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Rotavirus & Rotavirus Vaccine
ByDr. Asad Ramlawi
DGPHC & PH Beithlehem / Palestine
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
Lengthy (~5 days on average) and severe purging causes electrolyte depletion/ dehydration/ complications
Rotavirus often spreads beyond the intestines into the blood stream
Rotavirus can replicate in most organs
Rotavirus – Diarrhea/Vomiting/Fever plus viremia in 90% of infected children
Blutt et al. Rotavirus antigenemia in children is associated with viremia. PLoS Med 2007;4:e121.
Acute gastroenteritis• Virtually all children infected by age 3-5 years• “Democratic” virus• Highest rates of disease between 6-24 months• First infections are most severe
Natural infection confers immunity against subsequent severe re-infections• Vaccines mimic the protective first infection without
causing the severe illness
Worldwide distribution• accounts for ~5% of all deaths among children <5
years old
Epidemiology of rotavirus
Electron micrograph of rotavirusElectron micrograph of rotavirus
• Reovirus (RNA)• VP7 and VP4 antigens define virus serotype
and induce neutralizing antibody• 5 predominant strains in U.S. (G1-G4, G9)
and account for 90% of isolates• G1 strain accounts for 75% of infections• Very stable and may remain viable for weeks
or months if not disinfected
Rotavirus
Rotavirus Pathogenesis
• Entry through mouth
• Replication in epithelium of small intestine
• Replication outside intestine and viremia uncommon
• Infection leads to isotonic diarrhea
0
100
200
300
400
500
600
700
800
900Total N Tests Total N Positive
2001 2002 2003 2004 2005 2006 2007 20082000
Rotavirus seasonality (onset and peak) was very consistent during the pre-licensure period
“Winter gastroenteritis”
0
100
200
300
400
500
600
700
800
900Total N Tests Total N Positive
2001 2002 2003 2004 2005 2006 2007 20082000
Seasonality of rotavirus hospitalization rates, NVSN 2006-2008
0
20
40
60
80
100
120
140
160
January February March April May June
Month
Rot
avir
us h
ospi
tali
zati
on ra
te p
er 1
0,00
0 ch
ildr
en <
3 ye
ars
2006
2007
2008
Total AGE and Rotavirus AGE cases in NVSN, Jan-April, 2006-2008
405
481
283
207259
180
100
200
300
400
500
600
2006 2007 2008
Num
ber o
f cas
es
Total AGE Rotavirus
51 % EIA+
54 % EIA+
6 % EIA+
Centers for Disease Control and Prevention. Delayed onset and diminished magnitude of rotavirus activity – United States, November 2007-May 2008. MMWR 2008; 57:697–700.
Rotavirus hospitalization and ED rates, NVSN 2006-2008
0
5
10
15
20
25
30
2006 2007 2008
Year
Hos
pita
liza
tion
rat
e pe
r 10
,000
ch
ildr
en <
3 yr
s
0
50
100
150
200
250
300
350
ED
rate per 10,000 children <3 yrs
Hospitalization ED
6 Independent US Hospital-based Studies Reported 85-95% Reduction in Rotavirus Cases
2008 vs Previous Years
1. Clark F et al. 2. Daskalaki I et al. 3. Patel JA et al. 4. Harrison CJ et al. 5. Hatch S et al. 48th ICAAC / 46th IDSA Washington DC October 25-28, 2008; 6. Chang H et al. ACIP Atlanta October 22-23, 2008
Philadelphia, PA1
87% reduction in Community acquired cases (Children's Hospital of Philadelphia)
Kansas City, MO4
88% reductionHospitalization
Galveston, TX3
94% reductionHospitalization or ED
Philadelphia, PA2
94% reductionHospitalization (St Chris)
New York State6
85% reductionHospitalization/ED
Worcester, MA5
95% reductionHospitalization, ED , Outpatient
Epidemiological Implications
Monitoring for age redistribution:
Will severe rotavirus infections be deferred to older ages?
Varicella
Rotavirus Epidemiology
• Reservoir Human-GI tract
• Transmission Fecal-oral, fomites
• Temporal Fall and winter pattern (temperate areas)
• Communicability 2 days before to 10days after onset
Rotavirus Disease in the United States
• Annually* responsible for:– More than 400,000 physician visits
– More than 200,000 emergency dept visits
– 55,000-70,000 hospitalizations
– 20-60 deaths
• Annual direct and indirect costs are estimated at approximately $1 billion
*prevaccine era*prevaccine era
Rotavirus hospitalization and ED rates, NVSN 2006-2008
0
5
10
15
20
25
30
2006 2007 2008
Year
Hos
pita
liza
tion
rat
e pe
r 10
,000
ch
ildr
en <
3 yr
s
0
50
100
150
200
250
300
350
ED
rate per 10,000 children <3 yrs
Hospitalization ED
<1% coverage with >=1
dose
56% coverage with >=1
dose
31% coverage with >=1
dose
Estimates of annual rotavirus infection burden for U.S. children <3 years old, 2006
Payne DC, et al. Active, population-based surveillance for severe rotavirus gastroenteritis in children in the United States. Pediatrics 2008; 122:1235-43.
Risk Groups for Rotavirus Diarrhea
• Groups with increased exposure to virus– Children in child care centers
– Children in hospital wards (nosocomial rotavirus)
– Caretakers, parents of these children
– Children, adults with immuno- deficiency related diseases (e.g. SCID, HIV, bone marrow transplant)
Rotavirus 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
Rotavirus Complications
• Severe diarrhea
• Dehydration
• Electrolyte imbalance
• Metabolic acidosis
• Immunodeficient children may have more severe or persistent disease
Rotavirus Immunity
• Antibody against VP7 and VP4 probably important for protection
• First infection usually does not lead to permanent immunity
• Reinfection can occur at any age
• Subsequent infections generally less severe
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
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
Rotavirus Vaccine Effectiveness
Condition
Any rotavirus diarrhea
Severe diarrhea
Effectiveness74%-87%
95%-98%
Both vaccines significantly reduced physician visits for diarrhea, and reduced rotavirus-related hospitalization
Rotavirus VaccineRecommendations
• 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
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
• For both rotavirus vaccines– maximum age for first dose is 14 weeks 6
days– minimum interval between doses is 4 weeks– maximum age for any dose is 8 months 0
days
Rotavirus VaccineRecommendations
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
Rotavirus VaccineRecommendations
• 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
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
• For both rotavirus vaccines– maximum age for first dose is 14 weeks 6
days– minimum interval between doses is 4 weeks– maximum age for any dose is 8 months 0
days
Rotavirus VaccineRecommendations
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
• ACIP did not define a maximum interval between doses
• If the interval between doses is prolonged, the child can still receive the vaccine as long as it can be given on or before the child’s 8 month birthday
• It is not necessary to restart the series or add doses because of a prolonged interval between doses
Rotavirus VaccineRecommendations
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
• 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 VaccineRecommendations
MMWRMMWR 2009;58:(RR-2) 2009;58:(RR-2)
Rotavirus VaccineContraindications
• Severe allergic reaction to a vaccine component or following a prior dose of vaccine
Rotavirus VaccinePrecautions*
• Altered immunocompetence
• Acute, moderate or severe gastroenteritis or other acute illness
• History of intussusception
*the decision to vaccinate if a precaution is present should be made on a case-by-case risk and benefit basis
Vaccine Effectiveness
RotaTeq® & Rotarix® Clinical Trials Very large, multi-national clinical trials 90-100% effective in preventing severe rotavirus
gastroenteritis 74-85% effective against rotavirus of any severity
Post-licensure (RotaTeq®) case/control studies in US Texas Children’s Hospital (Houston) * New York * New Vaccine Surveillance Network (NVSN)
* presented to ACIP, Oct. 2008
Immunosuppressed Household Contacts of Rotavirus Vaccine Recipients
• Infants living in households with persons who have or are suspected of having an immunodeficiency disorder or impaired immune status can be vaccinated
• Protection provided by vaccinating the infant outweighs the small risk for transmitting vaccine virus
Pregnant Household Contacts of Rotavirus Vaccine Recipients
• Infants living in households with pregnant women should be vaccinated– majority of women of childbearing age have
pre-existing immunity to rotavirus– risk for infection by vaccine virus is
considered to be very low
Rotavirus VaccineAdverse Reactions
Vomiting 15%-18%Diarrhea 9%-24%Irritability 13%-62%Fever 40%-43%Serious adverse Nonereactions
Rotavirus Vaccine Storage and Handling
• Store at 36-46o F (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
THANK YOU !