Vaccination Infectious Diseases

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Pre-Lecture
1
 The major virulence factor of Corynebacterium
diphtheriae is
A.
B.
C.
D.
E.
Ability to multiply within macrophage
Capsule
Endotoxin
Exotoxin
Neurotoxin
Physician Assistant Review Lippincott Williams and Wilkins 2001
2
 A physician assistant student presents to the primary
care office with a lesion on his foot. History reveals he
walks barefoot in the shower at the local gym. The
lesion on the bottom of the foot is flat and has grown
inward. There is another lesion on the side of the foot
that appears filiform. Which of the following is most
likely the causative agent?
A.
B.
C.
D.
E.
Coronavirus
Papilloma virus
Poxvirus
Rubella virus
Togavirus
Physician Assistant Review Lippincott Williams and Wilkins 2001
3
Where does the rash begin in cases of
rubella?
A.
B.
C.
D.
E.
Back
Chest
Head/neck
Inguinal region
Wrist
Physician Assistant Review Lippincott Williams and Wilkins 2001
4
A three year old, unknown to your clinic previously,
presents and has a high fever, cough, coryza,
conjunctivitis, and a rash. Koplik spots are noted on the
buccal mucosa. The conjunctivae reveal a transverse
line of inflammation along the eyelid margin (Stimson
line). The rash is morbiliform, began on the head, and
then spread over most of the body in a descending
fashion within 18-20 hours. This clinical presentation is
consistent with a diagnosis of
A.
B.
C.
D.
E.
Herpes Zoster
Human Herpesvirus-6
Measles (Rubeola)
Rubella (German, 3-Day Measles)
Meningiococcal
Physician Assistant Review Lippincott Williams and Wilkins 2001
5
 www.khanacademy.org
 Under Biology—Review Physiology
 Role of Phagocytes in Innate or Nonspecific Immunity
 Types of immune responses: innate and adaptive
 B lymphocytes
 Professional Antigen Presenting Cells
 Helper T cells
 Cytotoxic T cells
 Review of B cells CD4 and CD8 T cells
 Inflammatory Response
Review
6
 To convert Fahrenheit temperatures into Celsius:
Tc=(5/9)*(Tf-32)
 Begin by subtracting 32 from the Fahrenheit number.
 Divide the answer by 9.
 Then multiply that answer by 5.
 To convert Celsius temperatures into Fahrenheit:
Tf=(9/5)*Tc+32
 Begin by multiplying the Celsius temperature by 9.
 Divide the answer by 5.
 Now add 32.
Review
7
Review Body’s Response to Infections
Vaccination Related Infectious Diseases
8
 To put things in perspective…
 Bacterial and viral diarrheas
 Bacterial pneumonias
 Tuberculosis
 Measles
 Malaria
 Hepatitis B
Kill more people each year
than all cancer and
cardiovascular diseases
combined
 Pertussis
 Tetanus
 Impact greatest in less developed countries
9
 Complex of properties that allows an organism to
establish infection and to cause disease or death
 Gain access to the body
 Avoid multiple host defenses
 Ex., Capsules prevent phagocytosis
 “Some killers have pretty nice capsules”
 S. pneumoniae, K. pneumoniae, H.
influenza, P. aeurginosa, N. meningitidis,
and the yeast C. neoformans
 Accommodate to growth in the human milieu
 Parasitize human resources
Review
10
 Mainly cause disease in hosts with impaired
defenses
 Many are part of normal endogenous
human or environmental microbial flora
 Take advantage of inadequate defenses to
attack more violently and concertedly
Review
11
 Anatomic Barriers
 Skin
 Aerodynamic filtration system of upper airway
 Mucociliary blanket of airway
 Anatomy Review: Which cells produce
mucous in respiratory tract?
 Goblet Cells
 Normal microbial flora
 Compete with outside organisms
Review
12
 Secretions
 Possess antimicrobial properties
 Nonspecific
 Lysozyme
 Specific
 Immunoglobulin A (IgA)
 Gastric Acid or bile
Review
13
 Binding molecule on an infecting organism with a
receptor molecule on the host
 If host lacks a suitable receptor, the organism
cannot attach
 Ex., Plasmodium vivax causes malaria
 Targets Duffy blood group determinants on
the red blood cell surface
 Many persons, particularly blacks, lack
these determinants and are not susceptible
to infection
Review
14
 Can affect outcome of exposure
 In Utero
 Ex., CMV, rubella, parvovirus interfere with fetal development
 Maternal response minimal; while potential fetal harm
 Normally, IgG—generated from mom previous infection—passively
crosses placenta and protects fetus
 Review: When does maternal IgG usually go away in child?
 About six months
 Children younger than 3
 Diarrhea
 Adults
 Chickenpox causes great problems
 Elderly
 Fare more poorly with almost all infections than younger persons
15
 Sexually transmitted infections
 Occupational exposure
 Wearing shoes
 Single most important factor in reducing soil
transmitted nematodes
 Eating undercooked foods
16
 Skin
 Burns or trauma
 Mucociliary apparatus
 Smoking or influenza
 Congenital absence of complement components
 C5 – C8
 Prevents membrane attack complex to fully function
 Co-morbid diseases
 May interfere with neutrophil production or function
17
CDC Scheduled Childhood Vaccination Related IDs
18
 Rotavirus
 Poliovirus
 Diphtheria
 Influenza
 Pertussis
 Measles
 Tetanus
 Mumps
 Haemophilus
 Rubella
 Pneumococcus
 Varicella
 Hepatitis A
 Meningococcal
 Hepatitis B
 Human Papilloma Virus
19
Most diarrhea of kids especially in winter!
20
 Most common cause of severe diarrhea worldwide
 Dehydration and death if untreated
 100 deaths in U.S.
 1 million deaths worldwide
 Double-stranded RNA
 Oral to fecal route
 Peak age of infection is 6 months to 2 years
 Virtually all infected by age of 5 years
 Adults usually mildly affected
 Can be re-infected
 Subsequent infections usually less severe
21
 Infects enterocytes of the upper small intestine
 Disrupts absorption of sugars, fats, and various ions
 Resulting osmotic load causes a net loss of fluid into
the bowel lumen
 Produces diarrhea and dehydration
 Review: What other disease process causes an osmotic
process? Hint: diuresis
 Diabetes mellitus
 Infected cells are shed from intestinal villi
 Regenerating epithelium initially lacks full absorptive
capabilities
22
 Largely confined to the duodenum and jejunum
 Shortening of the intestinal villi
 Mild infiltrate of neutrophils and lymphocytes
23
 Lethargy
 Child will not focus on you or less responsive to words/touch
 Vomiting
 2 to 3 days
 Fever
 Clinically defined as?
 Abdominal pain
 Profuse, watery diarrhea
 5 to 8 days
 Without fluid replacement, diarrhea can produce fatal
dehydration in young children
 Clinical presentation of dehydration?
24
http://www.articlediary.com/assets/rotavirus.jpg
25
 Direct immune based assays (ELISA or latex
agglutination) and PCR
 Fluid replacement
 Supportive
 BRAT diet
 Prevention
 Vaccination
26
Greek for “Leather”
27
 Necrotizing upper respiratory tract infection
 Infection with Corynebacterium diphtheriae
 Aerobic, pleomorphic, gram-positive rod
 Humans are the only known reservoir
 Most asymptomatic carriers
 Spreads from person to person in respiratory droplets
or oral secretions
28
 Bacterium enters the pharynx and proliferates
 Often on the tonsils
 Produces exotoxin causes an inflammatory response
 Also inhibits protein synthesis
 Toxin is absorbed systemically and acts on tissues
 Heart, nerves, and kidney most susceptible
29
 Characteristic lesions—Pseudomembranes
 Thick, gray, leathery membranes composed of sloughed
epithelium, necrotic debris, neutrophils, fibrin, and
bacteria that line affected respiratory passages
 Epithelial surface beneath the membranes is denuded, and
the submucosa is acutely inflammed and hemorrhagic
30
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31
 Fever
 Sore throat
 Malaise
 Cervical lymphadenopathy
 “Bull Neck”
32
http://www.vaccineinformation.org/photos/diphaap002.jpg
33
 Cardiac and neural symptoms develop in minority of
patients
 When heart affected, the myocardium displays fat
droplets in the myocytes and focal necrosis
 Neural tissue—affected peripheral nerves show
demyelination
 Cutaneous diphtheria
 Inoculation of the organism into a break in the skin and
manifests as a pustule or ulcer
 Rarely leads to cardiac or neurologic complications
34
http://upload.wikimedia.org/wikipedia/commons/1/1b/A_diphtheria_skin_lesion_on_the_leg._PHIL_1941_lores.jpg
35
 Mostly based on clinical presentation
 Definitive diagnosis
 Isolating C. diphtheriae from infected site
 Selective media needed for throat culture—routine methods
cannot isolate organism
 Positive toxin production assay
36
 Prompt administration of
 Antitoxin
 Antibiotics
 Isolation of patient/ hospitalization
 Manage complications
 Active immunity with DPT
 Immunity wanes over time
 Decennial booster doses are required to maintain protective
antibody levels
37
AKA Whooping Cough
38
 Bordetella pertussis
 Gram negative, pleomorphic coccobacilli
 Highly contagious
 Respiratory droplets
 Incubation period range 6 – 14 days
 Lasts 2 months
 Three phases
 Catarrhal -- 1 – 2 weeks
 Paroxysmal -- 2 – 4 weeks
 Convalescent -- 1 – 2 weeks
39
 Most contagious during this time
 Rhinorrhea
 Conjunctival injection
 Lacrimation
 Varies mild to hacking night cough
 Low grade fever
 May resemble a simple URI at this stage
40
 Episodes of cough increase in severity and frequency
 Forceful coughs during expiration are followed by a
sudden massive inspiration producing a whoop
 http://www.whoopingcough.net/cough-child-
muchwhooping.wav
 Facial petechiae and redness
 Cyanosis
 Posttussive vomiting
 Exhausting; appear apathetic
41
 Paroxysmal coughing and vomiting decrease in
frequency and severity
 Chronic cough may last for several months
42
 Elevated white blood cell count with lymphocytosis
 Isolation of B. pertussis by culture of nasopharyngeal
swab with Bordet-Gengou or other special medium
43
 Antibiotic may shorten contagious period but is of
little use during the paroxysmal stage
 Steroid may reduce inflammation and decrease
intensity
 Supportive care
 Warm mist oxygen
 Nasopharyngeal suctioning
 Parenteral fluids
 Prevention—immunization
 Neither complete nor permanent
44
AKA Lockjaw
45
 Clostridium tetani
 Gram positive spore forming rods that are obligate
anaerobes
 Flagellated and motile
 Proliferating cells elaborate one of the most potent
toxins known as tetanospasmin
 Causes systemic toxemia
 Binds to gangliosides in the CNS
 Substance suppresses inhibiting influences on motor
neurons and interneurons
46
Tetanus-Prone Wounds
Usually following a trauma
where the spores of C.
tetani are punctured into
the tissue.
Anaerobic
environment
Consider Burns or
Frostbite
http://4.bp.blogspot.com/umco405fqqM/Te76TPIHFVI/AAAAAAAAAJE/oITaeGSYXuI/s320/tetanus.jpg
Incubation period 3 – 21
days
47
 Local form—uncommon
 Spasm and increased muscle tone at site of injury
 2 week progression with recovery in 1 month
48
 Generalized tetanus, the most common type (about
80%
 Usually presents with a descending pattern
 Starting with trismus or lockjaw
 Difficulty opening mouth
 Followed by stiffness of the neck
 Difficulty in swallowing
 Rigidity of abdominal muscles
 Hyperextension of body
 Hyperactivity of DTR
 Difficulty in sucking
 Neonatal tetanus
http://2.bp.blogspot.com/_pOK9nKyAFVc/TFpDHrL3J_I/AAAAAAAAAFM/6miUlFsAG
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49
 Wound or recent history of wound
 Without clear history of tetanus toxoid immunization
 Moderate leukocytosis
 Normal CSF
 Normal serum calcium
 Attempts to culture C. tetani from wound not useful
50
 Supportive care until toxin metabolized
 May need respiratory support
 Avoid external stimuli
 Neutralize circulating toxin through tetanal immune
globulin (TIG)
 Passive immunization
 Active immunization must be started
 Must consider wounds that are “tetanus-Prone”
 Debride wounds
 Does not effect tetanus management
 Role of antibiotics not clear
 Conflicting studies
 Prevention – immunization
SAD RATS:
Sedation
Antitoxin
Debridement
Relaxant
ATB
Tracheostomy
Stimulants-avoid
51
“Blood loving”
52
 Pyogenic infections in young
 Involve the middle ear, sinuses, facial skin, epiglottis,
meninges, lungs, and joints
 Leading cause of bacterial meningitis worldwide
 Has almost disappeared from U.S. (vaccination!)
 Aerobic, pleomorphic, gram negative coccobacilli
 Encapsulated (Type B) or not (Type A)
 Type B are more virulent and cause 95% of the invasive bacteremic
infections
 Respiratory droplets and secretions from person to person
 Serious disease peaks at 6 to 18 months
 Corresponding to loss of maternal antibodies
 Incubation period unknown
53
 Unencapsulated H. influenzae strains spread locally
from their normal sites of residence to adjoining sterile
locations
 Organisms proliferate and elicit acute inflammatory
responses
 Encapsulated—capable of tissue invasion
 Capsular polysaccharide of type b organisms allows to
evade phagocytosis, and bacteremic infections are
common
 Elaborates an IgA protease
 Facilitates local survival in the respiratory tract
54
 Most common cause of meningitis in children younger
than the age of 2
 Vaccination has reduced this…
 Bronchopneumonia or lobar pneumonia
 Fever, cough, purulent sputum, dyspnea
 Epiglottitis
 Obstructs upper respiratory tract
 Septic arthritis
 Large weight bearing joints
 Fever, heat, erythema, swelling, and pain on movement
 Facial cellulitis
 Fever, profound malaise, raised hot, red-blue discolored area
of the face, usually cheek or eye
55
"Explaining Hot Neck Stiffness":
[In order from birth to death]:
E. coli, Group B Step [infants]
H. influenzae
[older infants, kids]
N. meningitis
[young adults]
S. pneumoniae
[older folks]
56
 Gram stain
 Culture
 Immunologic assays
 ELISA or EIA
57
 Antibiotics
 Supportive therapy
 Prevention
 Vaccination
58
AKA Streptococcus
59
 Second most common cause of
vaccine-preventable death in the U.S.
 After influenza
60
 Streptococcus pneumoniae major cause of pyogenic infections
 Aerobic, gram positive Lancet shaped diplococci
 Commensal
 Often have a capsule
 Increases virulence
 Infection occurs when organism gains access to sterile sites
 Prior splenectomy, alcoholism, asthma, HIV infection are
predisposing factors
 Advanced age at high risk of rapid, fulminant septic shock
and death
61
 Reservoir
Human carriers
 Transmission
Respiratory
Autoinoculation
 Temporal pattern
Winter and early spring
 Communicability
Unknown
Probably as long as
organism in respiratory
secretions
62
 Lobar pneumonia
 Most common cause of bacterial CAP
 Bacteremia
 Meningitis
 Most common
 Middle ear infections
 Usually by age of 5
 One of the top two causes
 Sinuses
63
 COMPS: mnemonic
Conjunctivitis
Otitis media
Meningitis
Pneumonia
Sinusitis
 Symptoms will depend on what tissue
is infected
64
 ATB
 Supportive therapy
 Prevention—vaccination
65
66
 Route of transmission:
 Fecal-oral transmission
 Sheds into bile which accounts for presence in feces
 "Vowels are bowels":
Hepatitis A and E transmitted by fecal-oral route
 Virus is resistant to gastric acid, absorbed by intestine,
excreted in bile, shed in stools
 Spread by poor hand washing, crowding, poor
sanitation, contaminated food and water
 May occur in epidemics or sporadic cases
 Risks—living in close quarters, household contacts,
eating uncooked shellfish
67
 Incubation period:
 Relatively short averages 30 days
 Rise in aminotransferase (AST) activity
 Markedly increased (>1,000 IU/dL)
 ALT commonly higher
 Virus is shed in stool 2 weeks BEFORE
clinical illness, and persists until 1 week
after
68
 Severity of Illness
 In kids, most cases are sub-clinical (asymptomatic) or
mild and self-limiting
 In adults, symptoms range from very mild to severe
 Severity increases with age
 30% of Americans are positive for HAV antibody, yet
only 3-5% remember having a hepatitis like illness
 Most are anicteric
 Most childhood
69
 Malaise
 May cause spiking fevers
 Myalgia
 Jaundice
 Arthralgia
 Easy fatigability
 URI like symptoms
 Anorexia
 Distaste for smoking
 Nausea and Vomiting
 In many cases, jaundice
never develops
 Acholic stools
 Lacking bilirubin pigment
 Cholecystitis occasionally
complicates the course
 RUQ pain
70
http://www.vaccineinformation.org/photos/hepaiac001.jpg
71
 Hepatomegaly
 Rarely marked
 Liver tenderness
 Systemic toxicity is most often encountered in
Hepatitis A
72
 Course of Illness
 Complete clinical and laboratory recovery in about 9
weeks is the usual outcome
 Causes “acute” hepatitis
 May last up to a year
 Relapses may occur before complete recovery
 Progression to fulminant hepatitis is rare
 Unless patient has underlying chronic liver disease
or Hepatitis C virus infection
 No carrier state and never chronic
73
 Serologic markers
 Antigen markers: none clinically
 Antibody markers:
 Anti-HAV (IgM) is detected (2 weeks) soon after the onset of
symptoms and lasts up to 3-6 months (acute markers)
 Good for dx acute hepatitis A
 Anti-HAV (IgG) is also detected soon after the onset of
symptoms, slightly after Anti-HAV (IgM), but persists for years
and provides lifelong immunity
 IgG anti-HAV indicates previous exposure to HAV, noninfectivity,
and immunity
 Viral RNA tests –not clinically done
74
UpToDate 2011
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 Supportive
 Must be cautious about transmission to others by not
sharing food or dishes and frequent hand washing
 Avoid alcohol or all other hepatotoxins
 Unvaccinated persons who are exposed should receive
post-exposure prophylaxis with a single dose of HAV
vaccine or immune globulin
 Vaccination
 Since 1996, rate has declined 92%
76
77
 Etiology:
 Caused by a hepadnavirus
 DNA virus
 More able to be incorporated into the
host’s genome
 Virus consists of a “core” surrounded by
an outer surface envelope, each of which is
antigenic
78
 Routes of transmission
 Parenteral, sexual, perinatal, transmucosal
 Virus has been found in blood, saliva, and
semen
 C-Section offers no protection
 Vertical is the most important route
worldwide
79
 Route of Transmission
 Highly prevalent in homosexuals and IVDA
 Most cases in US heterosexual transmission
 Others at risk
 Hemodialysis patients
 Lab and blood bank workers
 Healthcare workers
 Blood transfusion
80
 Incubation Period
 Long –6 weeks to 6 months
 Average of 3 months
81
 Severity of Illness
 May be asymptomatic, mild, moderate, or
fulminant (<1%)
 Liver damage occurs mainly from the immune
response to the virus
 Typically presents with a non specific flu-like
illness and abdominal pain
 30% become jaundiced
 Serum sickness type illness may develop
 Fever, rash, arthritis, glomerulonephritis,
vasculitis
82
 Course of Illness
 Elevations in AST and ALT are higher
 90% of HBV are ACUTE
 Most are asymptomatic and have a complete recovery
rate
 Those who are symptomatic
 Most of these recover
 10% of these develop CHRONIC infection
 Chronic is indicated by antigen > 6 months
 Progression is greater in IVDA and male
homosexuals
<1% of these develop a fulminant course, with
high mortality rate—60%
83
 Chronic Course of Illness:
 Chronic “carriers”
 Carriers mean that they don’t develop the
necessary antibodies to clear the antigen >
6 months
 2 types of chronic carriers
 Chronic active have ongoing viral
replication
 Bad prognosis
 Chronic persistent have minimal, if any,
viral replication
 Much better prognosis
 A number of patients eventually develop Anti
HBV and clear HB Ag
84
85
 Serologic markers
 Antigen markers
 HBsAg
 Surface antigen: from the surface of the viral
envelope
 HBcAg
 Core antigen: from inner core of the virusno test
 HBeAg
 Envelope antigen: a secretory form of viral
core antigen—maximally infective time
frame
86
 Serological Markers
 HBsAg
 First lab evidence of HBV infection
 Even before AST and ALT
 Indicates that patient is infected and
infectious
87
 HBeAg
 Rises about the same time but declines before
HBsAg
 Implies ongoing viral replication and greater
infectivity
 If present beyond 3 months, there is increased
likelihood of chronic infection
88
 Anti-HBc (IgM)
 The first evidence of host response to the
infection
 Implies a more recent infection
 IgM HBcAg alone in serum indicates
 False positive test
 Latent infection in HBV DNA
 Anti-HBc (IgG)
 Rises at the same time as the IgM form, but lasts
indefinitely
89
 Anti-HBs (IgG)
 Occurs after the clearance of HBsAg,
about 4-6 months after the initial
infection
 Occurs after immunization with vaccine
 Disappearance of HBsAg and the
appearance of anti-HBs signal recovery
from HBV infection, noninfectivity, and
immunity
90
 HBV-DNA
 The viral DNA can be detected and measured
 The most sensitive and specific marker of viral
replication and infectivity
 Interpretation of HBV-DNA values
 Normal/desired: 0 pg/mL
 Low viral replication: <200 pg/mL
 High viral replication: >200 pg/mL
91
http://www.medscape.com/viewarticle/743651_3
92
 “Carrier State”
 Chronic HBV (= antigen > 6 months)
 Chronic carriers don’t develop Anti-HBsAg
and therefore continue to carry (+)HBsAg
 Chronic active if (+)HBeAg with ongoing
viral replication
 Chronic persistent if (-) HBeAg with
minimal (if any) viral replication
 Chronic non carriers
 Eventually develop Anti-HBs and clear
HBsAg
93
 Antiviral
 Interferon
 Avoid hepatotoxins
 With chronic hepatitis B
 Monitor for hepatocellular carcinoma
 AFP
 USN
 Prevention
 Recombinant Vaccination
 Immunoglobulin
94
Polio or Poliomyelitis
95
 Global effort to eradicate disease
 350,000 cases in 1988 to 1,604 in 2009
 Afghanistan, Pakistan, Nigeria, India still epidemic
 Single stranded RNA virus
 Enterovirus
 Fecal – Oral or Oral transmission
 Highly contagious
 Incubation period 9 – 12 days from exposure
96
 95% asymptomatic
 Those who become ill
 Abortive poliomyelitis
 Nonparalytic poliomyelitis
 Paralytic poliomyelitis
97
 Abortive poliomyelitis—clinically only suspected
during epidemics
 Minor illness
 Fever
 HA
 Vomiting
 Diarrhea
 Constipation
 Sore throat
98
 Nonparalytic poliomyelitis—indistinguishable from
viral meningitis
 Similar symptoms of Abortive, plus
 Meningeal irritation
 Muscle spasm
 Absence of frank paralysis
99
 Paralytic poliomyelitis
 Two forms
 Spinal poliomyelitis
 Muscles innervated by the spinal muscles
 Bulbar poliomyelitis
 Weakness of muscles supplied by the cranial nerves (CN IX and X)
and of the respiratory* and vasomotor centers
 Review: What are CN IX and X?
 CN: IX—Glossopharyngeal





CN X: Vagus
Paralysis may occur at any time during febrile period
Tremors
Muscle weakness
Constipation
Ileus
100
 Cerebrospinal fluid pressure and protein are normal or




slightly increased
Glucose is not decreased
The virus can be recovered from throat washings and
stool
Neutralizing and complement fixing antibodies appear
during the first or second week of illness
Serologic testing cannot distinguish between wild-type
and vaccine related virus infections
 What does wild-type mean?
101
 Hospitalized
 Strict bed rest
 Reduces rates of paralysis
 Medically manage fecal impaction and urinary




retention
In cases of respiratory weakness, intensive care
Refer with neurologic compromise
Reportable condition
Prevention—vaccination
102
103
 Orthomyxovirus
 Transmitted by the respiratory route—droplet
 Viruses further subtyped based on the
 Hemagglutinin (H) and Neuraminidase (N)
 Annual epidemics usually appear in fall or winter
 Incubation period is usually 1 – 4 days
104
 Fever
 Lasts 1 – 7 days
 Chills
 Malaise
 Myalgias
 Substernal soreness
 HA
 Nasal stuffiness
 Nausea
 Nasal obstruction, sneezing,
and sore throat—Coryza
"Having Flu Symptoms Can
Make Moaning Children A
Nightmare":
Headache
Fever
Sore throat
Chills
Myalgias
Malaise
Cough
Anorexia
Nasal congestion
105
 Pharyngeal injection
 Flushed face
 Conjunctival redness
 Moderate cervical lymph nodes
 Fever
106
 Leukopenia common
 Leukocytosis may occur
 Virus may be isolated from throat or nasal washings
 RIA or EIA may be used
107
 Rest
 Antivirals
 Analgesics
 Supportive therapy
 Monitor for secondary bacterial infections
 Avoid aspirin in children
 Reye syndrome—fatty liver (leading to failure) with
encephalopathy
 Prevention—vaccination if not contraindicated
108
Rubeola or Morbilli
109
 The New York Times (7/6, Harris) reported, "An
increase in the number of measles outbreaks in
Europe, Asia and Africa in recent months is cause for
concern at the Centers for Disease Control and
Prevention in the" US. CDC spokesperson Candice
Burns Hoffman, "said in a release that the United
States was experiencing 'the highest number of
measles cases since 1996,' in large part because of
unvaccinated travelers recently returned from" abroad.
"As of June 17, 156 cases of measles from at least 25
states had been reported to the center this year."
110
 Single stranded RNA virus
 Paramyxoviral infection
 Respiratory aerosol and secretions
 Person to person
 Highly contagious
111
 Fever
 About four days or so
 Up to 104oC
 Cough
 Nasal obstruction, sneezing,
and sore throat—Coryza
 Red eyes—Conjunctivitis
 Stimson Line
 Rash—
http://www.health24.com/medical/Conditio
n_centres/777-792-823-1838,46960.asp
 Develops on head several days after fever
 Spreads to cover the rest of the body
112
http://missinglink.ucsf.edu/lm/IDS_105_skinILM/measles_files/image002.jpg
113
http://sciencephoto.com/image/259736/530wm/M2100363Koplik_s_spots_in_measles-SPL.jpg
114
 Typically clinical diagnosed
 Leukopenia usually present
 Thrombocytopenia common
 Virus may be cultured
 Detection of IgM measles antibodies with ELISA or a
fourfold rise in serum hemagglutination inhibition
antibody supports the diagnosis
 Fluorescent antibody staining
115
 Isolation with bed rest until afebrile
 Symptomatic therapy
 Antipyretics and fluids
 Vitamin A
 Maintains gastrointestinal and
respiratory epithelial mucosa
 Antivirals have been used
 ATB for any secondary bacterial infections
 Reportable condition
116
117
 Single stranded RNA virus—Paramyxovirus
 Infection of salivary glands
 Primarily the parotid glands
 Person to person
 Respiratory route
 Highly contagious
 Incubation period 18 days
 Cell necrosis, inflammation, mononuclear cell
infiltration
118
 Fever
 Headache
 Muscle aches
 Malaise
 Anorexia
 Swollen salivary glands
 Parotitis
 Bilateral or unilateral
 7 – 10 days
119
http://www.health.gov.on.ca/en/public/programs/mumps/images/m
ohltc_mump_boy.jpg
120
 Orchitis
 Most common complication in males
 Rarely, infertility
 Unilateral
 Oophoritis
 Meningitis
 Pancreatitis
 Exhibit elevated serum amylase activity
 Mastitis
 Deafness
121
 Usually a clinical diagnosis
 Isolate virus
 Serologic diagnosis by complement fixation test
 IgM antibodies by ELISA
122
 Supportive therapy
 Isolation of patient until glandular swelling subsides
 Usually noncontagious 9 days after onset of parotid
swelling
 Reportable condition
 Prevention
 Live attenuated vaccine
123
 Orchitis
 Oophoritis
Infertility
 Meningoencephalitis
 Pancreatitis
 Prostatitis
 Nephritis
 Myocarditis
124
In German, means “little red”
AKA—German Measles
Way to remember: think of a German ringing a little red bell…
125
 Rubella Virus
 Single stranded RNA
 Togavirus family
 Spreads person to person
 Primarily the respiratory route
 Incubation period 14 to 18 days
 Virus shed during this time
126
 What is the classic acronym of the five perinatal infections
with similar presentations, including a rash and ocular
findings?
ToRCHeS:
T:
Toxoplasmosis
O:
Other (Syphilis)
R:
Rubella
C:
Cytomegalovirus (CMV)
H:
Herpes Simplex Virus (HSV)
Toxoplasma
Other—parvovirus,
listeria
Rubella
CMV
Herpes simplex,
Herpes zoster
(varicella),
Hepatitis B,C,E
HIV
Enterovirus
Syphilis
Other diseases have been added!
127
 Teratogenic in (early) pregnant women
 *Deafness
 Cataracts / Glaucoma / Retinal Defects
 Heart defects
 Pulmonary valvular stenosis, pulmonary artery hypoplasia, VSD,
PDA
 Mental retardation
 Blueberry (muffin) spots
 Microcephaly / mental retardation
 Premature delivery
 Death
 Maternal infection after 20 weeks gestation usually does
not cause significant fetal disease
http://lessons4medicos.blogspot.com/2009/05/grey-baby-syndrome-bluebaby-syndrome.html
128
 Most patients
 Mild febrile disease—many asymptomatic postnatally
 Rhinorrhea
 Conjunctivitis
 Postauricular lymphadenopathy
 Arthritis
 Forscheimer Spots on Palate
 Petechiae on palate – are not pathognomic
129
 Rash
 Rapid Spread from face to trunk and extremities
 Lasts one to three days—Range 1 – 8 days
 Therefore, in past known as three day measles
 Also third exanthem in childhood
 Onset of rash—decrease in viremia
 Rash immune mediated?
 Presence of neutralizing antibodies
http://www.health24.com/med
ical/Condition_centres/777792-823-1838,46960.asp
130
http://ezproxy.butler.edu:4053/contents/image?im
ageKey=ID%2F12261&topicKey=ID%2F8301&source
=see_link&utdPopup=true
131
 Detection of rubella-specific IgM antibodies using an
enzyme immunoassay
 May isolate virus
 Rare
 Supportive care
 Reportable disease
 Prevent with vaccination
 Live attenuated virus
132
AKA Chickenpox and Shingles
133
 HHV-3
 Highly contagious—
 Inhalation of infective droplets
 Especially day before rash erupts
 Contact with lesions
134
 Generally disease of childhood
 Incubation period of 10 – 20 days
135
 Fever
 Malaise
Mild in children; more marked in adults
136
http://www.health24.com/medical/C
ondition_centres/777-792-8231838,46960.asp
 Pruritic
 Begins prominently on face, scalp, and trunk
 Later involves extremities to a lesser extent
 Maculopapules change in a few hours to vesicles
 These become pustular and eventually form crusts
 Crusts slough in 7 to 14 days
http://www.fastchickenpoxcure.com/
blog/wpcontent/uploads/2011/02/chickenpox-stage.jpg
137
http://www.healthcare.uiowa.edu/dermatology/Images%5CClin%5CVaricel02.jpg
138
 New lesions may erupt for 1 – 5 days
 Different stages of the eruption are usually present
simultaneously
 CROPS
139
http://www.vaccineinformation.org/photos/variaap001.jpg
140
 After the primary infection, the virus remains dormant
in cranial nerves sensory ganglia and spinal dorsal root
ganglia
 Latent VZV will reactivate as herpes zoster
 10 – 30%
141
 Incidence increases with age—more than half are > 60
years of age
 Due to age related decline in immunity against VZV
 Pain often severe and commonly precedes the
appearance of rash
 Acute neuritis
 Lesions follow a dermatomal distribution
 Usually thoracic and lumbar roots
 Usually unilateral
http://www.health24.com/medical/Condition_centres/777-792-823-1838,46960.asp
142
 Lesions on the tip of the nose, inner corner of the eye,
and root and side of the nose—Hutchinson sign
 Indicate trigeminal nerve involvement
http://eyewiki.aao.org/images/1/1/14/Herpes-zoster-ophthalmicus-395X275.jpg
143
 Facial palsy, lesions of the external ear with or without
tympanic membrane involvement, vertigo and
tinnitus, and deafness
 Signify geniculate ganglion involvement
 Ramsay Hunt Syndrome
144
Etiology:
Reactivated Herpes zoster
Complication:
Reduced Hearing
145
 Post Herpetic Neuralgia
 Most common complication
 ~15%
146
 Diagnosis made clinically
 PCR
147
 Antiviral
 Analgesic for acute neuritis
148
149
 Neisseria meningitidis
 Gram negative intracellular diplococci
 Typically serogroup C in U.S.
 40% are nasopharyngeal carriers of organism
 Disease develops in relatively few
 Clinical illness may take the form of
 Meningococcemia
 Meningococcemia with meningitis
 Meningitis
150
 High fever, stiff neck, HA are classic signs
 Chills
 Back, abdominal, and extremity pain
 Nausea and vomiting
 Rapidly developing confusion, delirium, seizures, and
coma occur in some
151
 Nuchal and back rigidity
 Pain with neck flexion
 Kernig sign
 http://www.youtube.com/watch?v=rJ-5AFuP3YA
 Brudzinski sign
 http://www.youtube.com/watch?v=jO9PAPi-
yus&feature=related
152
 Appearing generally in the lower extremities and at
pressure points
 Vary in size from pinpoint to large ecchymoses
 Skin gangrene can occur
http://www.health24.co
m/medical/Condition_c
entres/777-792-8231838,46960.asp
153
http://www.meningococcal.org/images/page_images/513.jpg
154
 Lumbar puncture—delay until clinically stable
 Cloudy or purulent cerebrospinal fluid
 Increased pressure
 Increased protein
 Decreased glucose
 PMNs predominating
 Gram negative intracellular diplococci gram stain
 May culture
 Gold Standard is CSF culture
155
 Supportive care
 Blood cultures
 IV fluids
 IV ATB
 Prevention
 Vaccination
 Prophylactically eliminating nasopharyngeal carriage—
ATB
156
HPV
157
 Nonenveloped
 Invade cutaneous and mucosal epithelium, proliferate,
and cause warts
 Most transient
 Those that persist are problematic
158
 Common skin warts—verucca vulgaris
 Hands and feet often
 Typically asymptomatic
 Plantar may be painful with pressure
 Vary in size and shape
 May be flat and superficial
 Plantar and deep
 Plantar warts lack dermatoglyphics—ridges, whorls, and
loops of sole print
 filiform
159
• Laryngeal warts
• May obstruct airway in children—removed surgically
• Commonly transmitted during childbirth—vaginal
canal
• Anogenital warts—types 6 and 11
• AKA Condyloma acuminata
• Sexually transmitted
• May be cancerous
• Cervical warts—types 16 and 18
 Sexually transmitted
160
 Histologic sampling
 With acetic acid develop acetowhitening
 Easier to biopsy
 Hyperplastic prickle cells with excess keratin—common
warts
 Koilocytotic or vaculoated squamous epithelial cells in
clumps—cervical warts
 HPV DNA in cervical swabs using molecular probes
161
 Spontaneous remission
 Recurrence common
 Liquid nitrogen
 Salicylic acid
 Immune modulators
 Surgical removal
 Prevention—
 Condoms
 Vaccine
162
Post-Lecture
163
 The major virulence factor of Corynebacterium
diphtheriae is
A.
B.
C.
D.
E.
Ability to multiply within macrophage
Capsule
Endotoxin
Exotoxin
Neurotoxin
164
 The major virulence factor of Corynebacterium
diphtheriae is
A.
B.
C.
D.
E.
Ability to multiply within macrophage
Capsule
Endotoxin
Exotoxin
Neurotoxin
165
 The exotoxin elaborated by C. diphtheriae causes a
pseudomembrane to form in the pharynx and is
absorbed by the circulatory system where further
damage ensues
Physician Assistant Review Lippincott Williams
and Wilkins 2001
166
 A physician assistant student presents to the primary
care office with a lesion on his foot. History reveals he
walks barefoot in the shower at the local wellness
center (gym). The lesion on the bottom of the foot is
flat and has grown inward. There is another lesion on
the side of the foot that appears filiform. Which of the
following is most likely the causative agent?
A.
B.
C.
D.
E.
Coronavirus
Papilloma virus
Poxvirus
Rubella virus
Togavirus
167
 A physician assistant student presents to the primary
care office with a lesion on his foot. History reveals he
walks barefoot in the shower at the local wellness
center (gym). The lesion on the bottom of the foot is
flat and has grown inward. There is another lesion on
the side of the foot that appears filiform. Which of the
following is most likely the causative agent?
A.
B.
C.
D.
E.
Coronavirus
Papilloma virus
Poxvirus
Rubella virus
Togavirus
168
Where does the rash begin in cases of
rubella?
A.
B.
C.
D.
E.
Back
Chest
Head/neck
Inguinal region
Wrist
169
Where does the rash begin in cases of
rubella?
A.
B.
C.
D.
E.
Back
Chest
Head/neck
Inguinal region
Wrist
170
A three year old, unknown to your clinic previously,
presents and has a high fever, cough, coryza,
conjunctivitis, and a rash. Koplik spots are noted on the
buccal mucosa. The conjunctivae reveal a transverse
line of inflammation along the eyelid margin (Stimson
line). The rash is morbiliform, began on the head, and
then spread over most of the body in a descending
fashion within 18-20 hours. This clinical presentation is
consistent with a diagnosis of
A.
B.
C.
D.
E.
Herpes Zoster
Human Herpesvirus-6
Measles (Rubeola)
Rubella (German, 3-Day Measles)
Meningiococcal
171
A three year old, unknown to your clinic previously,
presents and has a high fever, cough, coryza,
conjunctivitis, and a rash. Koplik spots are noted on the
buccal mucosa. The conjunctivae reveal a transverse
line of inflammation along the eyelid margin (Stimson
line). The rash is morbiliform, began on the head, and
then spread over most of the body in a descending
fashion within 18-20 hours. This clinical presentation is
consistent with a diagnosis of
A.
B.
C.
D.
E.
Herpes Zoster
Human Herpesvirus-6
Measles (Rubeola)
Rubella (German, 3-Day Measles)
Meningiococcal
172
 All pictures, audio, video previously referenced.
 CDC Vaccines and Preventable Diseases
http://www.cdc.gov/vaccines/vpd-vac/default.htm
 Current Medical Diagnosis and Treatment 2011, 50th
ed. McPhee SJ, Papadakis MA McGraw Hill
173
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