The influenza season of 2017-2018 was marked by widespread influenza activity across the United States. The powerful H3N2 strain, which was the biggest culprit of influenza infection, was reported in almost every state—a first in the 13 years that the Centers for Disease Control and Prevention (CDC) has been monitoring influenza activity in the country. This past influenza season was arguably one of the worst on record. Tens of thousands of people were hospitalized with influenza, and scores of deaths occurred.
Now that the next influenza season is rapidly approaching, we in the medical and laboratory communities must reflect upon lessons learned to ensure that we are well prepared and armed with insights to make the best decisions for our patients.
Lesson 1: Be mindful of vulnerable populations
Influenza infection rates vary widely among populations with different characteristics. Populations at higher risk for influenza infection include the elderly, pregnant women, and children. Individuals may also be at increased risk of influenza complications as a result of such medical factors as chronic heart, kidney, liver, or lung disease; certain blood disorders (such as sickle cell disease); extreme obesity; metabolic disorders (such as diabetes); or neurologic or neurodevelopmental conditions.1
According to the CDC, most people with influenza will have mild illness, will not need medical care or antiviral drugs, and will recover in less than two weeks. However, vulnerable populations are more likely to have influenza complications that can result in hospitalization and sometimes death. For these patients, it is important to consider a more aggressive approach to testing and treatment. Each individual is unique, so the care should be, too.
Lesson 2: Confirm with testing
While many clinicians may treat patients who present with an influenza-like illness empirically, there are many test choices available, and there are compelling reasons to consider testing. Several types of influenza tests are available to clinicians, with varying strengths and limitations. Choosing the right test enables clinicians to provide the best possible care to each patient. Options include viral cell cultures; immunochromatographic assays, known as rapid influenza diagnostic tests (RIDTs); and molecular tests.
In viral cell culturing, specimens are collected by swab or such other methods as bronchial wash. The specimens are then incubated in a cell-based culture system over a period of several days, while being monitored for cellular response to viral infection. Viral cultures can distinguish between influenza A and B. They generally take three to 10 days to produce a result, which makes them less than optimal for immediate treatment decisions, especially in vulnerable populations.
RIDTs are immunochromatographic assays designed to detect the viral antigens in a patient’s respiratory specimen resulting from an immune response to infection with the influenza virus. These tests can be conducted at the point of care, and results are typically available within 30 minutes. However, not all RIDTs can distinguish between influenza A and B, nor distinguish among the various strains of influenza A. Clinicians who choose to use RIDTs should understand the strengths and limitations of the test prior to use.
Molecular tests, which are recommended in current testing guidelines, are also performed on nasopharyngeal swab specimens, or specimens from other respiratory sources such as lower respiratory sources, and are intended to detect the presence of influenza viral RNA in those specimens. Molecular tests are the most sensitive and specific tests for detecting influenza viruses.2 Molecular test sensitivity for influenza A and B can be as high as 100 percent, and test specificity for influenza A and B ranges from 99.3 percent to 100 percent.3,4
Lesson 3: Don’t rely solely on RIDTs
Although RIDTs offer some value for everyday clinical practice, using them as the sole diagnostic for influenza in patients carries risks. While the specificity of RIDTs generally falls in the range of 90 percent to 95 percent, the sensitivity of RIDTs is often much lower, ranging from 50 percent to 70 percent. This can result in substantial numbers of false negative results occurring more commonly than false positive results during active influenza season.
Because of the known low sensitivity of RIDTs, the CDC recommends that clinicians consider following-up negative results with confirmatory tests (molecular or viral culture) if a laboratory-confirmed influenza diagnosis is desired.
Molecular testing that utilizes reverse transcription polymerase chain reaction (RT-PCR) has the highest degree of sensitivity and specificity, and is now considered by many to be the “gold standard” for influenza testing.5 In addition, molecular testing based on PCR amplification technologies has been shown to be the most cost-effective option for guiding the initiation of antiviral therapy in older adults.6
However, RT-PCR has its drawbacks. It requires sophisticated expertise and laboratory technology typically reserved for hospital and academic settings and commercial diagnostic companies. And while some rapid molecular tests can provide results in one hour, patient specimens must typically be transferred to these specialized laboratories for processing.
When it comes to influenza, both speed and accuracy of diagnosis are vital. There is no overestimating the value of an accurate diagnosis—as was tragically evident in reports of deaths of some individuals, including children, who were falsely diagnosed as influenza-negative during the 2017-2018 influenza season.
Lesson 4: Don’t over-treat
Treating for influenza without concurrent testing to confirm an influenza diagnosis can put individuals who do not actually have influenza (for example, those with respiratory syncytial virus) at increased risk for side effects from unwarranted treatment with antiviral agents. Treating without a confirmed diagnosis can also result in delayed or missed treatment for conditions that should have been treated with antibiotics. A thoughtful approach that includes diagnostics testing will result in the best health outcomes for the individual patient and larger population. A negative or positive result needs to be assessed in conjunction with the patient’s clinical findings and risk factors.
REFERENCES
- CDC. People at high risk of developing flu–related complications.
- CDC. Guidance for clinicians on the use of RT-PCR and other molecular assays for diagnosis of influenza virus infection.
- Simplexa Flu A/B & RSV [package insert] PI.MOL2600.IVD Rev. D]. Cypress, Calif: Focus Diagnostics, 2011.
- Mansuy JM, Mengelle C, Da Silva I, Grog I, Sauné K, Izopet J. Performance of a rapid molecular multiplex assay for the detection of influenza and picornaviruses. Scand J Infect Dis. 2012;44(12):963–968.
- Chartrand C, Pai M. How accurate are rapid influenza diagnostic tests? Expert Rev Anti Infect Ther. 2012;10(6):615–617.
- Lee BY, McGlone SM, Bailey RR, et al. To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling. PLoS One. 2010;5(6):e11284.
