2. Outline of Presentation
Introduction
Epidemiology and Disease Burden
The Rotavirus
Clinical Presentation
Prevention and Control
Vaccination
Surveillance
WHO Recommendations
Conclusion
3. 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
4. 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
7. 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
8. 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 !
9. 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
10. 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]
13. 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
14. 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
15. Clinical Presentation
Diagnosis
Mostly clinical
Rapid antigen detection by ELISA of rotavirus in stool
specimens.
Isolates may be further characterized by reverse-
transcriptase polymerase chain reaction
16. 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
17. 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.)
18. 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 rotavirus-
specific immunoglobolin preparation. Administer orally to decrease shedding
and ameliorate disease .
20. 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
22. 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
23. Rotavirus Vaccines
RotaTeq Rotarix
Manufacturer Merk & Co. GSK
Genetic framework Bovine Rotavirus – WC3 Human Rotavirus-89-12
Composition 5 Human, Bovine reassortant Single Human rotavirus
Genotypes G1, 2, 3, 4 and [P8] G1 [P8]
Dosage Schedule 3 doses at 2, 4 and 6 months 2 doses at 2 and 4 months
Route oral oral
Presentation liquid Lysophilized-reconstituted
Efficacy against severe 85% 95%
disease
Virus shedding Up to 13 % 17 % - 27%
25. Vaccine Efficacy
Rotavirus Efficacy in Clinical Trials in Africa and Asia
Vaccine Region Country Efficacy
RV1 (Rotarix) Africa South Africa, 62% (44% - 73%)
Malawi
RV5 (RotaTeq) Asia Bangladesh, 51% (13% - 73%)
Vietnam
RV5 (RotaTeq) Africa 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
26. 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 % Ghana, Kenya, Malawi,
Mali
46 – 72 % 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
27. 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
28. 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%
29. 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.
30. 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
32. 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
34. Rotavirus in HIV-infected Infants
HIV infected children with RV diarrhoea have similar short-
term 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 immune-
deficiency in HIV infected children.
Cunliffe NA et al. The Lancet; 2001; 358: 550-555 ; Jere C et al. AIDS 2001; 15: 1439-42
35. 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
36. 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
37. 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
38. 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.
39. References
• WHO Weekly Epidemiological Record 2008; 83 (47), 27 November 2008
• Global networks for surveillance of rotavirus gastroenteritis, 2001-2008. Wkly Epidemiol Rec 2008;83:421-428.
• Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect
Dis 2003;9:565-72.
• Chin, J. (Ed.). (2000). Control of Communicable Disease Manual. Wash. DC: American Public Health Association.
• American Academy of Pediatrics. (1997). Rotavirus. In Red book: Report of the committee on infectious diseases. (24th ed., pp.454 - 456). Elk
Grove Village, IL:Author.
• Velazquez F, Matson DO, Calya JJ, et al. Rotavirus infections in infants as protection against subsequent infections. N Engl J Med.
1996;335:1022-1028.
• Offit, P. A. & Clark, M. F. (2000). In G. L. Mandell, J. E. Bennett, & R. Dolin (Eds)., Principles and practice of infectious diseases. (5th
ed., pp.1696 -1703). Philadelphia, PA: Churchill Livingstone
• Estes M. Rotaviruses and their replication. In: Howley PM, ed. Fields Virology. 3rd ed. Vol. 2. Philadelphia, PA: Lippincott-Raven; 1996:1625-
55.
• Estes MK, Cohen J. Rotavirus gene structure and function. Microbiological Reviews 1989;53:410-49.
• Glass RI, Bhan MK, Ray P, et al. Development of candidate rotavirus vaccines derived from neonatal strains in India. J Infect Dis
2005;192(Suppl):S30-S5.
• Ward RL, Bernstein DI. Lack of correlation between serum rotavirus antibody titers and protection following vaccination with reassortant RRV
vaccines. Vaccine 1995;13:1226-32.
• Green KY, Taniguchi K, Mackow ER, Kapikian AZ. Homotypic and heterotypic epitope-specific antibody respones in adult and infant rotavirus
vaccinees: implications for vaccine development. J Infect Dis 1990;161:667-79.
• Madhi S, Cunliffe NA, Steele D, Witte D, Kirsten M, et al. N Engl J Med 2010: 362: 289-98
• Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J
Med 2006;354:23-33.
• CDC. Withdrawal of rotavirus vaccine recommendation. MMWR 1999;48:1007.
• Peter G, Myers MG. Intussusception, rotavirus, and oral vaccines: summary of a workshop. Pediatrics 2002;54:110.
• WHO. Report of the Global Advisory Committee on Vaccine Safety, December 1-2, 2005. Wkly Epidemiol Rec 2006;2:13-20.
• African Rotavirus Surveillance Network (AFRSN) – www.afro.who.int/en
• Rotavirus (ROTA) Surveillance: Rotavirus Report, National Institutes of Communicable Diseases, 2 March 2011.
• WHO Weekly Epidemiological Record. No. 51-52, 2009, 84, 533-540.
• Diarrhoea: why children are still dying and what can be done. Geneva, UNICEF and World Health Organization, 2009 (available from:
http://www.who.int/child_adolescent_health/documents/9789241598415/en/index.html; accessed November 2009).
• CDC, unpublished data, 2006.
Rotavirus strains are serotyped according to the neutralization of one of the two proteins present in the outer capsid: VP7, a glycoprotein, is neutralized in G types, and VP4, a protease-cleaved hemagglutinin, is neutralized in P types. G types 1, 2, 3, and 4 are responsible for most infections in children.Rotavirus was given its name when scientists observed its wheel-like appearance; it was named after rota, the Latin word for wheel. The inner hub of the rotavirus (yellow on the slide) is usually referred to as the G-type, and the spokes coming off of the inner hub (red on the slide) are usually referred to as the P-type. The G-type and P-type define the serotype of the virus and are critical to vaccine development because they are the vaccine targets for stimulating a protective immune response.
Two surface rotavirus proteins, VP7 (a glycoprotein—G protein) and VP4 (a protease-cleaved protein—P protein), inducehomotypic and heterotypic neutralizing antibody responses that are suspected to partly provide protective immunity after naturalinfection and vaccination
Before symptoms of rotavirus infection appear, feacal shedding occurs. Fever and vomiting precede diarrhoea, and hospitalization for dehydration usually occurs between days 2 and 6 after infectionFever and vomiting are usually the first symptoms, followed quickly by diarrhoea. Oftentimes the vomiting is a rate-limiting factor in attempts to provide oral rehydration. When hospitalization for dehydration does occur, it is usually 2 to 6 days into the illness, and intravenous fluid therapy is necessary.
The diarrhoea is usually non-bloody, profuse, and lasts for up to 3-8 days. Compared with children with non-rotavirus-related diarrhoea, rotavirus-infected children experience more vomiting and have a greater number of diarrhoea episodes per day, which explains why dehydration is so common with this illness.[13] Dehydration is commonly isotonic. Diarrhoea is watery without blood or mucous. Although coryza and cough may precede GI symptoms, replication of rotavirus in the upper respiratory tract is not important in the spread of the virus (4). Neurologic symptoms may occur in severe cases as a result of electrolyte imbalance or direct viral infection of the central nervous system (1).
Cause of diseaseRotavirus replicates in certain cells that line the inside of the small intestine. This replication decreases the ability of the intestine to absorb salts and water. Rotavirus has never been detected consistently in the blood or in other sites far from the intestine.
Cause of diseaseRotavirus replicates in certain cells that line the inside of the small intestine. This replication decreases the ability of the intestine to absorb salts and water. Rotavirus has never been detected consistently in the blood or in other sites far from the intestine.
In a cohort of Mexican children, nearly every child had a rotavirus infection by the age of 2 years. Rotavirus vaccination mimics the protection rates of one natural infection.The failure of a primary natural rotavirus infection to protect completely against subsequent infection may indicate the need for multiple vaccinations or for the administration of a polyvalent vaccine that can elicit full protection against all prevalent serotypes.It is encouraging that the degree of protection conferred by asymptomatic infection was similar to that afforded by symptomatic infection. The occurrence of two rotavirus infections, whether symptomatic or asymptomatic, resulted in complete protection against moderate-to-severe illness. This finding implies that an attenuated vaccine that caused asymptomatic infection could induce protective immunity. That two natural infections were required for complete protection against moderate-to-severe illness implies that more doses of an attenuated vaccine will be required to achieve efficacy similar to that from exposure to a wild-type strain adapted to the human intestine.
In a cohort of Mexican children, nearly every child had a rotavirus infection by the age of 2 years. Rotavirus vaccination mimics the protection rates of one natural infection.The failure of a primary natural rotavirus infection to protect completely against subsequent infection may indicate the need for multiple vaccinations or for the administration of a polyvalent vaccine that can elicit full protection against all prevalent serotypes.It is encouraging that the degree of protection conferred by asymptomatic infection was similar to that afforded by symptomatic infection. The occurrence of two rotavirus infections, whether symptomatic or asymptomatic, resulted in complete protection against moderate-to-severe illness. This finding implies that an attenuated vaccine that caused asymptomatic infection could induce protective immunity. That two natural infections were required for complete protection against moderate-to-severe illness implies that more doses of an attenuated vaccine will be required to achieve efficacy similar to that from exposure to a wild-type strain adapted to the human intestine.
Deaths also result from treatment. Hypotonic solution given in a large volume can create cerebral oedema. It is important to remember that the range of sodium excretion of rotavirus diarrhoea is around 30 to 60 mL equivalents per liter. Rehydration with fluid less than one-third normal saline causes total body sodium loss. The brain cannot correct fluid imbalance as quickly by moving solute as it can by moving water; patients who have been given too much free water may develop brain oedema and die.
Where is RV found ? Parents cannot prevent their children from getting a rotavirus infection. The primary mode of rotavirus transmission is fecal to oral. Rotavirus is highly communicable and transmissible. Close person-to-person contact and environmental surfaces are common vectors of transmission. It is impossible to keep contaminated fingers and objects from going into children's mouths. Even if a child is not cared for in a daycare setting, he or she is likely to have contact with other children or objects that other children have touched. Rotavirus is an extremely hardy pathogen. The incubation period is 1-3 days and large quantities of virus are shed in stool from just prior to onset of symptoms until about 10 days after onset. Rotavirus is highly transmissible. Under experimental conditions, almost 50% of rotavirus remains viable on contaminated hands for 60 minutes
Where is RV found ? Parents cannot prevent their children from getting a rotavirus infection. The primary mode of rotavirus transmission is fecal to oral. Rotavirus is highly communicable and transmissible. Close person-to-person contact and environmental surfaces are common vectors of transmission. It is impossible to keep contaminated fingers and objects from going into children's mouths. Even if a child is not cared for in a daycare setting, he or she is likely to have contact with other children or objects that other children have touched. Rotavirus is an extremely hardy pathogen. The incubation period is 1-3 days and large quantities of virus are shed in stool from just prior to onset of symptoms until about 10 days after onset. Rotavirus is highly transmissible. Under experimental conditions, almost 50% of rotavirus remains viable on contaminated hands for 60 minutes
RV1, the live-attenuated human rotavirus vaccine, was approved by the FDA in 2008 and contains one strain of live-attenuated human rotavirus, a G1 P[8] strain. RV1 shares neutralizing identity with G1, G3, G4, and G9 through the P[8] VP4 protein. RV1 does not share neutralizing identity with G2 P[4] strains, and a major concern with the RV1 strain is efficacy against G2 P[4] strains. RV5 The RV5 vaccine contains five reassortant viruses developed from human and bovine parent rotavirus strains and shares neutralizing identity with G1, G2, G3, G4, and P[8], the same P serotype as many of the G9 strains observed in the US. Phase 3 trials included more than 70,000 infants in 11 countries.2 The vaccine demonstrated 74% overall efficacy and 98% efficacy for severe rotavirus disease. In a cohort of infants for which data from clinic and ED visits were collected, there was an 86% reduction in the need for a physician visit for diarrhea and a 96% reduction in hospitalization.2 RV5 was effective against all the G serotypes tested
Defination of attenuated vaccine, monovalent, pentavalent
Do the rapid immunoassays detect vaccine-strain virus?Yes, the threshold for detection is on the order of 105 or 106 for the enzyme immunoassay. There is a low rate of shedding with the RV5 vaccine, while the rate of shedding is higher for the RV1 vaccine. Shedding is higher for the monovalent vaccine in part because it is better adapted to the host for replication.
Defination of attenuated vaccine, monovalent, pentavalent
After 1 year of follow up, the efficacy of Rotarix in preventing severe rotavirus gastroenteritis was 61.2% (95% CI, 44–73%) in the combined study populations,76.9% (95% CI, 56–88%) in South Africa and 49.5% (95% CI, 19–68%) in Malawi Despite its lower efficacy in Malawi, the number of episodes of severe gastroenteritis prevented by vaccination was higher (3.9/100 vaccinees) than in South Africa (2.5/100 vaccinees) because of the higher incidence of severe rotavirus gastroenteritis in young infants in Malawi.
Rotavirus vaccination is effective and is now affecting epidemiology. Most severe infections occur during the first year of life, and it appears as though vaccination is affecting exposure, which means that a person’s age of first exposure might be delayed. A change in the age distribution of severe infection is likely to be seen. The concern when measles vaccination was introduced was that if all children were immunized, the epidemiology of the disease would shift and older children and adults, when infected, would experience more severe disease since they lack previous natural exposure. In fact, there was a temporary shift toward older individuals getting infected, but the overall absolute number of cases declined drastically, and as you know, endemic measles transmission was eliminated in the U.S. in 2000 (despite recent outbreaks related to importations and pockets of undervaccination).
-25 countries based in Harare
SLIDE SHOWS REDUCTION OF rv CASES AFTER INTRODUCTION rv VACCINE IN THE usa
Routine immunization occurs in real-world conditions different from ideal clinical trial settings. Thus, monitoring postlicensure impact on rotavirus disease is crucial for ensuring that appropriate gains in terms of expected vaccination benefits are attained. Changes in the epidemiology of rotavirus disease might occur in the postlicensure era, such as shifts in average age at infection, seasonality of disease, and serotype distribution after vaccination or appearance of unusual genetic variants ensuring that protection is conferred through the first and second years of life when most severe disease and mortality from rotavirus occur will be crucial for the success of a rotavirus vaccination program. Finally, assessing whether vaccination has an affect on rotavirus transmission in the community, thus providing benefits to unvaccinated groups, is important. Monitoring impact with focus on these public health considerations will not only allow assessment of the effectiveness of rotavirus vaccines in routine use, but also generate the necessary evidence to inform public health policy decision-making and continued investment in rotavirus vaccines.
Herd immunity is when a vaccine protects even subjects not vaccinatedThis study confirms on a national scale that the 2008 rotavirus season among children aged <5 years was dramatically reduced compared to pre-RV5 seasons. … Based on the observed decrease during the 2008 season, we estimated that ~55,000 acute gastroenteritis hospitalizations were prevented during the 2008 rotavirus season in the United States. A decrease of this magnitude would translate into the elimination of 1 in every 20 hospitalizations among US children aged <5 years.Interestingly, the reduction in gastroenteritis wasn’t only in vaccinated children:In 2008, acute gastroenteritis hospitalization rates decreased for all children aged <5 years, including those who were either too young or too old to be eligible for RV5 vaccination. …These findings … raise the possibility that vaccination of a proportion of the population could be conferring indirect benefits (ie, herd immunity) to nonvaccinated individuals through reduced viral transmission in the community
Cunliffe NA et al. The Lancet; 2001; 358: 550-555Jere C et al. AIDS 2001; 15: 1439-42.
In December 2008, GACVS reviewed safety data from phase III efficacy studies of Rotarix and RotaTeq, as wellas postmarketing safety data from Australia, Latin America and the United States. GACVS concluded thatthese vaccines are safe and that a risk of intussusception of the order associated with the previously marketed,but now withdrawn, tetravalent reassortant rotavirus vaccine (RotaShield, Wyeth Lederle, Philadelphia,PA, USA) can be ruled out with confidence. In June 2009, GACVS stated that no data directly support a hypothesisthat administration of rotavirus vaccine even outside of the age range 6–15 weeks for the first doseand 32 weeks for the second dose is associated with an increased risk of intussusception..
In various settings, rotavirus vaccines have been found not to interfere significantly with the immunogenicityor safety of OPV or other childhood vaccines. OPV, however, appears to have an inhibitory effect on the immuneresponse to the first dose of rotavirus vaccine, although this interference does not persist after administrationof subsequent doses.