2

1
4
0011 0010 1010 1101 0001 0100 1011
 Type of
Hepatitis
0011 0010 1010 1101 0001 0100 1011

A B C D E

1
2
Source of feces blood/ blood/ blood/ feces
virus blood-derived blood-derived blood-derived

4
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
 Hepatitis A Virus
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Hepatitis A - Clinical
Features
0011 0010 1010 1101 0001 0100 1011

 Incubation period: Average 30 days

2
Range 15-50 days

1
 Jaundice by <6 yrs, <10%

4
age group: 6-14 yrs, 40%-50%
>14 yrs, 70%-80%
 Complications: Fulminant hepatitis
Cholestatic
hepatitis
Relapsing hepatitis
 Chronic sequelae: None
 Hepatitis A Virus Transmission
0011 0010 1010 1101 0001 0100 1011

• Close personal contact

2
(e.g., household contact, sex contact, child

1
day care centers)

4
• Contaminated food, water
(e.g., infected food handlers, raw shellfish)
• Blood exposure (rare)
(e.g., injecting drug use, transfusion)
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• Acute infection is diagnosed by the

1
2
detection of HAV-IgM in serum by EIA.

4
• Past Infection i.e. immunity is determined
by the detection of HAV-IgG by EIA.
 Hepatitis A Vaccination
Strategies
Epidemiologic
0011 0010 1010 1101 0001 0100 1011

Considerations
• Many cases occur in community-wide outbreaks

2
– no risk factor identified for most cases

1
– highest attack rates in 5-14 year olds

4
– children serve as reservoir of infection

• Persons at increased risk of infection

– travelers
– homosexual men
– injecting drug users
 Hepatitis B Virus
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Hepatitis B - Clinical
Features
0011 0010 1010 1101 0001 0100 1011

 Incubation period: Average 60-90 days

2
Range 45-180 days

1
 Clinical illness (jaundice): <5 yrs, <10%

4
5 yrs, 30%-50%
 Acute case-fatality rate: 0.5%-1%
 Chronic infection: <5 yrs, 30%-90%
5 yrs, 2%-10%
 Premature mortality from
chronic liver disease: 15%-25%
 Spectrum of Chronic Hepatitis B
0011 0010 1010 1101 0001 0100 1011
Diseases

1Chronic Persistent Hepatitis -

1
2
asymptomatic

4
2. Chronic Active Hepatitis -
symptomatic exacerbations of hepatitis
3. Cirrhosis of Liver
4. Hepatocellular Carcinoma
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Concentration of Hepatitis B
Virus in Various Body Fluids
0011 0010 1010 1101 0001 0100 1011

Low/Not

2
High Moderate Detectable

1
4
blood semen urine
serum vaginal fluid feces
wound exudates saliva sweat
tears
breastmilk
 Hepatitis B Virus
Modes of Transmission
0011 0010 1010 1101 0001 0100 1011

 Sexual - sex workers and homosexuals are

2
particular at risk.

1
 Parenteral - IVDA, Health Workers are at

4
increased risk.
 Perinatal - Mothers who are HBeAg positive are
much more likely to transmit to their offspring
than those who are not. Perinatal transmission is
the main means of transmission in high
prevalence populations.
 Diagnosis
0011 0010 1010 1101 0001 0100 1011
• A battery of serological tests are used for the diagnosis of acute and
chronic hepatitis B infection.

2
• HBsAg - used as a general marker of infection.

1
• HBsAb - used to document recovery and/or immunity to HBV
infection.

4
• anti-HBc IgM - marker of acute infection.
• anti-HBcIgG - past or chronic infection.
• HBeAg - indicates active replication of virus and therefore
infectiveness.
• Anti-Hbe - virus no longer replicating. However, the patient can still
be positive for HBsAg which is made by integrated HBV.
• HBV-DNA - indicates active replication of virus, more accurate than
HBeAg especially in cases of escape mutants. Used mainly for
monitoring response to therapy.
 Treatment
0011 0010 1010 1101 0001 0100 1011

• Interferon - for HBeAg +ve carriers with chronic active

2
hepatitis. Response rate is 30 to 40%.

1
• Lamivudine - a nucleoside analogue reverse transcriptase
inhibitor. Well tolerated, most patients will respond favorably.

4
However, tendency to relapse on cessation of treatment.
Another problem is the rapid emergence of drug resistance.
• Successful response to treatment will result in the
disappearance of HBsAg, HBV-DNA, and seroconversion to
HBeAg.
 Prevention
0011 0010 1010 1101 0001 0100 1011

• Vaccination - highly effective recombinant vaccines are now

2
available. Vaccine can be given to those who are at increased risk of

1
HBV infection such as health care workers. It is also given routinely
to neonates as universal vaccination in many countries.

4
• Hepatitis B Immunoglobulin - HBIG may be used to protect persons
who are exposed to hepatitis B. It is particular efficacious within 48
hours of the incident. It may also be given to neonates who are at
increased risk of contracting hepatitis B i.e. whose mothers are
HBsAg and HBeAg positive.
• Other measures - screening of blood donors, blood and body fluid
precautions.
 Hepatitis B Virus
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Hepatitis B Infection in Children
0011 0010 1010 1101 0001 0100 1011
• About 40% of infants born to HBsAg-carrier mothers will be infected at birth
– if mothers HBeAg + transmission rate about 90%

2
– risk of chronic carrier at least 90%

1
• Contribute as reservoir, source of transmission to others

4
(Euler, Gary et al., PIDJ Feb. 2003)

• Vaccination of infants and children, highest priority for Hepatitis B programs

MMWR, Sept. 2003

 Hepatitis B Vaccine, Birth Dose
0011 0010 1010 1101 0001 0100 1011

• To prevent perinatal HBV transmission, first dose

should be given within 24 hrs. (MMWR, Sept. 2003)

1
2
– Prevent vertical and diminish horizontal transmission

4
– Safety net to infants born to mothers with unknown status

• HBV vaccine strategies  universal immunization

must be started at birth.
 Hepatitis C - Clinical
Features
0011 0010 1010 1101 0001 0100 1011

Incubation period: Average 6-7 wks

2
Range 2-26 wks
Clinical illness (jaundice):
1
30-40% (20-30%)

4
Chronic hepatitis: 70%
Persistent infection: 85-100%
Immunity: No protective
antibody
response
identified
 Chronic Hepatitis C Infection
0011 0010 1010 1101 0001 0100 1011

• The spectrum of chronic hepatitis C infection is

1
2
essentially the same as chronic hepatitis B
infection.

4
• All the manifestations of chronic hepatitis B
infection may be seen, albeit with a lower
frequency i.e. chronic persistent hepatitis, chronic
active hepatitis, cirrhosis, and hepatocellular
carcinoma.
 Risk Factors
Associated with
Transmission
0011 0010 1010 1101 0001 0100 1011 of HCV
 Transfusion or transplant from infected donor

1
2
 Injecting drug use
 Hemodialysis (yrs on treatment)

4
 Accidental injuries with needles/sharps
 Sexual/household exposure to anti-HCV-positive
contact
 Multiple sex partners
 Birth to HCV-infected mother
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• HCV antibody - generally used to diagnose hepatitis C

2
infection. Not useful in the acute phase as it takes at least

1
4 weeks after infection before antibody appears.

4
• HCV-RNA - various techniques are available e.g. PCR
and branched DNA. May be used to diagnose HCV
infection in the acute phase. However, its main use is in
monitoring the response to antiviral therapy.
• HCV-antigen - an EIA for HCV antigen is available. It is
used in the same capacity as HCV-RNA tests but is much
easier to carry out.
 Treatment
0011 0010 1010 1101 0001 0100 1011

• Interferon - may be considered for patients with

2
chronic active hepatitis. The response rate is

1
around 50% but 50% of responders will relapse

4
upon withdrawal of treatment.
• Ribavirin - there is less experience with ribavirin
than interferon. However, recent studies suggest
that a combination of interferon and ribavirin is
more effective than interferon alone.
 Prevention of
Hepatitis C
0011 0010 1010 1101 0001 0100 1011

2
 Screening of blood, organ, tissue donors

1
4
 High-risk behavior modification

 Blood and body fluid precautions

 Hepatitis D (Delta)
δ Virus HBsAg
antigen
0011 0010 1010 1101 0001 0100 1011

2
1
RNA
4
 Hepatitis D - Clinical
Features
0011 0010 1010 1101 0001 0100 1011

 Coinfection

1
2
– severe acute disease.

4
– low risk of chronic infection.
 Superinfection
– usually develop chronic HDV infection.
– high risk of severe chronic liver disease.
– may present as an acute hepatitis.
 Hepatitis D Virus
Modes of
0011 0010 1010 1101 0001 0100 1011
Transmission

2
 Percutanous exposures
 injecting drug use
1
4
 Permucosal exposures
 sex contact
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Hepatitis D -
0011 0010 1010 1101 0001 0100 1011
Prevention
 HBV-HDV Coinfection

1
2
Pre or postexposure prophylaxis to prevent

4
HBV infection.
 HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
 Hepatitis E
Virus
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Hepatitis E - Clinical Features
0011 0010 1010 1101 0001 0100 1011

 Incubation period: Average 40 days

1
2
Range 15-60 days

4
 Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
 Illness severity: Increased with age
 Chronic sequelae: None identified
 Hepatitis E -
Epidemiologic
Features
0011 0010 1010 1101 0001 0100 1011

 Most outbreaks associated with faecally contaminated drinking

2
water.

1
 Several other large epidemics have occurred since in the Indian

4
subcontinent and the USSR, China, Africa and Mexico.
 In the United States and other nonendemic areas, where
outbreaks of hepatitis E have not been documented to occur, a
low prevalence of anti-HEV (<2%) has been found in healthy
populations. The source of infection for these persons is
unknown.
 Minimal person-to-person transmission.
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Prevention and Control
Measures for Travelers to HEV-
0011 0010 Endemic Regions
1010 1101 0001 0100 1011

 Avoid drinking water (and beverages with ice) of

2
unknown purity, uncooked shellfish, and

1
uncooked fruit/vegetables not peeled or prepared
by traveler.

4
 IG prepared from donors in Western countries
does not prevent infection.
 Unknown efficacy of IG prepared from donors in
endemic areas.
 Vaccine?
 Hepatitis G
0011 0010 1010 1101 0001 0100 1011

• Worlwide occurrence in adults and

2
children, seen in about 1.5% of blood

1
donors in the US.

4
• Infection has been reported in 10%-20% of
adults with chronic HBV or HCV infection
• Transmission: blood transfusion,
transplantation, IV drug use, hemodialysis,
sexual transmission, vertical transmission
 Hepatitis G
0011 0010 1010 1101 0001 0100 1011

• Clinical manifestation- associated only with mild

2
illness or no disease

1
• Diagnosis

4
– detection of HGV RNA by PCR in chronically
infected patients
– Detection of antibody to HGV in patients with
resolved infection
• Complications: no conclusive evidence for
fulminant or chronic liver disease
• Treatment - supportive
 Diphtheria
• 0010
0011 Greek diphtheria
1010 1101 0001(leather hide)
0100 1011

• Recognized by Hippocrates in 5th century B.C.

2
1
• Epidemics described in 6th century

4
• C. diphtheriae described by Klebs in 1883

• Toxoid developed in 1920s

 Corynebacterium diphtheriae
0011 0010 1010 1101 0001 0100 1011

• Aerobic gram-positive bacillus

1
2
• Toxin production occurs only when C.

4
diphtheriae infected by virus (phage) carrying tox
gene

• If isolated, must be distinguished from normal

diphtheroid
 Diphtheria Clinical Features
0011 0010
• 1010 1101 0001 0100 1011
Incubation period 2-5 days (range, 1-10 days)

2
• May involve any mucous membrane

• Classified based on site of infection

1
4
– Anterior nasal
– Tonsillar and pharyngeal
– Laryngeal
– Cutaneous
– Ocular
– Genital
 Pharyngeal and Tonsillar
Diphtheria
0011 0010 1010 1101 0001 0100 1011

• Insidious onset of exudative pharyngitis

1
2
• Exudate spreads over 2-3 days and may form adherent
membrane

4
• Membrane may cause respiratory obstruction

• Fever usually not high but patient appears toxic

0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

2
1
Cutaneous diptheria
4
 Diphtheria Complications
0011 0010 1010 1101 0001 0100 1011

• Most attributable to toxin

1
2
• Severity generally related to extent of local

4
disease

• Most common complications are myocarditis and

neuritis

• Death occurs in 5%-10% for respiratory disease

 Diptheria complications
0011 0010 1010 1101 0001 0100 1011

• Myocarditis

2
– Usually occurs during 2nd or 3rd week
– Cardiac failure may also occur

1
4
• Neuritis
 Treatment
0011 0010 1010 1101 0001 0100 1011
1. antitoxin
2. antibiotics: to eradicate the organisms and halt toxin

2
production and prevent carrier state

1
• PCN G 100,000 units/kg/day IV x 14 days

4
• Erythromycin 40 mg/kg.day oral or parenteral x 14
days
3. supportive: bedrest, adequate nutrition and hydration,
tracheostomy

Isolation of patient:
• Droplet precautions until 2 cultures are negative taken
at least 24 hours apart after cessation of antimicrobial
therapy
 Control measures
0011 0010 1010 1101 0001 0100 1011

• Care of exposed persons:

2
– All contacts irrespective of immunization

1
status should be cultured, kept under

4
surveillance for 7 days
– Antimicrobial prophylaxis: erythromycin
 Diphtheria Antitoxin
0011 0010 1010 1101 0001 0100 1011

• First used in 1891

1
2
• Produced in horses

4
• Used only for treatment of diphtheria

• Neutralizes only unbound toxin

 Diphtheria Epidemiology
0011 0010 1010 1101 0001 0100 1011

• Reservoir Human carriers

Usually asymptomatic

1
2
• Transmission Respiratory

4
Skin and fomites rarely

• Temporal pattern Winter and spring

• Communicability Up to several weeks

without antibiotics
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Tetanus
• First described by Hippocrates
0011 0010 1010 1101 0001 0100 1011

• Etiology discovered in 1884 by Carle

2
and Rattone

1
4
• Passive immunity used for treatment and
prophylaxis during World War I

• Tetanus toxoid first widely used during World War

II
 Clostridium tetani
• Anaerobic gram-positive, spore-forming bacteria
0011 0010 1010 1101 0001 0100 1011

• Spores found in soil, dust, animal feces; may persist

2
for months to years

1
4
• Multiple toxins produced with growth of bacteria

• Tetanospasmin estimated human lethal dose = 2.5

ng/kg
 Tetanus Pathogenesis
• Anaerobic conditions allow germination of spores and
0011 0010 1010 1101of
production 0001 0100 1011
toxins.

2
• Toxin binds in central nervous system

1
• Interferes with neurotransmitter release to block

4
inhibitor impulses.

• Leads to unopposed muscle contraction and spasm.

 Clinical Features
0011 0010 1010 1101 0001 0100 1011

Incubation period 2 – 14 days

2
• 1. Generalized tetanus:

1
trismus is the presenting symptom in half of

4
the cases
• 2. localized tetanus: painful spasms of the
muscles adjacent to the wound site
 Generalized tetanus
0011 0010 1010 1101 0001 0100 1011

• Most common form

2
• A. Neonatal tetanus:

1
– Onset: between 3 and 12 days old with progressive difficulty in
feeding with associated hunger and crying

4
– Jaw become so stiff the baby cannot suck or swallow
– Varied degrees of sustained, tonic or rigid states of muscle
contractions occurring spontaneously or provoked by stimuli
– Cry: varies from repeated , short, mildly hoarse cry to noiseless
– Constipation or urinary retention
– Cyanosis or pallor
– May end with flaccidity, anoxemia, exhaustion and finally death
 Generalized tetanus
0011 0010 1010 1101 0001 0100 1011

• B. in older children

2
– Progressively increasing stiffness of voluntary

1
muscles. Usual sequence of involvement:

4
• Jaw: trismus or lock jaw
• Neck and back: opisthotonus
• Face: risus sardonicus
• Trunk: abdomen boardlike
• Extremities: stiff and extended
• In more severe cases: laryngeal spasm, respiratory
distress, coma and death
 Tetanus
0011 0010 1010 1101 0001 0100 1011

• Excitants: touch, bright lights, noise or

2
mobement of the patient will produce the
spasm
1
4
• Fever usually absent may be high grade
• Sensorium intact
0011 0010 1010 1101 0001 0100 1011

2
1
Risus sardonicus

4
0011 0010 1010 1101 0001 0100 1011

2
1
Trismus or lock jaw

4
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Tetanus
0011 0010 1010 1101 0001 0100 1011

• Diagnosis : clinical

2
• Laboratory tests : normal

1
4
 Tetanus Complications
0011 0010 1010 1101 0001 0100 1011

• Laryngospasm

2
• Fractures
• Hypertension
1
4
• Nosocomial infections
• Pulmonary embolism
• Aspiration
• Death
 Tetanus treatment
0011 0010 1010 1101 0001 0100 1011

a. eradication of C. tetani:

2
• drug of choice: Penicillin G; metronidazole ( equally

1
effective)
b. Neutralization of toxin: antitoxin

4
c. control of seizure and respiration
• muscle relaxants: diazepam
d. palliation and provision of meticulous supportive acre
• quiet, dark, secluded setting
e. prevention of recurrences: immunize
 Tetanus Wound Management
0011 0010 1010 1101 0001 0100 1011
Clean, minor All other
wounds wounds

2
Vaccination History Td TIG Td TIG

1
4
Unknown or <3 doses Yes No Yes Yes

3+ doses No* No No** No

* Yes, if >10 years since last dose

** Yes, if >5 years since last dose
 Tetanus Prognosis
0011 0010 1010 1101 0001 0100 1011

• Favorable prognosis: long incubation

2
period, absence of fever, localized disease

1
• Unfavorable prognosis: short Incubation

4
period ( week or less between injury and
trismus; with 3 days or less between
trismus and onset of generalized tetanic
spasm)
 Tetanus Epidemiology
0011 0010 1010 1101 0001 0100 1011
• Reservoir Soil and intestine of
animals and humans

1
2
• Transmission Contaminated wounds

4
Tissue injury

• Temporal pattern Peak in summer or

wet season

• Communicability Not contagious

0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

• Which of the following WBC is most

2
suggestive of pertussis?
•
1
a. 49,000 with 30% eosinophils

4
c. 25,000 with 80% neutrophils
• b. 8,000 with 80% lymphocytes
d. 40,000 with 80% lymphocytes
0011 0010 1010 1101 0001 0100 1011

• The usual course of Pertussis in an infant is

characterized by

1
2
A. 4-5 days of high grade fever followed by
whooping and coughing

4
B. suddent onset of fever, cough and whooping
C. rhinitis & possibly low grade fever, followed
by gradual worsening of cough and finally
whooping
D. gradual onset of cough, followed by abrupt
onset of fever and cough
 Pertussis
• Highly contagious respiratory infection caused by
0011 0010 1010 1101 0001 0100 1011
Bordetella pertussis

2
• Outbreaks first described in 16th century

1
4
• Bordetella pertussis isolated in 1906

• Estimated 285,000 deaths worldwide in 2001

 Bordetella pertussis
0011 0010 1010 1101 0001 0100 1011

• Fastidious gram-negative bacteria

2
• Antigenic and biologically active components:
– pertussis toxin (PT)

1
4
– filamentous hemagglutinin (FHA)
– agglutinogens
– adenylate cyclase
– pertactin
– tracheal cytotoxin
 Pertussis Pathogenesis
• Attachment to cilia of ciliated epithelial cells in
0011 0010 1010 1101 0001 0100 1011
respiratory tract

2
• Pertussis antigens allow evasion of host defenses

1
(lymphocytosis but impaired chemotaxis)

4
• Local tissue damage in respiratory tract

• Systemic disease may be toxin mediated

 Pertussis Clinical Features
0011 0010 1010 1101 0001 0100 1011

• Incubation period 5-10 days (up to 21 days)

1
2
• Insidious onset, similar to minor upper respiratory

4
infection with nonspecific cough

• Fever usually minimal throughout course

 Pertussis Clinical Features
0011 0010 1010 1101 0001 0100 1011

• Catarrhal stage 1-2 weeks

2
1
• Paroxysmal

4
cough stage 1-6 weeks

• Convalescence Weeks to
months
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Pertussis in Adults
0011 0010 1010 1101 0001 0100 1011

• Accounts for up to 7% of cough illnesses per

2
year

1
4
• Disease often milder than in infants and
children

• Adults often source of infection for children

 Pertussis Complications*
0011 0010 1010 1101 0001 0100 1011
Condition Percent reported
Pneumonia 5.2

2
1
Seizures 0.8
Encephalopathy 0.1

4
Death 0.2
Hospitalization 20
*Cases reported to CDC 1997-2000 (N=28,187)
 Pertussis Complications by Age
Pneumonia Hospitalization
70

0011 60
0010 1010 1101 0001 0100 1011
50
40
Percent

2
30

1
20

4
10
0
<6 m 6-11 m 1-4 y 5-9 y 10-19 y 20+ y
Age group (yrs)

*Cases reported to CDC 1997-2000 (N=28,187)

 Pertussis Epidemiology
0011 0010 1010 1101 0001 0100 1011

2
• Reservoir Human

1
Adolescents and adults

4
• Transmission Respiratory droplets
Airborne rare

• Communicability Maximum in catarrhal stage

Secondary attack rate
up to 80%
 Pertussis
0011 0010 1010 1101 0001 0100 1011

Diagnosis:

1
2
• isolation of B. pertussis in a culture

4
medium is the gold standard
• CBC: leukemoid reaction
 Pertussis
Treatment:
0011 0010 1010 1101 0001 0100 1011

• Effective in aborting/attenuating disease in

2
preparoxysmal stage or catarrhal stage; if after

1
this, may prevent transmission to others but
will not alter course

4
• Erythromycin 40 to 50 mg/kg/day x 14 days
• Chemoprophylaxis: Erythromycin for 14 days
is recommended for all household contacts and
other close contacts, such as those in child
care, irrespective of age and immunization
status
 Whole-Cell Pertussis Vaccine
0011 0010 1010 1101 0001 0100 1011

• Developed in mid-1930s and combined as DTP

2
in mid-1940s

• 70%-90% efficacy after 3 doses

1
4
• Protection for 5-10 years

• Local adverse reactions common

 Acellular Pertussis Vaccine (DTaP)
0011 0010 1010 1101 0001 0100 1011

• Purified "subunit" vaccines

1
2
• Intended to reduce adverse reactions

4
• Licensed for fourth and fifth doses in 1991

• Licensed for full series in 1996

 Pertussis Vaccination of Children Who
Have Recovered From Pertussis
0011 0010 1010 1101 0001 0100 1011

2
• If documented disease, do not need additional doses of

1
pertussis vaccine

4
• Satisfactory documentation of disease:
– recovery of B. pertussis on culture, OR
– typical symptoms and clinical course when epidemiologically
linked to a culture-proven case
 DTP Contraindications
0011 0010 1010 1101 0001 0100 1011

• Serious allergic reaction to vaccine

2
component or following prior dose

1
4
• Encephalopathy occurring within 7 days
after vaccination not due to another
identifiable cause
 DTP Precautions (Warnings)*
0011 0010 1010 1101 0001 0100 1011
• Moderate or severe acute illness

2
• Temperature >105 F (40.5 C) or higher within 48 hours with no

1
other identifiable cause

4
• Collapse or shock-like state (hypotonic-hyporesponsive episode)
within 48 hours

• Persistent, inconsolable crying lasting >3 hours, occurring within

48 hours

• Convulsions with or without fever occurring within 3 days

*may consider use in outbreaks

0011 0010 1010 1101 0001 0100 1011

2
1
4
 • Causative Agent: Ricketsia rickettsii
0011 0010 1010 1101 0001 0100 1011

• Incubation Period: 3-12 days

1
2
• Period of Communicability: Not
communicable from person to person

4
0011 0010 1010 1101 0001 0100 1011

• Mode of Transmission: Wood, dog

2
or rabbit tick

1
4
• Immunity: Rocky Mountain
spotted fever vaccine
 • Seen most often during spring &
0011 0010 1010 1101 0001 0100 1011

early summer

1
2
• Signs & Symptoms:

4
• Reddened area develops on the site
of tick bite
• Typical rash (2-8 days)
0011 0010 1010 1101 0001 0100 1011
• Persistent headache

2
• High fever (104 degrees
Fahrenheit)
1
4
• Mental confusion
 • Rash begins as reddened macules then
0011 0010 1010 1101 0001 0100 1011

changing to petechiae

2
• Begins on the wrists & ankles, spreads
up the arms, legs & trunk
1
4
• Cover the palm of the hand & soles of
the feet
 Complications:
0011 0010 1010 1101 0001 0100 1011

• It can affect the central nervous system,

2
like seizures & stiff neck
• Cardiac & pulmonary symptoms –
1
4
pneumonia & heart failure
• Treatment: Tetracycline (7-10 days)
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Poliomyelitis
• First
0011 0010 1010 described by Michael
1101 0001 0100 1011 Underwood in 1789

• First outbreak described in U.S. in 1843

1
2
• 21,000 paralytic cases reported in the United States

4
in 1952

• Global eradication in near future

 Poliovirus
• Enterovirus (RNA)
0011 0010 1010 1101 0001 0100 1011

• Three serotypes: 1, 2, 3

1
2
• Minimal heterotypic immunity between serotypes

4
• Rapidly inactivated by heat, formaldehyde,
chlorine, ultraviolet light
 Poliomyelitis Pathogenesis
• Entry
0011 0010 1010 into
1101 mouth
0001 0100 1011

• Replication in pharynx, GI tract, local lymphatics

1
2
• Hematologic spread to lymphatics and central nervous

4
system

• Viral spread along nerve fibers

• Destruction of motor neurons

 Outcomes of poliovirus infection
0011 0010 1010
A s y m1101
p to m0001
a tic 0100 M in1011
o r n o n -C N S illn e s s
A s e p tic m e n ig itis P a ra ly tic

2
1
4
0 20 40 60 80 100
Percent
0011 0010 1010 1101 0001 0100 1011

2
1
Paralytic polio

4
 Poliovirus Epidemiology
0011 0010 1010 1101 0001 0100 1011

• Reservoir Human

1
2
• Transmission Fecal-oral
Oral-oral possible

4
• Communicability 7-10 days before onset
Virus present in stool
3-6 weeks
 Polio Vaccination of Adults
0011 0010 1010 1101 0001 0100 1011

• Routine vaccination of U.S. residents >18

1
2
years of age not necessary or recommended

4
• May consider vaccination of travelers to
polio-endemic countries and selected
laboratory workers
 Polio Vaccination of
Unvaccinated Adults
0011 0010 1010 1101 0001 0100 1011

• IPV

1
2
• Use standard IPV schedule if possible (0, 1-2

4
months, 6-12 months)

• May separate doses by 4 weeks if accelerated

schedule needed
 Polio Vaccination of Previously
Vaccinated Adults
0011 0010 1010 1101 0001 0100 1011

• Previously complete series

2
– administer one dose of IPV

1
4
• Incomplete series
– administer remaining doses in series
– no need to restart series
 Polio Vaccine Adverse Reactions
0011 0010 1010 1101 0001 0100 1011

• Rare local reactions (IPV)

1
2
• No serious reactions to IPV have been

4
documented

• Paralytic poliomyelitis (OPV)

 Vaccine-Associated Paralytic Polio
• Increased risk in persons >18 years
0011 0010 1010 1101 0001 0100 1011

• Increased risk in persons with immunodeficiency

1
2
• No procedure available for identifying persons at risk of paralytic
disease

4
• 5-10 cases per year with exclusive use of OPV

• Most cases in healthy children and their household contacts

0011 0010 1010 1101 0001 0100 1011

2
1
4
 Measles
0011 0010 1010 1101 0001 0100 1011

• Highly contagious viral illness

1
2
• First described in 7th century

4
• Near universal infection of childhood in
prevaccination era

• Frequent and often fatal in developing areas

 Measles Virus
• Paramyxovirus (RNA)
0011 0010 1010 1101 0001 0100 1011

2
• Hemagglutinin important surface antigen

1
4
• One antigenic type

• Rapidly inactivated by heat and light

 Measles Pathogenesis
0011 0010 1010 1101 0001 0100 1011

• Respiratory transmission of virus

1
2
• Replication in nasopharynx and regional lymph

4
nodes

• Primary viremia 2-3 days after exposure

• Secondary viremia 5-7 days after exposure with

spread to tissues
 Measles Clinical Features
0011 0010 1010 1101 0001 0100 1011

• Incubation period 10-12 days

Prodrome

1
2
• Stepwise increase in fever to 103 F or

4
higher
• Cough, coryza, conjunctivitis
• Koplik spots
 Measles Clinical Features
Rash
0011 0010 1010 1101 0001 0100 1011

• 2-4 days after prodrome,

2
14 days after exposure

1
• Maculopapular, becomes
confluent

4
• Begins on face and head
• Persists 5-6 days
• Fades in order of
appearance
0011 0010 1010 1101 0001 0100 1011

2
Enanthem:

Koplik’s Spots

1
4
•Appear 1-2
days after
onset of
symptoms
0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

• Missing 8

2
1
4
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Slide 9

0011 0010 1010 1101 0001 0100 1011

1
2
4
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Measles Complications
0011 0010 1010 1101 0001 0100 1011
Percent reported
Condition 8

2
Diarrhea 7

1
Otitis media 6

4
Pneumonia
0.1
Encephalitis
Death 0.2
Hospitalization 18

Based on 1985-1992 surveillance data

0011 0010 1010 1101 0001 0100 1011

1
2
4
Measles pneumonia
 Measles Complications by Age Group

0011 0010
30 1010Pneumonia
1101 0001Hospitalization
0100 1011
25

2
20
Percent

1
15

10

4
5

0
<5 5-19 20+
Age group (yrs)
 Measles Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• Isolation of measles virus from a clinical specimen

1
2
(e.g., nasopharynx, urine)

4
• Significant rise in measles IgG by any standard
serologic assay (e.g., EIA, HA)

• Positive serologic test for measles IgM antibody

 Measles Epidemiology
0011 0010 1010 1101 0001 0100 1011

• Reservoir Human

1
2
• Transmission Respiratory
Airborne

4
• Temporal pattern Peak in late winter and spring

• Communicability 4 days before to 4 days after

rash onset
 Measles Clinical Case Definition
0011 0010 1010 1101 0001 0100 1011

• Generalized rash lasting >3 days, and

2
1
• Temperature >38.3 C (101 F), and

4
• Cough or coryza or conjunctivitis
 Measles Vaccines
0011 0010 1010 1101 0001 0100 1011
1963 Live attenuated and killed vaccines
1965 Live further attenuated vaccine

1
2
1967 Killed vaccine withdrawn

4
1968 Live further attenuated vaccine
(Edmonston-Enders strain)
1971 Licensure of combined measles-
mumps-rubella vaccine
1989 Two dose schedule
 Measles Vaccine
• Composition
0011 0010 Live1011
1010 1101 0001 0100 virus

• Efficacy 95% (range, 90%-98%)

1
2
• Duration of

4
Immunity Lifelong

• Schedule 2 doses

• Should be administered with mumps and rubella as MMR

 MMR vaccination
• First dose of MMR at 12-15 months
0011 0010 1010 1101 0001 0100 1011

2
• Second dose of MMR at 4-6 years

1
4
• Second dose may be given any time >4 weeks
after the first dose
 Measles Mumps Rubella Vaccine
0011 0010 1010 1101 0001 0100 1011

• 12 months is the recommended and

2
minimum age

1
4
• MMR given before 12 months should not
be counted as a valid dose

• Revaccinate at >12 months of age

 Second Dose of Measles Vaccine
0011 0010 1010 1101 0001 0100 1011

• Intended to produce measles immunity in

2
persons who failed to respond to the first
dose (primary vaccine failure)
1
4
• May boost antibody titers in some persons
 ACIP Recommendations
0011 0010 1010 1101 0001 0100 1011

• All states ensure that 2 doses of MMR

2
required for school entry

1
4
• All children in kindergarten through grade
12 have 2 doses of MMR by 2001
 Measles Prevention
0011 0010 1010 1101 0001 0100 1011

• Active immunization with live,

2
attenuated measles vaccine
– DOH, EPI : 9 months of age

1
4
– Measles epidemic: early 2 dose measles
• 6 months: 1 dose; 12 months : booster dose
st

– If exposed ( unimmunized host) : within

3 days of exposure
 Measles prevention
0011 0010 1010 1101 0001 0100 1011

• Passive immunization with

2
immunoglobulin
a. Susceptible child with definite
1
4
exposure to measles
given within 6 days of exposure
– Dose: 0.25 ml/kg ( normal child)
0.5 ml /kg ( immunocompromised)
 Measles prevention
0011 0010 1010 1101 0001 0100 1011

• Passive immunization with

2
immunoglobulin

1
b. Children with contraindication to

4
vaccination when there is an
outbreak of measles
dose: 0.5 ml/kg ( max. 15 ml)
 Measles prevention
0011 0010 1010 1101 0001 0100 1011

• Passive immunization with

2
immunoglobulin

1
c. Infants younger than 5 months of

4
age whose mothers develop measles
also should receive IG
 Measles Immunity
0011 0010 1010 1101 0001 0100 1011

• Born before 1957

1
2
• Documentation of physician-diagnosed

4
measles

• Serologic evidence of immunity

• Documentation of receipt of measles-

containing vaccine
 MMR Adverse Reactions
• Fever
0011 0010 1010 1101 0001 0100 1011
5%-15%
• Rash 5%

1
2
• Joint symptoms 25%
• Thrombocytopenia

4
<1/30,000 doses
• Parotitis rare
• Deafness rare
• Encephalopathy <1/1,000,000 doses
 MMR Vaccine and Autism
0011 0010 1010 1101 0001 0100 1011

• Measles vaccine connection first suggested

2
by British gastroenterologist

1
• Diagnosis of autism often made in second

4
year of life

• Multiple studies have shown no association

 MMR Vaccine
Contraindications and Precautions
0011 0010 1010 1101 0001 0100 1011

• Severe allergic reaction to vaccine

2
1
component or following prior dose

4
• Pregnancy
• Immunosuppression
• Moderate or severe acute illness
• Recent blood product
 Measles Vaccine and HIV Infection
0011 0010 1010 1101 0001 0100 1011
• MMR recommended for persons with
asymptomatic and mildly symptomatic HIV

2
infection

1
4
• NOT recommended for those with evidence of
severe immuno- suppression

• Prevaccination HIV testing not recommended

 PPD and Measles Vaccine
0011 0010 1010 1101 0001 0100 1011

• Apply PPD at same visit as MMR

1
2
• Delay PPD >4 weeks if MMR given first

4
• Apply PPD first - give MMR when skin
test read
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Mumps
0011 0010 1010 1101 0001 0100 1011

• Acute viral illness

1
2
• Parotitis and orchitis described by Hippocrates in
5th century B.C.

4
• Viral etiology described by Johnson and
Goodpasture in 1934

• Frequent cause of outbreaks among military

personnel in prevaccine era
 Mumps Virus
0011 0010 1010 1101 0001 0100 1011

• Paramyxovirus

1
2
• RNA virus

4
• One antigenic type

• Rapidly inactivated by chemical agents, heat

and ultraviolet light
 Mumps Pathogenesis
0011 0010 1010 1101 0001 0100 1011

• Respiratory transmission of virus

1
2
• Replication in nasopharynx and regional lymph

4
nodes

• Viremia 12-25 days after exposure with spread to

tissues

• Multiple tissues infected during viremia

 Mumps Clinical Features
0011 • Incubation
0010 1010 1101period 14-18
0001 0100 days
1011

• Nonspecific prodrome of low-grade fever, headache,

2
malaise, myalgias

• Parotitis in 30%-40%
1
4
• Up to 20% of infections asymptomatic

• May present as lower respiratory illness, particularly in

preschool-aged children
 Mumps Complications
0011 0010 1010 1101 0001 0100 1011
CNS involvement 15% of clinical cases

2
Orchitis 20%-50% in post-

1
pubertal males

4
Pancreatitis 2%-5%

Deafness 1/20,000

Death 1-3/10,000
 Mumps Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• Isolation of mumps virus

• Serologic testing
1
2
4
– positive IgM antibody
– significant increase in IgG antibody between
acute and convalescent specimens
 Mumps Epidemiology
0011 0010 1010 1101 0001 0100 1011

• Reservoir Human

1
2
• Transmission Respiratory drop nuclei
Subclinical infections

4
may transmit

• Temporal pattern Peak in late winter and spring

• Communicability Three days before to four

days after onset of active
disease
 Mumps Clinical Case Definition
0011 0010 1010 1101 0001 0100 1011

• Acute onset of

2
unilateral or bilateral

1
tender, self-limited

4
swelling of the parotid
or other salivary gland
lasting >2 days
without other apparent
cause.
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Mumps

0011 0010 1010 1101 0001 0100 1011

2
1
4
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Rubella
• From Latin meaning "little red"
0011 0010 1010 1101 0001 0100 1011

• Discovered in 18th century - thought to be variant

1
2
of measles

4
• First described as distinct clinical entity in
German literature

• Congenital rubella syndrome described by Gregg

in 1941
 Rubella Virus
0011 0010 1010 1101 0001 0100 1011

• Togavirus

1
2
• RNA virus

4
• One antigenic type

• Rapidly inactivated by chemical agents,

low pH, heat and ultraviolet light
 Rubella Pathogenesis
0011 0010 1010 1101 0001 0100 1011

• Respiratory transmission of virus

1
2
• Replication in nasopharynx and regional lymph nodes

4
• Viremia 5-7 days after exposure with spread to tissues

• Placenta and fetus infected during viremia

 Rubella Clinical Features
• Incubation period 14 days (range 12-23 days)
0011 0010 1010 1101 0001 0100 1011

2
• Prodrome of low grade fever

1
4
• Lymphadenopathy in second week

• Maculopapular rash 14-17 days after exposure

0011 0010 1010 1101 0001 0100 1011

2
1
Forchheimer spots
4
 Discreet
maculopapular
0011 0010 rashes
1010 1101 0001 0100 1011

2
1
4
 Rubella Complications
Arthralgia or arthritis
0011 0010 1010 1101 0001 0100 1011

children rare

2
adult female up to 70%

1
4
Thrombocytopenic purpura 1/3000 cases
Encephalitis
Neuritis 1/6,000 cases
Orchitis rare
rare
 Congenital Rubella Syndrome
0011 0010 1010 1101 0001 0100 1011

• Infection may affect all organs

1
2
• May lead to fetal death or premature delivery

4
• Severity of damage to fetus depends on
gestational age

• Up to 85% of infants affected if infected during

first trimester
 Congenital Rubella Syndrome
0011 0010 1010 1101 0001 0100 1011

• Deafness

2
• Cataracts

1
• Heart defects

4
• Microcephaly
• Mental retardation
• Bone alterations
• Liver and spleen
damage
 Rubella Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• Isolation of rubella virus from clinical specimen

2
(e.g., nasopharynx, urine)

1
4
• Significant rise in rubella IgG by any standard
serologic assay (e.g., enzyme immunoassay)

• Positive serologic test for rubella IgM antibody

 Rubella Epidemiology
0011 0010 1010 1101 0001 0100 1011
• Reservoir Human

• Transmission Respiratory

2
Subclinical cases may

1
transmit

4
• Temporal pattern Peak in late winter and spring

• Communicability 7 days before to 5-7 days

after rash onset
Infants with CRS may shed
virus for a year or more
 Rubella Case Definition
0011 0010 1010 1101 0001 0100 1011

• Acute onset of generalized maculopapular

2
rash, and

1
4
• Temperature of >37.2 C (>99 F), if
measured, and

• Arthralgia or arthritis, or lymph-

adenopathy, or conjunctivitis
 Rubella Vaccine Arthropathy
• Acute joint symptoms in about 25% of susceptible
0011 0010 1010 1101 0001 0100 1011
adult women

1
2
• Frank arthritis occurs in about 10%

4
• Rare reports of chronic or persistent symptoms

• Population-based studies have not confirmed

association
0011 0010 1010 1101 0001 0100 1011

2
1
4
 Varicella
0011 0010 1010 1101 0001 0100 1011
• Acute viral illness

1
2
• Zoster described in premedieval times

4
• Varicella not differentiated from smallpox until end
of 19th century

• Infectious nature demonstrated in 1875

 Varicella Zoster Virus
0011 0010 1010 1101 0001 0100 1011

• Herpes virus (DNA)

1
2
• Primary infection results in varicella
(chickenpox)

4
• Recurrent infection results in herpes zoster
(shingles)

• Short survival in environment

 Varicella Pathogenesis
0011 0010 1010 1101 0001 0100 1011

• Respiratory transmission of virus

1
2
• Replication in nasopharynx and regional lymph

4
nodes

• Repeated episodes of viremia

• Multiple tissues, including sensory ganglia,

infected during viremia
 Varicella Clinical Features
0011 0010 1010 1101 0001 0100 1011

• Incubation period 14-16 days (range 10-21 days)

1
2
• Mild prodrome for 1-2 days

4
• Generally appear first on head; most concentrated
on trunk

• Successive crops (2-4 days) of pruritic vesicles

 Varicella
0011 0010 1010 1101 0001 0100 1011

• Generally, a mild infection

2
• In normal children, generalized
vesicular rash with very few
1
4
systemic effects
• Virtually, NO PRODROME
• The first manifestation is the
EXANTHEM
 Varicella
Hallmark of the rash :
• 1010 1101 0001 0100 1011
0011 0010
vesicular lesions
• Maculesmaculopapular
vesicular crusting scab

2
formation

1
• Intensely pruritic

4
• Lesions often appear first
on the scalp, face or trunk
• At any point in time, lesions
in various stages are
observed
0011 0010 1010 1101 0001 0100 1011

2
1
Tear-dropped shape lesion
4
 Varicella
0011 0010 1010 1101 0001 0100 1011

• Period of communicability:

2
– Transmission: airborne, contact

1
– Most contagious 1-2 days before and

4
shortly after onset of rash;
– Airborne and contact precautions :
minimum of five days after onset of rash
and as long as the rash remains vesicular
 Herpes Zoster
0011 0010 1010 1101 0001 0100 1011

• Reactivation of varicella zoster virus

1
2
• Associated with:

4
– aging
– immunosuppression
– intrauterine exposure
– varicella at <18 month of age
 Varicella Complications
0011 0010 1010 1101 0001 0100 1011

• Bacterial infection of lesions

2
• CNS manifestations

1
4
• Pneumonia (rare in children)

• Hospitalization ~3 per 1000

cases

• Death ~ 1 per 60,000 cases

 Groups at Increased Risk of
Complications of Varicella
0011 0010 1010 1101 0001 0100 1011

• Normal adults

1
2
• Immunocompromised persons

4
• Newborns with maternal rash onset within
5 days before to 48 hours after delivery
 Varicella Fatality Rate in Healthy
Persons
0011 0010
30 1010 1101 0001 0100 1011
25

20

2
Rate

15

1
10

4
5

0
<1 1-14 15-19 20-29 30+
Age group (yrs)

*Deaths per 100,000 cases

 Congenital Varicella Syndrome
0011 0010 1010 1101 0001 0100 1011
• Results from maternal infection
during pregnancy

2
1
• Period of risk may extend
through first 20 weeks of

4
pregnancy

• Atrophy of extremity with skin

scarring, low birth weight, eye
and neurologic abnormalities

• Risk appears to be small (<2%)

 Varicella Laboratory Diagnosis
0011 0010 1010 1101 0001 0100 1011

• Isolation of varicella virus from clinical

specimen

1
2
• Rapid varicella virus identification using direct

4
fluorescent antibody (DFA) testing

• Significant rise in varicella IgG by any standard

serologic assay (e.g., enzyme immunoassay)
 Varicella Epidemiology
0011 0010 1010 1101 0001 0100 1011
• Reservoir Human

2
• Transmission Airborne droplet

1
Direct contact with lesions

4
• Temporal pattern Peak in winter and early
spring (U.S.)

• Communicability 1-2 days before to 4-5

days after onset of rash
May be longer in
immunocompromised
 Breakthrough Infection
• Immunity appears to be long-lasting for most
0011 0010 1010 1101 0001 0100 1011
recipients

1
2
• Breakthrough disease much milder than in
unvaccinated persons

4
• No consistent evidence that risk of breakthrough
infection increases with time since vaccination
 Varicella Vaccine Recommendations
Children
0011 0010 1010 1101 0001 0100 1011

• Routine vaccination at 12 months of age

1
2
• Recommended for all susceptible children by

4
the 13th birthday
 Varicella Vaccine Recommendations
Adolescents and Adults
0011 0010 1010 1101 0001 0100 1011

• Persons >13 years of age without history of varicella

1
2
• Two doses separated by 4 - 8 weeks

4
• Up to 90% of adults immune

• Serologic testing may be cost effective

 Varicella Vaccine Recommendations
Adolescents and Adults
0011 0010 1010 1101 0001 0100 1011

• Susceptible persons at high risk of exposure or

2
severe illness

1
4
– Teachers of young children
– Institutional settings
– Military
– Women of childbearing age
– International travelers
 Varicella Vaccine Recommendations
Adolescents and Adults
0011 0010 1010 1101 0001 0100 1011

• Susceptible persons likely to expose

2
persons at high-risk for severe illness

1
4
– Healthcare workers
– Family members of immuno-
compromised persons
 Varicella Vaccine
Postexposure Prophylaxis
0011 0010 1010 1101 0001 0100 1011

• Varicella vaccine is recommended for use in

1
2
susceptible person after exposure to varicella
– 70%-100% effective if given within 72 hours of

4
exposure
– not effective if >5 days but will produce immunity
if not infected
 Varicella Vaccine
Use in Immunocompromised Persons
0011 0010 1010 1101 0001 0100 1011
• Most immunocompromised persons should not be
vaccinated

2
1
• Vaccinate persons with isolated humoral

4
immunodeficiency

• Consider varicella vaccination for asymptomatic

HIV-infected children with CD4% >25% (CDC class
A1 and N1)
 Varicella Zoster Immune Globulin (VZIG)
0011 0010 1010 1101 0001 0100 1011
• May modify or prevent disease if given <96 hours after
exposure

1
2
• Indications

4
– immunocompromised persons
– newborn of mothers with onset 5 days before to 2 days after birth
– premature infants with postnatal exposure
– susceptible adults and pregnant women
 Varicella Antiviral Therapy
0011 0010 1010 1101 0001 0100 1011
• Not recommended for routine use among otherwise
healthy infants and children with varicella

2
• Consider for persons age >13 years

1
• Consider for persons with chronic cutaneous or
pulmonary disorders, long-term salicylate therapy, or

4
steroid therapy
• IV in immunocompromised children and adults with
viral-mediated complications
• Not recommended for post-exposure prophylaxis

2003 AAP Red Book