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Depending upon the strain, the method of exposure, viral load, and an individual's immune response and overall health, human influenza A infection can present a wide range of symptoms, ranging from asymptomatic-to-sub-clinical, mild-to-moderate, all the way up to severe and even life threatening..
With seasonal flu, asymptomatic carriage has been estimated to run as high as 35%, while sub-clinical cases may account for > 60% of cases (see EID Journal: Prevalence of Asymptomatic Influenza Virus Infections).
A 2015 study (CID: Viral Detection Increases With Family Size), followed 26 households over the course of one year, testing family members for 16 different respiratory viruses, including influenza, rhinovirus, and RSV on a weekly basis.
While the incidence varied widely by household size (no surprise, the more kids in the house, the more sickness), across the board only about 50% of the PRC positive cases reported cold or flu-like symptoms.
Understandably, most influenza infections go unreported. Most people do not consult a doctor unless their symptoms are severe, and even when they do, sub-typing for novel strains is rarely done outside of a sentinel hospital.
Since 2010, the CDC has detected 500 novel flu infections in the United States (see chart below), although this almost certainly represents just the tip of the iceberg.
During a small outbreak of H3N2v (n=13) a dozen years ago, researchers estimated that fewer than 1 in every 200 cases was identified (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).
Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought.
We've seen similar estimates with H7N9 in China and MERS-CoV in Saudi Arabia. Quite obviously, there are some regions of the world better equipped to detect novel viruses than others, but even in the UK their Health Security Agency has warned of the difficulties in detecting community spread of HPAI H5N1.
A little over a year ago, the UKHSA published UK Novel Flu Surveillance: Quantifying TTD) which estimated the TTD (Time To Detect) a novel H5N1 virus in the community via passive surveillance might take 3-10 weeks, and the infection of dozens (or even hundreds) of people, before community spread could be established.
They present different scenarios based on various levels of testing, but even under the best case scenario, it could take weeks to detect ongoing community transmission of the virus.
While we can be comforted by the detection of only one mildly symptomatic (conjunctivitis) case in Texas, before the alert to monitor dairy workers went out a month ago, that case would likely have been dismissed as a mild viral infection, and testing would not have been done.
Mild or sub-clinical cases are obviously less worrisome in the short run, but they are much harder to detect.
The concern is, they give the virus additional opportunities to adapt to a new species, and potentially spread to their contacts. For a virus that hasn't quite adapted to human hosts, that's quite an advantage.
Yesterday the CDC published the following update on their efforts to detect any spread of the H5N1 virus early. Due to its length I've only posted some excerpts, so follow the link to read it in its entirety. I'll have a brief postscript after the break.
How CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation
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Updated April 24, 2024
Weekly Snapshot for Week Ending April 13, 2024CDC influenza (flu) surveillance systems show no indicators of unusual influenza activity in people, including avian influenza A(H5N1).
This page provides information on how CDC systems that monitor national, state, and local level influenza data are being used during the current avian influenza A(H5N1) situation
- Influenza virus and illness activity are monitored year-round through a collaborative effort between CDC and many partners, including state, local, and territorial health departments; public health and clinical laboratories; clinics; and emergency departments.
- Human cases of novel influenza, which are human infections with non-human influenza A viruses that are different from currently spreading seasonal human influenza viruses, are nationally notifiable. Every identified case is investigated and reported to CDC.
- CDC is actively looking at multiple flu indicators during the current situation to monitor for influenza A(H5N1) viruses, including looking for spread of the virus to, or among people, in jurisdictions where the virus has been identified in people or animals.
Monitoring for Novel Influenza A Virus Infections among People, including Influenza A(H5N1)
Rapid detection and reporting of human infections with novel influenza A viruses, including influenza A(H5N1), is important to facilitate prompt awareness and an effective public health response. For confirmed cases, the reporting jurisdiction completes a case report form, which is submitted to CDC. The information includes patient demographics, symptoms, the clinical course of illness, and exposure history. The reporting jurisdiction for influenza A(H5N1) cases reported in 2024 are summarized below.
Public Health Laboratory Reporting
Public health laboratories use CDC’s diagnostic tools to detect both seasonal influenza viruses and novel influenza A viruses including influenza A(H5N1). These diagnostic tools are used at more than 100 public health laboratories in all 50 U.S. states. The results of tests performed by these public health laboratories nationwide are summarized below.
Systems Used to Monitor Influenza Activity
Influenza activity is monitored year-round using multiple systems. These systems are used for monitoring seasonal influenza and, because influenza viruses are constantly changing in small, and occasionally more significant ways, these systems are also useful for monitoring signals and trends from novel influenza virus infections. Some examples are provided below.
Monitoring for Changes in Tests Positive for Influenza in Clinical Settings
Approximately 300 clinical laboratories located throughout all 50 states, Puerto Rico, Guam, and the District of Columbia report the results of clinical testing for influenza through either the U.S. WHO Collaborating Laboratories System or the National Respiratory and Enteric Virus Surveillance System (NREVSS). The results of tests performed by clinical laboratories nationwide are summarized below.
While these laboratories don’t test specifically for influenza A(H5N1) virus, by tracking the percentage of specimens tested that are positive for influenza A viruses, we can monitor for unusual increases in influenza activity that may be an early sign of spread of novel influenza A viruses, including H5N1.
While there is currently no indication of community spread of H5N1 anywhere in the world, the reality is there are many regions of the globe where low-level transmission could go unnoticed for quite some time.
A reminder than anything we say about the current threat posed by H5N1, COVID, H5N6, MERS-CoV, or any other pandemic threat must be tempered by the knowledge that we are always working with incomplete information.Even in places with more advanced surveillance capabilities - like the United States, the UK, and Europe - early detection of limited community spread might require a bit of luck.
