Circovirus in Shanghai

Circovirus genomeRecently thousands of dead and decaying pigs were pulled from rivers in Shanghai and Jiaxing, China. Apparently farmers dumped the animals into the water after the pigs became ill. Porcine circovirus has been detected in the in pig carcasses and in the water.

Porcine circoviruses are small, icosahedral viruses that were discovered in 1974 as contaminants of a porcine kidney cell line. They were later called circoviruses when their genome was found to be a circular, single-stranded DNA molecule. Upon entry into cells, the viral ssDNA genome enters the nucleus where it is made double-stranded by host enzymes. It is then transcribed by host RNA polymerase II to form mRNAs that are translated into viral proteins. There is some evidence that circoviruses might have evolved from a plant virus that switched hosts and then recombined with a picorna-like virus.

Porcine circoviruses are classified in the Circoviridae family, which contains two genera, Circovirus and Gyrovirus. There are two porcine circoviruses, PCV-1 and PCV-2; only the latter causes disease in pigs. Infection probably occurs via oral and respiratory routes, and leads to various diseases including postweaning multisystemic wasting syndrome, and porcine dermatitis and nephropathy syndrome. Virions are shed in respiratory and oral secretions, urine, and feces of infected pigs. Other circoviruses may cause diseases of birds, including psittacine beak and feather disease, and chicken infectious anemia, the latter caused by the sole member of the Gyrovirus genus. There are also circoviruses that infect canaries, ducks, finches, geese, gulls, pigeons, starlings, and swans.

We have no good evidence that porcine or avian circoviruses can infect humans. In the United States, porcine circovirus sequences can be detected in human feces. These most likely originate from consumption of pork products, most of which also contain porcine circoviruses. Circovirus sequences have also been found in commonly eaten animals such as cows, goats, sheep, camels, and chickens. Outside of the United States, the circoviruses found in human stools do not appear to be derived by meat consumption and might cause enteric infections.

Recently both PCV-1 and PCV-2 sequences were detected in Rotarix and RotaTeq, vaccines for the prevention of rotavirus disease in infants. The source of the contaminant was trypsin, an enzyme purified from porcine pancreas, which is used in the production of cell cultures used for vaccine production. Use of these vaccines was temporarily suspended, but resumed when the Food and Drug Administration concluded that there is no evidence that porcine circoviruses pose a safety risk to humans.

The good news is that porcine circoviruses in Shanghai’s waters are no danger to humans. But it is not a good idea to have rotting pig carcasses in a river that supplies some of Shanghai’s drinking water.

FDA clears rotavirus vaccines

The US Food and Drug Administration has updated its recommendations on both Rotarix and RotaTeq, vaccines for the prevention of rotavirus disease in infants:

Based on careful evaluation of a variety of scientific information, FDA has determined it is appropriate for clinicians and health care professionals to resume the use of Rotarix and to continue the use of RotaTeq.

In making its recommendation, the FDA considered the strong safety records of both vaccines, including clinical trials in tens of thousands of individuals and the use of the vaccines in millions of recipients. There is no evidence that either porcine circovirus type 1 or type 2 poses a safety risk to humans, and neither virus is known to infect humans or cause disease.

The FDA also noted that the benefits of the rotavirus vaccines are considerable and outweigh the small theoretical risk of the viral contaminant.

The product labels will be updated to reflect the fact that the vaccine contains a PCV contaminant. In addition, GlaxoSmithKline will rederive Rotarix so that it does not contain PCV. Merck has not yet made a decision about whether they should produce a PCV-free rotavirus vaccine. But if my suggestion carries any weight at Merck (I know it does not), they should not hesitate to follow GlaxoSmithKline’s lead.

Porcine circovirus DNA found in RotaTeq

The US Food and Drug Administration recently recommended that administration of Glaxo SmithKline’s Rotarix vaccine, which protects against rotavirus infection, be suspended after an independent research group found that the vaccine contains DNA of porcine circovirus type 1. Now the FDA reports finding circovirus DNA in the rotavirus vaccine made by Merck:

FDA recently received information from Merck & Co, Inc. that its preliminary studies have identified fragments of DNA from PCV1 and from a related porcine circovirus type 2 (PCV2) in its RotaTeq vaccine. Merck’s findings suggest that the number of PCV DNA fragments in its vaccine may be smaller than what has been found in Rotarix.

FDA has so far not recommended suspension of RotaTeq use. The Vaccines and Related Biological Products Advisory Committee meets today, after which FDA will make further recommendations on the use of the licensed rotavirus vaccines in the United States.

The source of porcine circovirus type 1 DNA in both Rotarix and RotaTeq is likely to be trypsin used during propagation of the cell cultures necessary for vaccine production. The enzyme is produced from porcine pancreas.

Update 10 May 2010: The FDA has posted a briefing document for the VRBPAC meeting that was held this past Friday. The Los Angeles Times reports on the outcome of the meeting:

Members of a Food and Drug Administration advisory committee meeting Friday urged physicians to continue using both commercial rotavirus vaccines despite evidence that both carry trace contaminants from a harmless pig virus. The panel did not take a formal vote on a recommendation, but a majority of participants said they thought the benefits of the vaccine far outweigh any potential risk. An agency spokeswoman said it would make no immediate recommendation on the vaccines, but would act expeditiously to come to a decision.

Finally, there are some good quotations from committee members in the article at Medscape Today.