Rotavirus vaccines statement

18 May 2010

Two oral rotavirus vaccines, Rotarix (sponsored by GlaxoSmithKline) and RotaTeq (sponsored by Merck) are currently approved for use in Australia and are included in the National Immunisation Program (NIP) for babies aged 2 to 6 months. These are used to prevent rotavirus infection in babies and young children. Rotavirus is a virus that may cause a form of gastroenteritis of particular concern as it can be severe or even fatal.

Prior to the introduction of rotavirus vaccination, it was estimated that in Australia, there were approximately 10,000 hospitalisations each year due to rotavirus in children less than 5 years of age each year. In addition, an estimated 5,000 children under 5 years of age visited a GP, 22,000 children required an emergency department visit due to rotavirus illness, and on average, there was one death due to rotavirus each year.

Clinical trial data and extensive experience to date have demonstrated that Rotarix and RotaTeq are effective in preventing infection with rotavirus and are well tolerated in babies.

On 17 March 2010 GlaxoSmithKline (GSK) notified the Therapeutic Goods Administration (TGA) and other regulatory agencies around the world that DNA fragments of a virus identified as porcine circovirus type 1 (PCV1), had been found in batches of the product.

On 5 May 2010 Merck notified the TGA and other regulatory agencies that it had identified fragments of DNA from PCV1 and a related virus, PCV2, in its bulk rotavirus vaccine RotaTeq.

PCV1 and PCV2 are viruses that can infect pigs. There is no evidence that either PCV1 or PCV2 cause any illness in humans.

Following the original notification by GSK, the TGA convened an expert panel of paediatricians, immunologists and vaccine specialists. This panel has since reviewed further information from the companies and the US Food and Drug Administration (FDA) and concluded that there is no evidence to suggest that the presence of PCV1 and PCV2 are of concern, and moreover that the evidence supports the continued use of these vaccines as strongly in the public interest.

Having considered all the relevant scientific information the TGA has concluded that the continued use of both vaccines is strongly supported by the weight of current evidence and the long history of safe use of the products. This view is consistent with the views of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

The TGA is maintaining contact with other regulatory agencies overseas and the companies, GSK and Merck, to obtain any new information and expert advice to ensure that the vaccines remain safe and effective.

A comprehensive list of Frequently Asked Questions follows.

Frequently asked questions

What is rotavirus?

Rotavirus is named after its characteristic wheel-like appearance when viewed under an electron microscope. Rotavirus is the leading cause of severe diarrhoea and dehydration in young infants worldwide. It is estimated to be responsible for the deaths of more than 500,000 infants around the world each year, primarily in low- and middle-income countries.

In Australia, prior to the introduction of rotavirus vaccination, it was estimated that there were approximately 10,000 hospitalisations due to rotavirus in children less than 5 years of age each year. In addition to hospitalised children, an estimated 5,000 children under 5 years of age visited a GP, and 22,000 children required an emergency department visit due to rotavirus illness each year. On average, there was one death due to rotavirus each year in Australia.

What are the symptoms of rotavirus infection?

Rotavirus infects the intestines. The illness usually begins with fever, an upset stomach, and vomiting, followed by diarrhoea, and generally lasts 3-8 days.

How is rotavirus infection treated?

There is no specific treatment for the rotavirus infection. The most serious problem caused by the disease is dehydration, so symptoms are treated mostly by oral rehydration. Severe cases require administration of intravenous fluids in a hospital. Rotavirus disease can be prevented with vaccination.

How does rotavirus spread?

Rotavirus is usually spread when children touch or place in their mouths small, usually invisible amounts of faecal matter found on surfaces such as toys, books and clothing, or on the hands of caregivers. The virus can also be transmitted through contaminated water or food, and possibly by respiratory droplets in a sneeze, cough, or exhalation. The virus is very contagious. Nearly all children are exposed to rotavirus at some point before the age of 5 years.

Rotavirus vaccines

After evaluating data from extensive clinical and non-clinical tests, TGA registered GlaxoSmithKline's Rotarix vaccine in March 2006. A second rotavirus vaccine RotaTeq is also marketed in Australia by Merck, Sharp & Dohme (Australia) Pty Ltd. TGA registered RotaTeq in May 2006. Pre- and post-market studies have shown both vaccines to be highly effective at preventing serious gastrointestinal disease caused by rotavirus. No serious or unexpected safety concerns have been identified in the postmarketing surveillance of either vaccine.

What is Rotarix?

Rotarix is a live-attenuated human rotavirus vaccine. It is available in Australia as an oral liquid suspension and is administered by mouth in a two-dose schedule on the National Immunisation Program between six and fourteen weeks of age. The first dose can be given beginning at six weeks of age and the second at least four weeks after the first dose, but before the child reaches 24 weeks of age.

What countries currently use Rotarix?

In addition to Australia, Rotarix is licensed in the United States, the European Union and nearly 100 other countries.

How many doses of Rotarix have been sold?

Rotarix is used predominantly in NSW, ACT, NT and Tasmania. It was previously used in WA during 2007 to 2009. Worldwide it is estimated that 68 million doses of the vaccine have been distributed to date, and more than 70,000 children have participated in clinical trials. No unexpected pattern of adverse reactions to the vaccine has been reported in any country.

What is RotaTeq?

RotaTeq is also a live-attenuated viral vaccine taken by mouth. It was tested in more than 70,000 children, primarily in the United States and Finland, and registered in Australia in May 2006. The vaccination is administered in a three dose schedule starting at 6 to 12 weeks of age, with the subsequent doses administered at 4- to 10-week intervals; the third dose should be given by 32 weeks of age.

What countries currently use RotaTeq?

In addition to Australia, RotaTeq is licensed in the United States, the European Union and at least 90 other countries.

How many doses of RotaTeq have been sold?

RotaTeq is currently used in Victoria, Queensland, SA and WA. Worldwide it is estimated that 37 million doses of the vaccine have been distributed to date. No unexpected pattern of adverse reactions to the vaccine has been reported in any country.

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Background on Porcine Circovirus Types 1 and 2

Porcine circovirus type 1 (PCV1) and type 2 (PCV2) are both small, circular viruses composed of a single strand of DNA and are common in pigs. PCV1 is not known to cause illness in pigs. PCV-2 is thought to be the causative agent in Postweaning Multisystemic Wasting Syndrome (PMWS) in pigs, and may also cause reproductive failure, respiratory disease, and an unusual skin and kidney disease referred to as porcine dermatitis and neuropathy syndrome (PDNS). Humans may be exposed to PCVs by ingestion of pig meat containing PCVs or from exposure to farm animals.

Is PCV1 and PCV2 pig material?

No. PCV1 and PCV2 are viruses. They are not animal material.

Detection of DNA from PCV1 in Rotarix

The presence of components of PCV1 in Rotarix was discovered when an independent US academic research team applied a new technology for detecting viral genetic material. The researchers detected DNA fragments of PCV1 in two lots of Rotarix vaccine. The researchers notified GSK of their findings on 9 February 2010. The company then initiated extensive experiments to confirm the results and undertake further investigations. These included a series of assessments on the same two lots of the finished vaccine, as well as on vaccine materials at different stages of the production process. These follow-up tests confirmed the presence of many copies of DNA from PCV1 in the two finished vaccine lots that had previously been tested, as well as in intermediates in the production process, and in the working cell bank and viral "seed" from which the vaccine was derived. Further testing has suggested that intact PCV1 virus may also be present.

The firm notified TGA of its findings on 17 March 2010. TGA staff then began to review the evidence, consult with experts, contact other public health officials in Australia, and communicate with international regulatory counterparts.

Has DNA from PCV1 been found in other lots of Rotarix?

In its follow-up assessments, GSK detected the presence of DNA from PCV1 in the working cell bank and viral "seed" used to produce Rotarix, confirming that the material has been present since the early stages of product development, including during clinical studies.

Why wasn't the presence of DNA from PCV1 detected in previous reviews of Rotarix?

Circoviruses such as PCV1 have not been associated with illnesses in humans, and the identification of DNA fragments by the academic researchers has only recently become possible due to technological developments. No regulatory agency has required testing for the presence of the virus or any components as this has not been possible previously.

Does the detection of DNA from PCV1 in Rotarix raise special concerns for influenza vaccines?

No. The manufacturing process for Rotarix is very different from the manufacturing process for influenza vaccines. Unlike Rotarix, a cell-based vaccine, the influenza vaccines currently on the market are egg-based vaccines. The cell-based influenza vaccine currently in development uses materials that are different from the one used to develop Rotarix.

Detection of DNA from PCV1and PCV2 in RotaTeq

The presence of components of PCV1 and PCV2 in RotaTeq was discovered when Merck tested RotaTeq after the discovery of PCV1 in Rotarix. Merck found evidence of the DNA from PCV1 and PCV2 in the unpurified product and evidence of PCV DNA in the final product. The TGA was notified of these findings on 5 May 2010. TGA staff then began to review the evidence, consult with experts, and communicate with international regulatory counterparts.

Why wasn't the presence of DNA from PCV1 and PCV2 detected in previous reviews of RotaTeq?

Circoviruses such as PCV1 and PCV2 have not been associated with illnesses in humans, and the identification of DNA fragments by the academic researchers in Rotarix has only recently become possible due to technological developments. No regulatory agency has required testing for the presence of the virus or any components as this has not been possible previously.

Does the detection of DNA from PCV1 and PCV2 indicate that the virus is present in RotaTeq?

Although DNA fragments from PCV1 and PCV2 have been detected in RotaTeq, it is not yet known whether this means that intact virus is present. Additional studies are currently being conducted to establish whether or not intact PCV1 or PCV2 are present in RotaTeq.

Does the detection of DNA from PCV1 and PCV2 in RotaTeq raise special concerns for influenza vaccines?

No. The manufacturing process for RotaTeq is very different from the manufacturing process for influenza vaccines. Unlike RotaTeq, a cell-based vaccine, the influenza vaccines currently on the market are egg-based vaccines. The cell-based influenza vaccine currently in development uses materials that are different from the one used to develop RotaTeq.

TGA actions

After learning of the detection of PCV1 DNA in Rotarix on 17 March 2010, the TGA reviewed the available evidence, and consulted with relevant clinical and scientific experts, conferred with public health officials, and exchanged information with regulatory counterparts in other countries to establish a better understanding of any possible risk. The TGA convened an expert panel of paediatricians, immunologists and vaccine specialists who provided advice.

After learning of the detection of DNA from PCV1 and PCV2 in RotaTeq on 05 May 2010 the TGA reconvened its expert panel which reviewed the new evidence, to establish a better understanding of any further risk.

Are follow-up assessments being conducted?

The TGA has reviewed all the available evidence on Rotarix and RotaTeq and this has been assessed by the TGA expert panel. The TGA will monitor the situation to see if any further information comes to hand.

Information for parents and caregivers

My child has received or is due to receive the Rotarix or RotaTeq vaccine. Should I be worried?

All available evidence, including clinical studies involving tens of thousands of children and its use worldwide in millions of children supports the safety of the vaccine. PCVs are not known to cause disease in humans. Children who have received Rotarix or RotaTeq need no additional medical follow-up. Scheduled vaccinations with Rotarix and RotaTeq should proceed as normal.

Information for healthcare providers and public health professionals

Is there any medical follow-up needed for children who have received the Rotarix or RotaTeq vaccine?

No. The risk of any illness from ingesting any such material is unlikely. TGA does not believe special medical follow-up is warranted for children who have been vaccinated with Rotarix or RotaTeq. Extensive pre- and post-market clinical studies involving tens of thousands of vaccine recipients support the safety and effectiveness of the vaccine.