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Influenza: Lauren Brett Caram, MD, discusses the clinical examination for influenza.
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Influenza: Lauren Brett Caram, MD, discusses the clinical examination for influenza.
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Language: EN.
Segment:0 .
>> I'm Joan Stephenson, editor of JAMA's Medical News and Perspectives section. Today this JAMAevidence podcast will focus on a topic that is likely on every clinician's mind Influenza. Our guest expert is Dr. Brett Caram, an infectious disease specialist and a contributor to the Influenza Education Guide Materials that augment the Rational Clinical Examination article on influenza. Dr. Caram, why don't you introduce yourself to our listeners? >> Sure. Hi, my name is Brett Caram, and as mentioned, I'm on faculty at Duke University in the Durham VA Medical Center in North Carolina, in the Division of Infectious Diseases.
>> What do we know about the prevalence of influenza? >> Well, first before we got started, I'd like to remind the listeners that the data presented in the Rational Clinical Examination article refers to influenza prior to the 2009 influenza season with the occurrence of the 2009 H1N1 Influenza A. Clearly there's forthcoming data that may show ways in which this influenza will clinically differ from previous seasonal influenzas given the age of the population which it affects, as well as the utility of diagnostic tests and treatments available.
So, in this interview, I'm going to focus mainly on the data relevant to influenza prior to the 2009 H1N1 influenza except when specifically noted. So that being said, I think again that prevalence of influenza was your question. And in an average year, prior to the 2009 pandemic that started earlier this year, 10 to 20% of people contract influenza. There are a couple of factors that impact annual severity and the prevalence of influenza, ranging from vaccine availability to antigenic shift or drift to suboptimal antigenic match in a vaccine.
However example in the United States, infection can result in upwards of about 10,000 pneumonia deaths a year, and somewhere between 30- to 40,000 respiratory and circulatory deaths per year. So the U.S. national average weekly patient visits in any given week for influenza-like illness is about 2.5%. And these visits are typically well below the rate from say April to September of every year. The visit rates start to pick up in November as most listeners will account to in at least the Northern Hemisphere.
And the 2.5 rate has been exceeded in Weeks 3 to 11 for the past three years, which is typically mid-January through the end of March. This was obviously different in the spring and summer of 2009 with the emergence of H1N1, and that national average has been exceeded actually by Week 36 and has remained above that 2.5% baseline since that time. In the past years, the typical high-risk influenza patient might include the very young, the very old, pregnant women, those with immunocompromised co-morbidities, but with this recent new influenza, this demographic shifted more heavily to weigh on those pregnant women, as well as those who are 25 years old or less for reasons that we're just now coming to understand.
>> The presence of which symptoms increases the probability that the patient has influenza? >> Well, that's a good question. Many clinicians may be making that personal association of fever, headache, myalgias, cough, or what my grandmother called the crud with influenza, but we'd like to remind the listeners that the symptoms are present in a multitude of respiratory viral infections, and they are often ones that are not assigned to an actual viral diagnosis, other than upper respiratory infection, not otherwise specified. And this is usually due to diagnostic constraints.
The strongest predictors of influenza is the clinical symptom complex called the influenza-like illness. This illness is defined by the U.S. Centers for Disease Control and Prevention, or the CDC, as feverishness or fever greater than 100 degrees Fahrenheit. And either sore throat or cough. And one particular symptom that actually lowers the likelihood that any patient, young or old, has influenza is the presence of a nasal congestion. In older patients, which is usually defined as those over 60, the presence of malaise makes the diagnosis more likely.
>> Which history and physical examination findings are helpful when diagnosing influenza? And which findings are not as helpful? >> So let me start first with the fact that upon extensive review of the literature, there's really no singular clinical finding which consistently has a positive likelihood ratio high enough to clinically rule in influenza. Nor does any single finding have a negative likelihood ratio low enough to rule out influenza. However there are patterns which evolve when the data are evaluated from multiple studies.
For example, across all age spectrums the absence of fever, the absence of cough, the absence of nasal congestion -- each have a likelihood ratio of less than 0.5. In older patient subsets, fever, malaise, and chills were the strongest predictors of infection, while the presence of sneezing reduces the likelihood of infections. In direct comparison to other signs and symptoms, fever and cough have the strongest diagnostic odds ratio. And this is part of the reason that they are featured so prominently in that CDC definition of influenza-like illness.
Although some studies have included fever and chills as predictive symptoms of influenza, these are included in the prior-mentioned CDC definition of influenza-like illness. So this data actually holds true for the 2009 H1N1 influenza as well. In a well-characterized outbreak in New York City in April of 2009 -- this is the one that occurred in a high school -- it was shown that greater than 95% of those individuals with documented H1N1 infection met criteria for this influenza-like illness definition, with 96% having had documented fevers or feverishness.
>> Dr. Caram, would you please describe the reference standard test for influenza? >> Sure. So the reference standard test for influenza infection has changed in the past few years. In years past, the reference standard was viral culture which was cumbersome, and often supplied the test results in retrospect for the patient or the clinical. The referencing for infection now is reverse transcriptase polymerase chain reaction; otherwise known as RT-PCR or PCR for short. There are several FDA-approved platforms for performing this test, and results are usually available within 3 to 6 hours after the sample is received and processed, depending on your institution.
This test performs with a sensitivity and specificity which approaches 99%, which is much better than viral culture. And some of these platforms test for influenza A and influenza B alone, while others detect a range of viral infections ranging from RSV to adenovirus to human metapneumovirus, in addition to influenza. >> What is the role of rapid influenza tests, and how useful are they? >> The role of rapid influenza tests otherwise known as rapid antigen tests are debatable, and this issue has actually become even cloudier in recent months.
So let's start with pre-2009 H1N1 influenza. So prior to the new H1N1 influenza, there were several rapid antigen test kits with a variety of performance characteristics. One single study by Rodriguez, et al. directly compared the foremost widely used rapid test kits to viral culture in children with an influenza-like illness. And they found that during this study period from 1999 to 2000, they detected influenza A in 49% of the samples, and 17% of those were detected by viral culture alone.
The sensitivity and specificity of the four test kits ranged anywhere from 72 to 95%, and 76 to 84% respectively. All four kits have similar positive likelihood ratios of 4.7, and a negative likelihood ratio of 0.06. Prior published data has shown that rapid testing is most cost-effective when the pretest probability of an infection is somewhere between 5% and 14%. For example, if your pretest probability of an infection is 50% and you obtained a negative rapid antigen test, then there's still a 6% chance that the patient has the infection.
So moving on to after the H1N1 outbreak this summer, recently the CDC has published data on their website, and then the MMWR, the Morbidity and Mortality Weekly Review, regarding testing characteristics of their rapid antigen tests with respect to the 2009 outbreak. And I'm going to summarize those recommendations by saying it performs even more poorly than with prior seasonal influenza, and really should be used with caution as a test to rule out infection. I also am going to refer the listeners to the CDC or the WHO home webpage for more information, and to their own institutions on policies regarding utilization of these different tests in this current setting.
>> Is there anything else that JAMAevidence users should know about influenza? >> Well, an important point I try to equate the clinicians I work with regarding influenza is that you really need to know what's going on in your own community. What is the current level of activity in your community? The prevalence of infection will clearly influence your pretest probability of infection, and then a decision to test, and which test to use, as well as the decision to treat, and which treatment to use, should be informed by the CDC, state Health Department, or national Health Department in other countries with regard to the ongoing epidemic.
The single most important thing that clinicians should know about influenza is that they should remain attentive to the recommendations that are forthcoming from the CDC or state Health Departments, or national Health Department in other countries, with regard to clinical illness, reporting requirements, testing, treatment, prophylaxis, and vaccination. It's a lot to keep up on. And also I would also note that none of the data that we present here should supersede the recommendations of any country's public health system, and shouldn't be taken as such.
I'd also like to thank listeners for their interest in the subject, and encourage them to go to the CDC or WHO website for more information on the 2009 H1N1 influenza outbreak. >> Thank you, Dr. Caram, for your insights into influenza and the 2009 H1N1 influenza outbreak. This has been Joan Stephenson of JAMA, interviewing Dr. Brett Caram about influenza for JAMAevidence. >> My pleasure. Thank you.
Segment:0 .
>> I'm Joan Stephenson, editor of JAMA's Medical News and Perspectives section. Today this JAMAevidence podcast will focus on a topic that is likely on every clinician's mind Influenza. Our guest expert is Dr. Brett Caram, an infectious disease specialist and a contributor to the Influenza Education Guide Materials that augment the Rational Clinical Examination article on influenza. Dr. Caram, why don't you introduce yourself to our listeners? >> Sure. Hi, my name is Brett Caram, and as mentioned, I'm on faculty at Duke University in the Durham VA Medical Center in North Carolina, in the Division of Infectious Diseases.
>> What do we know about the prevalence of influenza? >> Well, first before we got started, I'd like to remind the listeners that the data presented in the Rational Clinical Examination article refers to influenza prior to the 2009 influenza season with the occurrence of the 2009 H1N1 Influenza A. Clearly there's forthcoming data that may show ways in which this influenza will clinically differ from previous seasonal influenzas given the age of the population which it affects, as well as the utility of diagnostic tests and treatments available.
So, in this interview, I'm going to focus mainly on the data relevant to influenza prior to the 2009 H1N1 influenza except when specifically noted. So that being said, I think again that prevalence of influenza was your question. And in an average year, prior to the 2009 pandemic that started earlier this year, 10 to 20% of people contract influenza. There are a couple of factors that impact annual severity and the prevalence of influenza, ranging from vaccine availability to antigenic shift or drift to suboptimal antigenic match in a vaccine.
However example in the United States, infection can result in upwards of about 10,000 pneumonia deaths a year, and somewhere between 30- to 40,000 respiratory and circulatory deaths per year. So the U.S. national average weekly patient visits in any given week for influenza-like illness is about 2.5%. And these visits are typically well below the rate from say April to September of every year. The visit rates start to pick up in November as most listeners will account to in at least the Northern Hemisphere.
And the 2.5 rate has been exceeded in Weeks 3 to 11 for the past three years, which is typically mid-January through the end of March. This was obviously different in the spring and summer of 2009 with the emergence of H1N1, and that national average has been exceeded actually by Week 36 and has remained above that 2.5% baseline since that time. In the past years, the typical high-risk influenza patient might include the very young, the very old, pregnant women, those with immunocompromised co-morbidities, but with this recent new influenza, this demographic shifted more heavily to weigh on those pregnant women, as well as those who are 25 years old or less for reasons that we're just now coming to understand.
>> The presence of which symptoms increases the probability that the patient has influenza? >> Well, that's a good question. Many clinicians may be making that personal association of fever, headache, myalgias, cough, or what my grandmother called the crud with influenza, but we'd like to remind the listeners that the symptoms are present in a multitude of respiratory viral infections, and they are often ones that are not assigned to an actual viral diagnosis, other than upper respiratory infection, not otherwise specified. And this is usually due to diagnostic constraints.
The strongest predictors of influenza is the clinical symptom complex called the influenza-like illness. This illness is defined by the U.S. Centers for Disease Control and Prevention, or the CDC, as feverishness or fever greater than 100 degrees Fahrenheit. And either sore throat or cough. And one particular symptom that actually lowers the likelihood that any patient, young or old, has influenza is the presence of a nasal congestion. In older patients, which is usually defined as those over 60, the presence of malaise makes the diagnosis more likely.
>> Which history and physical examination findings are helpful when diagnosing influenza? And which findings are not as helpful? >> So let me start first with the fact that upon extensive review of the literature, there's really no singular clinical finding which consistently has a positive likelihood ratio high enough to clinically rule in influenza. Nor does any single finding have a negative likelihood ratio low enough to rule out influenza. However there are patterns which evolve when the data are evaluated from multiple studies.
For example, across all age spectrums the absence of fever, the absence of cough, the absence of nasal congestion -- each have a likelihood ratio of less than 0.5. In older patient subsets, fever, malaise, and chills were the strongest predictors of infection, while the presence of sneezing reduces the likelihood of infections. In direct comparison to other signs and symptoms, fever and cough have the strongest diagnostic odds ratio. And this is part of the reason that they are featured so prominently in that CDC definition of influenza-like illness.
Although some studies have included fever and chills as predictive symptoms of influenza, these are included in the prior-mentioned CDC definition of influenza-like illness. So this data actually holds true for the 2009 H1N1 influenza as well. In a well-characterized outbreak in New York City in April of 2009 -- this is the one that occurred in a high school -- it was shown that greater than 95% of those individuals with documented H1N1 infection met criteria for this influenza-like illness definition, with 96% having had documented fevers or feverishness.
>> Dr. Caram, would you please describe the reference standard test for influenza? >> Sure. So the reference standard test for influenza infection has changed in the past few years. In years past, the reference standard was viral culture which was cumbersome, and often supplied the test results in retrospect for the patient or the clinical. The referencing for infection now is reverse transcriptase polymerase chain reaction; otherwise known as RT-PCR or PCR for short. There are several FDA-approved platforms for performing this test, and results are usually available within 3 to 6 hours after the sample is received and processed, depending on your institution.
This test performs with a sensitivity and specificity which approaches 99%, which is much better than viral culture. And some of these platforms test for influenza A and influenza B alone, while others detect a range of viral infections ranging from RSV to adenovirus to human metapneumovirus, in addition to influenza. >> What is the role of rapid influenza tests, and how useful are they? >> The role of rapid influenza tests otherwise known as rapid antigen tests are debatable, and this issue has actually become even cloudier in recent months.
So let's start with pre-2009 H1N1 influenza. So prior to the new H1N1 influenza, there were several rapid antigen test kits with a variety of performance characteristics. One single study by Rodriguez, et al. directly compared the foremost widely used rapid test kits to viral culture in children with an influenza-like illness. And they found that during this study period from 1999 to 2000, they detected influenza A in 49% of the samples, and 17% of those were detected by viral culture alone.
The sensitivity and specificity of the four test kits ranged anywhere from 72 to 95%, and 76 to 84% respectively. All four kits have similar positive likelihood ratios of 4.7, and a negative likelihood ratio of 0.06. Prior published data has shown that rapid testing is most cost-effective when the pretest probability of an infection is somewhere between 5% and 14%. For example, if your pretest probability of an infection is 50% and you obtained a negative rapid antigen test, then there's still a 6% chance that the patient has the infection.
So moving on to after the H1N1 outbreak this summer, recently the CDC has published data on their website, and then the MMWR, the Morbidity and Mortality Weekly Review, regarding testing characteristics of their rapid antigen tests with respect to the 2009 outbreak. And I'm going to summarize those recommendations by saying it performs even more poorly than with prior seasonal influenza, and really should be used with caution as a test to rule out infection. I also am going to refer the listeners to the CDC or the WHO home webpage for more information, and to their own institutions on policies regarding utilization of these different tests in this current setting.
>> Is there anything else that JAMAevidence users should know about influenza? >> Well, an important point I try to equate the clinicians I work with regarding influenza is that you really need to know what's going on in your own community. What is the current level of activity in your community? The prevalence of infection will clearly influence your pretest probability of infection, and then a decision to test, and which test to use, as well as the decision to treat, and which treatment to use, should be informed by the CDC, state Health Department, or national Health Department in other countries with regard to the ongoing epidemic.
The single most important thing that clinicians should know about influenza is that they should remain attentive to the recommendations that are forthcoming from the CDC or state Health Departments, or national Health Department in other countries, with regard to clinical illness, reporting requirements, testing, treatment, prophylaxis, and vaccination. It's a lot to keep up on. And also I would also note that none of the data that we present here should supersede the recommendations of any country's public health system, and shouldn't be taken as such.
I'd also like to thank listeners for their interest in the subject, and encourage them to go to the CDC or WHO website for more information on the 2009 H1N1 influenza outbreak. >> Thank you, Dr. Caram, for your insights into influenza and the 2009 H1N1 influenza outbreak. This has been Joan Stephenson of JAMA, interviewing Dr. Brett Caram about influenza for JAMAevidence. >> My pleasure. Thank you.
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