Rotavirus

• First identified as cause of diarrhea in 1973

• Most common cause of severe diarrhea in infants
and children
• Nearly universal infection by 5 years of age
• Responsible for up to 500,000 diarrheal deaths
each year worldwide
 Rotavirus is the most common cause of severe,
dehydrating diarrhea among children worldwide

Each year it causes:

• 111 million cases
• 25 million outpatient visits
• 2 million hospitalizations
Global surveillance shows that
• Over
40% of500,000
diarrheal deaths
hospitalizations are due to
rotavirus
Electron micrograph of rotavirus
 ROTA Virus
Rotavirus is a double-stranded RNA virus of the family Reoviridae. The
virus is composed of three concentric shells that enclose 11 gene
segments. The outermost shell contains two important proteins: VP7, or
G-protein, and VP4, or P-protein. VP7 and VP4 induce neutralizing
antibodies that are believed to be involved in immune protection. From
1996 through 2005, five genotypes of rotavirus (G1P[8], G2P[4], G3P[8],
G4P[8] and G9P[8]) accounted for 90% of strains isolated from children

younger than age 5 years in the United States. Of these, genotype G1P[8]
accounted for more than 75% of strains
Rotavirus Pathogenesis
• Entry through mouth, Replication in epithelium of small intestine
• Replication outside intestine and viremia uncommon
• Infection leads to isotonic diarrhea.
• First infection usually does not lead to permanent immunity
• Reinfection can occur at any age ,Subsequent infections generally less
severe
 ROTA Virus- Clinical features
● Short incubation period(usually less than 48 hours)

● First infection after age 3 months generally most severe

● May be asymptomatic or result in severe dehydrating diarrhea with fever

and vomiting

● Gastrointestinal symptoms generally resolve in 3 to 7 days

Infants younger than age 3 months have relatively low rates of rotavirus
infection, probably because of passive maternal antibody, and possibly because
of breastfeeding. Rotavirus infection of adults is usually asymptomatic but may
cause diarrheal illness
Reservoir
The reservoir of rotavirus is the gastrointestinal tract and stool of infected
humans.
Transmission
Rotaviruses are shed in high concentration in the stool of infected persons.
Transmission is by fecal-oral route, both through close person-to-person
contact and by fomites (such as toys and other environmental surfaces
contaminated by stool).
Communicability
Rotavirus is highly communicable, Infected persons shed large quantities of
virus in their stool beginning 2 days before the onset of diarrhea and for up to
10 days after onset of symptoms. Rotavirus may be detected in the stool of
immunocompromised persons for more than 30 days after infection. Spread is
common within families, institutions, hospitals, and child care settings.
 Rota Vaccine
In 1998, a rhesus-based tetravalent rotavirus vaccine

(RRV-TV, Rotashield) was licensed and recommended for routine

immunization of U.S. infants. However, RRV-TV was withdrawn
from the U.S. market within 1 year of its introduction because of
its association with intussusception.

The risk of intussusception was most elevated (more than a 20-fold

increase) within 3 to 14 days after receipt of the first dose of RRV-
TV, with a smaller (approximately 5-fold) increase in risk within 3
to 14 days after the second dose.
 Rotavirus Vaccines

• RV1 (Rotarix ) ®

–Contains one strain of live attenuated human

rotavirus (type G1P[8])
–provided as a lyophilized powder that is
reconstituted before administration
–Contains no preservatives or thimerosal.
–Vaccine dose of ONE ml / vial
 Rotavirus Vaccines

• RV5 (RotaTeq ) ®

– Contains five reassortant rotaviruses developed from human

and bovine parent rotavirus strains
– Vaccine viruses suspended in a buffer solution
– Contains no preservatives or thimerosal .
– Vaccine dose of TWO ml / vial
 Rotavirus Vaccines – RV5 and RV1

RV5 RV1
RotaTeq (Merck & Co.) Rotarix (GSK)

Bovine rotavirus with

single human rotavirus Human rotavirus
gene substitution

G1 G3

P[8] G1P[8]
G2 G4

13
 Rotavirus Vaccine Effectiveness
Condition Effectiveness
Any rotavirus diarrhea 74%-87%
Severe diarrhea
95%-98%

Both vaccines significantly reduced physician

visits for diarrhea, and reduced rotavirus-
related hospitalization
 Duration of Immunity

The duration of immunity from rotavirus vaccine is

not precisely known. In the main clinical trials
described , good efficacy was demonstrated through
2 rotavirus seasons or to age 2 years for both
vaccines
 Rotateq Doses
–Three doses
–First dose at 2 months , Second dose at 4 months
and Third dose at 6 months

–maximum age for first dose is 12 weeks .

–minimum interval between doses is 4 weeks
–maximum age for second or third dose is 8 months
0 days
 Rotarix Doses
–TWO doses
–First dose at 2 months , Second dose at 4 months
–maximum age for first dose is 12 weeks .
–minimum interval between doses is 4 weeks
–maximum age for second dose is 24 weeks
–It is not necessary to restart the series or add
doses because of a prolonged interval between
doses
 Rotavirus Vaccine
Recommendations
• Routine immunization of all infants without a contraindication

• 2 (RV1) or 3 (RV5) oral doses beginning at 2 months of age

• Subsequent doses in the series should be separated from the

previous dose by 1 to 2 months.

• The providers not repeat the dose if the infant spits out or
regurgitates the vaccine

• Any remaining doses should be administered on schedule

 Rotavirus Vaccine
Recommendations
• Completed the series with the same product whenever possible

• If the product used for a prior dose or doses is not available or is not
known continue or complete the series with the product that is available

• If any dose in the series was RV5 (RotaTeq) or the vaccine brand used for
any prior dose in the series is not known, a total of three doses of rotavirus

vaccine should be administered

 Rotavirus Vaccine Contraindications
• Severe allergic reaction to a vaccine component or following a prior dose of
vaccine

• latex rubber is contained in the RV1 oral applicator

• History of intussusception
Rotavirus vaccine should generally not be administered to infants with acute,
moderate or severe gastroenteritis, or other acute illness until the condition
improves. However, infants with mild acute gastroenteritis or other mild acute
illness can be vaccinate.
 Rotavirus Vaccine
Adverse Reactions
Vomiting 15%-18%
Diarrhea 9%-24%
Irritability 13%-62%
Fever 40%-43%
Serious adverse None
reactions
 Rotavirus Vaccine
Storage and Handling
• Store at (2-8o C) and protect from light
• RV1 diluent may be stored at room temperature
• Do not freeze vaccines or diluent
• Administer RV5 as soon as possible after being
removed from refrigeration

• RV1 should be administered within 24 hours of

reconstitution
 Influenza virus

Influenza is a highly infectious viral illness. The name “influenza” originated

in 15th century Italy, from an epidemic attributed to “influence of the stars.”

The first pandemic, or worldwide epidemic, that clearly fits the description of

influenza was in 1580. At least four pandemics of influenza occurred in the

19th century, and three occurred in the 20th century. The pandemic of

“Spanish” influenza in 1918–1919 caused an estimated 21 million deaths

worldwide. The first pandemic of the 21st century occurred in 2009–2010.

 Influenza virus
Influenza is a single-stranded, helically shaped, RNA virus of the
orthomyxovirus family. Basic antigen types A, B, and C are determined by
the nuclear material. Type A influenza has subtypes that are determined by
the surface antigens hemagglutinin (H) and neuraminidase (N).
There are 18 different known H antigens (H1 to H18) and 11 different known
N antigens (N1 to N11). Eight H subtypes (H1, H2, H3, H5, H6, H7,H9,
H10) and six N subtypes (N1, N2, N6, N7, N8, and N9) have been detected in
humans. Type B influenza is classified into two lineages: B/Yamagata and
B/Victoria .All strains of influenza A virus have been isolated from wild
birds, and some isolates of them cause severe disease both in domestic
poultry and, rarely, in humans.
Influenza virus
 Influenza virus
The nomenclature to describe the type of influenza virus is expressed in
this order: 1) virus type, 2) geographic origin where it was first isolated, 3)
strain number, 4) year of isolation, and 5) virus subtype
 Antigenic changes
Virus surface antigens hemagglutinin and neuraminidase continually change.
Changes in influenza viruses can take the form of antigenic drift or antigenic
shift.

Antigenic drift involves small mutations in the genes of influenza viruses that
lead to changes in HA and NA that accumulate over time, resulting in the
emergence of novel strains that the human immune system may not recognize.

These novel strains are the influenza virus’s evolutionary adaptations to a

strong population-wide immune response. Antigenic drift is the primary reason
people can get influenza more than once and why it is necessary to annually
review and update the composition of influenza vaccines. Antigenic drift, along
with waning immunity, results in annual influenza epidemics, since the
protection that remains from past exposures to similar viruses is incomplete.
Antigenic shift involves an abrupt, major change in one or both surface
antigens (H or H-N combination). Antigenic shifts are probably due to
genetic recombination (an exchange of a gene segment) between influenza
A viruses that affect humans and/or animals. An antigenic shift may result
in a worldwide pandemic if the virus is efficiently transmitted from person
to person. Pandemics are rare; since the late 19th century, five antigenic
shifts have led to pandemics in 1889-1891, 1918-1920, 1957-1958, 1968-
1969, and 2009-2010
 Influenza virus

CDC antigenically characterizes about 2,000 influenza viruses eve

ry year
to compare how similar currently circulating influenza viruses are
to those that were included in the influenza vaccine and to monitor
for changes in circulating influenza viruses. Antigenic
characterization can give an indication of the flu vaccine’s ability
to produce an immune response against the influenza viruses
circulating in people. This information also helps experts decide
what viruses should be included in the upcoming season’s influenz
a vaccine
 Influenza virus- Clinical Features
The incubation period for influenza is usually 2 days, but can vary from 1 to
4 days. Influenza illness can vary from asymptomatic infection to severe. On
average, about 8% of the U.S. population gets sick from influenza each
season .
Onset of influenza symptoms is sudden. Respiratory symptoms include
cough, sore throat, and runny or stuffy nose. Systemic symptoms generally
include fever, chills, headache, malaise, and myalgia. Vomiting and diarrhea
may also occur, especially in children. Recovery is rapid; fever usually
resolves within 3 to 4 days and other symptoms within approximately 7 days.
Some patients may have lingering asthenia (lack of strength or energy) for
several weeks.
 Influenza virus
Complications
• Secondary bacterial pneumonia
• Exacerbations of underlying respiratory conditions
• Otitis media
• Laryngotracheobronchitis
• Bronchitis
• Other less common complications may occur
 Laboratory Testing
• Influenza is usually suspected based on characteristic clinical
findings, particularly if influenza has been reported in the
community. Diagnostic tests include:
• Molecular assays (i.e., rapid molecular assays, reverse
transcription polymerase chain reaction (RT-PCR), and other
nucleic acid amplification tests)

• Antigen detection tests (i.e., rapid influenza diagnostic tests and

immunofluorescence assays)

• In addition to diagnostic testing for only influenza virus, the Flu

SC2 Multiplex Assay is a real-time RT-PCR test that detects and
differentiates RNA from SARS-CoV2, influenza A virus, and
influenza B virus in upper or lower respiratory specimens.
 Influenza Vaccine

Characteristics
Two types of influenza vaccine are available, inactivated influenza vaccine
(IIV) and live attenuated influenza vaccine (LAIV).

IIV is administered by the intra- muscular or intradermal route. Trivalent

vaccine contains three inactivated viruses: type A(H1N1), type A(H3N2), and
type B. Quadrivalent influenza vaccines were introduced for the 2013-2014
season. They contain the same antigens as trivalent vaccines, with the
exception that quadrivalent vaccines contain two type B strains. The vaccine
is available in both pediatric (0.25-mL dose) and adult (0.5-mL dose)
formulations
 Immunogenicity and Vaccine Efficacy
For practical purposes, the duration of immunity following IIV is less than 1
year because of waning of vaccine-induced antibody and antigenic drift of
circulating influenza viruses.
Influenza vaccine efficacy varies by: the similarity of the vaccine strain(s) to
the circulating strain ;the age , and health status of the recipient.
Vaccines are effective in protecting about 60% of healthy vaccinees
younger than 65 years of age from illness when the vaccine strain is similar
to the circulating strain.
Although the vaccine is not highly effective in preventing clinical illness
among the elderly, it is effective in preventing complications and death.
Some studies show that, among elderly persons, the vaccine is 50%–60%
effective in preventing hospitalization and 80% effective in preventing
 Vaccination Schedule and Use -IIV

Influenza activity peaks in temperate areas between late December and early
March. IIV should be offered as soon as it becomes available. Organized
vaccination campaigns generally should be scheduled no earlier than mid-
October. Although most influenza vaccination activities should be completed
by December (particularly for high-risk groups), providers should continue to
provide vaccine throughout influenza season.
One dose of IIV may be administered annually for persons 9 years of age or
older.
Children 6 months through 8 years of age receiving influenza vaccine for
the first time should receive two doses administered at least 28 days apart.
Inactivated influenza vaccine should be given by the intra- muscular (IM) .
 Influenza vaccine-When vaccine supply is limited

vaccination efforts should focus on delivering vaccination to the following

groups of persons:
 children 6 months–59 months of age;
 persons 50 years and older;
 persons with chronic pulmonary (including asthma), cardiovascular
(except hypertension), renal, hepatic, neurologic, hematologic, or
metabolic disorders (including diabetes mellitus)
 persons who are immunosuppressed .
 women who are or will be pregnant during the influenza season;
 healthcare personnel;
Vaccination can occur during any trimester. Only IIV should be administered
to pregnant women.
 Influenza vaccine

Contraindications and Precautions

● Severe allergic reaction (e.g., anaphylaxis) to a vaccine component or
following a prior dose of inactivated influenza
● Moderate or severe acute illness
● History of Guillain-Barre syndrome (GBS) within 6 weeks following a
previous dose of influenza vaccine.
Adverse Reactions
● Local reactions (soreness, redness) 15% - 20%
● Fever, malaise, myalgia less than 1%
● Allergic reactions (hives, angioedema, anaphylaxis) rare
Recombinant Influenza Vaccine (RIV)
RIV was first approved for use in 2013. The RIV manufacturing process
uses recombinant DNA technology and does not require an egg-grown
vaccine virus. The resulting vaccine contains recombinant hemagglutinin.
Live, Attenuated Influenza Vaccine (LAIV)
LAIV was first approved for use in the United States in 2003.
The viruses are cold-adapted and replicate effectively in the mucosa of the
nasopharynx. LAIV is administered intranasally. The vaccine is provided in
a manufacturer-filled, single use, intranasal sprayer; half of the dose is
sprayed into each nostril.
Vaccinated children can shed vaccine viruses in nasopharyngeal secretions
for up to 3 weeks.
Transmission of shed LAIV viruses from vaccine recipients to
unvaccinated persons has been documented but has not been reported to be
associated with serious illness.

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