Bioterrorism Watch

Flu or anthrax? First inhalational cases yield clues for clinicians to make the critical call

Use case history, blood work, X-rays, rapid tests

There is a postal worker in your emergency department (ED) with flulike symptoms.

That once insignificant observation about occupation and illness now triggers a detailed algorithm created by the Centers for Disease Control and Prevention (CDC) in Atlanta. (To see algorithm, click here.) Is it flu or inhalational anthrax? Whether a realistic question or not, it is what many of your incoming patients may be asking — particularly if another wave of anthrax scares coincides with a nasty influenza season. Many of the initial symptoms are similar, but investigators dealing with the first inhalational anthrax cases have gleaned out key indicators that will help clinicians make the call.

"It is important to take a careful history from the [patients] when they present," says Julie Gerberding, MD, acting deputy director of CDC’s National Center for Infectious Diseases. "If the [patients are] mail handlers in a professional environment — where they’re dealing with large amounts of mail that is not their own — then the index of suspicion should be raised and more testing should be done to be sure there aren’t additional clues to suggest that it is not a common viral infection."

Using the first 10 cases of inhalational anthrax as a baseline patient profile, the CDC reports that the median age of the patients was 56 years (range: 43-73 years), and seven were men.1

The incubation period from the time of exposure to onset of symptoms when known (seven cases) was seven days (range: five to 11 days). The initial illness in the patients included fever (nine) and/or sweats/chills (six). Severe fatigue or malaise was present in eight, and minimal or nonproductive cough in nine. One had blood-tinged sputum. Eight patients reported chest discomfort or pleuritic pain. Abdominal pain or nausea or vomiting occurred in five, and five reported chest heaviness. Other symptoms included shortness of breath (seven), headache (five), myalgias (four), and sore throat (two). The mortality rate was 40% for the 10 patients, much lower than historical data indicated. Indeed, one of the critical reasons to recognize inhalational anthrax early is that it is far more treatable than originally thought.

The CDC gathered comparative data on the symptoms and signs of anthrax and influenza, finding, for example, that only 20% of the anthrax patients reported sore throat.2 Flu sufferers report a sore throat in 64% to 84% of cases. Likewise, 80% of the anthrax cases reported symptoms of nausea and vomiting. That symptom is reported in only 12% of flu cases. Shortness of breath appears to be another key distinguishing symptom, affecting 80% of the anthrax patients but seen in only 6% of flu patients.

"One of the other clues that we are noticing is that the patients with inhalation anthrax actually do not have nasal congestion or a runny nose," Gerberding says. "They don’t have the symptoms of an upper-respiratory tract infection. They have a more systemic chest presentation, and that may be another distinguishing characteristic."

Another finding on initial blood work is that none of the inhalational anthrax patients had a low white blood cell count (WBC) or lymphocytosis when initially evaluated. Given that, CDC officials note that future suspect cases with low WBC counts may have viral infections such as influenza. Chest X-rays were abnormal in all patients, but in two an initial reading was interpreted as within normal limits. Mediastinal changes including mediastinal widening were noted in all eight patients who had CT scans. Mediastinal widening may be subtle, and careful review of the chest radiograph by a radiologist may be necessary, the CDC advises.

Complementing the CDC’s effort, are the observations of the few clinicians who have actually seen inhalational anthrax cases come into their hospital systems. Two inhalational anthrax cases, both of which survived, were admitted to the Inova Healthcare System in Fairfax, VA (near Washington, DC).

"Clinically, I think the history of the people who presented here is useful," says Allan J. Morrison Jr., MD, MSc, FACP, health care epidemiologist for the Inova system. "They stutter-stepped toward their pulmonary symptoms. That had some mild symptoms and then they were sort of meta-stable.’ They were not relentlessly progressing. Then they progressed with symptoms more aggressively. Whereas with influenza — in our experience — once you start to get sick, it just keeps on progressing with very high fevers, chills, muscle aches, and pains. As a consequence, we feel there should be a good way to differentiate the two."

Since anthrax is a realistic concern in the Washington, DC, area, what about the aforementioned scenario of symptomatic postal workers in the ED? "We would take a very aggressive history, not only of occupation but physically where they have been," Morrison says. "If they are symptomatic and have been in or work around a hot zone’ — a location from which anthrax has either been cultured environmentally or patients have come from there — we will err on the side of being very aggressive about working up anthrax. By that I mean chest X-rays, chemistry profile, [etc.]"

In addition, the hospital system pushed early flu vaccination programs for staff and the surrounding community. "We want to move toward herd immunity," he says. "We are also working with our local hospitals to make sure that they have access to the rapid influenza tests. So for diagnosis — for obvious reasons — it is very helpful to make that distinction early."

One such rapid test is ZstatFlu (ZymeTX Inc., Oklahoma City), which the company claims can yield a diagnosis of influenza A or B some 20 minutes after a throat swab. The test detects neuraminidase, an influenza viral enzyme. However, Gerberding cautions clinicians not to rely solely on such tests. Rather, they should use the results of tests in combination with the patient history and clinical presentation, she says.

"So it is a constellation of history, clinical findings, and laboratory tests," she says. "Hopefully, when we get these all together, we’ll be able to at least reduce the anxiety among some people and help clinicians diagnose those patients who really do require the antibiotic treatment. What we don’t want to have happen is for everybody coming in with the flu to get an antibiotic because that undermines a whole other set of public health issues relating to antimicrobial resistance and proper management of influenza."

Even the vaccinated can still have flu

Complicating the issue is the fact that the flu vaccine efficacy can vary annually, but is usually 70% to 90% protective, says Keiji Fukuda, MD, a medical epidemiologist in the CDC influenza branch. Thus, depending on how well the vaccine matches the circulating strain, a certain portion of flu patients will tell clinicians they have been immunized. But in addition to vaccine breakthrough infections, there is a plethora of other viral and respiratory pathogens that will be creating similar symptoms, he says. In a somewhat sobering reminder — given that at this writing, the total anthrax cases remained in the double digits — Fukuda notes that a typical flu season will send 114,000 people to the hospital and 20,000 to their graves.

"There has been an awful lot of attention on the [anthrax] cases, but the bottom line is that there have been few cases, and these cases generally have occurred in a limited number of communities within a limited number of groups," he says. "And so the epidemiologic message is that anthrax really has not been diagnosed in most parts of the country, whereas we expect to see millions and millions of flu cases all over the place."

If facilities are faced with an onslaught of patients with respiratory illness there are several measures they can take, he notes. Those include:

  • Reduce or eliminate elective surgery.
  • Relax staff-to-patient ratios within the limits of your licensing agency.
  • Emphasize immunizing staff so more staff are available.
  • Identify ways to bring in extra staff to help out with the patients.
  • Set up walk-in flu clinics to triage the patients.


1. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. MMWR 2001; 50:941-948.

2. Centers for Disease Control and Prevention. Consideration for distinguishing influenza-like illness from inhalational anthrax. MMWR 2001; 50:984-986.