Rotavirus Prevention and Control
Dr Simba Takuva, MBChB, MSc.
Outline of Presentation
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Introduction
Epidemiology and Disease Burden
The Rotavirus
Clinical Presentation
Prevention and Control
Vaccination
Surveillance
WHO Recommendations
Conclusion
Introduction
 Rotavirus (RV) is the commonest cause of severe
diarrhoeal disease in infants and young children
globally
 527 000 children die each year
 Children under 5 most vulnerable
 Majority in low-income countries (85%)
 Country-specific data show 80-90 children die every
day in Nigeria from the disease, 50-60 deaths occur
daily in Cameroon, and 10-12 in South Africa
 Estimated cost to healthcare system: USD 264 to 318
million per year
 Estimated societal costs: USD 890 to 1 billion per year
Epidemiology and Disease Burden
Causes of Death in Children Under 5
Worldwide, 2008
15%
Diarrhoea
Pneumonia
37%
19%
Other infections
Non communicable diseases
7%
22%
Neonatal causes
15% = 1.3 million deaths annually !
Black RE, Lancet 2010; 375:1969-1987
Epidemiology and Disease Burden
Epidemiology and Disease Burden
Transmission
 Primary mode of transmission is feacal to oral
 Highly communicable and transmissible
 Close person-to-person contact and environmental
surfaces are common vectors of transmission
 Incubation period is 1 – 3 days
Transmission
 Large quantities of virus are shed in stool from just prior
to onset of symptoms until about 10 days after onset
 Amount of virus shed in stool:
 10-100 billion virions/gram of stool !
 Amount of ingested virus required to cause infection:
 As few as 10 infective virions !
 Amount of stool that needs to be ingested to potentially
result in infection:
 ≈ 0.000001mg !
The Rotavirus
First recognized in 1973, rotavirus belongs
to the viral family Reoviridae
Its wheel-like shape under an electron
microscope earned it the name of “rota”
virus
The rotavirus genome consists of 11
double-stranded RNA segments, each
encoding one viral protein
 A triple-layered capsule surrounds the
RNA
Scientists have described seven rotavirus
groups (A to G)
Only groups A, B, and C infect humans
 Group A, which has multiple
strains, causes the majority of childhood
infections
Vaccine candidates are designed to protect
against Group A rotaviruses
The Rotavirus
 The G-type and P-type define the serotype
 They are critical to vaccine development
because they are the vaccine targets for
stimulating a protective immune response
SEROTYPES
Source : WWW.ROTAPICTURES/BU/EDU
 G1P[8] is the most common serotype worldwide and accounts for over two
thirds of rotavirus infections worldwide
 Infections with G1, G2, G3, G4, and G9 together comprise almost 95% of
rotavirus serotypes observed
Because the 2 gene segments that encode these proteins can segregate
independently, a typing system consisting of both G and P types is used. i.e.
G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G9P[6]
Clinical Presentation
Timeline of Rotavirus Pathogenesis
Source:
Clinical Presentation
Clinical Triad of Rotavirus Infection
Clinical Presentation
Pathogenesis
 The virus causes diarrhoea by three principle mechanisms:
 infection of villus epithelial cells causes cell
destruction, decreased absorption of salt and water, and
decreased disaccharidase activity, increasing the osmotic
load in the gut lumen
 stimulation of the enteric nervous system, leading to
increased fluid secretion
 direct enterotoxin effects of nonstructural protein 4
(NSP4), the first viral enterotoxin to be described
 The osmotic load in the gut and increased fluid secretion lead
to diarrhoea and, if unchecked and without fluid
replacement, can ultimately lead to dehydration and acidosis
Clinical Presentation
Complications
• The major complication is the dehydration, which can lead to
acidosis and eventually to circulatory collapse.
 Also been associated with
 aseptic meningitis, necrotizing enterocolitis, acute
myositis, hepatic abscess, pneumonia, Kawasaki
disease, SIDS and Crohn's disease
 Rotavirus induced gastroenteritis in children with
immunodeficiency may cause persistent infection lasting
weeks or months
 Self-limited illness in immunocompetant
Clinical Presentation
Diagnosis
 Mostly clinical
 Rapid antigen detection by ELISA of rotavirus in stool
specimens.
 Isolates may be further characterized by reversetranscriptase polymerase chain reaction
Clinical Presentation
 In infants, natural rotavirus infection confers protection against subsequent
infection
 By the age of 2 years, nearly every child in a cohort of children in Mexico
had experienced at least one rotavirus infection
 These children had greater protection against severe diarrhoea with
subsequent infections
 Two natural infections were required for 100% protection against
moderate-to-severe diarrhoea
 The first exposure to rotavirus also protected 87% (95% CI, 54%, 96%) of
children from having severe disease from the second infection
 The protection rates observed with one natural infection are similar to
those observed with vaccine-induced protection
 Vaccination protects 84% to 98% of children against severe outcomes of a
second rotavirus infection
 Thus, the vaccines are mimicking the protection rates of one natural
infection
Source: Velazquez, FRet al. N Engl J Med. 1996;335:1022-1028
Clinical Presentation
Probability of RV Infection by Age
Cumulative Probability of First and Subsequent Natural Rotavirus Infections during the
First Two Years of life (Source: Velazquez, FRet al. N Engl J Med. 1996;335:1022-1028.)
Treatment
Therapy for rotavirus-induced diarrhoea involves replacement of fluids and
electrolytes lost during infection.
Priorities
 feeding (breast milk or diluted formula in infants and lactose free
carbohydrate rich foods in older children) within 24 hours after onset of
illness
the use of oral rehydration therapy in children with mild or moderate
dehydration.
Fruit juices and soft drinks are not recommended due to their high glucose
content, low sodium content and high osmolarity.
Antibiotics, antisecretory drugs, antimotility drugs, absorbents and
antiemetics do not ameliorate acute infection, prevent reinfection or reduce
fluid losses during rotavirus induced gastroenteritis, and therefore do not
play a role in treatment.
Children with immunodeficiency disorders may be treated with rotavirusspecific immunoglobolin preparation. Administer orally to decrease shedding
and ameliorate disease .
Prevention and Control
 Infection Control
 Vaccination
Infection Control
In the Home and Day-Care Facilities
 Hand-washing areas
 Food-preparation areas
 Diaper-changing surfaces
 Diaper disposal containers
 Toys
In Hospital Areas and Clinics
 Hand-washing areas
 Medication-preparation areas
 Equipment
 Patient care areas
Rotavirus Vaccination
Rotavirus Vaccines
Vaccine Efficacy
Vaccine Safety
Rotavirus and HIV-infected infants
WHO - EPI Recommendations
Rotavirus Vaccines
 Two oral, live, attenuated rotavirus vaccines
 Rotarix (GlaxoSmithKline Biologicals,Rixensart, Belgium)
 RotaTeq (Merck & Co. Inc., West Point, PA, USA)
 Available internationally
 Both vaccines are considered safe and effective
 WHO now recommends that infants worldwide be vaccinated
against Rotavirus
 Vaccines differ in composition and dosing schedule
 Rotarix (RV1) is a monovalent vaccine given in a 2-dose
schedule
 Rotateq (RV5) is a pentavalent vaccine given in a 3-dose
schedule
Rotavirus Vaccines
Manufacturer
Genetic framework
Composition
Genotypes
Dosage Schedule
Route
Presentation
Efficacy against severe
disease
Virus shedding
RotaTeq
Rotarix
Merk & Co.
GSK
Bovine Rotavirus – WC3
Human Rotavirus-89-12
5 Human, Bovine reassortant
Single Human rotavirus
G1, 2, 3, 4 and [P8]
G1 [P8]
3 doses at 2, 4 and 6 months
2 doses at 2 and 4 months
oral
oral
liquid
Lysophilized-reconstituted
85%
95%
Up to 13 %
17 % - 27%
Rotavirus Vaccine Clinical Trials
Vaccine Efficacy
Rotavirus Efficacy in Clinical Trials in Africa and Asia
Vaccine
RV1 (Rotarix)
Region
Africa
RV5 (RotaTeq) Asia
RV5 (RotaTeq) Africa
Country
South Africa,
Malawi
Efficacy
62% (44% - 73%)
Bangladesh,
51% (13% - 73%)
Vietnam
Ghana, Kenya, 64% (40% - 79%)
Malawi
Madhi SA, et al. N Engl J Med 2010;362:289-298
Armah GE, et al. Lancet 2010;376:606-614
Zaman K, et al. Lancet 2010;376:615-623
Vaccine Efficacy
Factors to Consider in Rotavirus Efficacy
Efficacy of Rotavirus Vaccines by Mortality Stratum and Country
Mortality rate
RV vaccine
Countries were studies
defined by WHO efficacy estimates were performed
HIGH
50 – 64 %
46 – 72 %
Ghana, Kenya, Malawi,
Mali
Bangladesh, South Africa
INTERMEDIATE
72 – 85 %
Vietnam, the Americas
LOW
85 – 100 %
The Americas, Western
Pacific and Europe
Adapted from WHO. Wkly Epidemiol Rec 2009;84:533-40
Rotavirus Surveillance in South Africa
 Diarrhoea sentineal surveillance programme implemented in April 2009 by
the NICD
 Five hospitals in four provinces (Gauteng, North-West, Kwazulu Natal and
Mpumalanga)
 The aim of the programme is to evaluate the prevalence of rotavirus in
diarrhoea cases and to monitor the effect of the introduction of the Rotarix
vaccine into the EPI
 The rotavirus vaccine was introduced in August 2009
 Children < 5 years admitted (slept overnight in hospital) to one of the
sentinel hospitals for acute diarrhoea (3 loose stools in 24 hour period and
onset within 7 days) are eligible for enrolment in the surveillance
 Stool specimens are collected and tested at the NICD/NHLS and at the
Diarrhoeal Pathogens Research Unit, MEDUNSA, using the Rotavirus ELISA
kit
Rotavirus Surveillance in South Africa
In the first year, coverage was less than 50%; data from early
2010 indicated uptake of 50-75%
Rotavirus in South Africa is a very seasonal disease, usually
peaking in May, with a second smaller peak a few months later
In summer months there is little rotavirus but quite a bit of
other diarrheal disease
Data collected from the sentinel sites through June 2010
showed a major decline in RV-positive stool samples in the 2010
rotavirus season, the first following the vaccine’s introduction
In vaccinated children, rotavirus was detected in 11% of stool
samples during the surveillance period, while in the unvaccinated
children the rate was 20%
Rotavirus Surveillance in South Africa
Cumulative number of specimens tested rotavirus positive and total number of
samples collected by hospital - Reporting period: 04/01/2010 to 30/12/2010.
Hospital
Rotavirus Positive
Total Samples
Chris Hani Baragwanath
128
541
Edendale
16
84
George Mukhari
46
232
Mapulaneng
10
67
Matikwane
41
218
Total
241
1142
Rotavirus also has a distinct seasonality with peaks in the winter months in
temperate climates
serotype G1 accounts for approximately 50% of infections in South Africa.
Other serotypes causing infection in South Africa include G2, G8, G9 and G12
Data courtesy of NICD Epidemiologic Report; ROTA Surveillance, 2011.
Rotavirus Surveillance in Africa
25-40% of African children hospitalized with
diarrheal illness are infected with rotavirus
By 18 months of age, 83% of children will have
contracted the virus
G1 is most prevalent strain in Africa, estimated
50% of cases, followed by G3 at 30%
G2 strain occurs in “waves” every 3 to 4 years
G4 and G8 strains occur in sporadic isolation
G9 is emerging in countries across the
continent
Mixed serotypes are increasingly common
Of the P genotypes, P6 is the most
common, accounting for 50-60% of
cases, followed by P8 (35-40% of cases).
An unusual VP4 serotype has also been
detected
African Rotavirus Surveillance Network (AFRSN) – www.afro.who.int/en
Rotavirus Surveillance
Other Effects of Rotavirus Vaccination
 Health Impact
 decrease in all-cause diarrhoea
 Herd Immunity
 protection extends to the unvaccinated
 Age specific incidence of disease
 change in age of exposure
 Season specific incidence of disease
 shift in onset of epidemics. Helps guide surveillance systems
 Long-term interaction of rotavirus vaccination and strain
ecology
 Strains may changes post-vaccination
Rotavirus Herd Immunity
Rotavirus in HIV-infected Infants
 HIV infected children with RV diarrhoea have similar shortterm clinical course and outcome.
 HIV infected children 4.7 fold more likely to have
ongoing, prolonged asymptomatic shedding of RV four weeks
post-diarrhoeal illness.
 RV IgG and IgA seroconversion post wild type RV illness similar
between HIV-infected and -uninfected children
 RV infection does not affect blood HIV viral load or CD4cell
counts
 RV vaccine not associated with progression of immunedeficiency in HIV infected children.
Cunliffe NA et al. The Lancet; 2001; 358: 550-555 ; Jere C et al. AIDS 2001; 15: 1439-42
Rotavirus Vaccine Safety
Intussuseption
 Currently NO data supports hypothesis of increased risk of
intussuseption with RV vaccines
 Rotavirus vaccines are safe
• Reviewed safety data from phase III efficacy studies of Rotarix
and RotaTeq, as well as postmarketing safety data from
Australia, Latin America and the United States
• Previous association with the now withdrawn
vaccine, RotaShield
Rotavirus Vaccine Safety
Contraindications
 Severe Combined Immunodeficiency Syndrome
 History of:
 severe allergic reaction to a prior dose of RV
 Severe allergic reaction to latex
 Intussuseption
 Some congenital GI malformations e.g. Meckel diverticulum
Vaccine-vaccine interactions
 RV vaccines have been found not to interfere significantly with
the immunogenicity or safety of other childhood vaccines
 However, OPV appears to have an inhibitory effect on the
immune response to the first dose of RV vaccine
WHO - EPI Recommendations
 RV vaccine should be included in all national immunization
programmes
 In countries where diarrhoeal deaths account for ≥10% of mortality
among children aged <5 years, the introduction of the vaccine is
strongly recommended
 WHO recommends that the first dose of either RotaTeq or Rotarix be
administered at age 6–15 weeks
 The maximum age for administering the last dose of either vaccine
should be 32 weeks.
 It is recommended that 2 doses of Rotarix be administered with the
first and second doses of DTP rather than with the second and third
doses
 This ensures maximum immunization coverage and reduces the potential for
late administration beyond the approved age window
 This schedule will be reviewed as new data become available
6 and 14 weeks in RSA EPI schedule
Conclusions
 Rotavirus vaccines are not the solution to controlling this
disease
 Disease Control involves an integrated approach
 Zinc treatment
 Improved oral rehydration solution (ORS)
 Exclusive breastfeeding
 Improved nutrition
 Community education
 Safe water, adequate sanitation and hygiene
 These can complement the impact of vaccines and together
have a huge impact in reducing the burden of diarrhoea – one
of the largest killer of young children.
References
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