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.

Wild poliovirus in China

The World Health Organization has confirmed that cases of poliomyelitis in China were caused by wild poliovirus type 1:

1 SEPTEMBER 2011 – The Ministry of Health, China, has informed WHO that wild poliovirus type 1 (WPV1) has been isolated from four young children, aged between four months and two years, with onset of paralysis between 3 and 27 July 2011. All four cases are from Hetian prefecture, Xinjiang Uygur autonomous region, China. Genetic sequencing of the isolated viruses indicates they are genetically-related to viruses currently circulating in Pakistan. The last WPV case in China was reported in 1999, due to an importation from India. The last indigenous polio case occurred in China in 1994.

Remember that only one in 100 poliovirus infections lead to paralysis. For the four paralytic cases reported in China, there are likely 400 individuals who were infected with the virus but did not display obvious symptoms. This suggests a lapse in immunization coverage in this region. Consequently a polio vaccination campaign is planned for early September, the target being 3.8 million children <15 years of age in the outbreak area.

Pakistan, which shares a border with Hetian prefecture, appears to be the origin of the poliovirus strain causing the outbreak. Wild poliovirus type 1 continues to circulate in Pakistan, causing 76 reported cases of paralytic disease so far this year. This incident emphasizes the need for continued high immunization coverage in all countries until eradication of the virus is achieved. It is estimated that China has achieved >99.5% coverage for the third dose of poliovirus vaccine. In a country of 1.3 billion people, that leaves a large number of susceptible individuals.

Hand, foot, and mouth disease outbreak in China

hand-foot-mouth-diseaseAn outbreak of hand, foot, and mouth disease in China has lead to 41,000 infections and 18 deaths this year. What is this disease and what causes it?

Hand, foot, and mouth disease (HFMD) is a rather common viral infection of children. There were 80,000 recorded cases of the disease just in China for 2007. The disease occurs globally, displaying seasonality (summer, early autumn) in temperate climates. It is caused by members of the genus enterovirus, Coxsackievirus A10 and A16 or enterovirus type 71, viruses that are related to poliovirus. The virions are composed of a positive-sense RNA surrounded by a capsid built with four different viral proteins. The predominant virus in the 2007 outbreak in China was enterovirus type 71. The identify of the virus causing the current outbreak is not known, but enterovirus 71 has already been identified in several patients.

HFMD is typically acquired through close contact with an infected individual. It begins with nonspecific symptoms such as fever and malaise, and is followed by the development of ulcerating sores on the tongue, gums, and insides of the cheeks. A skin rash then appears on the hands and soles of the feet. The infection is spread to others by the virus that is present in pharyngeal secretions, saliva, and fluid from the skin blisters.

Outbreaks of HFMD typically involve children because they are not immune to infection, and because children physically intereact in ways that promote transmission, especially in summer months when outdoor play is common. The disease is much less prevalent in adults because they are protected by immunity conferred by childhood infection.

HFMD is an acute viral infection which resolves within 1-2 weeks. When caused by Coxsackieviruses, the course of the disease is usually uneventful. However, enterovirus 71 can enter the central nervous system where it may cause encephalitis or a polio-like paralysis. How the virus reaches this site is not known. By analogy with poliovirus, we assume that the virus enters the bloodstream – possibly after replicating in the intestine – and then makes its way to the spinal cord. This virus has emerged as a significant neurological pathogen in Taiwan.

There are no vaccines or antiviral drugs available for treatment of HFMD, and little research is done on the viruses that cause the disease. This situation is likely to change with the emergence of enterovirus 71 as the most significant neurotropic enterovirus in some areas of the world.

Zhang, Y., Tan, X., Wang, H., Yan, D., Zhu, S., Wang, D., Ji, F., Wang, X., Gao, Y., & Chen, L. (2009). An outbreak of hand, foot, and mouth disease associated with subgenotype C4 of human enterovirus 71 in Shandong, China Journal of Clinical Virology, 44 (4), 262-267 DOI: 10.1016/j.jcv.2009.02.002

QIU, J. (2008). Enterovirus 71 infection: a new threat to global public health? The Lancet Neurology, 7 (10), 868-869 DOI: 10.1016/S1474-4422(08)70207-2

Arita, M., Wakita, T., & Shimizu, H. (2008). Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity Journal of General Virology, 89 (10), 2518-2530 DOI: 10.1099/vir.0.2008/002915-0