meninges, three layers of membranes called dura mater, arachnoid mater, and pia mater. • Blood-brain barrier greatly limits access to the brain. • Infection of the meninges is called meningitis, infection of the brain with its grey and white matter is called encephalitis. • Bacteria, viruses, fungi and parasites can cause meningitis and encephalitis. • Key symptoms of meningitis are fever, head aches and possibly vomiting. • Encephalitis is characterized by fever, headache and impairment of brain function and consciousness. • Specific diseases of the nervous system have unique symptoms

39. Check your understanding Tetanospasmin and botulinum toxin are alike in that they both A) cause muscle spasm B) cause flaccid paralysis C) affect the smooth muscles (e.g. in the intestine) D) are produced by the aerobic spore former Bacillus anthracis E) None of the above In contrast to meningitis encephalitis A) leads to generalized bleeding B) rather causes disturbances of the mental status C) is best diagnosed by a lumbar tap D) All of the above. E) None of the above.