New Study Looks at Why Flu is Minor for Some, Serious and Even Fatal for Others

In California, deaths from flu have soared this year over 2013 according to information recently released by the California Department of Public Health. The number of confirmed flu-related deaths as of February 14 for the state was 243, strikingly higher than the 26 deaths confirmed by the same point last year. The Centers for Disease Control and Prevention has reported similar increases in other parts of the country likely due to the H1N1 strain, the same strain that was responsible for many illnesses and death in 2009. Deaths could be higher if this year’s vaccine didn’t also include protection against the H1N1 strain, say experts. And, according to the CDC H1N1 is also a factor in the many hospitalizations for flu among younger people across the country.

Why do some people have such a serious, and sometimes fatal, reaction to the flu? In some cases it’s because of underlying conditions such as aging, heart disease and asthma. But new research from St. Jude Children’s Research Hospital in Memphis has identified some factors that may predict flu severity in patients and could result in new tests and treatments.

The St. Jude researchers have been tracking flu infections in individuals for several years—and that research is continuing. The new study, published in the American Journal of Respiratory and Critical Care Medicine focuses on the 2009-2010 and 2010-2011 flu seasons. The study authors found that patients with elevated levels of three particular immune system regulators, called cytokines, early in the infection were more likely to develop severe flu symptoms and to be hospitalized than patients with lower levels of the same regulators. Study participants ranged in age from 3 weeks to 71 years old and included 41 infants and toddlers aged 23 months or younger.

The researchers found that cytokine levels early in the infection predicted flu-related complications regardless of patient age, flu strain, the ability of the virus to replicate and other factors. The cytokines involved help to regulate inflammation driven by what is called the innate immune response which is the first wave of the body’s defense against flu and other threats until antibodies and T cells are ready to provide a more targeted defense.

“Patients in this study could handle the flu virus and clear it from their airways s in a week to 10 days. The problem for patients with this immune signature is likely the inflammatory environment in their airways created by the innate immune system in response to the virus,” said study author Paul Thomas, Ph.D., an assistant member of the St. Jude Department of Immunology. “Clinically, we need to explore targeted therapies to address this problem separately from efforts to clear the virus.”

Thomas says the study helps to show why oseltamivir (Tamiflu) is most effective in the early days of the flu.  “This drug helps get rid of the virus, but these patients do not appear to have a problem with that.”

The researchers tracked both the flu infection and the resulting immune response through blood, nasal swabs and nasal wash samples collected from patients with laboratory-confirmed flu and the researchers measured levels of flu virus in the nose and sinuses as well as 42 cytokines and antibodies against circulating flu viruses.

A key study finding is that the children in the study had a stronger inflammatory response than adults. “The fact that the innate immune response was stronger in the airways of children than adults was a surprise. Previous studies using different measures reported that children mounted a weaker immune response,” said study author Christine Oshansky, Ph.D., a St. Jude postdoctoral fellow.  The researchers also found that the cytokine levels were linked to white blood cells called monocytes that travel to the site of the infection and create a variety of inflammatory responses. While some of the responses may be helpful, others may get in the way of recovery from the flu.

Deborah Lehman, M.D., Associate Director of Pediatric Infectious Diseases at Cedars-Sinai Medical Center, calls the study “fascinating,” but says there are things we don’t know yet. This is a hint that the virus does something to the host, says Lehman.

For now, though, says Lehman, “since we don’t have enough information to know who will be on the respirator and who will just miss a couple of days of schools, the best thing we can do is vaccinate everybody.”  Lehman adds that the study suggests we’re on the road to a more targeted approach, looking at host response to different viruses. “I think that’s where the action is, but it will be years down the road. Maybe we can identify a better vaccine and perhaps one we don’t have to give every year, or identify people most at risk, probably because of a predisposition, likely genetic, to particular viruses.”

For now, public officials are reminding people that if you haven’t had a flu shot yet, getting one could still help avoid the flu.  “The season is far from over,” says Ron Chapman, M.D., director of the California Department of Public Health and the state health officer. “Unfortunately, this influenza season is still severe and the number of influenza related deaths continues to rise. Vaccination is still the best way to prevent illness and the spread of illness.”

The CDPH urges people still not vaccinated against the flu this year to visit a flu vaccine location near you to get immunized. Some local health departments may also offer free or low-cost flu vaccines.

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