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0

What are common causes of meningitis in neonates?

Listeria
E.coli K1
Group B strep

1

What are common causes of meningitis in post-neonatal life?

S.pneumo
H.influenzeae
N.meningitides

2

Cause of chronic meningitis?

Mycobacterium tuberculosis

3

Causes of bacterial encephalitis?

T.pallidum
Borrelia burgdorferi (Lyme Disease)

4

3 ways that microbes can penetrate the BBB

1. infection of the cells that comprise the barrier
2. passive transport through cells in vacuoles
3. carraige in WBCs

5

Why might steroidal anti-inflammatories be use in the treatment of meningitis?

Dampen the immune response
Decrease inflammation
Decrease infiltration of PMNs, macrophages and pathogens

WBCs -> cytokines -> inflammation, edema, additional WBC recruitment
inflamation and edema are conducive to infiltration (diapedesis)

6

What are symptoms of meningitis?

high fever, sever and persistent stiff neck, photophobia, N/V
Changes in behavior: confusion, sleepiness, difficulty in waking (indicative of need for emergency treatment)
Infant: irritability, tiredness, poor feeding, fever, *bulging fontanel*

7

meningitis causing, gram +, catalase -, a-hemolytic, optochin sensitive

S.pneumo - most common cause of meningitis in US

8

Is there a vaccine for S.pneumo?

Yes, 2:
23-valent: capsular PS from strains responsible for 90% of infections
7-valent: capsular PS from strains responsible for infections in children, immunocompromised, elderly

9

What is the leading cause of bacterial meningitis in US?
What is second?

1st: S.pneumo
2nd: N.meningitidis

10

What are the most common capsular serotypes of meningitis causing N.meningitidis and what are the relative frequencies:?

A: 4%
B: 50%
C: 20%
Y: 10%
W135: 10%

11

In addition to typical meningitis symptoms, what may be seen in patients w/ N.meningitidis meningitis?

Hemorrhagic rash often w/ petechiae - reflective of assoc. septicemia
-1/3 of instances rash is fulminating w/ complications due to disseminated intravascular coagulation (DIC), endotoxemia, shock, renal failure
-DIC may -> gangrene / necrosis in extremities

12

What does H.influenzae require for growth?

Factors X: NAD and V: hemin

13

What organisms are typically responsible for outbreaks at universities?
Risks?

S.pneumo, N.meningitidis
Risks: poor diet, behavioral changes (ETOH consumption, smoking), pulmonary infections -> changes in immune function and microbiota composition
Some schools -> vaccination program

14

What is the fatality rate of neonatal meningitis?
How do survivors do?

1/3 of cases fatal
Survivors: often long-term sequelae: cerebral palsy, epilepsy, mental retardation, hydrocephalus

15

What organism causes Lyme Disease?

Borrelia burgdorferi
Disseminated disease can -> bacterial encephalitis

16

What is Guillan Barre Syndrome and what causes it?

Caused by Campylobacter jejuni
Disease is result of cross-reaction between bacterial ganglioside-like epitopes in LPS and Schwann cell myelin Ags
Immunologic attack ->Demyelination

17

How is a brain abscess diagnosed?

CT scan recommended before lumbar puncture
Characteristic ring-enhancing lesion w/ contrast is diagnosis
-fibrous capsule forms w/in 4-5 days of infection

18

Symptoms of brain abscess

headache, confusion, drowsiness, hemiparesis, seizures, fever
*usually no stiff neck*

19

What organisms are most often isolated from a brain abscess?

Gram +: Streptococcus (anginosis, milleri), Peptostreptococcus, Staphylococcus, Nocardia, Actinomyces

Gram -: Prevotella, Fusobacterium, Bacteroides, E.coli, Citrobacter koseri, P.mirabilis

AIDS pts: cryptococcus, toxoplasma

Almost always polymicrobial. Strep most common - synergy w/ gram negs

20

What often cause chronic meningoencephalitis?

Cryptococcus neoformans
AIDS related

21

What are the functions of bacterial capsules in CNS infection?

Prevent phagocytosis, Ab binding, complement activation
Intracellular protection
Toxicity to host cells

22

What is and what causes Valley Fever?

Fungal infection beginning in the lungs 7-21 days post infection
Typically clears quickly, but can disseminate to meninges, bones, joints, subcutaneous and cutaneous tissues
25% of disseminated cases -> meningitis (1% of total cases)
Initially flu-like, then symptoms of meningitis
Fatal if not treated.
Caused by Coccidiodes imitis (Fungus)
Risk: dust storms, earthquakes, excavation

23

What is Chagas Disease?

Caused by Trypanosoma cruzi - parasite carried by Triatome bugs
Initial sore at site of bite followed by fever and acute encephalitis
Chronic disease may have heart, colon, and nervous system manifestations

24

Where is Trypanosoma cruzi endemic?

Southern US - Southern Argentina

25

What is the CNS manifestation of malaria?

If malaria left untreated, infection can travel to brain causing lesions, coma and rapid death (24-72 hours)
Acute, widespread brain disease w/ fever

Greatest risk <10 years of age

26

5 genra of picornoviruses and associated diseases

1. Enterovirus (Polio, Coxsackie A and B, Echo) - diseases of alimentary (GI) tract
2. Rhino - cold - naspharyngeal
3. Cardiovirus - murine encephalomycarditis
4. Apthovirus - Foot + Mouth disease (cloven footed animals)
5. Hepatovirus - Hepatitis A

27

Properties of Cardio, Hepato and Entero viruses

Resistant to low pH, grow at 37C
Fecal-oral transmission, GI is site of primary infection
CNS infection results - paralysis and encephalitis

28

General properties of Aptho and Rhino viruses

Labile at low pH, grow at 33C
Aerosol transmission - Upper Respiratory Tract is site of infection

29

Picornovirus genome

Unenveloped ss+RNA, 7-8kb
Long 5' untranslated end regulates translation - IREM (internal ribosome entry site)
VPg protein at 5' end - primer
3' end- short untranslated w/ poly-A tail

30

Where in the cell do picornaviruses replicate?

In cytoplasm

31

Describe protein product of picornovirus

Single polypeptide divided into 3 regions (P1,P2,P3)
3 regions cleaved - 11-12 proteins
P1: capsid proteins (VP1,2,3,4)
P2 and P3: protein processing and genome replication proteins

32

Describe the process of Picornavirus replication

virus attaches to host cell via VP1
Uncoating of genome
RNA translation -> P1 stays in cytoplasm, P2,3 and -RNA copies in vessicles
+RNA -> -RNA -> +RNA
Encapsidation and cell lysis

33

What do Picornaviruses do to host cell processes?

Shut off protein synthesis via cleavage of eIF-4G by VP 2A (entero and rhino) and L (aptho)

34

What are the non-structural proteins produced by Picornaviruses?

2A: protease (P1/P2)
2B: stim vessicle formation
2C: RNA helicase
3AB: stimulates 3D and 3CD protolytic cleavage
3C: protease (P2/P3)
3D: RNA dependent RNA polymerase
VPg: Poly(U) primer

35

How do picornaviruses infect?

fecal-oral transmission
infect via GI with primary target being lymph tissue of oropharynx and gut
If Ab does not clear infection, progression from blood to organs and major viremia, then CNS infection
Virus production in grey matter (motor neurons of anterior horn of SC and brain stem)
Severe illness, paralysis

36

What disease is caused by polio virus? symptoms?

Poliomyelitis
Destruction of motor neurons in anterior horn of SC -> Flaccid paralysis

Bulbar poliomyelitis: more severe - destruction w/in medulla oblongotta

37

2 polio vaccines

Salk - Inactivated - less local GI immunity, duration of immunity unknown
Sabin - Attenuated - oral - probable life long immunity

38

What diseases are caused by Coxsackie viruses?

A and B: aseptic meningitis
A: Herpangina - sudden onset fever w/ ulcers on tonsils and palate
A16: Hand Foot and Mouth disease
Role in Acute Juvenile diabetes (type I)?

39

What does rhinovirus cause?

Common cold

40

Pleconaril

Drug designed against entero and rhinoviruses
-not FDA approved
-initially rejected due to side effects

41

What does Apthovirus cause?

Foot and Mouth in animals
Vaccine available - effective against symptoms, but does not protect against transmission
Slaughter infected animals

42

What is the role of HIV in CNS infections

Neurological complications are common in AIDS patients
Virus found in CSF of patients w/ dementia
Virus infects or activates macrophages and microglia -> release of toxins deleterious to neurons and astrocytes
2 viral subtypes
-Tcell tropic
-Macrophage tropic

43

3 classes of HIV drugs and examples

Nucleoside RT inhibitor: Zidovudine, Didanosine, Zalcitabine, Stavudine, Lamivudine, AZT
Non-nucleoside RT inhibitor: Nevirapine, Delavirdine
HIV Protease inhibitor: Ritonavir, Indinavir, Saquinovir, Nelfinavir

44

What is HAART treatment?

Highly active anti-retroviral treatment
A "cocktail" of at least one nucleoside RT inhibitor and one or two Protease inhibitors
***Does not provide full protection against neurological damage in HIV infection - BBB only partially permeable to anti-retroviral agents***

45

What is HTLV and what does it cause?

Human T-cell Leukemia Virus
Causes:
1. Adult Tcell Leukemia
2. Tropical Spastic Paraparesis / HTLV-1associated myelopathy (TSP/HAM)

46

What treatments exist for HTLV?

No definitive treatment
Combination IFNa and Zidovudine (NRTi)
Chemotherapy (limited success)
Zidovudine, Danazol, Vitamin C -> temporary relief

47

What is a virus spread to humans via an insect bite?

Arbovirus
fleas, ticks, flies, etc. are vectors for transmission
Primary reservoir is birds

48

Name two families of viruses considered arboviruses

Flaviviridae, Togaviridae

49

What are the 3 genera of flaviviridae? What diseases are each responsible for?

Flavivius: YFV, WNV, DFV, JE
Hepacivirus: Hep C
Pestivirus: no human disease (Hog cholera, Bovine viral diarrhea)

50

Flavivirus structure

Enveloped, icosahedral virion, linear ss+RNA
3 structural proteins: envelope, prM (M separates @maturation, maturation signal), C (capsid)
Flavi, HepC: 5' cap, non-polyA 3'
Pesti: no caps, no poly-a IRES

51

What is Antibody Dependent Enhancement?

In Dengue Virus:
Initial infection with one serotype (strain 1) -> Ab response
Later infection with different serotype: anti-strain 1 Ab do not neutralize, but allow macrophage to take up virus more effectively. Inside macrophage virus repliates -> more severe infection due to additional mechanism of infection

52

Describe flavivirus process of cell infection / replication

Receptor mediated attachment and endocytosis (viral E protein)
pH induced membrane fusion and uncoating of virion
+RNA -> single viral protein
RNA synth via RdRp
C protein encapsidation in cytoplasm
Maturation of membranes in rER or golgi
Transport of virus to cell surface by secretory pathway

53

Structural and non-structural proteins of flavivirus

Structural:
E: binds cell surface receptors, facilitates entry
prM: maturation
C: encapsulation

Non-structural:
NS1: hemagglutinin -elicits humeral immune response
NS2A and B: RNA synthesis
NS3: protease
NS4A and B: RNA replication
NS5: RNA dependent RNA polymerase

54

West Nile symptoms

Moderate to high fever, flu-like
sore throat, headache, backache, fatigue
Rash, lymphadenopathy, myalgia
Acute aseptic meningitis or encephalitis

55

West nile treatment

No vaccine
Ribovarin
Mosquito control

56

Yellow Fever symptoms and treatment

High fever, chills, headache, vomiting
Jaundice, hemorrhagic complications, renal failure

Vaccine available
Mosquito (aedis aegypti) control important for prevention

57

Dengue fever transmission and symptoms

Person to person, mosquitos

symptoms: fever, headache, lumbosacral pain
also - Dengue hemorrhagic fever DHF
Dengue Shock Syndrome DSS

58

What is the distribution of Dengue Fever serotypes?

Serotype 2 - North America
Serotypes 1 and 3 - Central and South America

59

Is there a Dengue vaccine?

No
A tetravalent vaccine has been tested in Thailand - favorable results

60

What is St. Louis Encephalitis?

Flavivirus caused encephalitis (epidemic disease)
Transmitted by mosquito from birds to human
Febrile headache to meningo-encephalitis
Milder in children
Elders at risk

61

Hepatitis C treatment

IFN treatment
IFN induces genes that regulate viral proteins at transcriptional and translational levels
only effective in 15% of patients

IFN + ribavirin for relapsed patients

62

What viruses are Togaviruses?

EEE: eastern equine encephalitis
WEE: western equine encephalitis
Rubella

63

Characteristics of Togavirus and major proteins

Enveloped, ss+RNA
cytoplasmic replication
nsP2 protease
nsP4 RdRp

64

What is Eastern Equine Encephalitis?

togavirus transmitted from birds -> mosquitoes -> horses and humans
Fever, general muscle pain, severe headache, permanent brain damage, seizure, coma
Small brain hemorrhages and extensive neuronal damage

65

What virus causes Rabies?

Rhabdovirus

66

Rhabdovirus characteristics

bullet shaped, external glycoprotein coat and peripheral matrix protein
ss-RNA

Ribonucleoprotein is most infectious component

67

What is the incubation time for rabies?

up to 12 mos.

68

Rabies symptoms

difficulty breathing and swallowing
hydrophobia
Increased muscle tone
cytoplasmic eosinophilic inclusion bodies (Negri bodies) in neuronal cells and neuronal necrosis

69

Treatment for rabies?

Not after symptoms appear - 100% fatal
Post-exposure:
1) wash wound w/ soap and water - seek medical attention immediately
2) passive immunization - admin human rabies immune globin
3) vaccination (inactivated virus)

70

what is the major problem in meningitis? Why?

Increased ICP is major problem.
leads to decreased cerebral blood flow, loss of cerebrovascular autoregulation
Subarachnoid space inflammation -> cerebral vasculitis -> possibility of cerebral infarction

71

What organisms are typically seen in meningitis following head trauma or neurosurgery?

S.aureus
S.epidermidis
aerobic gram neg. rods (including pseudomonas)

72

What organisms are most often seen in meningitis assoticated with a basilar skull fracture and/or CSF leak?

S.pneumonia
H.influenzae
Group A B-hemolytic strep

73

What is normal CSF opening pressure?

10-20cm H2O

74

What bacterial antigen identification kits are available?

S.pneumoniae, N.meningitidis, HiB, E.coli, GBS

75

What are early and late complications of meningitis?

Early: shock, disseminated intravascular coagulation, respiratory failure (adult resp. distress syndrome), cerebral edema

Late: behavioral / learnig disabilities, hearing loss, seizures, hydrocephalus

76

How might neonatal CSF differ from adult?

Normal neonate CSF may have up to 30 WBC/mm3 (normal for adult is 0.5)
and up to 150 mg/dL protein (normal for adult 15-45)

77

Definition of aseptic meningitis

Meningitis with lymphocytic predominant pleocytosis in which bacterial stains and cultures are negative

78

Most common viruses in aseptic meningitis

enteroviruses
-most common in infants and young children
-usually less severe presentation
-most often late summer / early fall
-occurs in community outbreaks

79

What is the overall mortality for CA meningitis? What about individual pathogens?

CA meningitis: 25%
L.monocytogenes: 28.5%
S.agalactiae: 7-27%
S.pneumo: 19-26%
N.meningitidis: 10%
H.influenzae: 6%

80

CD4 TH1 cells do what?

Activate macrophages enabling them to destroy intracellular organisms

81

CD4 TH2 cells do what

stimulate B cells to differentiate into plasma cells to produce specific antibodies

82

What is a primary vs. secondary defect of the innate immune system?

Primary: congenital
Secondary: acquired - breach of mechanical barrier

83

What is chronic granulomatous disease and what is it an example of?

Defect in NADPH oxidase that prevents neutrophils from releasing a respiratory burst during phagocytosis.

Example of primary defect of innate immunity

Results in increased susceptibility to catalase positive organisms, esp. Serratia and Aspergillus

84

What is the most common cause of intravascular catheter associated infection?

Staph epidermidis

85

What infections are common at burn sites?

Polymicrobial infections due to bacteria and fungi

Mechanical breach, damage to neutrophil function and capacity for immune response

86

What is the most common cause of surgical wound infections? Why?

Staph aureus
Often impaired blood supply and foreign bodies (sutures) -> ease of colonization

May progress to endocarditis or osteomyelitis

87

How do staph species "hide" from antibiotics on plastic catheter material?

Grow as biofilm - produce and multiply within slimy, adherent material

88

What is post-obstructive pneumonia? What organisms are often seen?

infection develops in the lung distal to an occlusion such as a tumor or fibrotic growths following surgery. Results in stasis of body fluids distal to obstruction - favorable medium for bacterial growth.

Oropharyngeal aerobes and anaerobes are common

89

Obstruction of bladder or ureters can result in what serious complications? What could cause obstruction?

hydronephritis or pyonephritis
Could be caused by neoplasm of prostate, cervix, rectum, ovary, etc.

90

Neutropenia

Depressed neutrophil count. May be caused by a primary malignancy (leukemia) or chemotherapy.

91

What is the most commonly seen immune defect resulting in life threatening infections in compromised hosts?

Neutropenia

92

What is more common in neutropenic patients - gram (-) or (+) infection? How is empiric treatment influenced?

Gram (+) is more common
Treatment still geared toward gram neg. Can rapidly lead to lethal infection. (+) species tend to be less virulent.

93

What is the most common cause of secondary defects in adaptive immunity worldwide?

malnutrition

94

Humoral immune impairment produces increased susceptibility to what organisms?

encapsulated orgs such as Streptoccus pneumonia, Haemophilus influenzae, Neisseria meningitidis

95

What disease states are associated with humoral immune abnormality?

Multiple myeloma, chronic lymphatic leukemia, Waldenstrom's macroglobulinemia, sickle cell

96

What diseases are associated with cellular immune deficiency or defect?

Hodgkins and non-Hodgkins Lymphoma, Hairy Cell Leukemia, Chronic Lymphatic Leukemia

Chemotherapy, Corticosteroid treatment, transplant also associated.

97

What infections are more likely with impairment of the cellular immune system?

Intracellular bacteria, mycobacteria, viruses, fungi, protozoan

-pretty much everything
-prompt diagnosis is vital
-fixing underlying cause of the deficit is key!

98

Neurotropic vs. Neuroinvasive vs. Neurovirulent

Neurotropic: can infect neurons and/or assoc. cells regardless of route of infection or pathogenic consequence
Neuroinvasive: can enter CNS after infecting peripheral site
Neurovirulent: can cause disease by damaging nervous tissue

99

Herpesvirus genome

linear dsDNA (80+ genes)

100

What is the most common cause of sporadic fatal encephalitis in adults?

HSV-1

101

What part of the brain is most often involved in HSV-1 encephalitis?
Symptoms?

Temporal lobe
Fever, altered consciousness and behavior, disordered thinking

102

What abnormalities does brain tissue affected by HSV-1 encephalitis display?

Necrosis and punctate hemorrhage
Inferior frontal and temporal lobes

103

How are HSV infections of the CNS diagnosed and treated?

Diagnosis: PCR of CSF
MRI shows temporal lobe hemorrhage and/or edema
EEG spike and slow-wave activity

Treatment: acyclovir and other herpes viral drugs reduce mortality but most patients do not regain full mental function

104

What CNS diseases are caused by VZV?

Varicella:
encephalitis (.1-.2% cases)
transient cerebellar ataxia (.1%)
meningitis and transverse myelitis (rare)

Zoster:
post herpetic neuralgia (PNS)
encephalitis (.2-.5%)

105

Diagnosis and treatment of VZV infection of CNS

PCR of CSF
treat with Famciclovir or valacyclovir (higher bioavailability than fam)
Prevent w/ vaccines!!

106

What is the most common cause of birth defects and childhood disabilities in the US?

Congenital CMV

107

What are signs of congenital CMV that can be seen at birth?

Intrauterine growth retardation, hepatosplenomegaly, microcephaly

Later development of mental retardation, seizure, blindness, deafness, death

Non symptomatic at birth: 10-15% risk of developing hearing and vision problems, intellectual impairment.

108

What is treatment for CMV and prophylaxis for prevention of transplacental transmission?

IVIG to prevent congenital disease (result of uncontrolled trial)

Gancyclovir for treatment of congenital disease

109

Herpes B Virus

Cercopithecine herpesvirus 1
Biosafety Level 4 pathogen

Carried by monkeys, transmitted to humans via saliva, bodily secretions

High frequency of fatal encephalitis

treatable w/ high doses of acyclovir or gancyclovir

110

Polyomavirus and associated disorders

JC - Progressive Multifocal Leukoencephalopathy (immunodeficient patients, usually fatal)
BK - hemorrhagic cystitis (bone marrow transplant patients)
polyomavirus nephropathy (kidney transplant patients)

New: KIV, WUV - found in resp. sec., unknown pathogenicity
MCV - merkel cell cancer
SV40: humans infected via animal vaccines - unknown pathogenicity

111

PML: what is it, symptoms, treatment

Progressive multifocal leukoencephalopathy
JCV in immunocompromosed patients
Personality changes, intellectual deficit, loss of motor skills, sensory loss
Death in 2-12 months
Treament: HAART - immune recovery

112

What is the most common transmissable spongiform encephalopathy

Creutzfieldt-Jakob Disease

113

What are the forms of CJD?

Sporadic - unknown cause
Familial - Autosomal dom (onset 50yrs)
Iatrogenic - neurosurg, transplant, brain derived hormones
Variant - bovine spongiform encephalopathy (mad cow) -> humans

114

List oral anaerobes

Bacteroides
Prevotella
Porphyromonas
Fusobacteria
Peptostreptococcus

115

What virulence factors are associated with oral infections?

Oral bacteria produce lymphocyte activators that induce inflammatory response

Release of PMN contents and complement activation -> tissue damage.

116

What causes gingivitis?

Inflamation of the gums - marginal inflammation where teeth meet gums
Inflammatory infiltrate: PMNs and lymphocytes in tissue and connected to tooth

117

What is periodontitis?

Caused by progression of gingivitis. Results in resorption of bone around neck of tooth, destruction of periodontal ligament, and eventual loosening and loss of affected teeth.
Causative oral anaerobes live in dental plaque next to gingival tissues.

118

What organisms are associated with ulcerative gingivitis?

Prevotella, Fusobacteria - invade oral epithelium

119

Actinomyces israelii
ID, what it causes

Normal flora anaerobe in humans
Gram positive filamentous rod-shaped bacteria. "Sulfur granules" seen in pus - actinomyces elements mixed with tissue exudate
grows slowly in culture and may be overwhelmed by contaminating bacteria
Causes cervicofacial infections following oral trauma - tooth extraction - can travel down lymph tract

120

Viridans Streptococcus and oral infections

Virulence: attatch to teeth w/ glucans. May enter blood stream following dental procedure (tooth extraction) and produce subacute bacterial endocarditis

group includes Streptococcus Mutans - assoc. with dental carries.

121

ID Strep viridans

Gram pos, catalase neg
No lancefield group
Assoc. w/ dental caries.

122

Who is at risk for oral Candida infections?

Immunocompromised, chemo patients, those receiving antimicrobial therapy

123

Streptococcus pneumoniae virulence factors

Capsule - 84 serotypes
interferes with classical and alternative complement pathway
teichoic acid -> inflammation
specific Ab confers immunity

124

Upper respiratory infections caused by S.pneumoniae

acute otitis media - S.pneumo most common cause after 3 months old (viral infection or allergies predispose)

acute and chronic sinusitis (viral infection, allergies, mechanical blockage predispose)

125

Optochin test

P disk on agar innoculation
Streptococcus pneumoniae is suscetpible

Mnemonic: VROPS: Viridans Resistant to Optochin, Pneumoniae susceptible

126

Where does Haemophilus influenzae usually colonize? How does it differ from infectious HiB?

High carraige rate (50-80%) in URT
Normal flora strains lack capsule
Those isolated from cases of Otitis Media can't be typed - may not be protected by vaccine

127

Haemophilus influenzae ID

small, gram neg coccobacilli
requires X and V factor for growth
capsule serotyping

128

Moraxella catarrhalis

gram neg coccobacilli
normal flora of oropharynx
can cause otitis media
Throat flora in lab

129

What organism is associated with acute glomerulo nephritis and rheumatic heart disease? How does it contribute to those diseases?

GAS (S.pyogenes)
M protein in capsule is cross-reactive with proteins in heart muscle (mostly respiratory strains) and kidney (mostly skin strains)
Can lead to autoimmune attack in those organs.

130

What are SLO and SLS?

Streptolysins produced by GAS
SLO: O2 labile - only causes B-hemolysis in low oxygen environment
SLS: O2 stable - B-hemolysis in presence of oxygen

131

What is Spe (A-C)

Streptococcal Pyrogenic Exotoxins type A-C produced by GAS
Superantigens
Spe A produced by minority of bugs
Induce cytokine release, -> fever and rash, ->enhanced sensitivity to endotoxic shock
Toxic Shock Like Syndrome

132

What is an Aschoff body associated with?

Rheumatic heart disease.
Lesion of lymphocytes and macrophates around fibrinoid deposits in hearts of affected individuals
Cell mediated response

133

What is the most common bacterial cause of pharyngitis?

S.pyogenes (GAS)
must be treated promptly to prevent sequelae including scarlet fever and rheumatic heart disease

134

How does Diptheria toxin work?

AB toxin
B binds epidermal growth factor precursor -> endocytosis
Reduction in vessicle releases A subunit
A subunit ADP ribosylates elongation factor 2 (NAD + EF2 -> ADPR-EF2 + nicotinomide + H+
EF2 inactivated and translation ceases

135

How is diptheria toxin genetically regulated?

DT gene is carried by bacteriophages w and B
synthesis negatively regulated by iron - in humans iron is sequestered in RBCs - low levels in tissue where toxin acts

136

What is the pathogenesis of diptheria?

C.diptheria colonizes human pharynx
Spread by droplet, contact w/ cutaneous infection, or fomite
Causes "punched out" ulcer
Pseudomembrane forms - oropharynx down trachea - can obstruct breathing and -> death
Systemic manifestation: DT Can also attack heart and CNS

137

Describe the structure and function of pertussis toxin

AB toxin w/ 5 B subunits
A subunit ADP ribosylates Gs -> uncontrolled production of adenylate cyclase and massive increase in cAMP (same action as cholera toxin, but different target cells)
-histamine sensitization
-promotion of lyphocytosis
-insulin secretion
-diminished oxidative killing by macrophages

138

How does B.pertussis interfere with ciliary function?

Filamentous hemaglutinin binds cilia of epithelial cells,

139

Two ways B.pertussis increases cAMP levels in host cells

1: Pertussis toxin: ADP-ribosylation of Gs
2: Bacteria produce invasive AC : enters cell and requires calmodulin for function

140

Explain regulation of B.pertussis virulence factors

BvgS: transmembrane histidine kinase
-activated at 37C or w/ ionic changes
-phosphorylates BvgA in bacterial cytoplasm
BvgA: transcription factor that controls 20+ genes
-temporal delay due to cascade
-first Fha and pili genes activated
-later Btx and invasive AC genes activated -> cytotoxicity

141

What systemic effects can B.pertussis have?

edema and hemorrhages in brain

142

How is B.pertussis identified in the lab?

direct fluorescent Ab assay available, but results should be confirmed w/ culture

Culture: deep nasopharyngeal - plate and culture immediately (poor survival)
Growth on Bordet-Gengou or Charcoal blood agar + Abx media
-slow grow, 3-7 days

143

Causative organism of malaria

Plasmodium falciparum

144

What is the prognosis for untreated cerebral malaria?

if not treated: death in 24-72 hours

145

How is Legionella pneumophilia spread?

Not spread person to person
Organism exists inside amoebas
reservoirs include AC cooling towers, shower heads, faucets, hospital ventilators
Ubiquitous in nature
Reservoir is aerosolized and inhaled

146

Diseases caused by Legionella Pneumophilia

Legionnaires disease: severe pneumonia (2-10 days incubation), 60% mortality, nosocomial and community acquired
Pontiac disease: non-pneumonial fever 1-2 days incubation, self-limiting. May be immune response to dead or low virulence strains
Disseminated - rare

147

How does L.pneumophilia invade and survive within host cells?

coiling phagocytosis (alveolar macrophages) - does not necessitate opsonization
-inhibit phagosome/lysosome fusion
-induction of ribosome/ mitochondria accumulation around vessicle
-iron scavenging from ferritin
-reproduction w/in phagosome, then escape and cell-lysis

148

When is L.pneumophilia suspected and how is it identified?

Suspected in severe, progressive pneumonia with no known etiological agent
Rarely found in sputum and poor gram stain capability
Identified by ELISA, DNA homology

149

Acinobacter identification

Gram neg rod
resembles Haemophilus

150

What does acinobacter cause?

pneumonia
severe blood and wound infections in immunocompromised patients

151

What organism causes "walking" pneumonia?

Mycoplasma pneumoniae

152

How is mycoplasma pneumoniae identified?

Rarely found in sputum, does not stain well.
Diagnosed based on presence of complement fixing antibody
-long incubation period, so patient presents with high Ab titer

153

Describe Mycoplasma's morphology and growth requirements

lacks a cell wall - surrounded by triple membrane containing sterols - requires cholesterol for growth

154

4 organisms that cause "atypical" pneumonia

Mycoplasma pneumoniae
Legoinella pneumophila
Chlamydia pneumoniae

155

What cells does Chlamydia pneumonia infect?

Columnar epithelial cells
Remember - 2 stage life cycle
-Elementary body is infectious (carries adhesin)
-Reticulate body replicates - uses host ATP generating potential

156

What kinds of respiratory infections are S.aureus responsible for?

Acute pneumonia - secondary to some other insult to lung (influenza)
Empyema - purulent infection of pleural space - from surgery or chest tube
Lung abscess - complication of peumonia - usually involves aspiration of oral or gastric contents

157

Virulence factors of Mybacoterium tuberculosis

Capsule!!
-Mycolic Acid (cord factor) in cell wal
-long chain FA, resists drying and disenfectants,
hypersensitivity granuloma, promotes inflammatory response
(TNFa) - lung tissue dammage
-Lipoarabinomannan
-cell wall glycolipid. suppresses Tcell proliferation and
macrophage activation
-Sulfolipids: inhibit lysosome - phagosome fusion in macrophage
-Catalase: degrades H2O2
-Ammonia prod: prevents acidification of phagosome

158

What does Mycobacterium bovis cause?

Rarely causes TB, found in milk, eradicated through pasteurization.
Infects bone -> hunchback

159

What causes systemic TB symptoms?

cytokine response
Helpers and cytotoxic Tcells activate alveolar macrophages -> release of cytokines and systemic response (fever, weight loss

160

What is a tubercle composed of?

Tubercle is a microscopic granuloma containing M.tuberculosis.
Composed of multinucleate giant cells, activated macrophages, lymphocytes

161

Fates of tuberculosis tubercle

become fibrotic or calcified w/ dead bacteria - visible on CXR
Dormancy - reactivation later
necrotic tubercle may erode to blood vessel -> disseminated disease.

162

What is the basis of the TB skin test?

Delayed type hypersensitivity- effector Tcells recognize pathogen, attract macrophages -> local inflammation on pos. test

163

How long does it take for a positive TB test after primary infection? what does a positive test indicate?

6 weeks
Indicates exposure, not necessarily active disease.
6 weeks coincides with tubercle formation
Need CXR to confirm active process

164

How is TB identified?

Specimen: sputum, biopsy, blood w/ miliary TB (seen on CXR)
Staining of sputum - diagnosis before bacteria will grow.
gram +, but doesn't stain well
Acid fast w/ Fuchsin stain
Culture: condition w/ NaOH - inhibit other bacteria
-24 hr. doubling time - very slow growth

165

Cystic Fibrosis is associated with what bacterial lung infection?

Pseudomonas aeruginosa

Initial infection may be S.aureus, later infection w/ Pseudomonas

166

What organism is involved in Farmer's lung?

Aspergillus

167

Histoplasma capsulatum virulence factors (LRI)

dimorphic growth:
-environmental mold -> infectious conidia
-conversion to pathogenic yeast at 37C

can grow w/in macrophages and survive oxidative burst.

168

How is H.capsulatum encountered and where is it most prevalent?

Grows in soil w/ abundance of bird and bat droppings.
Most abundant in Mississippi River valley and Ohio River valley

169

What respiratory disease does Histoplasma capsulatum cause?

Chronic pneumonia

Looks like TB - granulomas, necrosis - may disseminate to reticuloendothelial system

170

How is histoplasma capsulatum diagnosed / identified?

Sputum of no use
Need CXR and biopsy or blood sample
Very slow growth in culture (weeks) - dimorphic - yeast and mold

171

How does Blastomyces dermatitidis growth differ from Histoplasma?

extracelular growth in lung - too large for phagocytosis

172

How is Blastomyces dermatitidis identified in the lab?

very slow culture (4wks)
large yeast cells with broad buds
serodiagnosis not very good- cross rxn with many other fungi

173

What causes Valley Fever? How does pathology work?

Coccidioides immitis - soil fungus
Arthroconidia inhaled (can be phagocytized ) and covert to Spherule (too large for phagocytosis) filled with endospores (can be phagocytized)

Spherules burst -> large Ag release -> large inflammatory response
May induce anergy

174

What does a negative Coccidioides skin test indicate?

True negative
Performed test too soon (takes 1-4 weeks after onset of disease for pos. test)
Anergy

175

What is Pneumocystis jiroveci?

Fungus causing PCP pneumonia in immunosuppressed patients
-AIDS, corticosteroids, leukemia

Classification uncertain: morphology - protist, gentic - fungus
Treatment: responds to antiprotozoal therapy - not antifungal

176

What is characteristic about PCP pneumonia?

Often concurrent infections
Alveoli filled with desquamated cells, organisms, monocytes, fluid - look "foamy"
Diffuse alveolar infiltrates on CXR

177

Symptomatic diagnosis of Pneumocytosis

Mild low grade fever
non-productive cough
progressive dyspnea and tachypnea
cyanosis, hypoxia
Death by asphyxiation

178

What causes most respiratory infections/

Viruses (80%)

179

What are mucins?

Protective proteins found in respiratory tract
Decoy receptors
Bind and occupy viral receptors rendering them unable to infect cells

180

Influenza is a member of what family? genome description? enveloped?

Orthomyxoviridae
(-) segmented RNA genome
Enveloped virus

181

What are influenza virus subfamilies and what strain causes pandemic flu?

A: pandemic - antigenic shift
B: as serious as A, but no pandemic
C: most common, but causes minor infection - not included in trivalent vaccine

182

Process of influenza virus infection / replication / release

HA binds sialic acid on cell - receptor mediated endocytosis
reduction in pH (5.3) -> HA conf. change, fusion of virion envelope w/ endosome
M2 channel: H+ entry -> RNA release
RNA -> nucleus -> transcription, replication -> virion assembly
Virion-> cytoplasm -> release by budding
NA: cleaves sialic acid from cell surface to prevent new virion from re-binding cell

183

What is the major target of influenza drugs?

NA protein
Olsemtamivir and Zamanivir

Amantidine and Rimantidine bind M2 - don't work on flu B
-most flu strains are resistant
-wide overuse and misuse, esp in Asia

184

Virus neutralizing antibodies target what protein on infuenza virus?

HA

Also NA

185

What Influenza A strains infect humans?

H1N1
H2N2
H3N2

186

Seasonal flu vaccine contains what 3 viruses?

A: (CA 2009) H1N1pdm09 like
A: (Victoria 2011) H3N2 like
B: Wisconsin 2010 like

187

What is H5N1?

Avian flu
Have been a few cases of animal (ferret model) -> human transmission, but no human-> human
Being watched as next potential pandemic flu virus

188

What viruses are in family Paramyxoviridae?

Subfamily Paramyxovirinae
Paramyxovirus: HPIV (Human Parainfluinza Virus) 1 and 3
Rubulavirus: Mumps, HPIV 2 and 4
Morbillivirus: Measles
Subfamily Pneumovirinae
Pneumovirus: Respiratory Syncytial Virus (RSV)
Metapneumovirus: Human Metapneumovirus (MPV)

189

What causes Croup and what is it?

Caused by HPIV-1
viral respiratory infection of infants and children
inflammation of larynx, trachea, bronchi
Stridor heard on exam - inspiratory sound
Respiratory distress - medical emergency
Fever, N/V

190

Viral cause of larnygitis?

HPIV - in adults and older children
vs. Croup in young children.

191

Bronchiolitis

Infection and inflammation of bronchioles
Adults - rare
Children - life threatening (esp under 1yr.)
-Usually caused by Respiratory Syncytial Virus
-Also MPV, HPIV-3
May -> pneumonia

192

What is the most common cause of LRI in children?

RSV
MPV probably second.

193

Mumps virus and symptoms

Rubulavirus (paramyxovirus)

Swelling of parotid gland (painful), swelling of cheeks and jaw, ear pain, fever and headache.

Less frequent: meningitis, inflammation of testes, rash

194

Measles virus and symptoms

Morbillivirus

More severe than mumps
Respiratory spread (14-18 day incubation)
Malaise, cough, coryza, headache, conjunctivitis
Koplik's spots - blue/white on buccal mucosa
Rash 5-7 days, face -> trunk -> limbs

195

Rubella

Togaviridae
Respiratory spread, 12-23 day incubation
Lymph node swelling, maculopapular rash, arthritis in adult women.
Risk of infection of fetus - congenital rubella syndrome

196

MMR vaccine

Live, attenuated
1st at 12-18 mos, 2nd at 4-6 yrs
Combo of 3 vaccines

197

What are heterophile antibodies?

Antibodies against unusual antigens to which host may not have been exposed

EBV activates Bcells -> Ab production

198

Burkitt's Lymphoma

African (endemic) form associated with EBV - most common childhood cancer in equitorial Africa
Sporadic form is not

199

Hairy Oral Leukopenia

Caused by EBV
Oral infection in AIDS patients
Lesions on side of tongue are areas of active viral replication

200

In a case of pneumonia accompanied by HSV labialis, what is the most likely pathogen?

Pneumococcal pneumonia

201

In a case of pneumonia accompanied by bullous myringitis, what is the most likely pathogen?

Mycoplasma pneumoniae

202

What pneumonia causing organisms do not show up in a gram stain?

Mycoplasma
TB
All viruses
Legionella
PCP

203

Rusty colored sputum is a symptom of what pneumonia causing organism?

Pneumococcus

204

In mycoplasma pneumonia, where is the focus of infection?

Bronchi - not in alveoli
Infiltrate in lung is due to immune response

205

What pneumonias have positive urine antigen test?

Legionella
Chlamydial pneumonia

206

Common causes and non-causes of nosocomial pneumonia

S.aureus (20-39%)
Gram neg aerobes
Candida commonly cultured - rare cause
No anaerobes

207

Mainstay treatment for bacterial meningitis

B-lactam, max dose
BacteriCIDAL is preferred