U.S. health officials are gearing up for the return this fall of the H1N1 swine flu virus that has sparked a global pandemic, but some government scientists say a second, potentially more severe wave of disease is not inevitable.

"Every influenza pandemic writes its own rules as it progresses," Dr. David Morens of the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health, said in a telephone interview on Tuesday.

Writing in the Journal of the American Medical Association, Morens and colleague Dr. Jeffrey Taubenberger said there is not enough evidence to conclude that the relatively mild spring wave of H1N1 flu is a harbinger of a more severe outbreak.

He said the common belief that severe flu pandemics are preceded by a milder wave of illness arose because of some accounts of the 1918-1919 "Spanish" flu pandemic that killed between 40 million and 100 million people.

The team analyzed 14 global or regional flu pandemics during the past 500 years and found past pandemics patterns vary widely. They said two other flu pandemics in the 20th century — in 1957 and 1968 — made just a single, seasonal appearance, and generally did not become significantly more serious in the early years of their circulation.

"Whatever happened in 1918 and 1919 for whatever reason was pretty clearly a one-off event. It's the only time in the 500 years that that pattern occurred," Morens said.

'HARD TO SAY'

The current H1N1 flu outbreak, declared a pandemic on June 11, has spread around the world since emerging in April and could eventually affect 2 billion people, according to estimates by the U.N. World Health Organization.

"We do think — everybody thinks — the virus will come back in the (northern hemisphere) fall," Morens said.

"Beyond that, it's hard to say what will happen — whether it will be more severe, less severe or just the same. If you look at past pandemics, any one of those things happened at a particular time," he said.

He said the possibility that some older people might have pre-existing immunity raises the hope that the current pandemic will cause fewer deaths than some past pandemics.

Companies are working to make a vaccine to protect people from the new swine flu, and people lined up at clinical trial sites this week to test it at many research centers across the United States.

The WHO said last week the first vaccines to combat H1N1 swine flu should be approved and ready for use in some countries starting in September.

Leading flu vaccine makers include Sanofi-Aventis, GlaxoSmithKline, Novartis, Baxter, CSL and Solvay.