VIRAL INFECTIONS

TOPICS
Viral exanthems
Measles
Roseola
Varicella
Rubella
Parvovirus B19

Mumps

Hepatitis (A, B, C, D, E)

Dengue k
 Measles
RUBEOLA OR MORBILLIVIRUS
 Measles
• Etiology:
Measles virus
•family Paramyxovirus
•genus Morbillivirus
•has an outer envelope composed of M-protein,
H-protein, F-protein, and internal core is RNA.
Measles
• an acute highly contagious viral
disease caused by measles virus. It
is characterized by fever, URT
catarrhal inflamation, koplik’s
spots and maculopapular rash.
 Measles
• Epidemiology:
• Source of infection
The patients are the only source of infection.
• Routes of transmission
• air-borne
• direct contact with infectious droplet
• transplacentally acquired immunity is protective for 4-6
months; disappear at variable rates
• Susceptibility of population
All age person is susceptible; 90% of contact people
acquire the disease.
The permanent immunity acquire after disease.
• Period of Communicability
– 1-2 days before the onset of symptoms (3-5
days before the rash) to 4-5 days after the
rash
– Very contagious. 90% of susceptible contacts
acquire disease
• Incubation Period: 8-12 days
PATHOGENESIS AND
PATHOLOGY
measles virus
↓respiratory tract
epithelial cells(multiply)
↓lymphoid tissue
blood (first viremia)
MPS(multiply)
↓
blood (second viremia)
↓
general toxic symptoms
 Measles
• Prodrome:
* 3 – 5 days
* Fever
* Colds, Cough,
Conjunctivitis
* Koplik spot
(pathognomonic
enanthem)
 CLINICAL
MANIFESTATIONS
• Typical type
• prodromal phase ( 3~4 days )
• Fever;
• Catarrhal inflammation of URT;
• Koplik’s spots;
• Eruptive phase
 Measles
• Rash
1st 24 hrs: Faint macules behind ears, along the hairline;
become confluent maculopapular as it spreads to
face, neck, upper arms and chest.

2nd 24 hrs: Spreads over back, abdomen, entire arms / thighs

3rd –4th days: Rash reaches legs and feet-→ Fading from head
to feet----→ Fine branny desquamation and
brownish discoloration

* Severity of disease is directly related to extent and

confluence of rash
• Fever:
* Temperature rises as rash appears
* Fever and symptoms subside within 2 days
once rashes are on legs and feet
* If persistent after D3-4 of exanthem, may
indicate complication

• Convalescent stage
– brown staining.
– fine branny desquamation.
– course:10-14 days
Measles
 Measles
• Other Manifestations:
* Anorexia
* Lymphadenopathy
* Diarrhea and vomiting
* Abdominal pain
* Slight splenomagaly
Modified Measles

• Occurs in partially immune hosts

* Partial protection from maternal Ab
* Partial vaccine failure
• Shorten prodrome ; cough and coryza are minimal
• Rash w/ same progression pattern w/o confluence
• Koplik spots few and transient; may not occur
• Diagnosis not made in the absence of cough
 Atypical Measles
* Associated with killed measles vaccine (until 1967)

* Less severe cases may follow live attenuated

measles vaccine

* Abrupt onset of high fever, headache, myalgia, dry

non- productive cough, vomiting,
pruritic chest pain and weakness

* Coryza and conjunctivitis not prominent

* Koplik Spots rare
 Atypical Measles
* 2 – 5 days later, maculopapules on palm, wrist,
soles and ankles--->centripetal direction---
>vesicular (w/o scab)---> purpuric
orhemorrhagic
* Lobular or segmental pneumonia with pleural
effusion is common

* Other Findings:
- marked hepatomegaly
- marked hyperesthesia
- numbness & paresthesia
• Diagnosis:
* Clinical / Epidemiological basis
* Definite diagnosis:
Measles IgM
Increase in measles IgG in
paired sera
Viral isolation (urine, blood,
NP secretions)
 Respiratory Complications
• Otitis Media
• Laryngitis, Tracheitis, Bronchitis
• Interstitial pneumonia
• Bronchopneumonia
• Most common complication and leading cause of death
• Due to secondary bacterial infection
(pneumococcus, streptococcus, staphylococcus, Hib)
• Exacerbation of an existing Tuberculous process
• Temporary loss of hypersensitivity reaction to tuberculin for 4 –
6 weeks
• Neurologic Complications:
* More common than in any other exanthems
* Encephalitis : 1 – 2 / 1000 cases
* Sub acute sclerosing panencephalitis
- Rare, degenerative CNS diseases
- Persistent measles virus infection
- Infections before 18 months increases risk
- Boys > Girls
- Insidious; acute, sub-acute, chronic progressive
- Subtle changes in behavior, deterioration of school
work ----> bizarre behavior---> frank dementia
- Massive, repetitive, symmetrical myoclonic jerks
- True seizures--->progresses to stupor and coma
- High measles antibody titers (HI&CF) in sera and
CSF
- Occur 10.8 years after original infection
* Others: Guillain – Barre Syndrome, Hemiplegia, Cerebral
thrombophlebitis, Retrobulbar neuritis
• Other Complications:
Myocarditis
Diarrhea with dehydration
Idiopathic thrombocytopenia
Hepatitis
Appendicitis
 Measles
• Management:
* Supportive (antipyretics, fluids and electrolytes)

* Appropriate antibiotics for bronchopneumonia

and otitis media

* Oral vitamin A
6 months to 1 year old: 100,000 “u”
1 year old and older: 200,000 “u”
dose repeated the next day and at 4 weeks if
with ophthalmologic evidence of
vitamin A deficiency
 Measles
* Active Immunization:
* Post-exposure immunization
- Measles vaccine if given within 72 hrs.
after exposure, may provide
protection in some cases
* Pre-exposure immunization
- 1st dose: at age 6 months
- 2nd dose: 6 – 9 months after 1st dose, as
monovalent vaccine or MMR
- 3rd dose: monovalent vaccine or MMR at 4
– 6 y/o or 11-12 y/o
Passive Immunization:
• Immune globulin can be given to prevent or
modify measles in a susceptible person
within 6 days of exposure
• Dose: 0.25 ml / K IM
• Indications:
a) Susceptible household
contacts especially < 1 year old
b) Pregnant women
c) Immunocompromised children
• Give measles vaccine 5 months after IG
 DIFFERENTIAL
DIAGNOSIS
• Rubella (German measles)
• Roseola infantum (infant subitum,
exanthem subitum)
• Drug rashes
GERMAN MEASLES
 Postnatal rubella
(German Measles)

● Etiology:
Rubella virus

Togaviridae family
 RUBELLA
● derived from the Latin, meaning little red
● Also called as three-day measles/German measles
● "3-day measles"
● that starts initially on the face and neck
● spreads centrifugally to the trunk and extremities within 24 hours.
● begins to fade on the face on the second day
● disappears throughout the body by the end of the third day.
● also known as German measles because the disease was
first described by German physicians, Friedrich Hoffmann, in
the mid-eighteenth century.
● generally mild disease
● Congenital rubella syndrome (CRS) described by Gregg in
1941
 EPIDEMIOLOGICAL
DETERMINANTS
● Agent factors
● Host factors
● Environmental factors
● Causative agent: Rubella
virus
● ssRNA Virus of the
Togaviridae Family
● genus Rubivirus
● One antigenic type
● Virus carry hemagglutinin
● Virus multiply in the
cytoplasm of infected cell
● At 4°C, virus is relatively
stable for 24 hours.
 AGENT FACTORS cont.

B- Source of C- Period of
infection communicability
● CASES ● It probably extends from a
● Subclinical (2/3 of week before symptoms to
infections) about a week after rash
● Clinical
appears.
● Congenital from infected
pregnant women to fetus. ● Infectivity is greatest when
the rash is erupting.
● There is no known carrier
state.
 HOST FACTORS
A- Age B- Immunity
● Disease of childhood 3-10 yrs
age group. ● One attack results in life long
● Following widespread immunity.
immunization campaigns ● Infants of immune mothers are
persons older than 15 yrs protected for 4-6 months.
account for 70% cases in
developed countries.
Immunity - Rubella
◆ Antibodies appear in serum
as rash fades and antibody
titers raise
◆ Rapid raise in 1 – 3 weeks
◆ Rash in association with
detection of IgM indicates
recent infection.
◆ IgG antibodies persist for life
 ENVIRONMENTAL FACTORS

● Disease usually occurs in seasonal pattern

● Person to person- via respiratory route:-
● Droplet from nose & throat
● Droplet nuclei (aerosols)
● Maintain in human population by chain
transmission.
● Acquired during pregnancy- vertical
transmission:-
● Virus can enter via the Placenta & infect the
foetus in utero (Congenital Rubella
Syndrome).
● Period of Communicability
● Few days before up to 5-7 days after the rash

● Incubation period
● 14-21 days
 Rubella Pathogenesis

● Respiratory transmission of virus

● Replication in nasopharynx and regional lymph nodes

● Viremia 5-7 days after exposure with spread to tissues

● Placenta and fetus infected via hematogenous spread

during viremia
Rubella Virus Developed in the nasopharynx

Respiratory Lymph Placenta or

Tract Skin Nodes Joints Fetus

• Cough • Mild
• Minor • Rashes arthralgia
sore • Lesions • arthritis • Placentitis
throat • Fetal
Damage
• Lymphadenopathy
 Transmitted Infects cells in
via respiratory the upper
Rubella virus droplets respiratory
tract

Virus
Virus replicates in Extends in the multiplies
the nasopharynx regional lymph
nodes

Infection is Virus can

established in the be found in
skin and other Forchheimer’s Rashes the skin,
tissues including Spot may develops, blood and
the respiratory develop cough etc. respiratory
tract tract
 Rubella Clinical Features

● Incubation period 18 days (range 14-21 days)

● Prodrome of low grade fever

● Lymphadenopathy in second week

● Maculopapular rash 14-17 days after exposure

 SIGNS AND SYMPTOMS
● RASH
● the primary symptom of rubella virus infection is the appearance of a
rash (exanthema) on the face which spreads to the trunk and limbs
and usually fades after three days with no staining or peeling of the
skin.The skin manifestations are called "blueberry muffin lesions."
● LYMPH NODE
● Tender lymphadenopathy (particularly posterior auricular and
suboccipital lymph nodes) persist for up to a week.
● TEMPERATURE
● Fever rarely rises above 38 oC(100.4 oF)

47
● Eye pain on lateral and upward eye movement (a
particularly troublesome complaint)
● Conjunctivitis
● Sore throat
● Headache
● General body aches
● Low-grade fever
● Chills
● Anorexia
● Nausea
● Forchheimer sign
Other manifestations & complications

◆ May produce transient

Arthritis, particular in
women.
◆ Serious complications
are-
◆ Thrombocytopenia
Purpura
◆ Encephalitis
Rubella Rashes
Rubella Rashes
Posterior auricular tender lymphadenopathy
Forchheimer’s Spot

●Fleeting enanthema
●Pinpoint or larger
petechiae that usually occur
on the soft palate in 20% of
patients
●Similar spots can be seen
in measles and scarlet
fever.
Systemic events of Rubella Infection

54
Main Clinical Events During Pregnancy

The clinical events occurring in the neonatal

age is more important and divided into two
major groups-
◆ 1 Congenital Rubella
◆ 2 Post Natal Rubella
● Occurs during the first trimester of
pregnancy.
● Affects the development of the
fetus.
● may lead to several birth defects.
● Infection may affect all organs.
● May lead to fetal death or
premature delivery.
● Severity of damage to fetus
depends gestational age.
● Infants: virus is isolated from urine
and feces.
 Rubella infection – At various trimesters

● Ist trimester infections

● lead to abnormalities in 85 % of cases. and greater damage to
organs
● 2nd trimester infections
● lead to defects in 16 %
● > 20 weeks of pregnancy
● fetal defects are uncommon
● Can also lead to fetal deaths, and spontaneous abortion.
● Intrauterine infections lead to viral excretion in various
secretion in newborn up to 12-18 months.
Rubella infection & Chance of CRS

● 0–28 days before conception - 43% chance

● 0–12 weeks after conception - 51% chance
● 13–26 weeks after conception - 23% chance
● Infants are not generally affected if rubella is
contracted during the third trimester
Classical Triad of congenital Rubella

◆ Cataract
◆ Cardiac abnormalities
◆ Deafness
Salt and pepper retinopathy
 Post natal Rubella
◆ Occurs in Neonates and
Childhood
◆ Adult infection occurs through
mucosa of the upper respiratory
tract spread to cervical lymph
nodes
◆ Viremia develops after 7 – 9
day
◆ Lasts for 13 – 15 days
◆ Leads to development of
antibodies
◆ The appearance of antibodies
coincides the appearance of
suggestive immulogic basis for
the rash
◆ In 20 – 50 % cases of primary
infections are subclinical.
http://classconnection.s3.amazonaws.com/6
47/flashcards/1625647/jpg/blueberry_muffin
_baby1346506291609.jpg
Diagnosis of Rubella in Adults

◆ ClinicalDiagnosis is unreliable
◆ Many viral infections mimic Rubella

◆ Specific diagnosis of infection with-

1 Isolation of virus
2 Evidence of seroconversion
Isolation and Identification of virus
◆ Nasopharyngeal or
throat swabs taken 6
days prior or after
appearance of rash is
a good source of
Rubella virus
◆ Using cell cultured in
shell vial antigens can
be detected by
Immunofluresecente
methods
● Rubella is a mild self limited illness.
● No specific treatment or Antiviral treatment is
indicated.
● Isolation and quarantine
● Increase fluid intake
● Encourage the patient to rest
● Good ventilation
● Encourage the patient to drink either lemon or
orange juice
● Provide health teaching about Rubella (cause,
immunizations)
● Rubella vaccine is given to
children at 15 months of age as
a part of the MMR (measles-
mumps-rubella) immunization.
● The vaccine is live and
attenuated and confers lifelong
immunity.
● Given to children 12 and 15
months and again between 3-6
years of age
 Treatment, Prevention, Control
in childbearing age women

◆ No specific treatment
is available
◆ CRS can be prevented by
effective immunization of the
young children and teenage
girls, remain the best option to
prevent Congenital Rubella
Syndrome.
◆ The component of Rubella in
MMR vaccine protects the
vaccinated
 Roseola Infantum
(exanthem subitum, or sixth disease )
• Roseola is a mild febrile, exanthematous
illness occurring almost exclusively during
infancy

• More than 95% of roseola cases occur in

children younger than 3 yr, with a peak at
6-15 mo of age

• Transplacental antibodies likely protect

most infants until 6 mo of age.

• Infants with classic roseola exhibit a unique

constellation of findings displayed over a
short period of time
 Etiology
● Human herpesvirus 6 (HHV-6) is the etiologic agent for most
cases of and human herpesvirus 7 (HHV-7) is in some cases
of roseola
● HHV-6 and HHV-7 belong to the β-herpesvirus subfamily of
herpesviruses
● The principal target cells for HHV-6 and HHV-7 infection in
vivo are CD4 T cells
● HHV-6 can also infect other cells, including : CD8
(suppressor) T cells, natural killer T cells, δγ T cells, glial
cells, epithelial cells, monocytes, megakaryocytes, and
endothelial cells

●
 Epidemiology
● Primary HHV-6 infection occurs early in life
● More than 90% of newborn infants are HHV-6
seropositive, reflecting transplacental transfer of
maternal antibodies.
● By 4-6 mo of age, the prevalence drops
significantly (0-60%).
● By 12 mo of age, 60-90% of children possess
antibodies to HHV-6,
 Epidemiology (cont.)
● Peak acquisition of primary HHV-6
infection, from 6-24 mo of age,
corresponds with peak acquisition of
roseola.
● Uncommon before 3 months or after 3
years.
● The incubation period averages 10 days
(range of 5-15 days).
 Pathogenesis
● Virus is probably acquired from the saliva
of healthy persons
● enters the host through the oral, nasal, or
conjunctival mucosa.
 Clinical Manifestations
● The prodromal period is usually
asymptomatic but may include mild
upper respiratory tract signs, among
them:
● * minimal rhinorrhea*slight pharyngeal
inflammation* mild conjunctival redness.
nClinical Manifestations:
Fever:
* Sudden onset, high grade, w/o apparent cause
* Child looks well
* Associated signs and symptoms
Bulging fontanels - 26 % - 30 %
Seizures - 5 % - 35 %
Occipital or Cervical
Adenopathy - 30 % - 35 %
Respiratory S/Sx - 55 % - 70 %
Edematous eyelids - 0 % - 30 %
Mild diarrhea - 55 % - 70 %

In Asian countries, ulcers at the uvulopalatoglossal junction (Nagayama

spots) are common in infants with roseola.
Rash:
* Appear as macules/maculopapules
during defervescence (D3-4)
* Initially seen on trunk, spread
rapidly to arms and neck,
less on legs and face
* Fades w/in 3 days w/o
desquamation or hyperpigmentation
Exanthems associated with roseola

The roseola rash begins

as discrete, small (2-5
mm), slightly raised pink
lesions on the trunk and
usually spreads to the
neck, face, and proximal
extremities
 Rash
● confused with exanthems resulting from
rubella, measles, or erythema
infectiosum
● not usually pruritic
● remain discrete but occasionally may
become almost confluent
 Subtle differences in clinical
presentation
● In roseola associated with HHV-7 Subtle
differences in clinical presentation compared with
HHV-6 cases include :
1. Slightly older age
2. Lower mean temperature
3. Shorter duration of fever
● These differences are insufficient to clinically
distinguish HHV-6- from HHV-7-associated
roseola
■ Other Manifestations Of Human Herpes
virus 6 & 7:
- Non specific febrile illness
- Febrile seizures w/o rash
- Encephalitis
- Idiopathic thrombocytopenia purpura
- Intussuception
- Infectious mononucleosis like
syndrome
- Fulminant hepatitis
- Hemophagocytic syndrome
 Roseola Infantum
● Diagnosis:
* Clinically recognized based on
fever,defervescence and exanthem pattern

* CBC show leukopenia with lymphocytosis

* Definite diagnosis ( Research labs )

Viral isolation ( Peripheral lymphocytes )
4 fold rise in Ab titer ( New infection
or reactivation )
Detection of HHV – 6 Ag by PCR
 DIFFERENTIAL DIAGNOSIS
1.Rubella
2.Measles
3.roseola-like illnesses i.e. Enteroviruses
4.Scarlet fever
5.Drug hypersensitivity
 Treatment
● The generally benign nature of roseola
precludes consideration of antiviral therapy
● Children with neurologic complications of roseola
● or immunocompromised children with severe
HHV-6 or HHV-7 infection may address the need
for specific antiviral therapy
● Children in the febrile, pre-eruptive phase of
roseola usually are quite comfortable and require
little supportive therapy
 VARICELLA (Chicken Pox) / HERPES
ZOSTER (Shingles)

• Etiology:
Varicella – zoster virus

Herpes viridae family

 Varicella
• Acute viral illness

• Zoster described in premedieval times

• Varicella not differentiated from smallpox

until end of 19th century

• Infectious nature demonstrated in 1875

 Varicella Zoster Virus
• Herpes virus (DNA)

• Primary infection results in varicella

(chickenpox)

• Recurrent infection results in herpes zoster

(shingles)

• Short survival in environment

 Varicella / Herpes zoster
• Epidemiology:
Mode of Transmission:
- Direct contact w/ skin lesions (varicella or herpes zoster)
- Airborn spread ( varicella)
- Highly contagious; 80% - 90% household transmission
rate

Period of Communicability:
- 1 – 2 days before the rash until 5 – 7 days after the rash
and lesions have crusted

Incubation Period:
- 10 – 21 days
- 1 – 16 days in infant born to mother with active varicella
 Varicella Pathogenesis
• Respiratory transmission of virus

• Replication in nasopharynx and regional

lymph nodes

• Repeated episodes of viremia

• Multiple tissues, including sensory ganglia,

infected during viremia
•
Varicella Clinical Features
Incubation period 14-16 days (range 10-21 days)

• Mild prodrome for 1-2 days

* 24 – 48 hrs before rash
* Fever, malaise, anorexia, headache and mild
abdominal pain

• RASH
• Generally appear first on head; most concentrated on trunk
* Appear as very pruritic macules on scalp, face or trunk
* Macules rapidly progress to vesicular--→ pustular—
→ crusting stages
* New crops of lesions daily X 3 – 7 days
* Various stages of evolution
* Ulcerative lesions in oropharynx, conjunctivae and
genital mucous membranes

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

CHICKEN POX
 Progressive Severe Varicella
• Continuing eruption of lesions ( large,
umbilicated and hemorrhagic) w/ high
fever unto 2nd week of illness

• Primary varicella pneumonia, hepatitis,

encephalitis

• Seen in healthy adolescent and adults, newborn

infants and immunocompromised patients
 Herpes Zoster
• Reactivation of varicella zoster virus

• Associated with:
– aging
– immunosuppression
– intrauterine exposure
– varicella at <18 month of age
 Herpes zoster
• Localized, unilateral vesicular lesions in 1 - 3
dermatomes
• Infrequently associated with localized pain,
hyperesthesia, pruritus and low grade fever
• Complete resolution in 1 – 2 weeks
• Postherpetic neuralgia (pain > 1 month) unusual
in children
• Disseminated cutaneous disease and/or visceral
dissemination in immunocompromised
patients
Herpes zoster
 Varicella Complications
• Bacterial infection of lesions

• CNS manifestations

• Pneumonia (rare in children)

• Hospitalization ~3 per 1000 cases

• Death ~ 1 per 60,000 cases

 Groups at Increased Risk of Complications of
Varicella

• Normal adults

• Immunocompromised persons

• Newborns with maternal rash onset within

5 days before to 48 hours after delivery
 Congenital Varicella Syndrome
• Results from maternal infection during
pregnancy

• Period of risk may extend through first 20

weeks of pregnancy

• Atrophy of extremity with skin scarring, low

birth weight, eye and neurologic
abnormalities

• Risk appears to be small (<2%)

• Diagnosis:
– Can be made clinically
– Definite diagnosis:
Tissue culture - distinguishes VZV from HSV
Direct fluorescent antigen - more rapid /
sensitive
than culture
Tzanck smear - not specific for VZV
PCR - distinguish wild type strains from
vaccine virus
Varicella IgG - Retrospective diagnosis
• Treatment:
Acyclovir is the drug of choice for varicella / herpes zoster when indicated

• For Varicella:
- Not routine in healthy children
- Considered for patients at increased risk of moderate to severe varicella:
a) > 12 years old
b) Chronic cutaneous or pulmonary disorders
c) Long term salicylate therapy
d) Short, intermittent or aerosolized courses of corticosteroid
- Dose:
Immunocompetent hosts:
Oral : 80 mg/K/day in 4 divided doses x 5 days
( max 3200 mg / day)
Immunocompromised hosts:
Intravenous :
< 1 yr. old: 30 mg/K/day in 3 divided doses x 7-10days
> 1 yr. Old: 1500 mg/m2/day in 3 divided doses x 7-10 days
• Treatment for Zoster

Immunocompetent host
IV all ages : 30 mkday x 7-10days

Oral >/=12y: 4000mg/day in 5 divided

doses x 5 – 7 days
Immunocompromised host
IV <12 y : 60 mkdy q 8 x 7-10 days
>12 y : 30mkdy q 8 x 7 days
• Complications:
Bacterial Superinfection:
Skin:
- secondary to Strep. pyogenes or Staph aureus
- range from superficial impetigo to cellulitis,
lymphadenitis and subcutaneous abscesses
- suspected if with erythema of the base of new
vesicle or recrudescence of fever 3 – 4 days
after initial rash

More Invasive Infections:

Sepsis Varicella gangrenosa
Pneumonia Necrotizing fasciitis
Arthritis Toxic shock syndrome
Osteomyelitis
 Varicella / Herpes zoster
• Complications:
* Pneumonia
Most common complication in adults
* Hepatitis
Relatively common; usually subclinical
* Encephalitis and Cerebellar ataxia
* Others:
Thrombocytopenia, nephritis/nephrotic
syndrome, hemolytic-uremic syndrome,
myocarditis/pericarditis, pancreatitis,
orchitis
Stigmata of Varicella-Zoster Virus Fetopathy

• Damage to Sensory nerves:

* Cicatricial skin lesions
* Hypopigmentation
• Damage to Optic Stalk and Lens Vesicle:
* Micropthalmia * Chorioretinitis
* Cataracts * Optic atrrophy
• Dang to Brain / Encephalitis:
* Microcephaly / Hydrocephaly
* Calcifications / Aplasia of brain
• Damage to Cervical or Lumbar Cord
* Hypoplasia of extremity
* Motor / Sensory deficits
* Absent DTR’s
* Anisocoria / Horner Syndrome
* Anal / Vesical Sphincter Dysfunction
 VARICELLA VACCINE
• Live attenuated wild Oka strain
• Dose: 0.5 ml SQ
• Immunogenicity:
Seroconversion rate
12 mos - 12 y/o : Single dose : 95 %
13 yr old & older: 1st dose : 78 - 82 %
2nd dose : 99 %
• Efficacy :
85 - 95 % effective for prevention of varicella
in children during outbreaks.
100 % effective for prevention of moderate or
severe disease
 Varicella / Herpes zoster
• Prevention:
Passive Immunization:
* Varicella zoster immunoglobulin
Candidates for VZIG after significant exposure:
- Immunocompromised patients w/o
previous infection
- Susceptible pregnant women
- New born whose mother had chicken pox
5 days before delivery or within 48 hrs. after delivery
- Hospitalized premature (>28 wks AOG) whose mother
w/o varicella or negative serostatus
- Hospitalized premature (<28 wks AOG) regardless
of maternal hx. of varicella or serostatus
HERPES SIMPLEX
Parvoviruses
 PARVOVIRUS B19
● Small, DNA - containing virus
EPIDEMIOLOGY:
● Humans are the only known hosts
● Transmitted primarily by respiratory secretion.
● Transmissible in blood / blood products
● Most adults have been infected
● Most infections are subclinical
● IgG is detectable in most healthy people
● Sporadic outbreaks, usually among children, occur each
year
● Transmission from patient to health care staff is not
uncommon
● Role in nosocomial transmission to other patients
 Parvovirus Infections in Humans

● Diseases
● Fifth disease (cutaneous rash)
● Transient aplastic crisis (severe
acute anemia)
● Pure red cell aplasia (chronic
anemia)
● Hydrops fetalis (fatal fetal anemia)
● B19 virus most common
Fifth Disease (parvovirus B19)
 Parvovirus Infections in Humans
● Fifth Disease
● Targets red blood cell
progenitors
● Pain in joints
● Results in lysis of cells, thus
depleting source of mature red
cells
● Anemia ensues
● Rarely fatal and without
complications
 Parvovirus Infections in Humans
● Transient aplastic crisis
● B19 infection of those with other
hemolytic anemias
● Sickle cell disease
● Thalassemias
● Can complicate crises
● Sometimes fatal
 Parvovirus Infections in Humans
● Infection of immunodeficient patients
● Can cause persistent infection in bone
marrow
● Suppress red cell maturation
● Leads to anemia
● Infection during pregnancy
● Can cause fetal anemia
● Usually not fatal to fetus
ERYTHEMA INFECTIOSUM
 PARVOVIRUS B19
Other Clinical Manifestations:

● Transient Aplastic Crises:

● Chronic Anemia in Immunodeficient Patients:

 PARVOVIRUS B19
Other Clinical Manifestations:
● Arthritis / Arthralgia:
● Fetal Infections:
● Occur with primary infection in mother
● 2nd trimester = most sensitive time
● Non-immune hydrops and/or Fetal Death
● Lytic infection of erythrocyte precursors--> red cell
aplasia---> profound anemia---> high output failure--->
Hydrops
● Infected infants in utero born normally at term even with
evidence of hydrops by ultrasound
● Some with chronic infection - with unknown significance
 PARVOVIRUS B19
OTHER CLINICAL MANIFESTATIONS:
● ASYMPTOMATIC INFECTIONS (20 %):
● MILD RESPIRATORY ILLNESS W/O RASH:
● RASH ATYPICAL FOR ERYTHEMA INFECTIOSUM
RUBELLIFORM OR PETECHIA:
● Papular-purpuric”gloves and socks” syndrome (PPGSS)

COMPLICATIONS:
● Persistent arthritis after EI
● Thrombocytopenic purpura
● Aseptic meningitis
● Virus - associated hemophagocytic syndrome
 PARVOVIRUS B19
DIAGNOSIS:
● Laboratory tests not routinely available
● Not isolated by culture
● based on observation of Typical Rash and exclusion of other
conditions
● (+) IGM anti-B19 - best marker of recent or acute infection
IgG anti-B19 - past infection or immunity

TREATMENT:
● No specific antiviral treatment
● IV Ig for immunodeficient patients with chronic anemia
● Transfusion and supportive care for patients with aplastic crisis
● Intra-uterine blood transfusion in some cases of B19 infected
hydrops fetalis
 Mumps
■ Epidemic partotitis
■ Paromyxovirus
■ 1 serotype
 MUMPS
■ an acute respiratory tract infectious
disease caused by mumps virus
■ occurs primarily in school-aged
children and adolescents
■ most prominent manifestation is
nonsuppurative swelling and
tenderness of the salivary glands with
■ one or both parotid glands involved in
most cases.
 Epidemiology
■ Sources of infection:
• Patients in early course of the disease, hosts
under covert infection.
• The period of peak contagion before or at
the onset of parotitis.
■ Route of transmission :
Via droplet nuclei or direct contact,
fomites
■ Life long immunity
 Pathogenesis and Pathology
■ The virus usually infecting
glandular tissue such as parotid,
orchis or oophoron.
■ The main pathologic findings are
nonsuppurative inflammatory
reactions.
■ The meningoencephalitis may
occur
 Clinical Manifestations
■ Incubation period: averages 16 to 18
days with a range of 2 to 4 weeks.
■ Subclinical- 30-40% of cases
■ Prodromal symptoms include low- grade
fever, anorexia,malaise and headache.
■ Parotid tenderness and ipsilateral earache
within 1 or 2 days after the illness
onset,then
parotid is visibly enlarged
■ The orifice of Stensen’s duct is edematous
and erythematous.
■ Parotid returns to normal size within a
week.
■ Patients with parotitis have difficulty with
pronunciation and mastication.
■ Citrus fruits and juices exacerbates the pain
■ Other salivary glands involved
submandibular adenitis and sublingual
adenitis.
■ Clinical meningitis occurs in 15% of patients
with mumps.
■ Its onset averages 4-5 days after parotitis but
may before, after or in the absence of parotitis.
Clinical features are headache, vomiting, fever
and nuchal rigidity.
■ CSF pleocytosis. Prognosis is benign.
■ The onset of orchitis is abrupt with high
temperature, chills , testicular pain and
swelling. Impaired fertility is rare.
■ Oophoritis develops in 5% postpubertal
women with mumps. Impaired fertility is
rare.

■ Pancreatitis is manifested by severe

epigastric pain and
tenderness,fever,nausea,and vomiting.
 Virus multiplies in ductal
Mechanism of spread of epithelial cells. Local
Inflammation causes
mumps virus within the Marked swelling
body
Parotid gland

Inoculation Testes
Local Systemic Ovaries
of viremia
replication infection Peripheral nerves
respiratory
tract Eye
Inner ear
CNS

pancreas

May be asso with onset of juvenile DM

■ Complications
• Meningoencephalitis
■ Most frequent complication in childhood
■ One of the most common causes of aseptic meningitis
■ Subclinical in>65% of patients, >10% symptomatic
■ Primary or postinfectious w/ demyelination w/o parotits
• Orchitis/epididymitis
■ 14-35% of adolescents & adults
■ Testes most often infected
■ Follow parotitis >8days after; or (-) gland swelling
■ Fever, chills, headache, nausea, lower abdominal pain
■ Absolute infertility rare
• Oophoritis
■ 7% of postpubertal female
■ Pelvic pain and tenderness
■ No evidence of impairment of fertility
• Pancreatitis
■ Mild or subclinical infection common
■ Salivary gland swelling may be absent
■ Epigastric pain, tenderness, fever chills, vomiting,
prostration
■ Increase serum amyulase w. or w.o s/sx of pancreatitis
■ Other complications
• Nephritis, thyroiditis, myocarditis,
mastitis, ocular complications, arthritis
• Deafness- mumps a leading cause of
UNILATERAL NERVE DEAFNESS
• Mumps embryopathy- increase chance of
abortion, no evidence that maternal
infection is damaging to the fetus
 DIAGNOSIS
■ made on the basis of a exposure history
and of parotid swelling and tenderness
accompanied other symptoms.
■ Laboratory confirmation is unnecessary
in typical cases, exception is the
absence or recurrence of parotitis and
extrasalivary glands involved.
■ Serologic tests, viral isolation. Amylase
and lipase.
■ Differential diagnosis:
• Parotitis of other origin
• Suppurative parotitis
• Recurrent parotitis
• Salivary calculus
• Cervial lymphadenitis
• lymphosarcoma
■ Treatment:
• Symptomatic
• Bed rest
• Diet adjusted according to patient’s
ability to chew
■ Prevention:
• Passive immunization: hyperimmune
mumps gammaglobulin NOT effective
• Active immunization : MMR at 12-15
months
97% protective against natural
infection
Hepatitis A-E
Viruses
 What is Viral Hepatitis?
• Is a systemic disease with primary
inflammation of the liver by any one of a
heterogenous group of hepatotropic
viruses.
 Hepatitis Viruses
• Hepatitis A (HAV) Picornaviridae (1973)
• Hepatitis B (HBV) Hepadnaviridae (1970)
• Hepatitis C (HCV) Flaviviridae (1988)
• Hepatitis D (HDV) (1977)
• Hepatitis E (HEV) (Caliciviridae) (1983),
Hepeviridae
• Hepatitis F – Not separate entity – Mutant of B
Virus
• Hepatits G (HGV) Flaviviridae (1995)
Viral Hepatitis - Historical Perspectives
Type of Hepatitis
 HEPATITIS A VIRUS (HAV)
• This picornavirus is the
causative agent of infectious
hepatitis.
– single strand, 3’-
polyadenylated, positive sense
RNA genome
– surrounded by a naked
(unenveloped) icosahedral
capsid that is around 28 nm in
diameter
– at the 5’ end of the RNA strand
is a viral protein called VPg.
– only one serotype of HAV.
 HEPATITIS A

• Etiology : Hepatitis A virus (HAV), 27 nm

RNA Picornavirus
• Incidence : endemic in developing
countries
• Source : contaminated food and water,
infectivity of human saliva, urine
and semen is unknown
 Hepatitis A - Clinical Features
■ Incubation period: Average 30 days
Range 15-50 days
■ Risk factors
■ Closed personal contact w/ a person infected w/ HAV
■ International travel
■ Child care center
■ Foodborn outbreaks
■ Sex (same sex)
■ Illegal drugs
■ Blood transfusion
■ Vertical transmission (mother to newborn seldom
occurs)
 Clinical Manifestation
1. Asymptomatic
- non-specific manifestation < 6years of age
- 30% of infected children will have jaundice
- acute, self-limited, fever, malaise, anorexia,
nausea, s/s last for less than 2 months
2.Symptomatic
- older children and adults
- 70% present with jaundice
- 10-15% have prolonged or relapsing
disease lasting as long as 6 months
pre-icteric
- fever,vomiting,profound anorexia &
abdominal discomfort.mild & unnoticed in
infants & young children.(+)diarrhea in
children, constipation in adults

icteric phase
- jaundice/dark urine after systemic
symptoms x a week. Subtle & unnoticed in
young kids. Appetite.well-being gradually
return to normal
3. Fulminant hepatitis is rare but common in
those with underlying liver disease

4. Chronic infection does not occur

 Clinical Manifestations
Asymptomatic or mild, nonspecific illness-
majority below 5 yo
Symptomatic
pre-icteric-fever,vomiting,profound anorexia &
abdominal discomfort.mild & unnoticed in
infants & young children.(+)diarrhea in
children, constipation in adults
icteric phase- jaundice/dark urine after
systemic symptoms x a week. Subtle &
unnoticed in young kids. Appetite.well-being
gradually return to normal
Extrahepatic- none
Diagnostic Test
• IgM anti HAV (+) indicates recent or
current infection (5-10 days before onset of
symptoms)
• IgM anti HAV (+) – 20% of vaccinees
detect 2 weeks after immunization
Treatment
• Supportive
• Hospitalization is not required with
uncomplicated HAV hence standard precaution
is recommended
• Control Measures
– General measure
• Improve sanitation
• Immunization Hep A vaccine
Preexposure Immunization:
2 doses, starting 12 months old, 6-12months apart
• Prevention
Postexposure Immunization:
Time since Future Age of Recommen
exposure exposure patient ded
/week likely prophylaxis

</= 2 wk No All age IG:0.02 ml/kg

Yes >/= 1yo IG:0.02ml/kg

+ Hepatitis A
vaccine

>2 wks No All ages No prophylaxis

Hepatitis A
Yes >/=1yo vaccine
• Administration of IG intramuscular given 2
weeks after exposure to Hep A virus
– 85% effective
– 1 dose 0.02 mL/kg confer protection against
Hep A for up to 3 months
– Dose of 0.06mL/kg protects 3-5 months
Lab Diagnosis
 Hepatitis B
• HBV – DNA
• Hepadnavirus
• May exist in multiple forms:
– Spherical particles (22nm)
– Tubular of filamentous forms
– Larger, 42nm spherical virions (originally referred to as Dane
particle)
• Humans: only reservoir
• Important component of viral particle
– Outer lipoprotein envelope containing HBs Ag
– Inner nucleocapsid containing Hep B core antigen (Anti HBc)
– e antigen (HBeAg) – indicator of transmissibility (mino
component of the core- antigenically distinct from HBcAg)
 Hepatitis B
• Etiology: Hepatitis B virus (HBV), DNA virus
• Epidemiology:
– Highly endemic: Southeast Asia, Central Asia, Africa,
Amazon basin, Pacific Islands,
– Endemicity is low: US, Canada Western Europe,
Australia
• Source:
– Virus concentration
• High: blood, semen, and serouc exudates
• Moderate: saliva, vaginal fluid and semen
• Low: breastmilk, feces and urine
– Primary reservoir: patients with chronic HBV infection
• Mode of transmission
– Perinatal exposure to a HBsAg
*risk 70-90% for infants born to mother who are
HBsAg and HBeAg (+)
*risk 5-20% of infants born to mother who are
HBsAg and HBeAg (-)

– Percutaneous and permucosal exposure to infectious

body fluids
– Sharing or using nonsterilized needles or syringes
– Sexual contact with an infected person
– Transfusion of contaminated blood/blood products
• Incubation period: 45 to 160 days
(average: 90 days)
• Period of communicability: for as long as
patient is positive for HbsAg
 Hepatitis B - Clinical Features
Age dependent
▪ Asymptomatic
▪ Symptomatic
➢ 1% younger than 1 year of age
➢ 5-15% 1-5 years of age
➢ 30-50% more than 5 years of age
▪ Spectrum of s/s
➢ subacute illness, non specific, anorexia, nausea,
malaise
➢ Clinical hepatitis - jaundice
➢ Fulminant hepatitis
Clinical manifestations

Anicteric-majority of cases including children

Icteric Phase-similar to hepatitis A or C, maybe more severe

Extrahepatic manifestations-occur early; may precede jaundice as arthralgia,

arthritis, macular rashes, thrombocytopenia, papular
acrodermatitis,(Gianotti-Crosti syndrome), glomerulonephritis, aplastic
anemia

Chronic infection
presence of any of the following in the serum for at least 6 months
- HBsAg
- HBV DNA
- HBeAg
age at the time of infection is the primary determinant of risk of progressing to
chronic infection
 Risk of Progression to
Chronic Infection
• 90% - perinatally to 1st year of life
• 25-50% - between 1-5 years of age
• 5-10% - all the children and adults
• In absence of treatment, 25% of infants
and children who acquire chronic Hep B
infection will die prematurely from Hep
HBV related hepato cellular CA or cirrhosis
 Risk factors for developing hepato
cellular CA
• Long duration of infection
• Male gender
• Elevation of ALT
• HBe Ag positivity
• Degree of histologic injury of the liver
• Replicative state of HBV DNA level
• Presense of cirrhosis
• Concomitant HCV
• HIV
 Resolved Hepatitis B
• Clearance of HBsAg
• Normalization of serum AT concentration
• Development of antibody to HBs Ag
(Anti HBs)
 Window period of HB infection
• Time between disappeance of HBs Ag and
appearance of anti HBs
• The only marker of acute infection is IgM
anti HBc (highly specific) but usually not
present in infants infected perinatally.
• Complications
– Acute Fulminant Hepatitis
• Occurs more frequently with HBV than with other
hepatotropic viruses
• Risk is further increased with co-infection or
superinfection with Hepatitis D virus
• Mortality is greater than 30%
• Characterized by progressive rise in serum
bilirubin, an initial rise in aminotransferase followed
by a fall to normal or low values, prolonged
prothrombin time, decreased serum albumin level,
and increased ammonia level
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course

Symptoms
HBeAg anti-HBe

Total anti-HBc
Titre

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100

Weeks after Exposure

 Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
 Outcome of Hepatitis B Virus Infection
by Age at Infection
100 100

80
Chronic Infection (%)

80

Symptomatic Infection (%)

60 60
Chronic Infection

40 Chronic Infection (%) 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
 Diagnosis
• HBsAg - general marker of infection.
• HBsAb - recovery &/or immunity to HBV infection.
• anti-HBc IgM - marker of acute infection.
• anti-HBc IgG - past or chronic infection.
• HBeAg - active replication of virus ; infectiveness.
• Anti-Hbe - virus no longer replicating; the patient can still
be (+) for HBsAg made by integrated HBV.
• HBV-DNA - active replication , more accurate than
HBeAg especially in escape mutants; for monitoring
response to therapy.
Control Measures/ Prevention
 Indications and dosing schedule for Hepatitis B Vaccine and
hepatitis B Immune Globulin
Groups Vaccine schedule HBIG Dose HBIG Schedule
(u/L)

Neonates
Infants HBsAg – (+) women Birth, 1, 6mo 0.5 Within 12 hr of birth
Inants HBsAg – (-) women Birth, 1-2,6-18 mo None

Children & Adolescents 0,1, and 6 mo None

(11-19yr)

Contact w/ acute HBv

Intimate 0-19 y/o Exposure, 1 and 6 mo 0.06/kg At exposure
> 19y/o Exposure, 1 and 6 mo 0.06/kg At exposure
Household None None
Casual none None

Contact w/ chronic HBv

Intimate and Household
0 -19 y/o Exposure, 1 and 6 mo None
> 19 y/o Exposure, 1 and 6 mo None
Casual None

Immunosuppressed or Exposure, 1 qnd 6 mo none

hemodialysis patients
Hepatitis B Vaccine
 Treatment
• No specific therapy
• HBIG & corticosteroids are not effective
• Screening periodically serum AT & α
fetoprotein
• Abdominal ultrasound
• Goal of treatment in chronic HBV Infection
is to prevent progression and cirrhosis,
hepatic failure and hepato cellular CA
 Indications for treatment of chronic
HBV
• Evidence of ongoing HBV viral replication
(+ HBV DNA > 20 thousand IU/mL for > 6
months)
• Without Hbe Ag + > 2000 IU/mL
• With Hbe Ag +
• Elevated serum ALT concentration > 6
months
• Evidence of chronic hepatitis in liver biopsy
 Treatment
• 3 nucleoside analogues entecavir, lamivudine, telbivudine
• 2 nucleotide analogues tenofovir, adefovir
• 2 interferon – α drugs (interferon α 2B, pegylated
interferon α 2A)
• FDA licensure (pediatric)
- interferon ≥ 1 year
- lamivudine ≥ 3 months of age
- adefovir ≥ 12 years
- telbivudine ≥ 16 years
- entecavir ≥ 16 years
 Control Measures
• Universal immunization of infants at birth
• Prevention of perinatal HBV
• Routine immunization children and
adolescent who have not received
immunization
• Immunization of adults who were not
previously immunized
Hepatitis C
 Hepatitis C
• Transmission : blood or body fluid

• Parenteral exposure to HCV-infected

blood: primary route; seroprevalence
depend on degree of exposure

• Perinatal transmission is uncommon(5-

6%)
 Degree of exposure Seroprevalence

Large,repeated exposure(IV drug 60=90%

users,hemophiliacs before 1987

Frequent ,smaller exposure(hemodialysis 10-20%

patient)

Inapparent percutaneous exposure(sex 1-10%

worker)

Sporadic exposure 1%
 Chronic Hepatitis C Infection

• HCV most likely to cause chronic infection;

85% become chronic
• After ~20-30 years,
about 25% ultimately progress to cirrhosis, liver
failure & occasionally primary hepatoCA
• Hepatocellular CA associated with HCV
- is less effective than HBV in causing primary hepatoCA almost
always occurs with cirrhosis;
- results from chronic inflammation & necrosis rather than
oncogenic effect of virus
Hepatitis C – Clinic Features
Outcomes of HCV Hepatitis
 Factors Affecting Progression
• 30yrs or longer if:
• Young at time of infection
• Healthy liver at time of infection
• Female

• 20yrs or less if:

• Drinking alcohol
• Co-infection (HIV, Hep B)
• Damaged liver before infection

Adapted from Bigham, BC Hepatitis Services 2002

Hepatitis C Virus Infection
 Laboratory Diagnosis

• HCV antibody - Not useful in the acute

phase ; at least 4 weeks after infection
before (+)
• HCV-RNA - PCR and branched DNA;
useful in the acute phase; used mainly in
monitoring response to antiviral therapy.
• HCV-antigen - by EIA , much easier
procedure
 Treatment

• Interferon - considered for chronic active

hepatitis;response rate ~ 50% but 50% of
responders will relapse upon withdrawal of
Tx.
• Ribavirin - recent studies suggest that a
combination of interferon and ribavirin is
more effective than interferon alone.
 Prevention of Hepatitis C

▪ Screening of blood, organ, tissue donors

▪ High-risk behavior modification

▪ Blood and body fluid precautions

 Hepatitis D (Delta) Virus
d antigen HBsAg

RNA
 Hepatitis D
• Is a highly defective virus
– it cannot produce infective virions without the help of a co-
infecting helper virus → HBV -- supplies the HBsAg surface
protein.
• In budding out of the cell, HDV acquires a membrane containing
HBsAg.
– HDV can only form an infectious particle if the cell in which it
replicates is co-infected with HBV since the latter provides
the surface HBsAg which is required for reinfection of another
cell.
• HDV has a small circular RNA genome (1,700 bases) that
encodes a protein called the delta antigen. This complexes with
the RNA.
• The RNA is single stranded negative sense and is a covalently
closed circle.
 Hepatitis D Virus Modes of
Transmission

▪ Percutanous exposures
▪ injecting drug use
▪ Permucosal exposures
▪ sex contact
 Hepatitis D - Clinical Features

▪ Coinfection
– severe acute disease.
– low risk of chronic infection.
▪ Superinfection
acute illness is rare
– chronic infection is common
risk of fulminant hepatitis is highest; suspect in
any child w/ acute liver failure
 Hepatitis D - Prevention

■ HBV-HDV Coinfection
Pre or postexposure prophylaxis to prevent
HBV infection.
■ HBV-HDV Superinfection
Education to reduce risk behaviors among
persons with chronic HBV infection.
 Hepatitis E Virus

• enteric non-A, non-B hepatitis

 HBV – HBD
Super Infections
 Hepatitis E - Clinical Features

■ Incubation period: Average 40 days

Range 15-60 days
■ Case-fatality rate: Overall, 1%-3%
Pregnant women,
15%-25%
■ Illness severity: Increased with age
■ Chronic sequelae: None identified
 Hepatitis E Virus Infection
Typical Serologic Course

Symptoms

ALT IgG anti-HEV

Titer IgM anti-HEV

Virus in stool

0 1 2 3 4 5 6 7 8 9 10 11 12 13

Weeks after Exposure

• Hepatitis F (HFV)

-in 1994, french researchers isolated an enteric agent

responsible for sporadic non- A-E hepatitis
-not confirmed by others
• Hepatitis G (HGV)
-RNA virus, flaviviridae family, 27% homology to HCV
-reported in adults and children
-seen in HIV pts and in 10-20% of adults with chronic
hepatitis B and hepatits C
-primary source: transfusion; organ transplant, IV drug
use, hemodialysis, sexual transmission
- accounts for only small proportion of cases of non-A-E
hepatitis
-most infection not associated with hepatic
inflammation ;doesn’t seem to worsen coinfection with
hepatitis B or C
-diagnosis: HGV RNA PCR
-prevention: none
 Dengue Virus
• Causes dengue
and dengue
hemorrhagic fever
• Has 4 serotypes
(DEN-1, 2, 3, 4)
• Infection w/ 1
serotype provoke
long-lasting
homotypic immunity
Dengue Epidemiology

• Dengue is the most rapidly spreading

mosquito-borne viral disease in the world.
• Has increased 30-fold with increasing
geographic expansion to new countries
• From urban to rural setting
• Constitute to be a public health emergency
of international concern due to rapid
epidemic spread beyond national borders
Areas/Countries at Risk for Dengue 2008
 Etiology
• RNA virus
– DENV1
– DENV2
– DENV3
– DEN4
• Life risk for up to 4 DENV infection
 Epidemiology
– Primarily transmitted to humans
• Bite of infected Aedes aegypti mosquito
• Less common Aedes Albopictus or Aedes polynesinensis
• Others
– Receipt of blood products, donor organs/tissue
– Percutaneous exposure to blood, exposure in utero & parturition
• Public health problem tropics & subtropics
• All ages can be affected
• Severe disease in children and women (pregnant) and
chronic diseases
(asthma, sickle cell anemia, DM)
 Aedes aegypti
• day-biting, infected
female mosquito
• Lives around human
habitation
• Lays eggs and
produces larvae
preferentially in
artificial containers
with clean stagnant
water or dirty water.
 Vector
• Aedes Aegypti
daytime biting mosquito with peak hours
6am – 10am 4pm – 6pm

• Aedes Albopictus
day and night time biting with attacks in
late afternoon
6pm – 8pm 11pm – 1am
 Dengue hemorrhagic fever
Immune Enhancement Theory of Halstead
• up tp 90% 0f DHF cases have previous immunity to a
dengue infection
• previous immunity:
– actively, by previous infection
– passively, from immune mothers
• (+) infectious immune complexes ( antigen + non
neutralizing antibodies)->enhanced cellular infection/viral
replication->increased viremia->release of cytokines
with vasoactive & procoaguant properties, interferon
gamma, soluble TNF,IL2, activation of complement->
increased vascular permeability & activation of blood
clotting /fibrinolytic system
Other possible causes:
• Difference in virulence between serotypes or
strains within serotypes
– type 2 more dangerous

• Host factors
1. race: dengue resistance gene?
2. nutritional status:
– protein-calorie malnutrition supresses immune
response ->reduces risk of dhf/dss

• Interaction of virus with other infectious agent

and /or environmental factors
2 pathophysiologic changes in DHF

1. Acute increase in vascular

permeability
– major pathophysiologic abnormality in DHF
– transient, functional vascular changes due to
cytokines
– leads to PLASMA LEAKAGE ->
hemoconcentration, hypoalbuminemia, serous
effusion, shock → metabolic acidosis -> death
2. Disorders in hemostasis
1. vascular changes
• increase in capillary fragility as reflected by a`(+)
torniquet test and easy bruisability

2. thrombocytopenia
• degree related to severity
• begin to fall D2-D3, lowest at D5 (shock phase),
increased D6-7, normal D7-10
• impaired production vs enhanced destruction
secondary to endothelial injury, action of virus, (+)
platelet-specific antibodies, immune complexes,DIC

3. Coagulopathy
• prolonged PTT/PT
 Dengue Case Classification
• Symptomatic dengue virus infection categories
1. undifferentiated fever
2. dengue fever
3. dengue haemorrhagic fever (DHF)
a. grade I
b. grade II
c. grade III
d. grade IV
DSS
 Grading of severity of DHF/DSS

• Grade I fever, non-specific symptoms like

anorexia, vomiting, abdominal
pain, (+)TT

• Grade II symptoms and signs of grade I +

spontaneous bleeding

• Grade III symptoms and signs of grade II +

evidence of circulatory failure: violaceous,
cold & clammy skin, weak pulses, narrowed
pulse pressure </=20 mm Hg or
hypotension

• Grade IV refractory or irreversible shock +/_ bleeding

 Incubation Period
• 8-12 days (extrinsic incubation)
– Mosquitos remain infections for life
• 3-14 days in humans (intrinsic incubation)
before symptoms onset
• Infected person can transmit DENV
– 1-2 days before symptoms develop and
throughout the 7 day viremia phase.
 Dengue Fever
• Biphasic Fever
• Headache
• Muscle and joint pain
• Nausea/vomiting
• Maculopapular rash w/c spares palms & soles
• Hemorrhagic manifestations
• Tourniquet test (infrequently +)
• Leucopenia, low platelets (rarely <100,000)
normal PTT,PT), no evidence of plasma leakage
 Hemorrhagic Manifestations
of Dengue
• Skin hemorrhages:
petechiae, purpura,
ecchymoses
• Gum bleeding
• Nose bleeding
• Gastro-intestinal
bleeding:
hematemesis, melena,
hematochezia
• Hematuria
• Increased menstrual flow
 Other manifestations

Gastrointestinal: diarrhea, vomiting, abdominal pain

Gallbladder/Liver involvement: tenderness at RUQ,
distended or contracted GB on
sonography,hepatomegaly, jaundice
Neurologic : encephalopathy/encephalitis, febrile
seizures
Cardiac: bradycardia, myocarditis, pericardial effusion,
fluid overload
Respiratory: coryza, cough, tonsillopharyngitis,
complicated by pneumonia, hemoptysis, pleural
effusion
Lymhadenopathy
 Tourniquet Test
• Inflate blood
pressure cuff to a
point midway
between systolic
and diastolic
pressure for 5
minutes
• Positive test: 20 or
more petechiae per
1 inch2 (6.25 cm2)
Pan American Health Organization: Dengue and Dengue
Hemorrhagic Fever: Guidelines for Prevention and
Control. PAHO: Washington, D.C., 1994: 12.
 Clinical Case Definition for
Dengue Hemorrhagic Fever
4 Necessary Criteria:
1. Fever, or recent history of acute fever
2. Hemorrhagic manifestations
3. Low platelet count (100,000/mm3 or less)
4. Objective evidence of “leaky capillaries:”
– elevated hematocrit (20% or more over baseline)
– low albumin
– pleural or other effusions
Vaughn DW, Green S, Kalayanarooj S, et al. Dengue in the early febrile CENTERS FOR DISEASE CONTROL
AND PREVENTION
phase: viremia and antibody responses. J Infect Dis 1997; 176:322-30.
 Clinical Course
• Febrile phase
– 2-7 days fever
– Muscle joint pain
– Headache
– Retrobulbar pain
– Facial erythema
– Injected oropharynx
– Maculopapular rash
– Leukopenia
– petechia/minor bleeding manifestation
 Clinical Course
• Critical phase
– Defervesence (3-7 day of illness)
– Increase vascular permeability
– Increasing hematocrit (hemoconcentration)
– Significant plasma leakage 24-48 hrs
– Late febrile phase → severe dengue
(persistent vomiting, abdominal pain, mucosal
bleeding, difficulty of breathing, signs of shock, and
hemorrhage, rapid decline of platelet and increase in
hematocrit)
● Indicators of Shock
◆Peripheral perfusion
➢Early indicator
◆Output
➢Based on ideal body weight
◆Blood pressure
◆mental state
◆CRT
◆Temperature
◆ respiratory rate
 Abnormal Laboratory Results
to be Corrected

Metabolic Acidosis
● Not respond to fluid resuscitation
● pH <7.35
● HCO3 <15meq/L
 Clinical course
• Convalescent phase
– Clinical Improvement
– Stabilization
– Increasing platelet
– Hematocrit normalization
 Warning Signs for Dengue
Shock Alarm Signals:
Four Criteria for DHF:
• Fever
• Hemorrhagic manifestations
• Excessive capillary
permeability
•  100,000/mm3 platelets
Initial Warning Signals:
• Disappearance of fever
• Drop in platelets
• Increase in hematocrit
• Severe abdominal pain
• Prolonged vomiting
• Abrupt change from fever
to hypothermia
•Change in level of
consciousness (irritability
or somnolence)
When Patients Develop
DSS:
• 3 to 6 days after onset of
symptoms
CDC
1 Febrile phase Dehydration; high fever may cause
neurological disturbances and
febrile
seizures in young children
2 Critical phase Shock from plasma leakage; Severe
hemorrhage; Organ impairment

3 Recovery Hypervolaemia ( only in excessive IVF

phase therapy) associated with pulmonary
edema or CHF
 Diagnostic Test
• Serum
– DENV RNA (RT-PCR)
– DENV NS1 (non-structural protein 1)
• Are detectable from beginning of febrile phase until
D7-D10 after illness
– Anti DENV IgG antibody remains elevated for
life after DENV infection.
• falsely positive in (1) people with prior infection,
(2) immunization against other
flavivirus (westnile, JE, yellow fever)
• Simple anti DENV IgG antibody titer of
≥1:1280 is highly suggestive of dengue
diagnosis
• IgM antibody detected 3 to 5 days after
illness
– Rise for about 2 weeks
– Undetected after 2 to 3 months
IgM : IgG > 1.2 (Primary)
IgM : IgG < 1.2 (Secondary)
 Treatment
1. No specific antiviral therapy
2. Febrile phase
1. Hydration
2. Avoid acetylsalicylates, ibuprofen, NSAID
3. Critical Phase
1. Recognition of shock, occult bleeding
2. Hemodynamic status
3. Fluid volume (plasma leakage, fluid overload,
organ failure)
 Refractory shock
- IVF (crystalloids, colloids)
- blood (FWB, PRBC)
- inotropes
4. Convalescent phase
- reabsorption of fluid to the IVC
- stabilization of hemodynamics
- diuresis
- reduction of haematocrit (dilutional effect)
5. Isolation of hospitalized patient
- standard precaution
- attention to potential bloodborn
transmission (secondary transmission)
6. Control measures
- dengue vaccine (9 – 45 years)
- aircon/screened windows, door,
- bed nets
- mosquito repellants
50% DEET – adults/pregnant
30% DEET – children > 2 months
Differential Diagnosis of Dengue
• Influenza • Leptospirosis
• Measles • Meningococcemia
• Rubella • Rickettsial infections
• Malaria • Bacterial sepsis
• Typhoid fever • Other viral
hemorrhagic fevers
 Criteria for discharge

• Afebrile for 72 hours

• Good appetite
• Visible clinical improvement
• Good urine output
• No bleeding
• Rising platelet count >/= 100,000
• No respiratory distress
• No evidence of cardiac/CNS involvement,other
complications
 Mosquito Barriers
• Only needed until fever subsides, to
prevent Aedes aegypti mosquitoes from
biting patients and acquiring virus
• Keep patient in screened sickroom or
under a mosquito net
 References
• Nelson’s Textbook of Pediatrics (19th ed.)
• Redbook of Pediatrics
• Fundamental of Pediatrics
Thank You