March 26, 2014
Influenza Cases May Be Undercounted, Inflating
Severity Rates

London—Influenza cases may be significantly undercounted, which makes the severity of the seasonal illness look greater than it actually is, a new British study suggests.

The study, published recently in Lancet Respiratory Medicine, indicates that about 20% of the population was infected during recent flu seasons and the 2009 H1N1 pandemic, but most showed few or no ill effects. In fact, the report points out, just 23% of the cases caused symptoms, and only 17% of the infected were ill enough to seek medical attention.

“Reported cases of influenza represent the tip of a large clinical and subclinical iceberg that is mainly invisible to national surveillance systems that only record cases seeking medical attention,” explains lead author Andrew Hayward, MD, from University College in London. “Most people don't go to the doctor when they have flu. Even when they do consult, they are often not recognized as having influenza. Surveillance based on patients who consult greatly underestimates the number of community cases, which in turn can lead to overestimates of the proportion of cases who end up in hospital or die. Information on the community burden is therefore critical to inform future control and prevention programs.”

An accompanying commentary raises a critical question, as yet unanswered: Are the asymptomatic and mild cases contributing to transmission of influenza?

For the Flu Watch study, researchers tracked five successive cohorts of households across England over six influenza seasons between 2006 and 2011. Nationally representative estimates of the incidence of influenza infection, the proportion of infections that were symptomatic, and the proportion of symptomatic infections that led to medical attention were all calculated.

Participants provided blood samples before and after each season for influenza serology, and all participating households were contacted weekly to identify any cases of cough, cold, sore throat or “flu-like illness.” Any person reporting such symptoms was asked to submit a nasal swab on day two of the illness to test for a variety of respiratory viruses using Real-Time, Polymerase Chain Reaction (RT-PCR) technology.

An average 18% of the unvaccinated community was infected with influenza each winter season—19% during pre-pandemic seasons and 18% during the 2009 pandemic, the results indicate. The rate of influenza across all winter seasons was an average of 22 times higher than rates of disease recorded by the Royal College of General Practitioners Sentinel Influenza-Like Illness Surveillance Scheme.

The rate of respiratory illnesses in those infected with influenza was 69 per 100 person-influenza-seasons compared with 44 per 100 in those not infected.

The study found that the age-adjusted attributable rate of illness, if infected, was 23 illnesses per 100 person-seasons (13—34), suggesting most influenza infections are asymptomatic. Overall, 25% (18—35) of all people with serologically confirmed infections had PCR-confirmed disease, and 17% (10—26) of people with PCR-confirmed influenza had medically attended illness.

“These figures did not differ significantly when comparing pandemic with seasonal influenza. Of PCR-confirmed cases, people infected with the 2009 pandemic strain had markedly less severe symptoms than those infected with seasonal H3N2,” the authors write.

“Despite its mild nature, the 2009 pandemic caused enormous international concern, expense, and disruption,” Hayward added. “We need to prepare for how to respond to both mild and severe pandemics. To do this we need more refined assessments of severity, including community studies to guide control measures early in the course of a pandemic and inform a proportionate response.”

Writing in a linked comment, Dr. Peter William Horby from the Oxford University Clinical Research Unit in Vietnam says, “In view of the undoubtedly high rates of subclinical influenza infection, an important unanswered question is the extent to which mild and asymptomatic influenza infections contribute to transmission…A large number of well individuals mixing widely in the community might, even if only mildly infectious, make a substantial contribution to onward transmission.”

He emphasizes that simply tracking medically attended illness “provides a partial and biased picture, and is vulnerable to changes in consulting, testing, or reporting practices. As such, it is clear that reliable estimates of the infection and clinical attack rates during the early stages of an influenza epidemic requires the collection of standardized data across the whole range of disease severity, from the community, primary care, and secondary care.”

U.S. Pharmacist Social Connect