PEDIATRICS II​ L​ ecturer: DR.

MARASIGAN 
S1-05c: Roseola TO hpV​ Date: 10-13-2020

g. Management
VIII.Rotavirus
OUTLINE a. Etiology
b. Epidemiology
I. Roseola c. Pathophysiology
a. Etiology d. Clinical manifestations
b. Epidemiology e. Diagnosis
c. Pathophysiology f. Management
d. Clinical manifestations IX. HPV
e. Diagnosis a. Etiology
f. Complications b. Epidemiology
g. Management c. Pathophysiology
II. HHV 8 d. Clinical manifestations
a. Etiology e. Diagnosis
b. Epidemiology f. Complications
g. Management
c. Pathophysiology
d. Clinical manifestations
e. Diagnosis References: Lecture Recording and Powerpoint
Presentation
f. Management
III. Influenza Virus
a. Etiology
b. Epidemiology
📖
Legend:

📣 Reference textbook
c. Pathophysiology
d. Clinical manifestations
💡 Audio from lecture recording
Nice-to-Know
⭐ TG Notes
e. Diagnosis
f. Complications
g. Management I. ROSEOLA INFANTUM
IV. Parainfluenza Virus
a. Etiology ● Exanthem subitum, Three Day Fever, 6th Disease,
b. Epidemiology “Tigdas Hangin”
c. Pathophysiology
d. Clinical manifestations A. ETIOLOGY
e. Diagnosis ● Etiologic agent:​ HHV 6 and 7
f. Complications ● Primary infection is acquired rapidly by essentially
g. Management all children following the loss of maternal
V. RSV antibodies in the 1st few months of infancy
a. Etiology ● HHV6: Peak age of infection is 6-9 months of life
b. Epidemiology ● Sporadic and without seasonal predilection or
c. Pathophysiology contact with other ill individuals o HH7 occurs later
d. Clinical manifestations in childhood in a slower rate
e. Diagnosis
f. Management B. EPIDEMIOLOGY
VI. Coronavirus ● Ages 6 months – 2 years old
a. Etiology ● “In a 12y/o patient, never think of roseola infantum
b. Epidemiology as a differential diagnosis”
c. Pathophysiology ● Not manifested in adults
d. Clinical manifestations ● Mode of transmission: Adult saliva
e. Diagnosis ● “​Especially asymptomatic adults kissing
f. Management babies​”
VII. Rhinovirus ● HHV6​: two mechanisms of vertical transmission:
a. Etiology transplacental infection and chromosomal
b. Epidemiology integration
c. Pathophysiology ● HHV7​: cervical secretions of pregnant women,
d. Clinical manifestations congenital infection has not been demonstrated
e. Diagnosis ● No prodromal period
f. Complications

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C. PATHOGENESIS ● Specific diagnosis of HHV6 or HHV7 is not usually
● Primary HHV6 Infection necessary except in situations in which
○ Causes a viremia that can be demonstrated manifestations of disease is severe
by coculture of the patient’s peripheral blood ● Viral culture is the gold standard
mononuclear cells ● Others: Immunofluorescence assays,
○ Infected cells exhibit a slightly prolonged enzyme-linked immunosorbent assays,
lifespan, but lytic infection predominates neutralization assays and immunoblot
○ Apoptosis of T cells and may lead to cell
expiration F. COMPLICATIONS
○ Can infect primary T cells, monocytes, NK ● Convulsions – most common
cells, dendritic cells, astrocytes, B cells ● Higher frequency of partial seizures, prolonged
● Lifelong latency or persistence of virus at multiple seizures, postictal paralysis, and repeated
sites seizures

D. CLINICAL MANIFESTATIONS G. TREATMENT

● Acute and self-limited
● Abrupt onset of high fever, which may be
accompanied by fussiness
● Fever usually resolves acutely after 72hr (crisis)
but may gradually fade over days (lysis)
● Mild upper respiratory signs
○ Cough and colds
● Mild infection of pharynx, palpebral conjunctiva,
tympanic membranes
● Irritability and anorexia, sometimes seizures and
high fever
○ High fever – most consistent findings
associated with primary HHV-6B
● Nagayama spots – ulcers at the uvulo
palatoglossal junction commonly observed in
Asian children
● Three day fever followed by rash at
defervescence of fever
○ Clue: see the rash only when the patient is
afebrile
○ Common mistake of students is associating
“3-day measles” with roseola infantum
■ 3-day measles is known as Rubella
○ Rash may last for 1-3 days, but frequently
evanescent
○ Rash is not distinctive, may appear from the
the trunk, to the face, and extremities
● Supportive, maintain hydration and give
antipyretics
● Routine antiviral therapy has not been
recommended except for unusual or severe
manifestations
● HHV6 and HHV7 is sporadic, no current vaccines
available
II. HHV 8
A. ETIOLOGY
● Human herpesvirus 8 (HHV-8, Kaposi's
sarcoma-associated herpesvirus, KSHV) was
identified from acquired immunodeficiency
syndrome (AIDS)-associated Kaposi's sarcoma in
1994.
● Both Epstein-Barr virus (EBV) and HHV-8 belong
to the gamma-herpesvirus subfamily, and the
latter is classified as a human g2-herpesvirus.
B. EPIDEMIOLOGY
● HHV-8 infection is very common in African
countries (30-50%), and common in certain
Mediterranean countries (10-30%), but
uncommon in Asian (2-4%) and northern and
southern American countries (5-20%).
● Most individuals with HHV-8 infection are
asymptomatic.
● HHV-8 is strongly associated with malignancies
such as Kaposi's sarcoma and malignant
lymphoma in immunocompromised persons such
as those with AIDS and organ transplant
recipients.
● Saliva-mediated vertical or horizontal
transmission is also likely to occur among
younger people.

C. PATHOGENESIS
● DNA fragments of HHV-8 have been detected in
more than 95% of Kaposi's sarcoma cases by
Figure 1.​ ​Nagayama Spots PCR and anti-HHV-8 antibodies are detected in
sera from patients with Kaposi's sarcoma,
E. DIAGNOSIS regardless of HIV infection.
● Lower mean numbers of total WBC (8,900/uL),
D. CLINICAL MANIFESTATIONS
lymphocytes (3,400/uL), and neutrophils
(4,500/uL) – most characteristic lab finding ● Kaposi’s Sarcoma

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● Primary Effusion Lymphoma
● Multicentric Castleman’s Disease
E. DIAGNOSIS
● Polymerase chain reaction (PCR), ​in situ
hybridization and immunohistochemistry are used
for detection of HHV-8.
● Serum antibodies against latency-associated
nuclear antigen, ORF59, ORF65, and K8.1
proteins are detected in the HHV-8-infected
individuals using enzyme linked immunosorbent
assay (ELISA) or immunofluorescence assay.
F. TREATMENT
● Kaposi's sarcoma is usually treated by irradiation,
cytotoxic chemotherapy, or surgical resection.
● Antiviral drugs against herpes viruses have some
prophylaxis activities on Kaposi's sarcoma in high
risk patients.
● Cytotoxic drugs are used for the treatment of
primary effusion lymphoma.
● Castleman’s disease could be more responsive to
antiviral therapies.
III. INFLUENCE VIRUS ​ 📖
⭐ Chapter 258 Nelson Textbook of Pediatrics 20th
Edition
● Cause a broad array of respiratory illnesses that
are responsible for ​significant morbidity and
mortality
● Influenza A viruses also have the potential to
cause periodic global pandemics with even higher
penetrance of illness than seasonal epidemics
A. ETIOLOGY
● Large, ​single-stranded RNA viruses
● Family: Orthomyxoviridae
● 3 Genera:
○ Influenza A - a primary human pathogen
(seasonal epidemic)
○ Influenza B - a primary human pathogen
(seasonal epidemic)
○ Influenza C - sporadic cause of mild URTI
● Influenza A Subtypes:
○ Influenza A (​H1N1​) & influenza A (​H3N2​)
○ based on 2 surface proteins that project as
spikes from the lipid envelope
■ hemagglutinin (HA)
■ neuraminidase (NA)
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Figure 2​. Schematic Diagram of Influenza A
● The HA and NA antigens from ​influenza B and C
viruses do not receive subtype designations​,
as there is less variation among influenza B and C
antigens
💡
​Strain variants are identified by antigenic
differences in their HA and NA and are designated
by the geographic area from which they were
originally isolated, isolate number, and year of
isolation.
● Transmission:
B. ETIOLOGY
○ Primarily via respiratory droplets
○ Contact with secretions and small-particle
aerosols also possible
○ Rapid transmission (highest incidence
occurring within 2 - 3 weeks of introduction to
community)
● Incubation: 12 - 72 hours (short)
● Antigenic Variation:
○ Influenza A and B viruses contain a genome
consisting of 8 single strand RNA segments
○ Antigenic Drift
■ Continuous point mutations leading to
MINOR changes in the subtype
■ Predisposed to ​HA > NA
■ Leads to new influenza strains of the
same HA type
■ Occurs in ​BOTH influenza A and B
viruses
■ Occurs almost yearly
○ Antigenic Shift
■ MAJOR changes in subtype
■ Less frequent but more dramatic
■ Occurs ​when there is simultaneous
infection by more than 1 strain of
influenza​ in a single host
■ Occurs in ​influenza A viruses MOSTLY
○ 💡 (avian and mammalian hosts)
Major Global Influenced Pandemics (in the
last 100 years):
■ 1918
● Influenza A[H1N1] virus
● Most severe pandemic (50M people)
● Avian source
■ 1957
● (A[H2N2])
■ 1968
3

● (A[H3N2])
■ 2009
● influenza A[H1N1] virus
● Avian, swine, and human source
● Seasonal Influenza
○ Annually 3 - 4 influenza virus types or
subtypes typically co-circulate
○ Although 1 subtype usually predominates in
any given season, it is difficult to predict which
will be predominant
○ This is why the ​influenza vaccine varies
annually and contains 3 or 4 antigens
representing the expected circulating
types
C. PATHOPHYSIOLOGY
● Infect the respiratory tract epithelium, ​primarily
the ciliated columnar epithelial cells
● HOW?
○ Using the HA to attach to sialic acid residues
○ Virus is then adsorbed and virus replication
occurs (4 - 6 hours)
○ Infectious virus is then released, infecting
neighboring cells
● Rarely detected in extrapulmonary sites
● Causes a lytic infection of the respiratory
epithelium with:
○ loss of ciliary function
○ decreased mucus production
○ desquamation of the epithelial layer
● Changes permit secondary bacterial invasion
either:
○ Directly through the epithelium
○ Obstruction of the normal drainage through
the eustachian tube (middle ear space)
● Immune Response:
○ Induction of cytokines that inhibit viral
replication
■ Interferons and tumor necrosis factor
○ Other host defenses
■ Cell-mediated immunity, and local and
humoral antibody defenses
○ Secretory antibodies
■ Produced by the respiratory mucosa
immunoglobulin A antibodies
■ Effective and immediate response
○ Serum antibody levels inhibiting HA activity
can usually be detected by the 2nd week after
infection.
■ These antibodies are also generated by
vaccines, and high HA inhibition titers
correlate with protection.
D. CLINICAL MANIFESTATIONS
● Often abrupt
● SYSTEMIC SYMPTOMS:
○ Moderate to high fever, myalgias, chills,
headache, malaise,​ and anorexia
■ Febrile illness is 2 - 4 days
○ ⭐ ​Underlined symptoms ​- among the
respiratory viruses it is INFLUENZA that
causes these MOST
● Less PROMINENT symptoms:
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○ Coryza, pharyngitis, and dry cough
■ Cough may persist for than 4 days
■ Evidence of small airway dysfunction is
often found weeks later
● Less COMMON symptoms:
○ Abdominal pain, vomiting, and diarrhea
● Respiratory manifestations can include:
○ Isolated URTI ex. croup
○ Progression to LRTI ex. bronchiolitis or
pneumonia
● Influenza is a less distinct illness in younger
children and infants
● The infected young infant or child may be highly
febrile and toxic in appearance, ​prompting a full
diagnostic work-up
● Clinical presentation is often indistinguishable
from other respiratory viruses
E. DIAGNOSIS
● Laboratory Findings:
○ Relative leukopenia is frequently seen
○ Chest radiographs may show evidence of
atelectasis or infiltrate
● Diagnosis depends on epidemiologic, clinical, and
laboratory considerations
● Rapid Influenza DT:
○ Often employed due to ease of use and
speed
○ Suboptimal sensitivity, especially for novel
strains
○ Sensitivity: 50 - 70 % (compared to viral
culture or RT-PCR)
○ Specificity: 95 - 100 %
■ Therefore, ​false-negative results occur
more often than false-positive results
● For ​patients with high risk of complications:
○ Early empiric treatment should be given
regardless of a negative result
○ Another type of test may be performed ex.
RT-PCR, direct fluorescent antibody, or viral
culture
● Patients with higher risk of complications:
○ Younger than 2 y/o
○ Younger than 19 y/o receiving long-term
aspirin therapy
○ With chronic disease (all systems)
○ Immunosuppressed (either from HIV or
medication)
○ Pregnant or postpartum (within 2 weeks after
delivery)
○ Mordibly obese
4
 S1-05C: roseola to hpv
○ Toxic shock syndrome
● Central nervous system complications
○ Encephalitis, myelitis, and Guillain-Barré
syndrome
● Reye syndrome can result with the use of
salicylates​ during influenza type B infection

G. MANAGEMENT
● 2 Classes of Drugs:
○ NA inhibitors
■ Oseltamivir and zanamivir

Table 2.​ CDC Recommended Dosage and Schedule

of Influenza Antiviral Medications

○ Adamantanes
■ Amantadine and rimantadine,
■ Effective only against influenza A
viruses
■ Not approved for use in children younger
than 5 y/o
● Prognosis:
○ Generally excellent,
○ Full recovery usually requires weeks rather
than days
Table 1. ​Diagnostics Tests for Influenza ○ Severe influenza disease can be associated
with hospitalizations and death, even among
F. COMPLICATIONS previously healthy children
● Common in ​young children: ● Prevention:
○ Otitis media and pneumonia ○ Influenza vaccination is the BEST
○ Acute otitis media may be seen in up to 25% PREVENTION ​(50 - 80% effective in reduced
of cases of documented influenza risk)
○ Pneumonia accompanying influenza may be a ○ Advisory Committee on Immunization
primary viral process or a secondary bacterial Practices ​(ACIP) recommended that all
infection (usually ​Staphylococcus aureus)​ children from ​6 mo to 18 y/o be vaccinated
● UNUSUAL ​clinical manifestations: for influenza unless they have a specific
○ Acute myositis​ seen with influenza type B contraindication
■ marked by muscle weakness and pain, ○ Chemoprophylaxis​ with antiviral medications
particularly in the calf muscles ■ Secondary means of prevention, and
○ Myoglobinuria NOT a substitute for vaccination
● Other Clinical Manifestations: ● VACCINES:
○ Myocarditis in Influenza A and B ○ 2 Main Classes:

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■ Inactivated influenza vaccine (IIV)
● IM administration IV. PARAINFLUENZA VIRUS
● Trivalent vaccine (IIV3) - 2 influenza ⭐ Chapter 259 Nelson Textbook of Pediatrics 20th
A strains and 1 influenza B strain Edition
● Quadrivalent vaccine (IIV4) -
second influenza B strain of an ● Common ​causes of acute respiratory illness in
antigenically distinct lineage infants and children
■ Live-attenuated influenza vaccine (LAIV) ● Important causes of lower respiratory tract
● Nasal spray disease in young children and
● Weakened virus immunocompromised persons.
● Recommended for 2 - 8 y/o ● Particularly ​associated with croup
💡 3RD VACCINE CATEGORY - Recombinant
hemagglutinin influenza vaccine (trivalent formula)
(laryngotracheitis or
laryngotracheobronchitis), bronchiolitis, and
pneumonia
○ Special vaccination instructions for children 6 A. ETIOLOGY
mo to 8 yr of age should be followed ● Family: Paramyxoviridae
■ depending on vaccination history, some
● 3 Pathogenic Types in Humans:
children will require 2 doses of seasonal
○ Type 1 - 4
influenza vaccine (administered a ○ Type 4
minimum of 4 wk apart) to optimize
■ 2 antigenic subgroups
immune response
● A and B
○ Common Side Effects: ● Nonsegmented, ​single-stranded RNA genome
■ soreness, redness, tenderness,
with a lipid containing envelope ​derived from
swelling from injection, and nasal
budding through the cell membrane
congestion ● Major antigenic moieties are
● CHEMOPROPHYLAXIS:
○ HN and F envelope spike glycoproteins
○ Considerations For Use:
■ Exhibit hemagglutinin-neuraminidase
■ Unvaccinated persons at high risk of and fusion functions, respectively.
influenza complications
■ Persons for whom vaccine is B. EPIDEMIOLOGY
contraindicated or expected to have low
● By 5 yr of age, most children have
effectiveness
■ Residents/patients in care facilities during experienced primary infection with PIV types
1, 2, and 3
institutional influenza outbreaks
● PIV-3 infections occur often at 1st 6 months of life
○ Adamantanes < NA in use due to
adamantanes resistance ● PIV-1 and PIV-2 more common after infancy
○ 60 - 75 % at 5 y/o
○ Recommend chemoprophylaxis for a
● Incubation period from exposure to symptom
minimum of 2 wk and up to 1 wk after the
last known case is identified, whichever is onset is 2 - 6 days
longer
C. PATHOGENESIS
● Replicate in the ​respiratory epithelium
● Preferential replication in the larynx, trachea,
and bronchi in comparison with other viruses
● In children, the most severe illness coincides with
the time of maximal viral shedding

Figure 3. ​Dosing for Children 6 months to 8 y/o

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Figure 5. ​Steeple Sign

● Conventional laboratory diagnosis of infection is

accomplished by
○ PIV isolation in tissue culture
○ Direct immunofluorescent staining
○ PCR assays
■ Greatly increase sensitivity of PIV
detection

F. COMPLICATIONS
● Eustachian tube obstruction can lead to
secondary bacterial invasion of the middle ear
space and acute otitis media in 30 - 50% of PIV
● Sinusitis​ from obstruction of paranasal sinuses
● The destruction of cells in the ​upper airways can
lead to
○ Secondary bacterial invasion and resultant
bacterial tracheitis
Figure 4.​ Diagram of PIV Pathogenesis ● Antecedent PIV infection of ​lower airways may
predispose to ​bacterial pneumonia
D. CLINICAL MANIFESTATIONS ● Non-respiratory complications (rare)
○ Aseptic meningitis, encephalitis, acute
● Fever
disseminated encephalomyelitis,
● Rhinorrhea rhabdomyolysis, myocarditis, and pericarditis
● Cough
● Diarrhea G. MANAGEMENT
● Parotitis
● EXCELLENT prognosis with no pulmonary
● Hoarseness
● Pharyngitis sequelae
● No specific antiviral drug
● Croup
● For Croup (Steeple Sign)
● Steeple sign
○ Corticosteroids, dexamethasone (oral or IV),
E. DIAGNOSIS
budesonide nebulization improve the
symptoms within 6 hours
● The diagnosis of PIV infection in children is often
■ Single dose (0.6 mg/kg in the ER)
based only on clinical and epidemiologic criteria
■ Nebulized epinephrine (either racemic
● Croup epinephrine 2.25% solution, 0.05 to 0.1
○ Clinical diagnosis for RSV
ml/kg/dose)
○ Must be distinguished from foreign body
■ Maximum dose is 0.5 ml/kg/dose 1:1000,
aspiration, epiglottis, pharyngeal abscess, Max dose 5 mL
and subglottic hemangioma
■ Children should be observed after 2 hours
○ Characteristics of croup: STEEPLE SIGN
■ Oxygenation and antipyretics is
or Wine Bottle Sign reasonable for management of PIV
■ Tapering of the upper trachea on a frontal
infection
chest radiograph reminiscent of a church
steeple
V. RESPIRATORY SYNCYTIAL VIRUS ( RSV )

⭐ Chapter 260 Nelson Textbook of Pediatrics 20th

Edition

● Major cause of bronchiolitis and viral pneumonia

in children <1 y/o
● Most important respiratory tract pathogen of
early childhood

A. ETIOLOGY
● Enveloped RNA virus with a single-stranded
negative-sense genome
● Replicates entirely in the cytoplasm of infected
cells
● Matures by budding from the apical surface of the
cell membrane

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● Has a ​non-segmented genome​, it ​CANNOT
undergo antigenic shift by reassortment like the
influenza viruses do
● Family: Paramyxoviridae (same with
parainfluenza and measles)
● Subfamily: Pneumovirinae
● 2 Antigenic Subgroups:
○ differentiation based primarily on variation in 1
of 2 surface proteins
■ G glycoprotein
● Responsible for attachment
B. EPIDEMIOLOGY
● Worldwide distribution
● Transplacentally acquired anti-RSV maternal
immunoglobulin G serum antibodies
○ Provide partial but incomplete protection if
concentration is high enough
● Breastfeeding provides substantial protection
against severe disease to female infants but
NOT to male infants
● All RSV diseases of the lower respiratory tract
(excluding croup) have their ​highest incidence at
6 wk to 7 mo of age and decrease in frequency
thereafter
● Bronchiolitis and pneumonia resulting from RSV
are more common in boys than in girls by a ratio
of approximately 1.5 : 1
● The incubation period from exposure to first
symptoms is approximately 3 - 5 days
C. PATHOPHYSIOLOGY
● Bronchiolitis is caused by ​obstruction and
collapse of the small airways during expiration
● Infants are particularly apt to experience small
airway obstruction due to the ff reasons
○ Small size of their normal bronchioles (airway
resistance is proportional to 1/radius)
● Airway narrowing likely is caused by
○ Virus-induced necrosis of the bronchiolar
epithelium
○ Hypersecretion of mucus
○ Round-cell infiltration and edema of the
surrounding submucosa
● Changes result in
○ Formation of mucus plugs obstructing
bronchioles
○ Consequent hyperinflation or collapse of distal
lung tissue
D. CLINICAL MANIFESTATIONS
● Typically, the first sign of infection in infants is
rhinorrhea
○ Can be accompanied by
■ Cough (may be at the same time or after
an interval of 1 - 3 days)
■ Sneezing
■ Fever
● Inconstant sign in RSV infection
● Auscultation: diffuse fine inspiratory crackles and
expiratory wheezes
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● CXR: normal (30 % cases) while 70 % showing
hyperexpansion of the chest, peribronchial
thickening, and interstitial infiltrates
● If the illness progresses
○ Cough and wheezing worsen
■ Air hunger ensues with increased
respiratory rate
○ Intercostal and subcostal retractions
○ Hyperexpansion of the chest, restlessness
○ Peripheral cyanosis
● SEVERE (life-threatening):
○ Central cyanosis,
○ Tachypnea of > 70 breaths/min
○ Listlessness
○ Apneic spells
○ Chest may be significantly hyperexpanded
and almost silent to auscultation because of
poor air movement
E. DIAGNOSIS
● Bronchiolitis is a clinical diagnosis
● The most important diagnostic concern is to
identify bacterial or chlamydial involvement
● When bronchiolitis is NOT accompanied by
infiltrates on chest radiographs, there is little
likelihood of a bacterial component
● In infants 1 - 4 mo of age, interstitial pneumonitis
may be caused by ​Chlamydia trachomatis
○ There may be a history of conjunctivitis, and
the illness tends to be of subacute onset
○ Coughing and inspiratory crackles may be
prominent, but wheezing is not
○ Fever is usually absent
● DEFINITIVE DIAGNOSIS of RSV infection is
based on the detection in respiratory
secretions of live virus by cell culture
● Presence of viral RNA is strongly supportive in the
right clinical setting
○ Detected by
○ Molecular diagnostic test using reverse
transcription PCR
○ Viral antigens
● Sensitivity: (Most sensitive) RT-PCR > Culture >
Antigen Test (Least sensitive)
● Optimal specimen: ​aspirate of mucus or a
nasopharyngeal wash from the child’s posterior
nasal cavity
F. MANAGEMENT
● The treatment of ​uncomplicated cases of
bronchiolitis is symptomatic
● Humidified oxygen and suctioning
○ Usually indicated for hospitalized infants who
are hypoxic
● Corticosteroid therapy is not indicated except in
older children with an established diagnosis of
asthma, because its use is associated with
prolonged virus shedding and is of no proven
clinical benefit
● In nearly all instances of bronchiolitis,
antibiotics are not useful​, and their
inappropriate use contributes to development of
antibiotic resistance
8

● Ribavirin
○ Antiviral agents delivered through an oxygen
hood, face mask, or endotracheal tube with
use of a small-particle aerosol generator most
of the day for 3 - 5 days
● Monoclonal antibody ​PALIVIZUMAB is licensed
for ​prophylaxis in high-risk infants
● PROGNOSIS:
○ Recurrent wheezing in 30-50% of children
with severe RSV bronchiolitis in infancy
○ The likelihood of recurrence is increased in
the presence of an allergic diathesis
○ With a clinical presentation of bronchiolitis in a
patient older than 1 yr of age
■ Increasing probability that, although the
episode may be virus induced, this is
likely the first of multiple wheezing attacks
that will ​later be diagnosed as
hyperreactive airways disease or
asthma
● PREVENTION:
○ Most important preventive measures are
aimed at blocking nosocomial spread
○ Wear PPE when handling infected infants
○ Passive Immunoprophylaxis:
■ Administration of PALIVIZUMAB
● 15 mg/kg IM once a month
■ Those considered for treatment:
● < 29 wk of gestation in the 1st yr of
life
● < 32 wk of gestation, who have
chronic lung disease of prematurity in
the 1st year of life
● < than 1 y/o with hemodynamically
significant CHD
● Children 24 mo or younger w/
immunosuppression
● Infants who have congenital or
neuromuscular disease in the 1st
year of life
● Administration in the 2nd yr of life
is recommended for children
○ Required 28 or more days of
oxygen after birth
○ Ongoing treatment for chronic
pulmonary disease
VI. CORONAVIRUS
● Common ​causes of acute respiratory illness in
infants and children
● Implicated in more serious diseases: croup,
asthma exacerbations, bronchiolitis, and
pneumonia
● Neonates and infants - may cause enteritis or
colitis
● Agent of meningitis or encephalitis but is
underappreciated
● Endemic in humans:
○ HCoVs 229E
○ OC43
○ NL63
○ HKU1
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● 2 epidemics in the past: significant respiratory
distress and high mortality rates in infected
individuals: SARS-CoV and MERS-CoV
A. ETIOLOGY
● Enveloped viruses of medium to large size
(80-220 nm)
● Possess the largest known single stranded
positive sense RNA genomes
● Encodes the protein nsp14-Exon which is the
first known RNA proofreading enzyme and is
likely the cause of the evolution of genome
● Derived their name from characteristic surface
projections of spike protein which give
crown-like appearance on negative-stain
electron microscopy
● In 2002-2003: Sars-CoV which is a novel
coronavirus caused the SARS outbreak,
SARS-like coronavirus in live animal market in
the Guangdong province in Southern China,
animal to human infection, asymptomatic
Chinese horseshoe bats feces have
SARS-like precursors, uses ACE-2
● In June 2012: novel coronavirus MERS-CoV
was isolated from a man with acute
pneumonia and renal failure in Saudi Arabia,
differ from SARS as less communicable, uses
dipeptidyl peptidase 4 as its cellular receptor
B. EPIDEMIOLOGY
● Seroprevalence: antibodies against 229E and
OC43 increase rapidly in early childhood. At
adulthood:90-100% of persons are
seropositive
● Some degree of strain-specific protection in
recent infections but reinfections are common
and occur despite the presence of
strain-specific antibodies
● Attack rates are similar in different age groups
● Infections peak during the winter and early
spring for each HCoV
● In the US: outbreaks of OC43 and 229E
occurred in 2- to 3- yr alternating cycles
● It has a worldwide distribution
● Studies using PCR and and viral culture
demonstrates that the virus occurs as
coinfection with other respiratory viruses
(RSV, Adenovirus, Rhinovirus, or Human
Metapneumovirus)
● OC43 and 229E are transmitted
predominantly through respiratory route
● Droplet spread is the most important although
aerosol transmission may occur as well
C. PATHOPHYSIOLOGY
● Principle target: ciliated cells
● Cytopathology from other HCovS may be from
direct cell infection and loss
● Infection with OC43 and 229E
● Associated with elaboration of cytokines
(interleukin-8 and interferen-γ)
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D. CLINICAL MANIFESTATIONS ○ Immunoglobulin G seroconversion may be
● Respiratory infections: delayed for up to 4 weeks
○ Cold symptoms ● Mainstay of early diagnosis is RT-PCR
■ Indistinguishable from other respiratory
viruses F. MANAGEMENT
○ Ave. incubation period: 2 - 4 days ● No available antiviral agents for clinical use
○ MOST COMMON SYMPTOMS: ● Treatment is primarily SUPPORTIVE
■ Rhinorrhea, cough, sore throat, ● A potential vaccine target is the viral spike protein,
malaise, and headache which could be delivered as a recombinant protein
○ Fever (30 %) or via viral or DNA vectors.
○ Wheezing in asthmatic children BUT lower ○ Approach appears to be effective against
frequency and severity compared to closely related strains of SARS-CoV but not
rhinovirus and RSV necessarily early animal or human variants.
○ URTI
■ Acute otitis media
● Can be isolated from middle ear fluid VII. RHINOVIRUS
*Similar to RSV or rhinovirus ● Most frequent cause of common cold in both adults
● Non-respiratory Sequelae and children
○ Gastrointestinal disease, particularly in young ● Associated with lower respiratory infections
children ● HRVs do not grow in culture
○ Characterized by: ● Molecular diagnostic tools (e.g. PCR) revealed that
■ diarrhea, bloody stools, abdominal HRVs are leading causes of both mild and serious
distention, bilious gastric aspirates, and respiratory illness in children
classic necrotizing enterocolitis
● SARS-associated Coronavirus A. ETIOLOGY
○ 2 Phases: ● Picornaviridae family
■ Viral Replication
● HRVA​ and ​HRVB
■ Immunologic Phase
○ Identified via ​immune antiserum virus typing
○ Incubation: 10 days ● HRVC
○ Clinical Manifestations:
○ Identified by​ reverse transcriptase PCR
■ Non-specific
○ Genetically distinct and diverse species
■ Fever, cough, malaise, coryza, chills or
rigors, headache, and myalgia B. EPIDEMIOLOGY
■ Coryza - more common in children < 12
● Distributed worldwide
y/o
● HRVC - more strongly associated with ​Lower
■ Systemic symptoms - in teenagers
● MERS-Coronavirus Respiratory Infection and asthma
● Persistence in a community over an extended
○ Incubation: 10 days
period
○ Less transmissible that SARS-CoV
○ Symptoms: ● HRVC ​=​ seasonal
○ Exchanges dominance with HRVA
■ Acute respiratory infection
● Rhinoviruses are ​major infectious triggers for
■ Fiver higher than 38°C (100.4°F)
■ Cough asthma among young children
● Peak incidence in tropical countries during the
■ Pulmonary parenchymal disease
rainy season, from June to October
● Pneumonia
● ARDS
C. PATHOPHYSIOLOGY
E. DIAGNOSIS ● Infect respiratory epithelial cells via ​intercellular
● Conserved PCR primers for coronaviruses in adhesion molecule-1​; some may utilize the
low-density lipoprotein receptor
multiplex RT-PCR viral diagnostic panels now
allows widely available and sensitive detection of ● No known receptor for HRVCs
the viruses ● Infection begins in the nasopharynx -> nasal
mucosa -> bronchial epithelial cells (in some
● The diagnosis of SARS-CoV infection can be
confirmed by cases)
○ Serologic testing ○ Infection of bronchial epithelial cells in vitro
induces secretion of ​inflammatory cytokines
○ Detection of viral RNA using RT-PCR
○ Isolation of the virus in cell culture and chemokines
● Serology for SARS-CoV ● Pathogenic effects due to host immune
response​; rhinoviruses do not cause significant
○ Sensitivity and specificity approaching
100% direct cellular damage
○ BUT Antibodies are not detectable until 10 ● HRV-specific nasal ​IgA = detected on ​day 3 after
infection
days after the onset of symptoms
● Serum​ IgM and IgG​ = after​ 7-8 days

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● Neutralizing IgG may prevent or limit severity of G. MANAGEMENT
illness following reinfection ● Supportive care = mainstay of treatment
● Exposure to allergen and elevated IgE ○ Analgesics
predispose patients with asthma to more severe ○ Decongestants
respiratory symptoms in response to HRV infection ○ Antihistamines
○ May be due to ​abnormalities in host response ○ Antitussives
to HRV infection ○ Antibiotics (for bacterial superinfections)
■ Leads to ​impaired apoptosis and increased ● Good handwashing remains the mainstay of
viral replication prevention
○ Should be reinforced frequently, especially in
D. CLINICAL MANIFESTATIONS young children which the predominant vectors for
● 15% are asymptomatic disease
● Incubation period of 1-4 days
○ Sneezing, nasal congestion, rhinorrhea, sore
VIII. ROTAVIRUS, CALICIVIRUS AND
throat
ASTROVIRUS
○ Cough and hoarseness in some
○ Fever is less common
● Symptoms frequently more severe and last longer A. ETIOLOGY
in children ● In early childhood, the single most important cause of
○ Symptoms may last up to day 10 severe dehydrating diarrhea is Rotavirus infection
● Viral shed as long as 3 weeks ● Rotaviruses
● HRVs are the most prevalent agents associated ○ Reoviridae family and cause disease virtually all
with ​acute wheezing, otitis media, and mammals and birds
hospitalization for respiratory illness ​in ○ wheel- like, triple-shelled double stranded RNA
children ○ Rotavirus strains are species specific and do not
● Important cause of severe pneumonia and cause disease in heterologous hosts.
exacerbation of asthma or COPD in adults ● Caliciviruses
● HRV-associated hospitalizations ○ Caliciviridae family
○ More frequent in young infants and in children ○ Most common cause of gastroenteritis
with a history of asthma or wheezing outbreaks​ in older children and adults
● HRVC may be more pathogenic than others ○ also causes rotavirus-like illness in young infants
○ have been named for locations of initial
E. DIAGNOSIS outbreaks
● Culture is labor intensive and low-yield ■ Norwalk, Snow Mountain,Montgomery and
● RT-PCR​ is a sapporo
○ Pros: ○ Caliciviruses and Astroviruses -small, round
■ Sensitive virues
■ Specific ● Astroviruses
○ Cons: ○ Astroviridae family
■ Does not identify HRV type ○ Important agents of viral gastroenteritis in
■ Cannot distinguish between newly acquired young children ​with high incidence in both
vs prolonged shedding developing and developed coutries
● Serology = impractical due to great number of HRV ● Enteric Adenovirus
serotypes ○ Common cause of viral gastroenteritis in
● Presumptive clinical diagnosis = not specific infants and children
● Bacterial culture or antigen testing ○ Only serotype​ 40​ and​ 41​ causes ​gastroenteritis
○ Rules out strep pharyngitis
● Rapid detection techniques B. EPIDEMIOLOGY
○ To lessen use of unnecessary antibiotics or ● Rotavirus
procedures ○ most common in winter months
○ tends to be more severe in patients 3-23 months
F. COMPLICATIONS ○ <3months are relatively protected by
● Sinusitis transplacental antibody and possibly
● Otitis media breastfeeding
● Asthma exacerbation ○ spread efficiently via​ fecal-oral route
● Bronchiolitis ○ outbreaks are common in children’s hospitals
● Pneumonia and childcare centers
● Death (rarely) ○ virus is shed in stool at very high concentration
● Childhood asthma before and for days after clinical illness
○ HRV-associated wheezing during infancy is a ● Astroviruses
significant factor for development ○ common cause of mild-moderate watery
○ Genetic variants at the 17q21 locus diarrhea ​in children and infants, uncommon in
adults

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○ hospital outbreaks is common
● Enteric Adenovirus
○ gastroenteritis occurs year-round
○ mostly children younger 2 year of age
● Calicivirus
○ best known for causing ​large, explosive
outbreaks​ among children and adults
○ in setting such as schools, cruise ships and
hospitals
○ often a single food​, such as shellfish or water
used in food preparation is identified as source
C.PATHOPHYSIOLOGY
● Viruses that cause human diarrhea selectively
infects and destroy villus tip cells​ thus lead to:
a.decreased absorption of salt and water and an
imbalance in the ratio of intestinal fluid
absorption to secretion
b.diminished disaccharide activity and
malabsorption of complex carbohydrates,
particularly​ lactose
● Most evidence supports altered absorption ​as the
more important factor in the genesis of viral
diarrhea
D. CLINICAL MANIFESTATION
● Rotavirus Infection
○ incubation period of ​<48 hours (range 1-7days)
with mild to moderate fever as well as vomiting
○ followed by the onset of frequent, watery stools
○ all 3 symptoms are present in 50-60% of cases
○ stool is without gross blood or white blood cells
○ most severe disease typically occurs among
4-36 months of age
● Adenovirus enteritis
○ tend to cause ​diarrhea of longer duration​,
often​ 10-14 days
● Norwalk Virus
○ has a short incubation period (12-hr)
○ vomiting and nausea tend to predominate
○ duration is brief and usually consisting 1-3 days
of symptoms
○ The clinical and epidemiologic picture of
norwalk virus often ​closely resembles
so-called food ​poisoning from preformed
toxin​ ​S.aureus and B.cereus.
E. DIAGNOSIS
● In most cases, a satisfactory diagnosis can be
made on the ​basis of clinical and epidemiologic
features.
● ELISA
○ >90% specificity and sensitivity
○ available for detection of group A rotavirus,
calicivirus and enteric adenovirus in stool
samples
● The diagnosis of viral gastroenteritis should
always be questioned​ in patients with persistent
or high fever, blood or white blood cells in the
stool, or persistent severe or bilious vomiting,
especially in the absence of diarrhea
● Most common finding​ in children with severe viral
enteritis:​ Isotonic dehydration with acidosis
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● Stools are free of blood and leukocytes
F. MANAGEMENT/TREATMENT
● TREATMENT
○ Main goal of treatment of viral enteritis: Avoiding
and treating dehydration
○ Secondary goal​: Maintenance of the nutritional
gastroenteritis
○ No routine role for antiviral drug ​treatment for
viral gastroenteritis
○ No benefit and significant risk for serious side
effects: ​anti-emetics or anti-diarrheal drugs
○ Therapy with probiotics ​organism such as
lactobacillus s​ pecies- ​helpful only in mild
cases ​and ​not​ in dehydrating disease
● SUPPORTIVE TREATMENT
○ After rehydration has been achieved, resumption
of a normal diet for age has been shown to result
in a more rapid recovery
G. PROGNOSIS AND PREVENTION
● Children may be infected with rotavirus each year
during the 1st year of life but each subsequent
infection decrease in severity
● PREVENTION
○ Good hygiene reduces the transmission of viral
gastroenteritis, but even the most hygienic
societies, virtually all children become infected
as a result of efficiency of infection of the
gastroenteritis virus
● VACCINE
○ A ​trivalent rotavirus vaccine was linked to an
increased risk for intussusception ​especially
during 3-14 day period after the 1st dose and 3-7
day period after the 2nd dose
○ A live, oral ​pentavalent ​rotavirus protect against
rotavirus gastroenteritis when administered as a
3 dose at a 2,4 and 6 month of age
○ new attenuated ​monovalent rotavirus vaccine
administered as 2 oral doses at 2 and 4 months
of age, and is effective in prevention of all 4
common serotype of human rotavirus,
IX. HUMAN PAPILLOMAVIRUSES
A. ETIOLOGY
● Papillomaviruses are small, DNA containing that are
ubiquitous in nature
● Strains specific
● Most HPV related infections in children and
adolescents are benign
● Cause a variety of proliferative cutaneous and
mucosal lesion:
○ common skin warts
○ benign and malignant anogenital tract lesions
○ oropharyngeal cancers
B. EPIDEMIOLOGY
● HPV infection of the​ skin are common
○ all transmission is presumably from person to
person
12

○ common warts including palmar, and plantar are
frequently seen in children and adolescents
○ typically infect the hands and feet, common
areas of frequent trauma
● HPV is the most prevalent viral sexual transmitted
infection in U.S
○ sexual transmission
○ most have their first infection within the 3 yr
beginning sexual intercourse.
○ greatest risk for HPV in seuxually active
adolescents is exposure to new sexual
partners or having more than 1 partner.
● In adolescents, HPV DNA is most commonly
detected ​without evidence of any lesion and hence
does not represent true infection.
● Most common clinically detected lesion in
adolescents women is the cervical lesion termed
low-grade squamous intraepithelial lesion (LSIL)
● Some ​infants may acquire papillomaviruses during
passage an infected birth canal leading to j​uvenile
laryngeal papillomatosis (respiratory
papillomatosis)
● Genital warts appearing in childhood may result from
sexual abuse, with HPV transmission during abusive
contact.
C. PATHOGENESIS
● Initial HPVl infection of the cervix is by ​viral invasion
of the ​basal cells​ of the epithelium
● Evidence of productive viral infection occurs in
benign lesion such as external genital warts and
LSILs
● Low risk HPV types 6 and 11 are most commonly
found in genital warts
● High risk 16 and 18
● Most infants with recognized genital warts are
infected with low-risk types , in contrast children with
history of sexual abuse consisting of mixed low and
high risk type
D. CLINICAL MANIFESTATION
● SKIN LESION
○ proliferative, papular and hyperkeratotic
○ common warts are - raised circinate lesion with
keratinized surface
○ multiple warts are common and may create
mosaic patter
● GENITAL WARTS
○ May be found throughout the perineum around
the anus, vagina and urethra
○ External genital warts can be flat, dome shaped,
keratotic, pedunculated and cauliflower shaped
● LARYNGEAL PAPILLOMATOSIS
○ Median age at diagnosis is 3 yr.
○ children present with hoarseness, an altered cry
and sometimes stridor
○ occlude upper airway
○ lesion may recur within weeks of removal,
requiring frequent surgery
E. DIAGNOSIS
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● Diagnosis of external genital warts and common
warts reliably determined by visual inspection of a
lesion by an experienced observe and does not
require additional test for confirmation
● Biopsy should be considered if diagnosis is uncertain
● Screening for cervical cancer in young women -
papanicolaou smear or liquid based cytology
● Diagnosis of juvenile laryngeal papillomatosis is
made based on laryngeal examination.
F. TREATMENT
● No effective antivirals available
● Most common warts eventually resolve
spontaneously (plantar, plamar, skin)
● Skin warts can be destroyed by freezing (liquid
nitrogen) and areas of cervical dysplasia (genital
warts) by laser treatment
● Many slower (chemical) methods are used
(podophyllin, salicylic acid)
G. PROGNOSIS AND PREVENTION
● With all forms of therapy, genital warts commonly
recu and approximately half of children and
adolescents require a 2nd or 3rd treatment
● Prognosis of cervical disease is better with 85-90%
cure rates after single treatment with excision
procedure.
● PREVENTION
○ the only prevention is to avoid direct contact with
the lesion
○ condoms may reduce the risk for HPV
transmission
● VACCINE
○ GARDASIL
■ against HPV 6,11,16,18
■ Recommended for girls aged 9-26
■ 3 injections over 6 months
○ CERVARIX
■ HPV 16 and 18
■ recommended for girls aged 10-45
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Happy Peanuts Tiny Peanut Team 2:
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