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Influenza Update

Matthew DeLaney, MD and Mizuho Morrison, DO
00:00
22:13

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Matthew Delaney on the prevention, diagnosis and treatment of influenza.

Pearls:

  • Mortality from influenza is typically seen in the very young and the very old.  However, in a pandemic year with high mortality, death rates are also high among healthy younger adults.

  • The evidence is clear. You can diagnose influenza based on your clinical judgement. You do not have to test these patients to prove it.

  • Know the CDC’s high risk criteria.

  • Discuss treatment options and CDC recommendations with the patient. Let them know what the treatment can and cannot do for them, and let the patient make the decision.  

 

EPIDEMIOLOGY

  • Influenza is one of the biggest causes of upper respiratory tract illness worldwide.  It is a cold-weather virus and in the northern hemisphere, we see from November to March or April.

  • There are several different types of flu virus. The big ones are Influenza A and B.  Clinically, they look identical.

    • Influenza A is more common and the cause of the big flu pandemics, from the Spanish flu in 1918 to the more recent Swine flu epidemic

  • Children have the highest prevalence of influenza infection, and when they are infected, they have a higher viral load than adults.  

  • The elderly population is the most concerning because in most years, patients over the age of 65 have the highest mortality from the flu.

  • 2015 was a mild year for the flu, and there were 4600 deaths.  

  • Most years, death from flu is seen primarily in the very young and very old, but in a pandemic year with high mortality, the increased death rate is largely due to an increase in mortality amongst those in their 20s, 30s and 40s.  


PRESENTATION

  • Fever or feeling feverish/chills

  • Cough

  • Sore throat

  • Runny or stuffy nose

  • Muscle or body aches

  • Headache

  • Fatigue

  • Nausea/vomiting

 

  • These clinical criteria are reliable.

Monto AS, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000 Nov 27;160(21):3243-7 [Free open access link]

  • Looked at 3,700 patients with possible flu. Of those that had the flu

    • 93% had cough

    • 68% had fever

    • 91% had nasal congestion

    • Cough + fever during flu season had a PPV of 79%

CLINICAL COURSE

  • Uncomplicated influenza is characterized by the abrupt onset of fever, nasal congestion, cough, sore throat, malaise, myalgias. In someone with an intact immune response, symptoms should start resolving in 3-7 day, but malaise and cough can linger up to 2 weeks.

  • Complications

    • Viral pneumonia

    • Bacterial pneumonia

    • Bronchitis

    • Sinus infections

    • Ear infections

    • Worsening of chronic health conditions like asthma, CHF, COPD, etc.

PREVENTION

  • Flu vaccine

    • Tries to match the seasonal strains of influenza (2 influenza A strains and at least 1 influenza B strain).  

    • The effectiveness of the vaccine is dependent on how closely matched the flu vaccine is to the influenza strains that are circulating around the country. If the vaccine closely matches the circulating strains, the number-needed-to-treat (NNT) with the flu vaccine to prevent a case of the flu is 33. If the vaccine does not closely match the circulating strains, the NNT drops to 100.   

    • There is some benefit to the vaccine, but it is not a magical shield.

      • The vaccine tends to work better in children.  

      • The vaccine is less efficacious if you are sick when you get the vaccine.  You need to be able to mount a strong immune response to the vaccine.

      • In most years, if you get the flu vaccine, you are less likely to need to seek medical treatment for an influenza-like illness.  

      • The data is not good enough to tell us whether the vaccine prevents complications like hospitalization or secondary bacterial pneumonia.

DIAGNOSIS

  • Rapid flu swab – not a very good test

    • Sensitivity 50-87%

    • More sensitive in children because they have a higher viral load.

    • Generally better at identifying influenza A than B. We do not know how it performs in the setting of a pandemic.

      • In 2009, when H1N1 (influenza A) was a big player, there were a lot of false negatives with the rapid flu test

      • Positive flu-tests are very reliable with very few false-positives:

Jacobus CH, et al. How accurate are rapid influenza diagnostic tests? Ann Emerg Med. 2013 Jan;61(1):89-90. [PMID: 22841177]

  • Looked at 159 flu studies across a wide range of populations.

  • Found that a positive flu test had a positive likelihood ratio of 34.5.

  • The negative likelihood ratio was only 0.38 which means that if you have a negative rapid flu test, it does not effectively rule out influenza.  

TREATMENT

  • The most recent guidelines from the CDC say that in a patient with a high clinical likelihood of influenza, any treatment decision should not be based on a negative rapid flu test. There is an increasing emphasis on treating potential flu victims, rather than making an accurate diagnosis. However, the data does not necessarily support the idea that serious outcomes can be prevented by treatment.

  • High risk:

    • Children < 5 years old, especially those < 2 years

    • Adults 65 and older

    • Pregnant woman and up to 2 weeks postpartum

    • Residents of nursing homes and other long-term care facilities

    • Cultural populations including American Indians and Alaskan Natives (who are at higher risk of flu complications)

    • Chronic medical conditions (this category is very broad)

      • Asthma

      • Neurologic disorders

      • Heart conditions

      • Blood disorders

      • Endocrine disorders (including any type of diabetes)

      • Kidney disorders

      • Liver disorders

      • Any type of weakened immune system

      • Long term aspirin therapy

      • BMI > 40

 

  • Treatment medication: Oseltamavir (Tamiflu) is the most widely prescribed influenza treatment and it has somewhat of a shady history.

    • The 2 initial RCTs published were drug-company sponsored and 8 additional RCTs were withheld for unclear reasons. Eventually all the data was released.

    • In 2013, Ebal et al, looked at all the data, the previously released studies and the unpublished data.

      • Concluded that there is a minor benefit to using oseltamivir.  On average there is a 24 hour reduction of symptoms and the sooner you start it, the better.

      • Using the antivirals did not reduce hospitalization, but did possibly minimally reduce the development of pneumonia.

    • Side effects include nausea and vomiting.  

    • There is also an odd spike in psychiatric symptoms including hallucinations and delirium and that are seen mostly in Japanese children.

    • Oseltamavir costs $120 dollars.  The cost-benefit analysis for a 24 hour difference in symptoms is vary by patient.

    • The drug is effective in 58% of cases when used prophylactically within families.

 

SUMMARY

  • If a patient has symptoms consistent with the flu during flu season, diagnose them with the flu.

  • Evaluate patients with high-risk conditions according to the CDC criteria. If they have high risk conditions, talk to them and tell them the government recommends treatment with Tamiflu and offer them a prescription.  

  • If the patient is not in the high-risk category, talk to them about the option of treatment, the cost of treatment, the side effects and potential benefit.  Allow the patient to make the choice.  

  • It is an expensive medication, but overall it is a benign medication.  

  • Sample macro for your documentation MDM

Clinically, I think this patient has an influenza-like illness. Given the unreliable nature of the rapid-flu test, I do not think they require any additional testing emergently.  They are/are not at high risk for bad outcomes per the CDC guideline. I discussed the role of antivirals with the patient and we have decided to/not to treat with antivirals.  

 

Ian L., Dr -

The Canadian Pediatric Society and Infectious Diseases and Immunisation Commitee in Pediatric Child Health 2013 Mar;18(3)155-158 Notes : that if children are to be treated with a neuramidase inhibitor treatment the benefits of treatment within less than twelve hours are much greater than at 48 hours .
Prompt initiation of therapy within hours if possible is a vital message for patients at high risk and the benefits are not slight but substantial and from current evidence save lives .

Mike W., MD -

Agreed!

LeaAnne S. -

The idea of offering Tamiflu- even to those who aren't high risk- seems like it would open the door to building resistance to Tamiflu- and then it wouldn't be effective for those who really need it.
L A

Mike W., MD -

Yeah. A classic case of minimal upside and potential downside...

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