The discovery is also changing the way that scientists think about infectious diseases in general.

"This study shows that what we thought we knew about foot-and-mouth disease is not entirely true," said Mark Woolhouse from the University of Edinburgh, a co-author of the study. "So, what we think we know about human influenza and other infectious pathogens might not be completely accurate either."

The report appears in the 6 May issue of the journal Science, which is published by AAAS, the international nonprofit science society.

Foot-and-mouth disease virus, or FMDV, is an RNA virus that infects cattle and other livestock animals, causing lesions on the tongue and feet, fever, and a runny nose. Each year, it's responsible for huge losses in the global livestock trade. Countries with endemic FMDV spend tremendous amounts of money vaccinating their cattle and farmers often kill off large numbers of livestock to control the disease once a clinical case has been confirmed.

In 2001, the United Kingdom experienced the biggest FMDV epidemic to strike a developed country in several decades. Hundreds of thousands of animals were killed and billions of British Pounds were lost before the disease was controlled.

Now, researchers have performed experiments with cattle to characterize the precise incubation and infectious periods of the disease-causing virus in live animals.

They found that even if the virus can be detected in a cow's blood sample-the traditional way of measuring infectiousness-it does not actually mean that the animal is infectious. In fact, a cow with FMDV is only infectious for 1.7 days, they say. After that, immune responses kick in and limit virus replication.

Bryan Charleston and colleagues from Pirbright Laboratory in the United Kingdom, along with Dr. Woolhouse, infected "source" cows with FMDV and studied how the virus was transmitted to other, uninfected cows.

Their experiment is different from previous studies that have only estimated transmission rates for groups of animals, rather than individuals.

"We have pinned down, very specifically, the relationship between when the animals are infectious with FMDV and when they show clinical signs of the infection," said Woolhouse.

"Normally, we only know if a person or animal is infected with disease when their clinical signs appear. But, what we didn't know before this is how those signs relate to infectiousness. In the case of FMDV, the clinical signs and infectiousness seem to occur around the same time."

In 28 attempts to infect healthy cows with FMDV (by placing them in close proximity to an infected cow for eight hours), the researchers only observed eight successful transmissions of the virus. In light of their results, Charleston and his colleagues suggest that cows with FMDV only become infectious for a brief period of time-approximately 0.5 days after clinical signs of the disease appear.

"We now know that there is a window where, if affected cattle are detected and removed from the herd promptly, there may be no need for pre-emptive culling in the immediate area of an infected farm," said Woolhouse. "We have an opportunity now to develop new test systems which can detect infected animals earlier and reduce the spread of the disease."

Their findings are consistent with a rarely tested theory that disease symptoms may be functionally linked to infectiousness.

"If you do things like measure virus in the blood, you're taking no account of the clinical state of the animal," said Woolhouse.

"People might imagine that the clinical signs of a virus-the symptoms, such as sneezing-have something to do with its transmission. But, while there has been a lot of thoughtful speculation on the topic, there haven't been many actual studies."

Charleston and his team are now calling for practical tools that could diagnose foot-and-mouth disease in the field before clinical signs appear.

According to the researchers, if FMDV could be detected in livestock just 24 hours before clinical signs appear, then farmers might have time to remove the infected animals before they transmit the virus.

"If the benefits of this research are going to be realized in the field, we are going to have to implement pre-clinical diagnostics," said Woolhouse.

"It's technically and logistically challenging, but our work shows that the potential benefits would be much greater than we've previously realized. So, at the very least, we should take a look at the possibilities for detecting FMDV early on."

The researchers also propose that similar studies could reveal much more about other animal (and human) pathogens in the future.

"We urgently need to evaluate other infections," said Woolhouse. "Until we do that, we can't evaluate how effective control measures like quarantining individuals, prophylaxis, anti-virals or the pre-emptive culling of livestock are going to be."

The funding for this research was born out of a special initiative, launched by the U.K. Biotechnology and Biological Sciences Research Council after the horrific 2001 outbreak of foot-and-mouth disease in that country. The researchers involved say that such direct experiments are vital to our understanding of public health.

"If you're going to make informed decisions about controlling infectious diseases, you need the right kinds of scientific evidence-and this study provides that, even if it wasn't easy or cheap to come by," concluded Woolhouse.

"People have used short-cuts before and we can end up with misleading information. This new research tells me that we can't afford to take those short-cuts. This is the kind of work we need to be doing to learn how to manage infectious diseases in the future."

The report by Charleston et al. titled, "Relationship Between Clinical Symptoms and Transmission of an Infectious Disease and the Implications for Control" appears in the 6 May issue of the journal Science. A related Perspective article by Graham Medley titled, "Diagnosing the Individual to Control the Epidemic" appears in the 11 May issue of Translational Medicine.

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