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A New Normal: Surveillance and Epidemiology of Severe Acute Respiratory Pathogens Using Multiplex PCR

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Doctor takes a multiplex PCR test sample from a young girlLong before SARS-CoV-2 turned the world upside down, severe acute respiratory disease was already a major cause of morbidity and mortality for adults and children all over the world. As of 2019, acute respiratory infections accounted for more than 2.6 million deaths1, with pneumonia and bronchiolitis accounting for the largest number of cases.

Acute respiratory infections also have a significant impact on the economy. Globally, viral respiratory illnesses are the most common reason for patients to seek out and access healthcare services. As a result, they contribute to increased healthcare expenses, workplace absenteeism, and reduced productivity. It’s imperative to understand the etiology and epidemiology of these infections to develop better prevention and control measures.

Anna K. Strain, PhD, Manager of the Infectious Disease Laboratory at the Minnesota Department of Health, recently explained how clinicians and public officials can improve their ability to identify and track severe respiratory infections. Once you read the highlights, view the presentation here.

Emerging Respiratory Pathogens

Anyone who practices public health, from government employees to hospital clinicians, should be concerned about emerging respiratory pathogens. These pathogens spread through person-to-person contact, resulting in significant morbidity and mortality. For more than a century, influenza has been one of the main culprits, but SARS, H5N1 high-pathogenic influenza, MERS, and SARS-CoV-2 are becoming more common.

Although specific threats to human health have changed over time, one thing remains constant: the need to implement disease surveillance programs that are capable of rapidly detecting new viruses and monitoring the changing patterns of known viruses.

Global Burden of Severe Acute Respiratory Infection (SARI)

Before SARS-CoV-2 emerged, most SARI surveillance took place in countries outside of the United States. In communities with limited public health resources, it’s fairly simple to implement a surveillance program designed to monitor disease severity (hospitalization) or track hypoxemia and other warning signs of SARI.

Children are especially vulnerable to these infections. According to the World Health Organization, acute respiratory tract infections led to approximately 4.2 million hospitalizations in children under 5 years old in 2019. As a result, nearly 700,000 children under 5 died from pneumonia, making SARI a serious concern. Most of those deaths occurred outside of a hospital setting.

Respiratory Surveillance

The Minnesota Department of Health participates in two surveillance programs in conjunction with the CDC: FluSurv-NET and IISP. FluSurv-NET is a population-based program designed to identify cases of influenza in hospitalized patients. The program includes hospitals in a seven-county metropolitan area.

The Influenza Incidence Surveillance Project (IISP) is an outpatient surveillance program that uses test results from throughout Minnesota to track the spread of influenza during each flu season.

Due to the increase in viral threats, state, national, and international agencies are working harder than ever to set up effective surveillance programs. For example, the national respiratory and enteric virus surveillance system allows users to view data related to the number of influenza-positive specimens compared to the total number of specimens tested each week.

In 2009, the Binational Border Infectious Disease Surveillance Program initiated surveillance for SARI at the Mexico/Arizona border. Thousands of people move across this border each week, making the region ideal for studying patterns of disease transmission.

Surveillance Beyond Influenza

Long before COVID, clinicians and public health officials realized influenza wasn’t the only potential cause of a severe infection. In a study assessing the accuracy of clinical diagnosis in patients presenting to the emergency department with influenza-like illnesses, Hansen et al. determined that clinician assessment had a 36% predictive value2, while using the CDC/WHO definition (fever, cough, shortness of breath) had a 31% predictive value.

A second study showed that it was possible to identify additional pathogens3 using a multi-pathogen panel. But why is it so important to identify more than one pathogen? Because coinfections have a big impact on how an illness progresses. For example, a patient with influenza A and a viral coinfection is more likely to require hospitalization than a patient who has influenza A on its own.

SAR Surveillance (2013-2016)

In 2013, MDH established the SARI program to detect the burden, etiology, and risk factors for severe acute respiratory illness in Minnesota residents. In one SARI case, a patient was admitted to the hospital with acute respiratory symptoms, including shortness of breath, cough, or respiratory distress. Participating hospitals sent residual specimens to MDH for additional testing.

Over a 3-year period, MDH received 9,000 specimens, making it much easier to identify and track everything from seasonal coronaviruses to Bordetella pertussis. During the second year of the program, MDH added influenza C and started looking for cases of EV-D68 in hospitalized patients. In 2016, the SARI program switched to the Luminex Respiratory Pathogen Panel.

Of the 9,000 specimens received, 62% were positive for at least one pathogen. The majority of samples with two or more pathogens came from children under 2. During the final funding year, MDH employees tested additional samples to determine if it would be appropriate to provide continued SARI testing. According to their results, it’s possible to miss clinically significant pathogens because many hospitals don’t do systematic testing for respiratory pathogens.

Expanded Respiratory Testing Options

Although the SARI program ended in 2016, it paved the way for today’s surveillance programs. It’s more important than ever to test for coinfections, so many laboratories and hospitals are using advanced equipment to identify and track pathogens. Learn more about using the Seegene Novaplex* and Allplex** Respiratory Panel Assays to improve your testing and surveillance efforts.

*Novaplex™ Assays are For Research Use Only. Not for Use in Diagnostic Procedures.

**Allplex™ 2019-nCoV Assay is for Emergency Use Authorization.

 

  1. Roussel Y, Girard-Gatineau A, Jimeno MT, Rolain JM, Zandotti C, Colson P, Raoult D. SARS-Co-V2: fear vs. data. Int J Antimicrob Agents. 2020; 55(5).
  2. Hansen GT, Moore J, Herding E, Gooch T, Hirigoyen D, Hanson K, Deike M. Clinical decision making in the emergency department setting using rapid PCR: Results of the CLADE study group. J. Clin. Virol. 2018; 102:42-49.
  3. Dugas AF, Valsamakis A, Atreyaa MR, Thinda K, Manchegoa PA, Faisala A, Gaydos CA, Rothman RE. Clinical diagnosis of influenza in the emergency department. Am. J. Emerg. Med. 2015 June; 33(6): 770-775.
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