Shifting healthcare needs dictate change for respiratory pathogen diagnostics

Respiratory pathogens pose a significant challenge to clinicians due to their prevalence, the vast number of viral and bacterial pathogens, and the non-specific nature of their clinical presentation. While a majority of respiratory tract infections are caused by a viral pathogen, clinicians are always conscious of the risk of the infection being caused by a bacterial pathogen, which leads to the frequent misuse of antibiotics. A recent publication in the Journal of the American Medical Association (JAMA) by the Centers for Disease Control and Prevention (CDC), in collaboration with the Pew Charitable Trusts and other public health and medical experts, highlighted this. It noted that of the 154 million antibiotic prescriptions written in doctor’s offices and emergency departments in the United States each year, 30 percent, or about 46 million, are unnecessary.¹ Forty-four percent of the antibiotic prescriptions in outpatient settings are written to treat patients with acute respiratory conditions, with nearly 50 percent of these believed to be unnecessary.¹

Advances in rapid diagnostic solutions for respiratory pathogens have improved the overall management of patients with acute respiratory conditions; however, as the recent CDC report suggests, there remains plenty of room for growth in the clinical utility of rapid diagnostics in order to get a better handle on the misuse of antibiotics associated with acute respiratory infections (ACI).

Flu facts

Viral infections of the respiratory tract are far more common than bacterial infections. These infections are costly; influenza epidemics alone can cost between $71 billion and $167 billion annually in the U.S.² Non-influenza infections can cost around $40 billion annually.³ Each year, as many as five percent to 20 percent of the U.S. population contracts influenza.⁴ Flu activity varies from season to season and is dependent upon how well the flu vaccine is made, how many people get the vaccine, and the virulence of the influenza strains circulating that season. Anyone can get the flu, but people at high risk include those who are 65 and older and those with chronic medical conditions.⁵ The flu can also aggravate chronic conditions. Most flu patients recover in a few days to less than two weeks, but sometimes complications can result. Sinus and ear infection are minor complications, while pneumonia is a serious one.

Similar to flu, respiratory syncytial virus (RSV) can cause serious infection in certain patient populations, also with complications such as bronchiolitis and pneumonia. With exposure to RSV, 25 percent to 40 percent of children under the age of one develop bronchiolitis or pneumonia symptoms.⁶ RSV mostly affects young children, but the elderly and adults with co-morbidities are also at risk of RSV. In addition, although RSV and influenza are the most commonly known respiratory pathogens, adenovirus, human metapneumovirus, parainfluenza, and rhinovirus are also common viruses that cause respiratory tract infections and can be associated with mortality and morbidity.^7-10

The diagnostic landscape

Diagnostics for respiratory pathogens have advanced greatly from the original gold standard of viral culture, in order to better address the needs of providers and patients to enable better patient care. The emergence of multiplexed molecular tests during the past decade now provides laboratories with a more complete answer than ever before, producing a more clinically relevant turnaround time, highly sensitive and specific test results, waived complexity testing platforms for the physician office and emergency department settings, moderate complexity sample-to-answer testing for hospital laboratory settings, and a breadth of respiratory pathogen coverage required to better support the decision-making needs of the physician.

Unfortunately, a majority of the currently available tests cannot alone meet the physician’s need for coverage of the full continuum of respiratory infections, the patient’s desire for appropriate and cost-effective testing, and the lab’s workflow and cost needs. In many labs, the current solution is to choose among utilizing multiple platforms; selecting one abbreviated panel that does not provide the necessary coverage, and then sending the remaining samples to a reference laboratory; or running a one-size-fits-all panel for all patients, which may be too broad in some cases, yet not broad enough in others. None of these solutions is seen as ideal by most laboratorians.

Flexible testing panels

As labs focus on becoming more cost-effective and efficient and healthcare is pushing for more individualized patient care, diagnostic test manufacturers will have to evolve to better address the changing needs of providers, patients, and laboratories. A recent attempt to address these changing needs is through the use of flexible testing panels. With flexible testing, each test can report a full syndromic panel or any subset of targets offered on the test panel that the clinician orders. Users only see results for the targets selected and pay only for the targets selected, but have the ability to reflex instantly to results not initially selected if the clinician seeks additional information to manage his or her patient.

This flexible testing concept is new to the clinical microbiology laboratory, but is not a new concept within clinical laboratories. As an example, with allergen testing, multiple targets are tested for at one time, but results are only released based on individual orders by the clinician. Flexible respiratory testing allows for one diagnostic test to be able to provide a narrow test panel to address the clinician’s needs for outpatients and a broad test panel to satisfy clinician needs for inpatients. By doing this, flexible testing can minimize unnecessary cost to the patient and provide a testing algorithm preferred by many of the private payers. While this model can be achieved using multiple respiratory tests on multiple platforms, achieving this with a flexible test on one platform is very favorable for many labs.

Host response biomarkers

An alternative approach to complement fixed and flexible pathogen identification diagnostic tests currently available, with the same goal of better minimizing the unnecessary use of antibiotics, is the use of host response biomarkers. The host’s peripheral blood gene expression response to infection may provide a quicker, more accurate, and comprehensive way to rapidly discriminate between bacterial, viral, and non-infection in patients with suspected ACI. This would greatly improve antibiotic prescribing practices to minimize the use of unnecessary antibiotics. Tsalik et al. recently described an algorithm of host response biomarkers for the classification of bacterial ARI, viral ARI, or a noninfectious cause of illness. Overall accuracy was 87 percent for the classification of illness, which exceeded that of procalcitonin (78 percent; p < 0.03).¹¹ While additional research and population-based studies stand between host-response research and ultimate clinical adoption, this work provides an exciting and seemingly viable alternative to address the perceived shortcomings of pathogen detection diagnostics and to alleviate clinician concerns about missing a bacterial respiratory pathogen.

As the needs of providers, patients, and laboratorians shift, so too will the test deliverables of diagnostics manufacturers. There is no better example currently than respiratory pathogen diagnostics. With unnecessary cost and misuse of antibiotics highlighting two of the most prominent challenges associated with respiratory tract infections, the introduction of new diagnostics solutions that deliver more clinically meaningful value cannot come soon enough.

REFERENCES

Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010 – 2011. JAMA. 2016;31 (17):1864-1873.
Meltzer MI, Cox NJ, Fukuda K. The economic impact of pandemic influenza in the United States: priorities for intervention. Emerg Infect Dis.1999;5(5):659-671.
Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163(4):487-494.
Molinari NA, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of a seasonal influenza in the U.S.: measuring disease burden and costs. Vaccine. 2007;25(27):5086-5096.
Center for Disease Control and Prevention (CDC). Influenza: information for specific groups. http://www.cdc.gov/flu/groups.htm.
Centers for Disease Control and Prevention (CDC). Respiratory syncytial virus infection (RSV): Frequently asked questions. Content source: National Center for Immunization and Respiratory diseases, Division of Viral Diseases. http://www.cdc.gov/rsv/about/faq.html.
Centers for Disease Control and Prevention (CDC). Adenovirus: clinical overview. Content source: National Center for Immunization and Respiratory diseases, Division of Viral Diseases. http://www.cdc.gov/adenovirus/hcp/clinical-overview.html.
Kahn JS. Epidemiology of human metapneumovirus. Clin Microbiol Rev. 2006;19(3):546-547.
Counihan ME, Shay DK, Holman RC, et al. Human parainfluenza virus-associated hospitalizations among children less than five years of age in the United States. Pediatr Infect Dis J. 2001;20(7):646-653.
Miller EK, Lu X, Erdman DD, et al. Rhinovirus-associated hospitalizations in young children. J Infect Dis. 2007;195:773-781.
Tsalik EL, Henao R, Nichols M, et al. Host gene expression classifiers diagnose acute respiratory illness etiology. Science Translational Medicine 2016;8(322):1-10.