1. Microbial Diseases of the Nervous System DR SONNIE P. TALAVERA 08162009 OLFU

2. How Microbes Enter the Nervous System Skull or backbone fractures Medical procedures Along peripheral nerves Blood or lymph

3. The Nervous System Figure 22.1

4. Microbial Diseases of the Nervous System Bacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS. The blood brain barrier (capillaries) prevents passage of some materials (such as antimicrobial drugs) into the CNS. Meningitis: Inflammation of meninges. Encephalitis: Inflammation of the brain.

5. The Meninges and Cerebrospinal Fluid Figure 22.2

6. Bacterial Meningitis Fever, headache, and stiff neck Followed by nausea and vomiting May progress to convulsions and coma Diagnosis by Gram stain or latex agglutination of CSF Treated with cephalosporins

7. Bacterial Meningitis Figure 22.3

8. ACUTE BACTERIAL MENINGITIS infection and inflammation of the meninges infection of other parts of the CNS

10. headache

11. stiff neck

12. irritability (children)

13. neurologic dysfunction

14. lethargy

15. confusion

16. uncharacteristic sleepiness

18. E. coli K1

20. Neisseriameningitidis

23. Neisseria Meningitis, Meningococcal Meningitis N. meningitidis Gram-negative aerobic cocci, capsule 10% of people are healthy nasopharyngeal carriers Begins as throat infection, rash Serotype B is most common in the United States Vaccination recommended for college students.

24. Neisseria Meningitis, Meningococcal Meningitis N. meningitidis causes meningococcal meningitis. This bacterium is found in the throats of healthy carriers. The bacteria probably gain access to the meninges through the bloodstream. The bacteria may be found in leukocytes in CSF. Symptoms are due to endotoxin. The disease occurs most often in young children. Purified capsular polysaccharide vaccine against serotypes A, C, Y, and W-135 is available.

25. Neisseria Associated Diseases (ophthalmia neonatorum)

26. Differential Characteristics of Commonly Isolated Neisseria spp.

28. Second most common cause (behind S. pneumoniae) of community-acquired meningitis in previously healthy adults

30. Pili-mediated, receptor-specific colonization of nonciliated cells of nasopharynx

31. Antiphagocytic polysaccharide capsule

33. Meningitis

34. Septicemia (meningococcemia) with or without meningitis

35. Meningoencephalitis

36. Pneumonia

37. Arthritis

40. Person-to-person transmission by aerosolization of respiratory tract secretions in crowded conditions

43. Organisms are internalized into phagocytic vacuoles, avoid intracellular killing

45. most clinical manifestations including

46. diffuse vascular damage,

47. vasculitis,

48. thrombosis,

51. complementsystem is required for clearance of the organisms

53. Transparent, non-pigmented nonhemolytic colonies on chocolate blood agar with enhanced growth in moist atmosphere with 5% CO2

54. Oxidase-positive

56. Chloramphenicolor cephalosporins as alternatives

57. Chemoprophylaxis of close contacts with rifampin or sulfadiazine (if susceptible)

59. Haemophilusinfluenzae 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

60. Haemophilusinfluenzae Meningitis H. influenzae requires blood factors for growth there are six types of H. influenzae based on capsule differences. H. influenzae type b the most common cause of meningitis in children under 4 years old. A conjugated vaccine directed against the capsular polysaccharide antigen is available.

61. Differential Characteristics X factor = hemin (hematin) V factor = (NAD or NADP) nicotinamide adenine dinucleotide

63. Obligate Parasites of Man and Animals

64. Major pathogens for which humans are natural hosts

65. Haemophilusinfluenzae

66. Acute pyogenic, normally invasive infections

67. Chronic infections with H. influenzae as 2opathogen

68. Haemophilusducreyi

69. True pathogen (i.e., not found in healthy individuals)

71. Haemophilusinfluenzae Diseases

73. new vaccine composed of type b carbohydrate coupled to protein has drastically reduced meningitis by Hib

75. Streptococcus pneumoniae Meningitis, Pneumococcal Meningitis Hospitalized patients and young children are most susceptible to S. pneumoniae meningitis. It is rare but has a high mortality rate. A conjugated vaccine is available.

77. Listeriosis Listeria monocytogenes Gram-negative aerobic rod Usually foodborne; it can be transmitted to fetus. Reproduce in phagocytes. Figure 22.5

78. Listeriosis causes meningitis in newborns, the immunosuppressed, pregnant women, and cancer patients. Acquired by ingestion of contaminated food, it may be asymptomatic in healthy adults. L. monocytogenes can cross the placenta and cause spontaneous abortion and stillbirth. Figure 22.5

80. Multiply at refrigerator temperatures (4oC)

81. Tumbling motility at room temperature

83. Persists in soil

84. Soft cheeses & unwashed raw vegetables

85. Raw or undercooked food of animal origin

86. Luncheon meats

87. Hot dogs

91. Natural Reservoirs Common Routes for Human Exposure Population at Greatest Risk Epidemiology of Listeria Infections

93. Granulomatosisinfantiseptica

94. Transmitted to fetus transplacentally

95. Early septicemic form: 1-5 days post-partum

96. Delayed meningitic form: 10-20 days following birth

97. Intracellular pathogen

98. Cell-mediated and humoralimmunity develop

100. Tetanus 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 (DTP) and booster (dT). Treatment with tetanus immune globulin.

101. Tetanus produces the neurotoxin tetanospasmin, which causes the symptoms of tetanus: Spasms contraction of muscles controlling the jaw death resulting from spasms of respiratory muscles.

102. Tetanus grow in deep, unclean wounds and wounds with little bleeding. Acquired immunity results from DPT immunization that includes tetanus toxoid. Following an injury, an immunized person may receive a booster of tetanus toxoid. An unimmunized person may receive (human) tetanus immune globulin. Debridement (removal of tissue) and antibiotics may be used to control the infection.

104. Tetanus Figure 22.6

105. Summary of C. tetani Infections

106. Summary of Clostridium tetani Infections(cont.)

107. Clostridium tetani Gram Stain NOTE: Round terminal spores give cells a “drumstick” or “tennis racket” appearance.

108. Clinical Forms of Tetanus

111. Opisthotonos in Tetanus Patient

112. RisusSardonicus in Tetanus Patient

113. Mechanism of Action of Tetanus Toxin

114. Botulism 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.

116. Botulism Botulism is caused by an exotoxin produced by C. botulinum growing in foods. Serological types of botulinum toxin vary in virulence, with type A being the most virulent. The toxin is a neurotoxin that inhibits the transmission of nerve impulses.

119. Botulism Type A 60-70% fatality, most heat resistant and proteolytic Found in CA, WA, CO, OR, NM. Type B 25% fatality,; proteolytic and nonproteolytic Europe and eastern United States Type E Found in marine and lake sediments Pacific Northwest, Alaska, Great Lakes area Non proteolytic, grow in ref temp and less anaerobic condition

120. Botulism Blurred vision occurs in 1 to 2 days progressive flaccid paralysis follows for 1 to 10 days possibly resulting in death from respiratory and cardiac failure.

121. Botulism C. botulinum will not grow in acidic foods or in an aerobic environment. Endospores are killed by proper canning. The addition of nitrites to foods inhibits growth after endospore germination. The toxin is heat labile and is destroyed by boiling (100°C) for 5 minutes

123. Summary of C. botulinum Infections

124. Summary of C. botulinum Infections (cont.)

125. Mechanism of Action of Botulinum Toxin

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

128. Botulism For diagnosis, mice protected with antitoxin are inoculated with toxin from the patient or foods.

129. Diagnosis Figure 22.8

130. Leprosy Mycobacterium leprae causes leprosy, or Hansen’s disease. Acid-fast rod that grows best at 30°C. Grows in peripheral nerves and skin cells. Transmission requires prolonged contact with an infected person.

131. Mycobacterial Clinical Syndromes

132. Leprosy Leprosy is not highly contagious and is spread by prolonged contact with exudates. Untreated individuals often die of secondary bacterial complications, such as tuberculosis. Patients with leprosy are made noncontagious within 4 to 5 days with sulfone drugs and then treated as outpatients. Leprosy occurs primarily in the tropics.

133. Leprosy

134. Leprosy Laboratory diagnosis is based on observations of acid-fast rods in lesions or fluids and the lepromin test.

135. Acid-Fast (Kinyoun) Stain of Mycobacterium NOTE: cord growth (serpentine arrangement)of virulent strains

136. Eight Week Growth of Mycobacterium tuberculosis on Lowenstein-Jensen Agar

137. Mycobacterium leprae Infections (cont.)

138. Tuberculoid vs. Lepromatous Leprosy Clinical Manifestations and Immunogenicity

139. Lepromatous vs. Tuberculoid Leprosy

140. Lepromatous Leprosy (Early/Late Stages)

141. Lepromatous Leprosy Pre- and Post-Treatment

142. Clinical Progression of Leprosy

143. Leprosy Figure 22.9

145. 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).

146. Poliomyelitis The symptoms of poliomyelitis headache sore throat fever stiffness of the back and neck occasionally paralysis (fewer than 1% of cases) Poliovirus is transmitted by the ingestion of water contaminated with feces.

147. Poliomyelitis Poliovirus first invades lymph nodes of the neck and small intestine. Viremia and spinal cord involvement may follow. Diagnosis is based on isolation of the virus from feces and throat secretions.

148. Poliomyelitis The Salk vaccine (an inactivated polio vaccine, or IPV) involves the injection of formalin-inactivated viruses and boosters every few years The Sabin vaccine (an oral polio vaccine, or OPV) contains three live, attenuated strains of poliovirus and is administered orally. Polio is a good candidate for elimination through vaccination.

149. Poliomyelitis Figure 22.11

151. Rabies Virus (Rhabdovirus) 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. Preexposure prophylaxis: Infection of human diploid cells vaccine. Postexposure treatment: Vaccine plus immune globulin.

152. RABIES Rabies virus (a rhabdovirus) causes an acute, usually fatal, encephalitis called rabies. Rabies may be contracted through bite of a rabid animal by inhalation of aerosols invasion through minute skin abrasions The virus multiplies in skeletal muscle and connective tissue.

155. RABIES Encephalitis occurs when the virus moves along peripheral nerves to the CNS. Symptoms of rabies include spasms of mouth and throat muscles followed by extensive brain and spinal cord damage death.

156. RABIES Laboratory diagnosis may be made by direct FA tests of saliva, serum, and CSF or brain smears. Reservoirs for rabies in the United States include skunks, bats, foxes, and raccoons. Domestic cattle, dogs, and cats may get rabies. Rodents and rabbits seldom get rabies. Current postexposure treatment includes administration of human rabies immune globulin (RIG) along with multiple intramuscular injections of vaccine. Preexposure treatment consists of vaccination. Other genotypes of Lyssavirus cause rabies-like diseases.

157. How Is Rabies Transmitted?

158. How Is Rabies Transmitted?

159. How Is Rabies Transmitted?

178. Rabies Virus (Rhabdovirus) Figure 22.12

179. Rabies Virus (Rhabdovirus) Figure 22.13

180. Arboviral Encephalitis Arboviruses are arthropod-borne viruses that belong to several families. Prevention is by controlling mosquitoes. Figure 22.14

181. Arboviral Encephalitis Symptoms of encephalitis are Chills Headache Fever Coma Many types of viruses (called arboviruses) transmitted by mosquitoes cause encephalitis.

182. Arboviral Encephalitis The incidence of arboviral encephalitis increases in the summer months, when mosquitoes are most numerous. Notifiablearboviral infections are eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis (SLE), California encephalitis (CE), West Nile virus (WNV).

183. Arboviral Encephalitis Diagnosis is based on serological tests. Control of the mosquito vector is the most effective way to control encephalitis.

184. Arboviral Encephalitis

185. Cryptococcus Neoformans Meningitis (Cryptococcosis) Figure 22.15

186. Cryptococcus Neoformans Meningitis (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.

187. Cryptococcus Neoformans Meningitis (Cryptococcosis Cryptococcus neoformans is an encapsulated yeastlike fungus that causes cryptococcosis. The disease may be contracted by inhalation of dried infected pigeon or chicken droppings. The disease begins as a lung infection and may spread to the brain and meninges.

189. Cryptococcus Neoformans Meningitis (Cryptococcosis Immunosuppressedindividuals are most susceptible to Cryptococcus neoformans meningitis. Diagnosis is based on latex agglutination tests for cryptococcal antigens in serum or CSF.

190. African Trypanosomiasis Trypanosoma brucei gambiense infection is chronic (2 to 4 years). T. b. rhodesiense infection is more acute (few months). Transmitted from animals to humans by tsetse fly. Prevention: Elimination of the vector. Treatment: Eflornithine blocks an enzyme necessary for the parasite. Parasite evades the antibodies through antigenic variation.

191. Tsetse fly.The vector of African trypanosomiasis

192. African Trypanosomiasis African trypanosomiasis is caused by the protozoa Trypanosomabruceigambiense and T. b. rhodesiense and transmitted by the bite of the tsetse fly. The disease affects the nervous system of the human host, causing lethargy and eventually coma. It is commonly called sleeping sickness. Vaccine development is hindered by the protozoan’s ability to change its surface antigens.

193. African Trypanosomiasis Figure 22.16

194. TRYPANOSOMA BRUCEI

195. TRYPANOSOMA BRUCEI Lab Dx: Giemsa stained thick and thin blood smears or lymph exudate (early stage); Giemsa stained smears of CSF (late stage)

197. A dividing parasite is seen at the right. Dividing forms are seen in African trypanosomiasis, but not in American trypanosomiasis (Chagas' disease)

198. Winterbottoms sign

199. Ramana's sign: unilateral conjunctivitis and orbital edema

201. Naegleriafowleri Protozoan infects nasal mucosa from swimming water. Figure 22.17

202. Naegleriafowleri Encephalitis caused by the protozoan Naegleriafowleri is almost always fatal. Granulomatous amebic encephalitis, caused by Acanthamoeba spp. and Balamuthiamandrillaris, is a chronic disease.

204. Naegleria: Primary Amebic Meningoencephalitis (PAM)

205. Acanthamoeba: Chronic Granulomatous Amebic Encephalitis and keratitis

207. Naegleria: nose

208. Acanthamoeba: respiratory tract or ulcers in skin or mucosa / direct invasion of eye

209. Source of infection:

210. Naegleria: warm lakes, streams, ponds or inadequately chlorinated swimming pools

212. N. fowleri trophozoites cultured from cerebrospinal fluid: cells have characteristically large nuclei, with a large, dark staining karyosome. The amebae are very active and extend and retract broad pseudopods. Trichrome stain.

213. Naegleria spp.: trophozoite stained with Greenstein’s five dye stain And observed under dark field microscope.

214. PRIONS Diseases of the CNS that progress slowly and cause spongiform degeneration are caused by prions. Sheep scrapie and bovine spongiform encephalopathy (BSE) are examples of diseases caused by prions that are transferable from one animal to another. Creutzfeldt-Jakob disease and kuru are human diseases similar to scrapie. They are transmitted between humans. Prions are self-replicating proteins with no detectable nucleic acid.

215. Transmissible Spongiform Encephalopathies Caused by prions Sheep scrapie Creutzfeldt-Jakob disease Kuru Bovine spongiform encephalopathy Transmitted by ingestion or transplant or inherited. Chronic and fatal

216. Transmissible Spongiform Encephalopathies Figure 22.18