May 7, 2009 (CIDRAP News) – In their most detailed profile of H1N1 swine influenza cases so far, federal health officials reported today that only 5% of US patients were older than 50 and that 38% of patients had gastrointestinal problems, well above what's typical for seasonal flu.

The report by the Centers for Disease Control and Prevention (CDC) also says that 9% of patients for whom details were available were hospitalized and that more than half of the patients who had severe cases had typical risk factors for complications from seasonal flu.

The report, published online today by the New England Journal of Medicine (NEJM), also presents a genetic mystery: how two genes found in Eurasian swine flu viruses reached North America and managed to combine with six genes from North American swine flu viruses to create the new hybrid that's infecting humans.

The report came as the CDC raised the US swine flu case count today to 896, including 2 deaths. The latest global count from the World Health Organization is 2,371 cases in 24 countries, with 44 deaths, 42 of them in Mexico.

Age range and possible reasons
Reporting on the 642 confirmed US cases reported through May 5, the CDC says that 60% of patients were younger than 19, 40% were between 10 and 18, and only 5% were 51 or older. For cases with available data, 18% of patients had traveled to Mexico, and 16% were connected to school outbreaks.

The CDC says the predominance of younger patients suggests several possibilities: that young people are more susceptible to the virus; that differences in social networks have delayed transmission to older people; that older people have some cross-protection from existing antibodies; or that more young people are being tested because of outbreaks in schools.

The most common signs of illness were fever (94% of patients), cough (92%), and sore throat (66%), the report says. In addition, 25% of patients had diarrhea and the same fraction had vomiting. In all, 38% of patients had one or both gastrointestinal problems, "neither of which is typical of seasonal influenza," the report states.

"Because of this observation, we are recommending that clinicians think about transmission not only through the respiratory route but also through the gastrointestinal route, through fecal-oral transmission," said Fatimah S. Dawood, MD, first author of the report, in a CDC teleconference today.

Also at the briefing, CDC officials said they don't know yet how long the new virus may survive on environmental surfaces. "We haven't had the virus long enough to do studies on this particular one," said Michael W. Shaw, PhD. He noted that other flu viruses survive longer on hard surfaces than porous ones but are quickly killed by heat.

Severe cases profiled
Of 399 patients whose status was known, 36 (9%) were hospitalized , the CDC reports. They ranged in age from 19 months to 51 years.

Investigators obtained detailed data on 22 hospital patients. Four of these were children younger than 5 years, 1 was pregnant, and 9 had chronic medical conditions. In all, 12  of the 22 hospital patients had risk factors for complications from seasonal flu.

Eight of the 22 hospital patients were treated in intensive care units, and four needed mechanical ventilation. As of May 5, 18 of the 22 patients had recovered, two remained critically ill with respiratory failure, and two (a 22-month-old child and a 33-year-old pregnant woman) had died.

Genetic enigma
The report also discusses the genetics of the novel virus. It says its eight gene segments include six genes that come from swine flu viruses that have been circulating in North American in recent years. (Those viruses themselves are hybrids described as "triple reassortants," meaning they contain elements from swine, human, and avian flu viruses. The triple-reassortant viruses were identified in 11 human cases identified over the past 3 years, which are described in another NEJM report published today.)

The other two genes in the novel virus now infecting people trace back to Eurasian swine flu viruses, and experts have no clue when or how they reached North America.

"Those genes had never been seen in North America before," said Shaw at the news briefing. "There's clearly a gap in the surveillance, because there are no close relatives, no immediate precursors."

Shaw observed that both the new human swine flu strain (which the CDC is calling swine-origin influenza A/H1N1, or S-OIV) and the triple-reassortant swine virus ultimately trace their ancestry to the 1918 pandemic flu strain, the first to be called H1N1. That virus established itself in both humans and pigs and subsequently evolved on separate tracks, but its descendants can still sometimes jump from pigs to humans or vise versa, he said.

In a NEJM editorial also published today, Robert B. Belshe, MD, discusses the connection to the 1918 strain further.

"Most adults have substantial immunity to H1 variants that have circulated among humans from 1918 through 1957 and then again from 1977 through the present," he states, referring to the H1N1 strains that make up one of the three flu subtypes that appear each flu season.

Belshe says it is unknown whether antibodies left from previous H1 infections will provide some protection against the new virus, but the evidence so far suggests that there may be partial protection.

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009 Jul 2; early online edition;361 [Full text]

Belshe RB. Implications of the emergence of a novel H1 influenza virus (editorial). N Engl J Med 2009 Jul 2; early online edition;361 [Full text]

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