Deploying New Molecular Influenza Tests in the Fight Against Antimicrobial Resistance

By Norman Moore, PhD

During influenza season, which can start as early as October and end as late as May, tens of thousands of people visit physicians because of influenza-like illness (ILI). Given the concentrated volume of patients presenting with these symptoms and the similarity of ILI symptoms with those of other common respiratory infections, it is not surprising that these patients are generally treated empirically, without a formal diagnosis.

While many patients’ symptoms may be resolved following empirical treatment, this practice is problematic because it contributes to antimicrobial resistance. Patients with ILI are often treated with antibiotics, even though the most common cause for this set of symptoms is influenza, a viral infection. The problem of empirical treatment also extends to influenza antivirals.  When antibiotics are inappropriately prescribed for influenza, it can delay the use of antivirals, which are only effective if prescribed within 48 hours of onset of symptoms. Conversely, when antivirals are automatically prescribed to symptomatic patients, and the cause is not influenza, it can delay appropriate treatment which may increase patient morbidity and mortality.

Clearly, many patients with ILI symptoms are treated inappropriately, and this has been borne out in studies, which show that evaluating patients for influenza based on clinical symptoms alone is inaccurate.   The inappropriate use of antibiotics and antivirals not only compromises patient outcomes, but it also leads to resistance.  Few healthcare professionals today are unaware of the growing crisis of antibiotic resistance.  But in fact, sporadic resistance has also been observed with the antiviral oseltamivir (Tamiflu®), and we have no further line of defense currently. During the 2007-2008 influenza season, oseltamivir resistance among influenza A(H1N1) viruses increased significantly for the first time worldwide. And during the 2009 flu pandemic, further reports of resistance occurred.

The key to prescribing – and withholding – antibiotics and antivirals appropriately is rapid testing. Today, rapid influenza assays that provide lab-accurate results quickly enough to allow providers to prescribe the appropriate treatment during the patient’s visit are more widely available than ever. Already, data have shown that physician awareness of a rapid diagnosis of influenza decreases antibiotic use.   In a retrospective analysis spanning three flu seasons, significantly more patients diagnosed without rapid influenza diagnostic tests (RIDTs) were given antibiotics compared with those who were diagnosed with rapid testing. Similarly, three times as many patients diagnosed with RIDTs received antivirals as those who were not diagnosed with RIDTs. And, as expected, receiving the right treatment right away improves patient outcomes as well, as demonstrated in a study in which rapid diagnosis helped reduce hospitalizations, length of hospital stays, ancillary tests and complications. 

The evolution of rapid influenza tests experienced a significant leap forward over the past year with the introduction of rapid point-of-care molecular flu tests that offer the gold-standard accuracy of polymerase chain reaction (PCR) and other amplified molecular tests with the ease of use and speed of antigen tests. These tests now empower clinicians to make informed treatment decisions in an actionable timeframe – in as quickly as 15 minutes – and obviate the trade-off between accuracy and speed that clinicians have traditionally had to make when selecting a diagnostic assay for their practice.

In addition, as molecular flu testing platforms like the Alere™ i Influenza A&B are CLIA-waived, healthcare providers can screen patients in a broad range of settings – increasing access to testing and streamlining care.

Despite the growing availability of rapid molecular tests that help physicians prescribe the right treatment right away, many physicians continue to treat ILI symptoms empirically, citing reports of false positives with older flu tests, or the weak economic rationale of investing in an assay that is generally used for less than half the year.

Determining the cost-effectiveness of influenza screening is complicated by the wide range of variables at play, such as the seasonal nature of flu testing, the duration and severity of a given flu season, the volume and multiple testing target capacity of tests, and utilization of antivirals. Similarly, parsing the cost of testing is difficult and requires accounting not only for the test itself but also for the reagent, instrumentation for sample extraction, and labor.

However, there are best practices that healthcare providers should adopt to maximize both the utility and cost-effectiveness of molecular flu testing:

• Limit testing to high-risk patients and time periods. Testing should be offered only during flu season, or once influenza has been reported in your area. Administering flu tests off-season can affect the positive predictive value, which is based on prevalence. Office and hospital staff can use tools like the CDC Flu Map to track the spread of viral activity. 
• Test early in illness as much as possible. Flu tests are most sensitive early in illness, when patients are more infectious, and antiviral therapy for infected patients is most effective when initiated early.
• Train staff on correct specimen collection. Collecting nasopharyngeal samples is not difficult, but care must be taken to obtain ciliated epithelial cells, which are located almost as deep as the front of the ear. A good collection may be uncomfortable for the patient, but is essential for optimal testing. 
• Testing platforms that also detect other illnesses like RSV and Strep A have utility throughout the year and are more cost-efficient. Additionally, economies of scale can make higher-complexity tests have less labor per sample if done in high volume.

Rapid point-of-care molecular tests are quickly becoming the new gold standard in influenza diagnosis. Not only do these tests help optimize patient outcomes and reduce transmission, they also help protect the long-term viability of antibiotics and antivirals by enabling physicians to limit their use to only appropriate cases.

Norman Moore, PhD, is director of scientific affairs, infectious diseases, for Alere.

 References:
1. Monto AS, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000;160(21):3243-7.
2. Dharan, N.J. et al. Infections with Oseltamivir-Resistant Influenza A (H1N1) Virus in the United States. JAMA 2009. Vol. 301 No. 2.
3. Monto AS, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000;160(21):3243-7.
4. Rapid influenza diagnostic tests increased antiviral use. J Ped Infect Dis (2013) doi: 10.1093/jpids/pit071.First published online: November 13, 2013.
5. Williams, KM, Jackson MA, Hamilton M. Rapid diagnostic testing for URIs in children: impact on physician decision making and cost. Infect Med. 2002;19(3):109-111.
6. Bonner AB, et al. Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics. 2003;112(2):363-7.
 7.  Dugas AF, et al. Cost-utility of rapid polymerase chain reaction-based influenza testing for high-risk emergency department patient. Ann Emerg Med. 2013;62(1):80-88.