Jim Martin, Commissioner
Kathleen
E. Toomey, M.D., M.P.H., Division Director
Jim Martin, Commissioner
Kathleen
E. Toomey, M.D., M.P.H., Division Director
Approaches To a Clinical Conundrum: Influenza vs. Anthrax (revised 11/6/2001)
Q: Since the initial symptoms of anthrax and influenza may be similar, does CDC or GDPH recommend that everyone get an influenza immunization (flu shot) so that if they later have flu-like symptoms they will know they don’t have influenza?
A: No. CDC and GDPH do not recommend that influenza vaccination be considered as a way to avoid confusing influenza disease with suspected anthrax illness. Symptoms such as fever, body aches, and headaches are common to many different infections besides influenza and anthrax. Most flu-like illness is not caused by influenza (or anthrax). Influenza vaccine prevents influenza, but does not prevent other viral causes of flu-like illness. Influenza vaccine is not 100% protective and some people who have been vaccinated will still develop influenza. The influenza vaccine will not protect all vaccine recipients against flu-like illness.
Influenza vaccination should be targeted to persons who are at high risk for death or serious complications from influenza infection (including the elderly, persons with certain high-risk medical conditions, and pregnant women after the first trimester), those who live with or work with high-risk persons, and health care providers. Depending on vaccine availability, other persons who wish to reduce the likelihood of becoming ill with influenza should also receive vaccine.
Q: Can rapid influenza diagnostic tests be used to assess the risk for anthrax by "ruling in" or "ruling-out" influenza as a cause of flu-like illness?
A: None of the 5 currently available rapid influenza diagnostic tests are perfectly sensitive and specific, which means for any given individual the test result could be correct or incorrect (see table: Rapid Influenza Diagnostic Tests 2001, below). Up to 30% of patients with influenza may have a negative rapid test. Rapid tests are most useful for diagnosing influenza when the influenza virus is circulating at high levels in the community, at which time a positive test is likely to be true-positive, but a negative test does NOT rule-out influenza. Samples for rapid influenza testing should be obtained during the first 1 to 4 days of illness.
It is important to realize that many respiratory viruses can cause flu-like illness. Some examples include adenovirus (many types), respiratory syncytial virus, parainfluenza virus 1, 2, and 3, rhinovirus (many types), coronavirus (many types), coxsackievirus A and B, and echovirus (many types). During peak influenza activity, researchers are only about 60% accurate in their ability to clinically diagnose influenza. Rapid tests are potentially very useful for establishing the presence of circulating influenza virus in the population served by the testing facility, especially when used with confirmatory viral cultures. Information about circulating respiratory viruses in Georgia can be found on the Georgia Division of Public Health website, at http://health.state.ga.us. A negative test for influenza (1) can occur when a patient has influenza, (2) can occur when a patient has one of many other viral infections, and (3) does not increase the likelihood that the patient has anthrax. Furthermore, a positive test for influenza does not rule-out concomitant anthrax. Risk assessment for anthrax should be conducted separately from risk assessment for influenza (see Risk Assessment for Anthrax, below).
Q: Are there clinical signs or symptoms that distinguish influenza from early inhalational anthrax?
A: No. There are no foolproof clinical signs or symptoms that distinguish influenza from early inhalational anthrax. Because of this, risk assessment for anthrax exposure should be part of clinical decision making when treating patients with flu-like illness.
Inhalational anthrax is sufficiently rare that clear descriptions of early symptoms are uncommon. Textbook descriptions of inhalational anthrax describe a biphasic illness, with a prodromal period of malaise and fatigue, along with non-specific symptoms such as fever, cough, headache, vomiting, chills, weakness, abdominal pain, and chest pain. Coryza and rhinitis are not typical of early inhalational anthrax. Radiologic signs of inhalational anthrax may be subtle in the early stages of disease. The second stage of anthrax develops after a few hours to a few days, with abrupt onset fever, dyspnea, diaphoresis, and shock. Persons with respiratory symptoms for a week or more, who have not taken antibiotics, are unlikely to have had anthrax. Among the first 10 patients identified with confirmed or suspected inhalational anthrax associated with bioterrorism, initial illness was characterized by fever (nine) and/or sweats/chills (six). Severe fatigue or malaise was present in eight and minimal or nonproductive cough in nine, including one with 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) (CDC. MMWR 50(43);941-8, November 2, 2001).
Classical influenza presents suddenly, such that many persons can pinpoint the hour they became ill. Systemic symptoms such as fever, myalgias, and severe malaise may predominate over respiratory symptoms such as nonproductive cough. Many (but not all) persons with influenza and other respiratory viral infections have watery eyes, rhinitis, and severe sore throat as part of the early symptom complex, symptoms that are not typical of early inhalational anthrax. However, these common symptoms could be present in a person who also develops inhalational anthrax.
Some persons with influenza will have a more subtle illness, clinically indistinguishable from symptoms seen in early inhalational anthrax. The spectrum of influenza illness varies from asymptomatic infection, to febrile respiratory illness, to severe systemic involvement. The symptoms of influenza are also difficult to distinguish from illness caused by other respiratory viruses, which frequently co-circulate during the winter season. Even during peak influenza activity, influenza can be predicted with only ~60% accuracy, depending upon the prevalence of other respiratory viruses relative to the level of influenza activity.
Risk Assessment for Anthrax
Anthrax continues to be a rare disease in the United States even after bioterrorism-related intentional exposures began in September 2001. Because early symptoms of inhalational anthrax are non-specific, the risk of exposure to anthrax spores is a more important predictor of anthrax disease than any particular clinical symptoms and signs, and should be considered in evaluating the possibility that a patient with flu-like symptoms might have early inhalational anthrax. The initial groups with elevated risk for anthrax disease included persons who worked in media companies in Florida and New York, federal government employees in Washington DC, and postal workers employed in facilities serving these agencies in Florida, New York, Virginia, and New Jersey. Because communities where anthrax exposures have occurred and activities associated with exposure may change over time, clinicians should stay abreast of such information, or consult with public health regarding identified risk groups.
If and when anthrax exposure may occur in Georgia, information will be made available through:
Rapid Diagnostic Tests for Influenza 2001
| Test | Manufacturer | Detects | CLIA-waived | Specimen | Time | Cost *
(list) |
Sensitivity† | Specificity† |
| Directigen Flu A | Becton Dickinson | Influenza A nucleoprotein only | No
(MC¶) |
Nasopharyngeal (NP) wash, NP aspirate, NP swab, throat swab | 15 min., 7 steps | $20-21 | 91% | 95% |
| Directigen Flu A + B | Becton Dickinson | Influenza A nucleoprotein,
Influenza B nucleoprotein (Test distinguishes between influenza A and B) |
No
(MC¶) |
NP wash, NP aspirate, NP swab, lower nasal turbinate swab, throat swab, bronchoalveolar lavage specimen | 15 min., 7 steps | $24-25 | Influenza A 86%, Influenza B 81% | Influenza A 91%, Influenza B 100% |
| Flu OIA | BioStar | Influenza A or B nucleoprotein, non-specific | No
(MC¶) |
Nasal aspirate, NP swab, throat swab, sputum | 15-20 min., 9 steps | $16-17 | 62 to 88% | 52 to 80% |
| QuickVue | Quidel | Influenza A or B nucleoprotein, non-specific | Yes | Nasal swab, nasal aspirate | 10 min., 4 steps | $16-17 | 73 to 81% | 96 to 99% |
| ZstatFlu | ZymeTx | Influenza A or B neuraminidase, non-specific | Yes | Throat swab | 20 min., 4 steps | $13-15 | 62% | 99% |
*List price per manufacturer; prices may differ when ordering from distributor
†Sensitivity and specificity according to manufacturers. No direct comparisons have been made between these tests.
¶ MC= moderate complexity
Refs: Medical Letter 1999; 41 (1068), 121-122, test manufacturers, package inserts.
Clinical evaluation of persons with possible inhalational anthrax (Adapted from MMWR 50 (43);941-8, November 02, 2001).
Symptoms
NO YES
† Serologic testing available through Georgia Public Health Laboratory may be an additional diagnostic technique.
References
Clinical evaluation of persons with possible cutaneous anthrax (Adapted from MMWR 2001;50(43);941-8).