Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        "Flu" viral influenza
      

There are lots of other infections (virus & other agents) which, early on, seem like they could be "flu". In the second half of 2014, enterovirus 68 (was first identified in 1962) became a problem. In September 2014, the first known Ebola virus case (among several) enterred the USA, with one dying in Dallas. Though these cases were western Africa outbreak related, Ebola & Marburg viruses (filoviruses) and Lassa & Machupo viruses (arenaviruses) are category A bioterrorism agents under the heading of hemorrhagic fever viruses who also can present like flu9. After an incubation period without symptoms, there is onset of fever, muscle aches (myalgia), weakness, and headaches9.

The 2014-15 vaccine choices vary from trivalent to quadrivalent to recombinant, live attenuated to inactivated, HERE.

The USA vaccine for the 2010-11 flu season was trivalent & provides protection against:

  1. "2009 H1N1" (pandemic) influenza A
  2. seasonal H3N2 influenza A
  3. an influenza B

"Flu & Swine Flu" 9/14/2012 "heads up":8 In view of the possibility of false negative results due to (1) poor specimen or (2) test-system insensitivity, clinical correlation (as always) is vital (to include the consideration of mixed pathogens)! Beginning 8 Oct. 2012, we will have a menu of THREE "flu tests", ALL needing an excellent high, superior NP-swab harvesting of cellular sample; each test route requires its own sample:

  1. Rapid influenza A/B: best TAT = 30-45 minutes; non-PCR, first-line, card-type method which detects viral protein antigen & 80% sensitive for A & 60% for B. The BinaxNOW system.
  2. Influenza Rapid PCR: best TAT = 90 minutes; LMC has had this one several years; a molecular test, it is reported to also detect "swine flu" [H3N2] & lump it in with an "A" positivity, if detected; batch testing of up to 16 samples. The Cepheid PCR system.
  3. Respiratory Pathogen Rapid PCR (FilmArray): [*currently undergoing evaluation to determine if suitable*] best TAT = 120 minutes; no batch testing...one patient at a time; the possible test method...if evaluation confirms vendor claims...for more seriously ill patients (variously detects indluenza A (H1; H2; H3), B; parainfluenza [1, 2, 3, 4]; coronavirus [4 types]; adenovirus; metapneumovirus; rhinovirus...enterovirus; RSV; Mycoplasma pneumoniae; Chlamydia pneumoniae (TWAR); and Bordetella pertussis. The FilmArray Multiplex Rapid PCR system.

9/12/2012: "I'm in process of negotiating for, and validating a multiplex PCR system that will rapid test... The currently used rapid flu test will not reliably detect the H3N2 virus. Hopefully this molecular testing...will be useful in evaluation of some ED patients as it [can potentially] also test for Bordetella and some variants of community-acquired pneumonia." However, this platform did not gain traction and was discontinued in our lab.

There are 3 influenza virus types: A, B, and C (C is a mild non-epidemic type not covered by vaccines). [all types HERE] The Fujian strain of around 2004 is an "A" which does not grow well in chicken eggs (the growth medium to produce "flu" vaccine). About 10-20% of Americans get flu each year, and about 36,000 die. Complicating bacterial co-infections are an additional life-threatening hazard, being the lethal factor in a large percentage of deaths. In 2009, we were concerned about the highly contagious but less morbid "novel H1N1" A, "swine flu" (otherwise, "2009 H1N1"). Here is a source on influenza. SEE OUR TEST STRATEGY, BELOW.

Fluids &Nasal washings: Positive is positive & negative is indeterminate. Our doctor offices and CMCs are all able to obtain normal-saline-flushed nasal (or NP) washings/aspirates (as for RSV testing) or internal, high-up, nasopharyngeal (NP) swabs (barely internal nasal swabs are less good because the area is lined mostly by virus deficient squamous epithelium rather than the glandular epithelium the virus tends to populate) as samples for testing in the Lexington Medical Center main hospital lab (and as of 12/8/03 in the CMC labs). Bronchoalveolar lavage (BAL) specimens might result from bronchoscopy. Infected cells are more plentiful early in the coarse of disease (first 3 days of viral shedding giving the most concentrated viral load).The sample MUST contain enough infected cells (both live and dead viruses)...a large enough viral antigen load...in order for a positive case to actually trigger a positive test (a hypocellular specimen hazards a false negative test result). FAILURE TO OBTAIN ENOUGH VIRUS = FALSE NEGATIVE TEST! While our tests can be positive whether virus is dead or alive, successful culture of an influenza-virus-containing specimen requires live virus.

Clinical index of suspicion (intuitive & experiential idea of the prevalence of the disease in patients with the cluster of findings): To overcome some of the inherent diagnostic problems of lab tests due to the statistics[see ref. links below] in low prevalence of the target disease (real A or B flu), one should clinically increase the prevalence in the tested population pool by testing only those with a high "index of clinical suspicion". This statistical phenomenon is at play in all tests of every type. Low true disease prevalence = high false positive test rate. [to see this phenomenon, use the below7 online calculator by your own examples of varying prevelance of the disease]

TEST STATISTICS: As to false positive & negative tests, nasal washing "flu tests" are inherently relatively ineffective when loosely ordered because real flu (influenza) is not that prevalent in the population, and so the tests are relatively insensitive (compared to viral culture)...86% for seasonal A & 81% for B...(although pretty specific, accurate...when positive: 91% for A and 99% for B...so there are some false positive diagnoses [hence the public health need for confirmatory cultures with DHEC]). When ordered for LOW index of suspicion, most "positive tests" will be false positives.

In backing up our ER, it is a rapid test. If positive, we report out as "positive"; and, if negative, "presumptively negative". There is enough poorness of predictive value of a negative test that one can never say that a negative test in a suspicious case has ruled out flu. Definitive positivity is by another nasal washing for culture (which we set up & send to the state DHEC lab)...results in weeks. (Serum IFA Serology may be available @ LML upon very special request approved by Dr. Carter [LML medical director]). For public health reasons, it may be wise to send samples on at least the strongly suspected cases to DHEC if/when the lab is unable to obtain rapid test kits.

Why the "rush"? Because, if clinical features are "right" and the rapid test is positive, (1) the clinician has firmer grounds for instituting expensive antiviral medication treatment which may be effective if begun within the first 48 hours of illness. (2) Or, if too far into the illness, a positive test may help in treatment decisions concerning those close contacts (of the "index case") subsequently developing flu findings. (3) And, a positive test will cause people around patient to be extra careful to avoid transmission.

For 2009, we used the rapid screen "Directigen Flu A+B" (Becton-Dickinson) kit only which indicated whether positivity is for A or B (doesn't test for C).

For 2010-11, we first use the rapid screen first. If (1) it is negative and (2) there is a high index of suspicion and (3) the patient needs admission for treatment, we use4 Xpert Flu A Panel performed on the Cepheid GeneXpert Diagnostic system, a real-time PCR assay which initially tests for influenza A matrix gene (Flu A target). And, if it is positive, we second stage test for the hemagglutinin gene of novel 2009 H1N1. That is, the first step is determining presence or absence of A virus; and, if it is positive, then is it novel 2009 H1N1? If not, then it must be either seasonal H1N1 or H3N2. The PCR test is currently in very short supply, having been issued under an FDA EUA (emergency use authorization). Here are possible lab test results:

  1. Flu A positive, novel 2009 H1N1 detected.
  2. Flu A positive, novel 2009 H1N1 not detected.
  3. Negative for any Flu A.
  4. Indeterminate.

Positive & negative predictive values on THIS test are both greater than 95%

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A flu epidemic (regional or national outbreak) would typically kill 36,000 people in America (as with the Hong Kong Flu pandemic of 1968-69). A pandemic is a world-wide outbreak, and there have been two others in past 100 years: the Spanish Flu of 1918-19 (killed 500,000 Americans and 20,000,000 worldwide) & the Asian Flu of 1957-58 (killed 70,000 Americans).

References & update sources:

  1. CDC website
  2. Dr. Carter's 8 Dec. 2003 lab memo to CMC directors.
  3. our NewsPath (special edition) of August 2009 about A (both novel & seasonal H1N1 as well as H3N2) and B...scroll down this page to the link to the PDF file.
  4. Dr. McMaster's 6 October 2010 e-mail to the LMC MSO Infect. Disease doctors.
  5. Directogen info HERE.
  6. Cepheid info HERE.
  7. about testing statistics, such the statistics of sensitivity, specificity, false positive & false negative tests, and predictive value, BRIEFLY and mathematically HERE & in another layman-like version HERE, Wikipedia extensively HERE, and the Vassar Stats online calculator HERE.
  8. Dr. John Carter's "flu" memo to ER & ID docs, 3 Oct. 2012.
  9. Guarner J, "When the Rubber Meets the Road: Dealing With a Returning Traveler From West Africa During the Ebola Outbreak of 2014, AJCP 142(4):428-430, October 2014

(posted 25 Nov. 2002; latest full update, 2011; latest small additions 16 October 2014)

 
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