1. Microbial Diseases of the Nervous System
Chapter 22
Microbial Diseases of the Nervous System

3. Central nervous system (CNS)
Figure 22.1 The human nervous system.
Brain
Central nervous system (CNS)
Spinal cord
Peripheral nervous system (PNS)

4. The Nervous System Meninges protect brain and spinal cord
Dura mater: outermost layer
Arachnoid mater: middle layer
Subarachnoid space contains cerebrospinal fluid (CSF)
Pia mater: innermost layer
Blood–brain barrier

5. Cerebrum Skull bone Cerebellum Spinal cord
Figure 22.2 The meninges and cerebrospinal fluid.
Skull bone
Cerebrum
Subarachnoid space (contains cerebrospinal fluid)
Skull bone
Dura mater
Arachnoid mater
Cranial meninges
Pia mater
Blood vessel
Cerebrum
Cerebellum
Spinal cord
Dura mater
Arachnoid mater
Spinal meninges
Subarachnoid space of spinal cord
Pia mater
Subarachnoid space (contains cerebrospinal fluid)
Central canal

6. The Nervous System Meningitis: inflammation of meninges
Encephalitis: inflammation of the brain
Meningoencephalitis: inflammation of both

7. 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

8. Fourth lumbar vertebra
Figure 22.4 Spinal tap (lumbar puncture).
Spinal needle is inserted, usually between the fourth and fifth lumbar vertebrae
Cerebrospinal fluid
Spinal cord
Fourth lumbar vertebra L4
Cauda equina L5
Sample of cerebrospinal fluid
Longitudinal section of the spine
Fifth lumbar vertebra

9. Haemophilus influenzae Meningitis
Occurs mostly in children (6 months to 4 years)
Gram-negative aerobic bacteria, normal throat microbiota
Capsule antigen type b
Prevented by Hib vaccine

10. Neisseria Meningitis Also called meningococcal meningitis
Caused by N. meningitidis
Gram-negative, aerobic cocci with a capsule
10% of people are healthy nasopharyngeal carriers
Begins as throat infection, rash
Serotypes B, C, Y, W-135
Serotype B & C in United States
Serotype A in Africa
Vaccination (A, C, Y, W-135 capsule) recommended for college students

11. N. meningitidis Cilia N. meningitidis
Figure 22.3 Neisseria meningitis.
N. meningitidis
Cilia
N. meningitidis

12. Streptococcus pneumoniae Meningitis
Also called pneumococcal meningitis
Caused by S. pneumoniae (a gram-positive diplococcus)
70% of people are healthy nasopharyngeal carriers
Most common in children (1 month to 4 years)
Mortality: 30% in children, 80% in elderly
Prevented by vaccination

13. Listeriosis Caused by Listeria monocytogenes Gram-negative aerobic rod
Usually foodborne; it can be transmitted to fetus
Reproduce in phagocytes
Spread phagocyte-to-phagocyte

14. Listeria monocytogenes
Figure 22.5 Cell-to-cell spread of Listeria monocytogenes, the cause of listeriosis.
Listeria monocytogenes
Macrophage
Macrophage
Pseudopod

15. Diseases in Focus: Meningitis and Encephalitis
A worker in a day-care center in eastern North Dakota becomes ill with fever, rash, headache, and abdominal pain. The patient has a precipitous clinical decline and dies on the first day of hospitalization. Diagnosis is confirmed by Gram staining of cerebrospinal fluid.
Can you identify infections that could cause these symptoms?

16. Gram stain of cerebrospinal fluid.
Diseases in Focus: Meningitis and Encephalitis.
Gram stain of cerebrospinal fluid.

17. Tetanus Caused by Clostridium tetani
Gram-positive, endospore-forming, obligate anaerobe
Grows in deep wounds
Tetanospasmin released from dead cells blocks relaxation pathway in muscles
Prevention by vaccination with tetanus toxoid (DTaP) and booster (Td)
Treatment with tetanus immune globulin (TIG)

18. Figure 22.6 An advanced case of tetanus.

19. Botulism Caused by Clostridium botulinum
Gram-positive, endospore-forming, obligate anaerobe
Intoxication comes from ingesting botulinal toxin
Botulinal toxin blocks release of neurotransmitter, causing flaccid paralysis
Prevention
Proper canning
Nitrites prevent endospore germination in sausages

20. Botulism Treatment: supportive care and antitoxin
Infant botulism results from C. botulinum growing in intestines
Wound botulism results from growth of C. botulinum in wounds

21. Botulinal Types Type A toxin Type B toxin Type E toxin 60–70% fatality
Found in CA, WA, CO, OR, NM
Type B toxin
25% fatality
Europe and eastern United States
Type E toxin
Found in marine and lake sediments
Pacific Northwest, Alaska, Great Lakes area

22. Figure 22.8 Diagnosing botulism by identifying botulinal toxin type.

23. Leprosy Also called Hansen’s disease Caused by Mycobacterium leprae
Acid-fast rod that grows best at 30°C
Grows in peripheral nerves and skin cells
Transmission requires prolonged contact with an infected person

24. Leprosy
Tuberculoid (neural) form: loss of sensation in skin areas; positive lepromin test
Lepromatous (progressive) form: disfiguring nodules over body; negative lepromin test

25. Tuberculoid (neural) leprosy Lepromatous (progressive) leprosy
Figure 22.9 Leprosy lesions.
Tuberculoid (neural) leprosy
Lepromatous (progressive) leprosy

26. Diseases in Focus: Diseases with Neurological Symptoms or Paralysis
After eating canned chili, two children experience cranial nerve paralysis followed by descending paralysis. The children are on mechanical ventilation. Leftover canned chili is tested by mouse bioassay.
Can you identify infections that could cause these symptoms?

27. Gram stain from canned chili.
Disease in Focus: Diseases with Neurological Symptoms or Paralysis
Gram stain from canned chili.

28. Poliomyelitis (Polio)
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: vaccination (enhanced-inactivated polio vaccine)

29. Number of confirmed polio cases
Figure Worldwide annual incidence of poliomyelitis.
7,000
6,000
2,000
5,000
1,000
4,000
Number of confirmed polio cases
3,000
2008
2009
2010
2,000
1,000
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Year

30. Rabies Caused by the rabies virus Transmitted by animal bite
Furious rabies: animals are restless, then highly excitable
Paralytic rabies: animals seem unaware of surroundings

31. Virus reaches brain and causes fatal encephalitis.
Figure Pathology of rabies infection.
Virus reaches brain and causes fatal encephalitis.
Virus ascends spinal cord.
Virus enters salivary glands and other organs of victim.
Virus moves up peripheral nervous system to CNS.
Virus replicates in muscle near bite and enters neuron of peripheral nervous system.
Virus enters tissue from saliva of biting animal.

32. Figure 22.13 Reported cases of rabies in animals.
Areas of the United States in which rabies predominates in certain wildlife species. Rabies-infected bats were reported in 47 of the 48 contiguous states. In eastern states in which raccoons are the predominant rabies-infected animal, many cases were also reported in foxes and skunks.
KEY
Skunk
Raccoon
Fox
Fox and skunk

33. Figure 22.13 Reported cases of rabies in animals.
Rabies cases in various wild and domestic animals in the United States. Rabies in domestic animals such as dogs and cats is uncommon because of high vaccination rates. Raccoons, skunks, and bats are the animals most likely to be infected with rabies. Most human cases are caused by bites of bats. Worldwide, most human cases are caused by bites of dogs.
Raccoons
35.5%
Bats
24.8%
Skunks
24.5%
Foxes
7.7%
Cats
4.6%
Dogs
1.2%
KEY
Cattle
1.1%
Wild
Horses/mules
0.6%
Domestic 10 20 30 40 50

34. Clinical Focus: A Neurological Disease, Figure B.
Silver-haired bat.

35. Rabies Virus
Virus multiplies in skeletal muscles and then brain cells, causing encephalitis
Initial symptoms may include muscle spasms of the mouth and pharynx and hydrophobia

36. Prevention of Rabies
Preexposure prophylaxis: injection of human diploid cells vaccine (HDCV)
Postexposure treatment: vaccine plus rabies immune globulin (RIG)

37. Arboviral Encephalitis
Arboviruses
Arthropod-borne viruses that belong to several families
Prevention: controlling mosquitoes

38. Figure 22.14 California serogroup arbovirus cases: 1964–2009.VT NH 1 MA
366 58
586 RI 1 29 8
134 CT 2
898
241
143 28 1 NJ 3 1 14 22
215
154 DE 2 3 5 14 7 25 MD 2 4 25 DC 4 WV
594

39. Arboviral Encephalitis

40. Arboviral Encephalitis

41. Diseases in Focus: Types of Arboviral Encephalitis
An 8-year-old girl in rural Wisconsin has chills, headache, and fever and reports having been bitten by mosquitoes.
Which type of encephalitis is most likely?

42. Culex mosquito engorged with human blood.
Diseases in Focus: Types of Arboviral Encephalitis.
Culex mosquito engorged with human blood.

43. Cryptococcus neoformans Meningitis
Also called cryptococcosis
Soil fungus associated with pigeon and chicken droppings
Transmitted by the respiratory route; spreads through blood to the CNS
Mortality up to 30%
Treatment: amphotericin B and flucytosine

44. Figure 22.15 Cryptococcus neoformans.
Capsule

45. African Trypanosomiasis
Trypanosoma brucei gambiense
Chronic (2 to 4 years)
T. b. rhodesiense infection
Acute (few months)
Transmitted from animals to humans by tsetse fly

46. African Trypanosomiasis
Prevention: elimination of the vector
Treatment: eflornithine blocks an enzyme necessary for the parasite
Parasite evades the antibodies through antigenic variation

47. Clone A Clone B Clone C 1 2 3 4 Weeks after infection
Figure How trypanosomes evade the immune system.
Clone A
Clone B
Clone C
Relative number of trypanosomes 1 2 3 4
Weeks after infection

48. Naegleria fowleri Protozoan infects nasal mucosa from swimming water
Ameboid-flagellate-cyst

49. Figure 22.17 Naegleria fowleri.
Dead ameba
Naegleria fowleri

50. Chapter 22, unnumbered figure, page 635.
Flagellate
Ameba
Cyst

51. Figure 22.18 Spongiform encephalopathies.
Holes

52. Transmissible Spongiform Encephalopathies
Caused by prions
Typical diseases
Sheep scrapie
Creutzfeldt-Jakob disease
Kuru
Bovine spongiform encephalopathy
Chronic and fatal

53. Figure 13.22 How a protein can be infectious.
PrPc
PrPSc 1
PrPc produced by cells is secreted to the cell surface. 2
PrPSc may be acquired or produced by an
altered PrPc gene. 3
PrPSc reacts with PrPc
on the cell surface. 4
PrPSc converts the PrPc to PrPSc. 5
The new PrPSc converts more PrPc. 6
The new PrPSc is taken in, possibly by receptor-mediated endocytosis.
Lysosome 7 8
PrPSc continues to accumulate as the endosome contents are transferred to lysosomes. The result is cell death.
PrPSc accumulates in
endosomes.
Endosome

54. Prion Diseases of the Nervous System
Acquired by
Ingestion
Inheritance
Transplant
Difficult to destroy

55. Endospores of bacteria
Figure 7.11 Decreasing order of resistance of microorganisms to chemical biocides.
Most resistant
Prions
Endospores of bacteria
Mycobacteria
Cysts of protozoa
Vegetative protozoa
Gram-negative bacteria
Fungi, including most fungal spores
Viruses without envelopes
Gram-positive bacteria
Viruses with lipid envelopes
Least resistant

56. Preventing Prion Diseases
Sterilization of surgical instruments by NaOH with extended autoclaving at 134°C

57. Chronic Fatigue Syndrome
Also called myalgic encephalomyelitis (ME)
Unexplained fatigue that lasts at least 6 months, plus four of these symptoms:
Sore throat
Tender lymph nodes
Muscle pain
Pain in multiple joints
Headaches
Unrefreshing sleep
Malaise after exercise
Impaired short-term memory or concentration

58. Chronic Fatigue Syndrome
Experimental treatment promotes antiviral interferons