Rotavirus

What

Before rotavirus vaccines were available, rotavirus infection was the most common cause of severe gastroenteritis in infants and young children. The illness usually begins suddenly with vomiting followed by diarrhoea. Rotavirus infection can result in dehydration and hospitalisation.

Who

All infants <6 months of age are recommended to receive a course of oral rotavirus vaccine.

How

All infants <6 months of age are recommended to receive a course of either Rotarix or RotaTeq.

The vaccination course of Rotarix is 2 doses, at 2 and 4 months of age.

The vaccination course of RotaTeq is 3 doses, at 2, 4 and 6 months of age.

Why

Infants and children can be infected with rotavirus several times during their lives. Rotavirus vaccination significantly reduces rotavirus-specific and all-cause hospital presentations for gastroenteritis.

Rotavirus vaccines available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Dose and route

Rotavirus vaccines are for oral administration only. However in children with a nasogastric tube or percutaneous endoscopic gastrostomy, rotavirus vaccines may be given via the feeding tube.⁶ Never inject rotavirus vaccines.

Rotarix

Infants receive Rotarix as a 2-dose course. Upper age limits apply (see Table. Upper age limits for dosing of oral rotavirus vaccines). 

Rotarix is a clear, colourless liquid formulation in an oral applicator. The applicator may be: 

• a syringe-type applicator with a plunger stopper
• a squeezable tube

To administer, squeeze the 1.5 mL dose of vaccine onto the inside of the infant’s cheek. Do not dilute or reconstitute.

RotaTeq

Infants receive RotaTeq as a 3-dose course. Upper age limits apply (see Table. Upper age limits for dosing of oral rotavirus vaccines).

RotaTeq is a pale-yellow, clear liquid that may have a pink tint. It comes in a squeezable plastic, latex-free dosing tube with a twist-off cap.

To administer, squeeze the 2 mL dose onto the inside of the infant’s cheek. Do not dilute or reconstitute.

Repeating doses

Limited data are available on:

• the safety of giving higher than the recommended dose of rotavirus vaccine
• the efficacy of a partially administered dose

If an infant spits out or vomits most of a vaccine dose within minutes of receiving it, give 1 repeat dose during the same visit.

If an infant spits out or vomits only a small part of a vaccine dose, it is still considered valid — do not repeat the dose.

Co-administration with other vaccines

Rotavirus vaccines can be co-administered with other vaccines or immunisation products (such as RSV-specific monoclonal antibody).  

Co-administration of oral rotavirus vaccines is safe and effective. Rotavirus vaccines do not interfere with the immune response to antigens in other vaccines (DTPa [diphtheria-tetanus-acellular pertussis], Hib [Haemophilus influenzae type b], polio, hepatitis B and pneumococcal conjugate vaccines).^5,7,8

There are no restrictions on the timing of any other live vaccines in relation to rotavirus vaccines.⁹ These may include BCG (bacille Calmette–Guérin) vaccine or oral poliomyelitis vaccine given overseas.

Interchangeability of rotavirus vaccines

Try to use the same brand of vaccine for the entire vaccination course. Few studies address the interchangeability of the 2 available rotavirus vaccines. ¹⁰

However, if an infant received dose 1 or 2 as RotaTeq, give a 3rd dose of either rotavirus vaccine. The upper age limits and minimum intervals between doses must still be met, as defined in Table. Upper age limits for dosing of oral rotavirus vaccines.

Contraindications

The contraindications to rotavirus vaccines are:

• anaphylaxis after a previous dose of any rotavirus vaccine
• anaphylaxis after any component of a rotavirus vaccine
• history of intussusception
• congenital abnormality that may predispose to intussusception
• severe combined immunodeficiency in infants

Intussusception

Intussusception is a form of bowel obstruction, most often seen in young children. Rotavirus vaccination is associated with an increased risk of intussusception. See Adverse events.

If an infant has had intussusception before, their risk of having it again is about 10%.¹¹ Certain congenital malformations that affect the gut, such as Meckel diverticulum, also increase the risk of intussusception.

Infants with severe combined immunodeficiency

Infants with severe combined immunodeficiency are unlikely to generate a protective immune response to vaccination, and there is a risk of harm from the vaccine. In case reports from the United States, infants with severe combined immunodeficiency had prolonged gastrointestinal disease after rotavirus vaccination, associated with the vaccine virus. ^12-14

For infants with less severe immunocompromising conditions, the risk of vaccine-associated disease is likely to be less than the risk of natural rotavirus infection. See Infants who are immunocompromised in Precautions.

Precautions

Infants with acute gastroenteritis

Do not vaccinate infants with moderate to severe acute gastroenteritis until they have recovered. Rotavirus vaccines have not been studied in infants with acute gastroenteritis.

Infants with mild gastroenteritis (including mild diarrhoea) can receive the vaccine.

Infants with underlying conditions that predispose them to severe rotavirus gastroenteritis

Conditions that predispose infants to severe or complicated rotavirus gastroenteritis include: ¹⁵

• metabolic disorders
• chronic gastrointestinal disease, such as Hirschsprung disease
• malabsorption syndromes
• short gut syndrome

Data are limited about the safety of rotavirus vaccines in these groups. In one report, 8 of 9 infants with high-output ileostomies tolerated RotaTeq, and 1 infant had an increase in ileostomy losses.¹⁶

Because of the greater risk of serious rotavirus disease, the benefits from vaccination are expected to outweigh the risk in these infants. These infants are recommended to receive the vaccine.

Infants who are immunocompromised

There are theoretical concerns that vaccine-associated gastrointestinal disease could occur in immunocompromised infants who receive rotavirus vaccines. The risk from vaccination for infants with less severe immunocompromising conditions may be lower than the risk from natural rotavirus infection. Consider the risks and benefits of vaccination in the context of the infant’s specific immunocompromising condition. Seek appropriate specialist advice.¹

See Vaccination for people who are immunocompromised.

Infants with HIV

Infants with HIV have received rotavirus vaccines in clinical trials.^17-19 Data are limited, but suggest that the vaccines are safe and immunogenic in children with HIV who are clinically stable.^20,21

See also People with HIV: recommendations for vaccination and Table. Levels of immunocompromise in children and adults with HIV.

Infants born to mothers with immunocompromising conditions

Most infants exposed to biological disease-modifying therapies in utero can safely receive rotavirus vaccine, except those exposed to anti-CD20 therapies such as rituximab.

Infants exposed to TNF-alpha inhibitors and other biological therapies (such as eculizumab, belimumab, vedolizumab, natalizumab) in utero have safely received oral rotavirus vaccine without significant adverse events.^22-30

Notably, infants exposed to anti-CD20 therapies (such as rituximab) should not receive oral rotavirus vaccine.^31,32 Rituximab can cross the placenta, and has been associated with low or absent B-cells in infants exposed in the 2nd or 3rd trimester in utero.^32,33 The potential immunosuppressive effects of rituximab exposure last beyond the upper age limit for administration of rotavirus vaccine (see Table. Upper age limits for dosing of oral rotavirus vaccines). Given the lack of published data on the safety of oral rotavirus vaccine in these infants, and the low incidence of rotavirus disease in Australia,³⁴ these infants should not receive rotavirus vaccine.

See Infants exposed to immunosuppressive therapy in utero or through breastmilk and Use of immunosuppressive therapy during pregnancy in Vaccination for women who are planning pregnancy, pregnant or breastfeeding.

Infants living in households with people who are immunocompromised

Infants living in households with people who are immunocompromised are recommended to receive rotavirus vaccine. The exception to this is infants who were born to mothers who received anti-CD20 therapies (such as rituximab), particularly in the 2nd and 3rd trimester. These infants are not recommended to receive rotavirus vaccine (see Vaccination for infants exposed to immunosuppressive therapy in utero or through breastmilk).

In general, vaccinating young children in the household protects immunocompromised household members. This should outweigh the risk of transmitting vaccine virus to the immunocompromised household member, however, no studies have addressed this question.¹

Washing hands and carefully disposing of soiled nappies will minimise the risk of vaccine virus transmission to other household members. See Close contacts of people who are immunocompromised.

Infants who recently received antibody-containing blood products

Infants who have recently received antibody-containing blood products and are of an eligible age can receive rotavirus vaccine. Rotavirus vaccine can be given at any time before or after, or at the same time as, any antibody-containing products.¹

Minimal data are available on the impact of blood products on the immune response to the rotavirus vaccine in these infants. Completing the full rotavirus vaccine series will optimise protection.¹

Hospitalised infants

Giving rotavirus vaccine to hospitalised infants, including preterm infants, is likely to carry a low risk for transmission of vaccine viruses if standard infection control precautions are maintained.

Do not delay vaccination if the infant is medically stable. In particular, do not delay vaccination if this would mean the infant is beyond the upper age limit for vaccination. See Recommendations.

If a recently vaccinated child is hospitalised for any reason, take standard infection control precautions to prevent the vaccine virus spreading in the hospital.

Intussusception

Clinical trials of Rotarix and RotaTeq found no association between vaccination and intussusception.³⁵ See Vaccine information.

However, some studies have shown a link. See Australian studies and Overseas studies below.

Importantly, Australian^36-39 and international⁴⁰ studies have demonstrated the substantial impact of vaccination in preventing rotavirus morbidity and mortality. See also Epidemiology. Rotavirus vaccines continue to be recommended based on the positive benefit-to-risk profile.

Immunisation providers should inform parents and carers about the rare risk of intussusception, and how to be alert for its signs and symptoms.

Infants who have had a confirmed intussusception should not receive rotavirus vaccine. There may be an increased risk of the condition recurring. See Contraindications and precautions.

Australian studies

The baseline risk of intussusception for Australian infants is around 80 cases per 100,000 infants.⁴¹ A post-marketing study in Australia found a 4- to 5-fold increase in intussusception risk in the 7 days after the 1st dose of either Rotarix or RotaTeq.⁴² However, no overall increase in the risk of intussusception was detected during the first 9 months of life.⁴²

Another Australian study estimated the increased risk of intussusception for either vaccine to be:⁴³

• about 9-fold in the first 7 days after dose 1
• 2-fold in the first 7 days after dose 2

This study shows that rotavirus vaccination may be associated with about 6 additional cases of intussusception for every 100,000 infants vaccinated. This equates to 14 more cases per year in Australia.⁴³ This estimate assumes that infants who have intussusception shortly after vaccination would not have otherwise had a ‘natural’ episode of intussusception. However, this cannot be determined from current data.

Overseas studies

An apparent increase in risk for intussusception after the 1st dose of Rotarix has been observed in Mexico, and a smaller increase after the 2nd dose of Rotarix in Brazil.⁴⁰

A study in the United States found a small increased risk of intussusception after receiving RotaTeq.⁴⁴ The study was underpowered to detect a risk after Rotarix.⁴⁴

Other adverse events

Several studies followed up several thousand infants who received Rotarix. Vaccinated infants had no significant increase in post-vaccination vomiting, diarrhoea or fever compared with unvaccinated infants.^35,45

A detailed follow-up study of 11,700 recipients of RotaTeq or placebo reported no increase in fever or irritability in the week after vaccination among vaccinated infants. There was a small increase in the incidence of vomiting (7% versus 5%) and diarrhoea (10% versus 9%).⁴⁶ Post-marketing surveillance of rotavirus vaccines has not reported vomiting and diarrhoea as important adverse events after immunisation.

Infants who report an episode of diarrhoea or vomiting after vaccination should still receive subsequent rotavirus vaccine doses to complete the schedule. Potential causes of diarrhoea or vomiting after vaccination include:

• gastroenteritis that is unrelated to rotavirus vaccination or infection (that is, another virus)
• natural rotavirus infection (vaccination does not protect immediately or completely against all disease)
• symptoms from vaccine virus replication (less likely)

Infants who spit out or vomit the rotavirus vaccine may require a repeat dose. See Interruption to oral rotavirus vaccination in the Administration of vaccines chapter.

Detecting rotavirus in routine stool tests

If routine stool testing detects rotavirus in a recently vaccinated infant, this can indicate either natural infection or vaccine virus. Vaccine virus shedding commonly occurs after vaccination. See Vaccine information.

Specific testing can differentiate between vaccine virus and natural infection, but this is rarely needed.

Rotaviruses are non-enveloped RNA viruses. They are classified according to the 2 surface proteins they contain:

• VP7, the ‘G’ glycoprotein
• VP4, the protease-cleaved ‘P’ protein

The G and P proteins are targets for the neutralising antibodies that help protect against reinfection and disease.^15,47

Rotavirus strains are most commonly referred to by their G serotype. G1, G2, G3, G4 and G9 account for around 90% of serotypes, both globally and in Australia.^48,49 The most common P types found in combination with these G types are:⁵⁰

• P1A[8], found with all common G types except G2
• P1B[4], usually found in combination with G2

Transmission

Infected children shed high concentrations of rotaviruses in their stools. Viruses are transmitted by the faecal–oral route, through both close person-to-person contact and fomites.⁵¹ Rotaviruses might also be transmitted by other modes, such as through faecally contaminated food and water, and probably through respiratory droplets.^1,52

The incubation period is 1–3 days.

Rotavirus is the main agent of severe dehydrating gastroenteritis in infants and young children in developed and developing countries.^15,47 The spectrum of rotavirus infection can include:

• asymptomatic infection
• mild, watery diarrhoea of limited duration
• severe dehydrating diarrhoea with vomiting, fever, electrolyte imbalance, shock and death

Rotavirus infections are often more severe than other common causes of diarrhoea. These infections are more likely to result in dehydration and hospitalisation.^1,15

The illness usually begins suddenly with vomiting, followed by diarrhoea.¹ Up to one-third of patients have a temperature of >39°C in the first few days of illness. Symptoms generally resolve in 3–7 days.

Natural infection and immunity

Prior to the availability of vaccine, infection in early childhood was thought to be universal in children. People can be infected several times in their lives. The first infection, which typically occurs between 3 and 36 months of age, is most likely to cause severe diarrhoea and dehydration.^53,54 

The degree of protection after natural infection varies. After a single natural infection:⁵⁴

• 40% of children are protected against any subsequent infection with rotavirus
• 75% are protected against diarrhoea from a subsequent rotavirus infection
• 88% are protected against severe diarrhoea caused by rotavirus

Repeat infections provide even greater protection.

Hospitalisation and deaths from rotavirus infection in Australia

Rotavirus vaccines were added to the National Immunisation Program in 2007. Before this, about 10,000 children <5 years of age were hospitalised because of rotavirus each year in Australia. ^55,56 This equated to around half of all hospitalisations for acute gastroenteritis in this age group.^57,58 Rotavirus affected about 3.8% of all children (1 in 27) by the age of 5 years.

In addition to hospitalisations:^57,59

• about 115,000 children <5 years of age saw a general practitioner
• 22,000 children attended an emergency department because of rotavirus

On average, 2 deaths were attributed to rotavirus each year in Australia, but this is likely to be a minimum estimate.⁵⁵

Since 2007, both rotavirus-specific and all-cause hospital presentations for gastroenteritis have reduced by more than 70%.⁵⁶ Emergency department visits for acute gastroenteritis have also declined, as have rotavirus notifications.⁵⁶

Patterns of rotavirus infection in Australia

Seasonal patterns

In temperate Australia, rotavirus infections follow a seasonal pattern. The peak incidence is in mid to late winter.

The northern tropical and arid regions do not show a consistent seasonal pattern. Disease peaks are unpredictable, ⁶⁰ and widespread epidemics cause severe strain on healthcare services.^61,62

In Aboriginal and Torres Strait Islander children

Rotavirus hospitalisation rates in Aboriginal and Torres Strait Islander infants and children have decreased by approximately 80%.⁵⁵

Compared with their non-Indigenous peers, Aboriginal and Torres Strait Islander infants and children are hospitalised with rotavirus gastroenteritis about 3–5 times more often.^55,56,63

Rotavirus infection in people who are immunocompromised

Immunocompromised children and adults are at increased risk of severe, prolonged and even fatal rotavirus gastroenteritis.^15,64,65 This includes people with congenital immunodeficiency, or people who have received a haematopoietic stem cell transplant or solid organ transplant.

Rotavirus is an important cause of nosocomial gastroenteritis.^66-70 It can also cause disease in adults, especially among people caring for children and people residing in aged care facilities.^15,71,72

Two oral rotavirus vaccines are available in Australia. Their efficacy and safety in preventing rotavirus gastroenteritis have been extensively evaluated.^{17-19,35,73-75} Both are live attenuated vaccines given orally to infants, but the component vaccine viruses differ.

Rotarix (GlaxoSmithKline) contains 1 strain of attenuated human rotavirus (G1P[8] strain). It protects against non-G1 serotypes based on other shared epitopes.

RotaTeq (Merck Sharp & Dohme) contains 5 human–bovine reassortant rotavirus strains: G1, G2, G3, G4 and P1A[8]. Protective efficacy against different serotypes is similar in both vaccines.^35,73,75

Efficacy and effectiveness in middle- and high-income countries

In middle- and high-income countries, a course of vaccination with either Rotarix or RotaTeq prevents:^73,75-77

• rotavirus gastroenteritis of any severity in approximately 70% of recipients
• severe rotavirus gastroenteritis and rotavirus hospitalisation for 85–100% of recipients for up to 3 years

Vaccination is also highly effective in preventing visits to the emergency department, clinic or general practitioner.^75,76 In pre-market clinical trials, rotavirus vaccination prevented around half (42–58%) of hospital admissions for acute gastroenteritis of any cause in young children. This suggests that rotavirus is responsible for more gastroenteritis than is detected using routine testing and admission practices.^73,75,76

Post-marketing studies in Australia and the United States have confirmed high vaccine effectiveness and impressive reductions in both rotavirus-coded and all-cause gastroenteritis hospitalisations.^39,78-83 

Hospitalisations have also decreased in age groups that are not eligible for vaccination, suggesting that rotavirus vaccines have herd-protective effects.^39,78,81 

Efficacy and effectiveness in rural and resource-poor areas

Rural and resource-poor settings have reported more modest estimates of efficacy.^17-19,84 However, post-marketing studies in Brazil and Mexico (middle-income countries) have shown substantial reductions in diarrhoea-related mortality since rotavirus vaccines were introduced.^85,86 

Lower vaccine effectiveness among Aboriginal and Torres Strait Islander children have been reported for both Rotarix and Rotateq vaccines.^56,82,87,88 The remote Australian setting is unique, and these results should not be extrapolated to elsewhere in Australia.

Efficacy in preterm infants

In clinical trials, RotaTeq or placebo was given to 2070 preterm infants (25–36 weeks gestational age; median 34 weeks). Efficacy against rotavirus gastroenteritis of any severity appeared to be comparable with efficacy in full-term infants (73%; 95% CI: –2% to 95%).⁸⁹

Rotarix should give the same results, because it appears to be safe and immunogenic in preterm infants.⁹⁰

Vaccine virus shedding

Vaccine viruses replicate in the intestinal mucosa. Vaccinated people can shed the virus in their stools, particularly after the 1st dose.

Vaccine virus shedding is more common with Rotarix. Virus is detected in stools 1 week after vaccination in up to: ^7,8

• 80% of 1st-dose recipients
• 30% of 2nd-dose recipients

In 1 study of 80 sets of twins, 15 vaccinated infants transmitted the Rotarix vaccine strain, G1P[8] to their unvaccinated twin.⁷⁸ This suggests that vaccine virus can be transmitted to unvaccinated contacts, but the clinical implication of this has not been studied. See Contraindications and precautions.

RotaTeq is only shed after the 1st dose in up to 13% of recipients.⁷⁵

Porcine circoviruses in rotavirus vaccines

Adventitious DNA fragments of porcine circoviruses have been detected in both Rotarix and RotaTeq vaccines. However, porcine circoviruses have never been shown to cause illness in humans and are considered non-pathogenic.

Transport according to National Vaccine Storage Guidelines: Strive for 5.⁷⁹ Store at +2°C to +8°C. Do not freeze. Protect from light.

Rotavirus is a notifiable disease in some states and territories in Australia.

State and territory public health authorities can provide advice about the public health management of rotavirus, including management of cases and contacts.

Rotarix

The product information for Rotarix states that the vaccine should not be given to people with any chronic gastrointestinal disease.

The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that pre-existing chronic gastrointestinal disease is not a contraindication to rotavirus vaccination. The exceptions are conditions that may predispose to intussusception. See Contraindications and precautions. 

RotaTeq

The product information for RotaTeq states that if a dose of vaccine is spat out or vomited, a replacement dose should not be given.

ATAGI recommends that infants who spit out or vomit most of a dose can receive a single replacement dose. See Vaccines, dosage and administration.

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