Study Shows Novel Influenza Virus Infections in Humans in the United States Would Likely be Detected Through Existing Health Care Surveillance

CDC Update

May 29, 2024 – A new CDC modeling study suggests that influenza testing in health care settings in the United States can serve as an effective warning system in the event of an outbreak of a novel (non-human) influenza virus with pandemic potential.

The study, published May 26 in the journal Influenza and Other Respiratory Viruses, reports that existing flu surveillance in health care settings in the United States would likely detect at least one case of novel influenza virus infection in people, even when the virus has yet to spread widely.

The likelihood of detecting at least one case, which would prompt a public health response, increased with severity of illness. The findings are relevant in light of the current outbreak of avian influenza A(H5N1) ("A(H5N1) virus") in U.S. dairy cows, which has resulted in two recently reported cases of human infection in dairy farm workers. AThey also underscore the critical role health care providers play as a first line of defense by maintaining the rates of testing for influenza performed during the influenza season and forwarding clinical specimens to public health laboratories for further testing as recommended.

The study estimated the probability that at least one human infection with a novel influenza virus would be detected in three different health care settings, each reflecting different care-seeking behaviors and testing practices. Those include:

• outpatient urgent care and emergency departments (UC/ED);
• inpatient hospital settings; and
• intensive care units (ICU).

In each setting, the researchers used a modeling framework informed by data collected from existing influenza surveillance platforms to estimate the likelihood of detection of novel influenza virus infections in a variety of scenarios. Each scenario accounted for different

• rates of new cases (incidence);
• degrees of symptom severity, including the absence of symptoms;
• rates of testing for influenza virus infection; and
• percentages of clinical specimens forwarded to a public health laboratory for further testing.

In a baseline scenario that assumed the presence of 100 cases in the population, with symptom severity similar to that of infection with a seasonal influenza virus, the likelihood of detecting at least one case of novel influenza virus infection per month was highest in community and UC/ED settings at 77% and 72%, respectively. That's compared to less than 15% in hospital and ICU settings.

As the assumed severity of illness caused by the novel influenza virus increased, the probability of detection also increased across all settings due to the greater probability that an infected person would require medical attention. Assuming severity equal to that observed with A(H5N1) cases worldwide (about 50% case-fatality proportion), the researchers found that the probability of detecting at least one case was close to 90% in UC/ED settings and 100% in hospital and ICU settings.

In addition to severity, the probability of detection was greatly influenced by assumptions about the proportion of clinical specimens forwarded to public health laboratories. Since most commercial assays used to test for human influenza viruses cannot distinguish novel influenza A viruses from seasonal influenza A viruses, further testing at a public health laboratory is required for a positive specimen to be identified as a novel virus.

But that doesn't always happen, and the study's baseline scenario reflected that reality with the assumption (based on real-world data) that 50% of positive specimens were forwarded on for further testing. Increasing that percentage to 75% or 100%, the study found, substantially increased detection probabilities across all health care settings.

Greater detection probability was also associated with higher rates of testing in each health care setting. While seasonal flu activity is low in most of the country, ongoing A(H5N1) outbreaks in dairy cows and poultry continue to pose a challenge, and health care providers should continue to test for influenza whenever influenza virus infection is suspected.

The percent of total novel influenza cases detected in any health care setting was relatively low. However, even when the prevalence of novel virus cases was low, the probability of detecting at least one case was generally high. That's important because one case would trigger the implementation of public health measures aimed at identifying and preventing additional cases, which can include increased testing and further virus characterization, as is happening in states currently experiencing outbreaks in dairy cows or poultry flocks.

These findings are informing enhanced testing strategies amid the ongoing multistate outbreak of A(H5N1) virus in dairy cows and other animals in the United States to ensure that even rare cases of novel influenza viruses can be detected. Additionally, CDC is supporting states that are monitoring people with exposure to animals infected or potentially infected with A(H5N1) viruses. Monitoring people with relevant exposure history is important to helping CDC better understand the risk to human health and potential for spread between animals and people and from person to person.

CDC considers the human health risk to the U.S. public from HPAI A(H5N1) viruses to be low at this time; however, people with close, prolonged, or unprotected exposures to infected birds, cows, or other animals, to unpasteurized ("raw") milk, or to environments contaminated by infected birds, cows, or other animals, or by raw milk, are at a greater risk of infection. It's important to note that because influenza viruses constantly evolve, CDC's risk assessment for the general public could quickly change. Continual surveillance is critical to ensuring public health preparedness and readiness to respond.

While these findings indicate that existing flu surveillance systems are likely to detect at least one novel influenza case before the virus has spread widely, CDC is asking that health care providers remain vigilant for signs and symptoms of influenza virus infection over the summer and maintain high rates of testing. They should also forward influenza A virus-positive specimens to public health laboratories when recommended, such as when specimens are unsubtypeable or were collected from hospitalized patients with influenza-like illness. Specimens that are unsubtypeable or that test presumptive positive for novel influenza A virus at the state public health laboratory should be sent immediately to CDC for further testing.