Darwin Chronicles

July 2005

Health officials query Chinese about avian influenza

WHO and the Food and Agriculture Organization (FAO) are investigating reports that Chinese farmers gave amantadine to poultry flocks, rendering the H5N1 strain resistant to the drug, according to a WHO spokesman.

Last year, researchers treating patients in Vietnam and Thailand found that amantadine had become resistant, and they began to suspect that farmers, with the endorsement of the government, were using the product in their flocks, according to a report by The Washington Post. Chinese authorities, however, deny the report.

In its story, the Post said that pharmaceutical executives and veterinarians in China confirmed that farmers were using the drug widely during the 1990s to control the virus – before China reported the avian influenza outbreak. China reported the outbreak in February 2004.

According to the article, the Chinese government approved the sale of the drug for use in poultry flocks. Such use is barred in the United States and many other countries. China denies the allegations, but in an interview with Infectious Disease News, a spokesman for WHO said that WHO and FAO were investigating the published reports as of press time. He added that the H5N1 strain is resistant to amantadine and is only vulnerable to oseltamivir.

In early June, health officials in Hong Kong confirmed that officials in the Xinjiang region of China had suspended the export of live birds. In a public statement, health officials from Hong Kong said that more than 13,000 ducks and chickens had been culled from one area of Xinjiang, a farm in Tacheng.

According to the CDC, outbreaks of avian influenza have occurred among poultry in eight countries in Asia, including China, Vietnam, Cambodia, Indonesia, Japan, Laos, South Korea and Thailand, during late 2003 and early 2004. At that time, more than 100 million birds either died from the disease or were culled.

In other news, four more human cases of H5N1 avian influenza were confirmed in Vietnam. As of press time, there were 108 cases between January 2004 and June 2005 in Vietnam, Thailand and Cambodia; 54 of those cases were fatal, according to a recent Morbidity and Mortality Weekly Report (2005;54[25]:633). From mid-December through last month, 60 cases had been reported from Vietnam alone.

Mad cow confirmed in the United States

The Department of Agriculture (USDA) recently confirmed a case of bovine spongiform encephalopathy (BSE) in an animal that was removed from the food supply last November. As a result, the department will change its testing method to find BSE.

Repeated tests were contradictory. At first they were negative, then they were positive. Finally, the materials were sent to a BSE reference laboratory in Weybridge, United Kingdon (UK), which has been battling this problem for some time. That test confirmed BSE in the animal, Mike Johanns, U.S. agriculture secretary, said at a press conference.

“The results confirm the presence of BSE in this animal, an animal that was blocked from entering the food supply thanks to the firewalls that are in place. It is critically important to note that this animal was identified as a high-risk animal. A sample was taken, and the carcass was incinerated,” Johanns said.

The department said the animal lived in Texas its entire life. The animal was born 12 years ago, before the United States instituted a ruminant-to-ruminant feed ban in August 1997, since this is the primary way BSE prions are transferred to cattle.

The downed animal was tested because it was considered to be at higher risk for BSE. An initial screening test in November 2004 was inconclusive, triggering the department to conduct an immunohistochemistry (IHC) test. Those results were negative. Earlier in June, the USDA’s office of inspector general recommended using the Western blot, which was reactive. This prompted the agricultural officials to send samples to the UK. Weybridge officials confirmed the positive result.

Johanns, who was not agriculture secretary when the animal was first tested, said that he was concerned about the testing process and instituted some changes. First, parts of the infected carcass were stored with those of four other animals, making it difficult to isolate the parts. All the animals were incinerated, he said, and controls were tightened in the facility. In addition, he has asked for an analysis of the sampling and segregation procedures to ensure accuracy.

“My second concern relates to an experimental test that was run on this sample back in November in addition to the standard test. A sample this sensitive should not be subjected to additional tests for research purposes without specific protocol to guide that action,” he said.

“I also want to mention that the experimental test revealed abnormalities. Because the test was not validated and because it followed the two approved IHC tests that came out negative, the results were not reported out of the lab.”

He has asked scientists to work with their overseas colleagues to develop protocols to govern research and reporting.

Despite these lapses, this downed cow was prohibited from entering the human food supply. Research has shown that BSE is most likely found in older downed cattle, animals showing signs of central nervous system disorders, injured or emaciated animals and cattle that have died for unexplained reasons. The USDA’s testing program targets these animals.

USDA has run 388,000 tests for BSE; three were inconclusive, and only one has been positive. John Clifford, DVM, chief veterinary officer of the USDA, said with a program of that size, one positive result was not unexpected.

Danny Matthews, TSE program manager at the Weybridge laboratories, said he was “pretty confident” rates of BSE in the United States were low. – Marie Rosenthal

Cancer drug targets poxvirus in mice

Mice given a targeted cancer therapy can survive an otherwise lethal dose of vaccinia virus, according to a recent study.

Although smallpox was eradicated in 1980, it is considered a potential bioweapon. For this reason, scientists are researching smallpox treatments and vaccines. The new findings suggest that imatinib (Gleevec, Novartis) might be useful for treatment.

Poxviruses co-opt various cellular molecules and processes to enter a cell, replicate and spread to uninfected cells, according to Daniel Kalman, PhD, of Emory University School of Medicine, Atlanta. Kalman and his colleagues identified specific cell proteins that vaccinia uses to detach from an infected cell and move toward an uninfected cell. The proteins, members of the Abl-family of tyrosine kinases, are well-known to cancer investigators because mutation of one family member, Abl, causes chronic myelogenous leukemia (CML). Imatinib inhibits Abl-family tyrosine kinases and has proved very useful in treating CML.

Researchers treated mice with imatinib at a dose equivalent to that given to humans being treated for CML or a placebo. Next, they exposed the mice to vaccinia. All of the imatinib-treated mice survived, while 70% of the untreated mice died.

“What I like about this article is that the authors identified a molecular mechanism that vaccinia uses for cell-to-cell spread. This mechanism turned out to be an imatinib target, hence it was rational to test whether imatinib could protect against vaccina infection,” said Brian J. Druker, MD, of the Howard Hughes Medical Institute and Oregon Health & Science University, both in Portland, who pioneered the development of imatinib.

This finding, published in Nature Medicine, suggests that imatinib, given for a short period, could hamper the cell-to-cell spread of virus.

A grant from NIAID supported the research.