SARS in check in the U.S., but that could change

One super-spreader’ may be all it takes

Five health care workers in the United States have contracted suspected severe acute respiratory syndrome (SARS), but timely and thorough infection control precautions appear to be holding the emerging infection at bay in the United States.

As of April 14, 2003, the Centers for Disease Control and Prevention (CDC) was investigating 193 cases in the United States. In addition to the five health care workers, another 15 of the cases involve transmission to family contacts. There have been no deaths.

The relative containment of what appears to be a novel, emerging coronavirus has sparked a few theories and discussions among investigators and the medical press. Is the SARS virus in the United States a weaker mutant strain? Do we have fewer cases of so-called "super-spreaders"? Or it is a combination of early warning and a well-trained cadre of national infection control professionals? Though clearly concerned that we may simply be basking in fickle "luck," Julie Gerberding, MD, director of the CDC, gives a few kudos to the entrenched IC programs in this country.

SARS patients are being put in isolation rooms with an air exchange appropriate to minimize airborne transmission — if it is occurring. Health care personnel and visitors to the patient must wear N95 respirators. Incoming suspect cases wear a surgical mask in some settings. In addition, workers take infection control measures to avoid droplet, splatter, and hand-to-hand or hand-to-surface contamination.

"These are standard infection control precautions that have been used for a variety of infectious disease such as tuberculosis or many other infections," she says. "I think the health care environment has a long tradition of familiarity with them. That may be one of the reasons why we have had a little more success with containment here. We have been using these standards for many, many other infectious diseases for a long period of time, and we’re trained to know how to use them."

Or are we seeing a surveillance artifact?

In addition, some of the difference could simply be a surveillance artifact due to catchment of milder cases in the United States that are not true SARS. The CDC is tightening its case definition to bring it more in line with that used by the World Health Organization (WHO). "When we make that transition, you’re going to see a reduction in the number of cases that we are reporting as SARS in the WHO list, because they have a more stringent definition than we do, and many of the people who we’re counting are not going to meet the WHO case definition," Gerberding says. The CDC will still follow those cases, however, "because we want to err on the side of caution and isolate anybody who might possibly be in this category."

With the situation much in flux, there is little celebration among U.S. investigators who appear to be currently fighting a milder epidemic than their colleagues in the Far East and Canada. With more than 3,000 people infected worldwide, there is little time for resting on the proverbial laurels.

"Despite the fact that we do seem to be able to contain the spread of this disease in the United States and are not right now experiencing a situation that looks like the patterns in Hong Kong, we have to remain vigilant," she says. "Because only one highly transmissible patient can infect a very large number of people." The term "super-spreader" has been used to give a plausible explanation for a pattern of epidemiology, but it still has aspects of speculation, Gerberding reminds.

"We don’t know whether the virus is associated with a lot of spread in an individual cluster because of something having to do with the infected person or if it has to do with the type of containment or failure of the containment procedures that are present there," she says. "So we need to understand the whole picture, why are some clusters expanding so rapidly and other clusters are extinguished or die out?"

Thus far in the global outbreak, the largest SARS clusters have been transmitted by very sick people with full-blown pneumonia. Thus it is possible they have higher titers of virus in the blood and can more efficiently transmit it into the surrounding environment. "Even though we would like to be able to take a deep breath and relax a little bit here, this is absolutely the wrong time to do that," Gerberding says. "We must continue to identify suspect cases, to isolate individuals as quickly as we can, and to do everything possible to prevent the spread of this illness into our community, so that we don’t end up with an epidemic that is as rapidly progressive as we are seeing in some parts of Asia."

Clinical tests on immediate horizon

In a recent development that could lead to SARS tests for clinicians, both the CDC and Canadian researchers have sequenced the entire genome of the new coronavirus. What they have found tells little of its origin because it is distinctly different from the known coronaviruses.

"This virus is like a totally separate group, related to part of the coronavirus family, but distinct from all the other known coronavirus — both animal and the two human strains," says Larry Anderson, MD, one of the leading CDC researchers on the microbiology of the virus.

That finding is consistent with the emergence of a new virus as the source of the SARS epidemic, but the CDC withheld pronouncing the etiology of the outbreak solved. Likewise, the prevailing theory that the bug moved from an animal host to man remains to be proven.

"We need to go back to the very first cases of SARS that probably occurred in the Guangdong province and really do the kind of shoe-leather epidemiology that it takes to know: Who were those people? Where were they? What were they doing? What life were they leading? What did they come in contact with?," Gerberding says. "And then, for example, if those patients were in a situation where they were exposed to animals, or birds, or some other kind of environment, to go and try to recover viruses from the animal kingdom that are implicated in this detective story. But it’s a story that’s going to unfold over some time."

In the short run, having the genetic information will be critically important for developing diagnostic tests, antivirals, and farther down the road, a SARS vaccine.

"The virus has been put in a number of animal tissues, and we’re hopeful that one of these will not only create a disease that would allow it to fulfill the conditions for saying that coronavirus is definitely the cause, but also be a model in which we could test antiviral drug treatments or other therapies," she explains. "[A vaccine] will take some time, and I think it would be naive to say that we would have it in under a year."

The most immediate use is likely to be in enhancing diagnostic testing by using polymerase chain reaction (PCR) to amplify a piece of the virus in a test tube. That could lead to a licensed diagnostic test, which will probably be based on one of the three field tests the CDC is using to identify cases.

"What we have right now is a PCR test, which is useful in identifying virus material in the respiratory secretions of patients," she says. "The advantage of this test is that it would be positive early in the course of illness. We also have two different antibody tests. The advantage of the antibody tests is they’re generally easier to do than a PCR test, but the results in a given patient may not be positive until several days have passed after the onset of infection."