Hepatitis A virus is a common companion for people in developing countries, roaming the land by way of contaminated water, person-to-person contact, perhaps even flies.
But it's a relative stranger in places with good sanitation, and scientists say that lack of familiarity explains, in part, why it has had such a large impact in four U.S. outbreaks this fall.
Where the virus is routinely found, it usually infects children, who exhibit few symptoms and develop lifelong immunity. So scallions contaminated with hepatitis A virus, the likely culprit in the recent outbreaks, wouldn't cause a problem if they were consumed by adults in Mexico, for example.
But those same scallions can sicken hundreds and even cause deaths when served in a place such as Beaver County, where most adults lack immunity.
Now that the United States' food supply increasingly includes produce from developing countries, some say the recent outbreaks raise the possibility that many more Americans, possibly starting with children in their regular course of inoculations, should be vaccinated against hepatitis A.
That's especially true, they say, when considering the dirty little secret of hepatitis A: There are thousands of infections and perhaps even scores of small outbreaks going on all the time in this country. They're just never identified as such.
"If there was ever a time to think about widely using hepatitis A vaccine, it's now," said Michael Osterholm, an epidemiologist at the University of Minnesota.
The path of the virus
The virus attacks slowly. It usually infects liver cells, but is unique among viruses in that it doesn't quickly kill the cells it infects. Rather, it quietly replicates within them for weeks before the body finally notices and mounts an immune response.
Only then do symptoms start, which explains why the hepatitis A outbreak among patrons at the Beaver Valley Mall Chi-Chi's surfaced in late October and early November, roughly a month after people ate scallions at the restaurant.
As the virus gains a foothold in liver cells, it gets dumped into the intestines along with cell-produced bile, thereby making its way into fecal matter. The body's immune response to hepatitis A kills infected cells and the remains also are discarded into the intestines, another reason why infected people shed virus in their feces.
Hepatitis A isn't devastating like the smallpox virus, which rampaged through populations. It doesn't change rapidly like the influenza virus, which is an elusive target for vaccine makers due to yearly mutations.
Instead, it is stable and hardy.
"This guy is a leopard who never changes his spots," said Dean Cliver, a virologist at the University of California-Davis who has studied food safety issues for 41 years.
Hepatitis A virus can survive for months in ice and weeks in dried fecal matter -- a long life span outside the human body compared with other viruses. Cooking can kill the virus, but it can withstand high temperatures. It has flourished for centuries, in part because it doesn't kill its host.
"There's a school of thought out there that viruses like this have made a deal with their host: In usual circumstances, we won't kill," said Dr. Tony Fiore, a hepatitis expert with the Centers for Disease Control and Prevention. "It's viruses that are unfamiliar with hosts that kill people. Ebola and HIV are viruses that haven't struck this deal yet."
More cases than reported
The Beaver County experience put a spotlight on hepatitis A illnesses and outbreaks, but that awareness is unusual.
There were about 10,600 cases of hepatitis A reported to public health authorities in 2001, yet CDC estimates that there were about 93,000 actual infections that year. The under-reporting stems from the fact that most illnesses are mild and don't prompt medical testing. The telling symptom of hepatitis is jaundice, but it doesn't occur in many cases.
"For half of people with confirmed cases, we don't know what their risk factor is," Fiore said. "It's many people's belief that some unknown proportion of those ... might have something to do with food."
Of the nearly 2,500 food-borne outbreaks that occurred between 1990 and 2002, 46 involved hepatitis A contamination, according to the Center for Science in the Public Interest. In many outbreaks, contamination came by way of infected food handlers with dirty hands.
Hepatitis A is spread by the fecal-oral route, and a single worker failing to wash hands after using the bathroom can cause trouble for hundreds.
"I've counseled a lot of food workers and told them: Toilet paper is not an effective barrier," said Kathy Blair, epidemiologist with the Milwaukee Health Department. Blair investigated a 1992 outbreak in which an infected sandwich-maker, perhaps by way of chopped tomatoes, apparently passed the virus to 230 people.
But a growing number of hepatitis A outbreaks apparently involve contamination of produce on farms. Scallions were implicated in four outbreaks that sickened more than 100 people combined between 1996 and 2000.
The true impact of those outbreaks, as well as those this year in Beaver County, Tennessee, Georgia and North Carolina, could be even greater than is currently recognized.
A green onion-related outbreak surfaced during 2000 at Kentucky and Florida branches of a chain restaurant. When CDC investigated, it asked health departments around the country to send blood samples from hepatitis A patients who were sick at roughly the same time.
Sophisticated tests of the various viral strains reached an intriguing conclusion: The strains sickening people in the Kentucky and Florida restaurants had also caused one hepatitis A case in Nevada, while a closely related strain was circulating in Texas.
Were there also contaminated scallions in the other states? Investigators could never say for sure.
CDC's work in the Beaver County outbreak has uncovered at least one similar result. A few people who came down with hepatitis A in October in Oklahoma have viral strains that match the strain that circulated here.
Lauri Smithee, epidemiologist with the Oklahoma State Department of Health, said some of those sickened ate green onions, while others said they hadn't. With so few cases, it's impossible to make firm conclusions about whether a particular food product was involved.
It could be that Oklahoma patients encountered the viral strain by a different route -- contact with a human source who was somehow related to the source of the scallion contamination. But it's also possible, given the lengthy incubation period for hepatitis A, that all the Oklahoma patients did eat scallions, but either forgot they had done so or didn't realize that they had.
Fiore said he couldn't speak to the particulars of the Oklahoma cases, but in general it's possible that the green onions might have been more widespread.
"Instead of getting into a restaurant ... it might have had a more limited dispersal, such as to a family where only a few people got sick."
Questions about the true scope and frequency of outbreaks will remain unanswered until genetic testing for hepatitis A cases becomes commonplace, which won't happen for another five to 10 years, Fiore said.
Is vaccination the answer?
Rather than wait for investigative improvements, some say vaccination to prevent cases is a better approach.
"The need has been there for years," said Cliver, of the University of California-Davis. "If these outbreaks are a wake-up call, then we need to wake up and do something."
Routine childhood hepatitis A immunization is recommended in regions of the United States where incidence rates are twice the national average. Eleven Western states meet that criteria.
But the decision to mandate vaccination could be cost-effective elsewhere, too, argued Dr. David P. Greenberg, a vaccine expert at Children's Hospital of Pittsburgh, and others writing in the October edition of Journal of Pediatric Infectious Diseases. In 1997, hepatitis A cost the United States an estimated $489 million in work loss, lost productivity and medical costs, the doctors noted.
While children have the mildest cases of hepatitis A, they would be the logical candidates for vaccination because there's already a well-established route by which many children get shots. What's more, children lacking hepatitis A symptoms can still pass the virus to adults, who get worse cases.
National vaccination would prevent 75,000 cases of overt hepatitis A.
In a sense, vaccinating children would afford the protection that children in developing countries have, without subjecting them to the many risks that come from poor sanitation.
Hepatitis A vaccine is administered in two doses, with the second dose coming six to 12 months after the first. In the wake of the Beaver County outbreak, the Allegheny County Health Department has been having a vaccine sale, charging $27 for adults and $21 for children. The full market price, which previously was $52 and $30,will be charged for the second dose.
More than 600 people here have opted for vaccination since mid-November.
Even so, Dr. Bruce Dixon, Health Department director, said he didn't see a need for mandatory vaccination in states such as Pennsylvania.
"Put the Chi-Chi's experience aside, and ordinarily, we don't have nearly enough cases of hepatitis A to warrant mandatory vaccination," he said. "I think it becomes a cost-benefit issue, and I don't think we're there yet."
The CDC has not recommended broader hepatitis A vaccination, saying the number of people sickened by the disease in most groups is so low that it doesn't argue for mandates.
Another solution is improving living conditions in the developing world, said Dr. Robert Tauxe, chief of the food-borne and diarrhea disease branch in the Center for Infectious Diseases at CDC. Hepatitis A vaccine won't protect people against shigella, salmonella and a host of other organisms that are also on food as a result of problems with sanitation and hygiene.
"Maybe the solution is to make sure the water is clean, the workers are healthy and their kids are healthy," Tauxe said. "Let's consider general improvements to sanitation at the source."