Predicting the future with any sort of specificity is notoriously difficult, and applied to influenza it means that the focus on H5N1 may, in the end, turn out to be for the birds. But it's not difficult to predict that another pandemic flu strain will develop eventually, and there's always the annual round of season influenza - which is called the "Rodney Dangerfield of diseases" by the Centers for Diseases Control and Prevention because it kills roughly 36,000 annual in the U.S. alone, but still gets no respect.

Some recent research takes an indirect approach to understanding factors that determine both what makes influenza strains pandemic material, and what can help or hurt the fight against influenza in developing nations. Epidemiological research presented at the National Institutes of Health suggested that influenza may be more common than thought in sub-Saharan Africa, and that being able to fight it effectively, be it seasonal or pandemic, will necessitate paying attention to its relationship to both malaria and parasitic infections. And on the cellular level, a recent paper in the Proceedings in the National Academy of Sciences reports cell biology findings on the binding properties of influenza B.

On Monday, more than 200 scientific journals simultaneously published papers as part of a Council of 2007 Global Theme Issue on Human Poverty and Development. Seven of those papers were highlighted in presentations at the NIH.

The presentations covered diverse topics, but a unifying (and depressing) theme of the presentations was that while health problems can be isolated and conquered in a context of wealth, poverty turns such issues into a morass that needs multiple simultaneous avenues of attack.

Such is the case, Maria Yazdanbakhsh told the audience at the symposium, for influenza in sub-Saharan Africa. The first problem is that influenza may not be recognized as such. "Doctors will say, 'We don't encounter influenza,'" she told the audience.

Instead, a feverish child most likely will be diagnosed as having a flare up of chronic malaria - and treated with chloroquine, which, as an immune suppressant, is counterproductive for influenza infection.

Yazdanbakhsh, a professor of parasitology at the University of Leiden in the Netherlands, said influenza is "neglected but highly active in Africa." The researchers investigated the response to vaccination in Gabonese children. Despite doctors' claims of not encountering influenza, the scientists found the majority of children they tested had antibodies to several influenza strains.

Yazdanbakhsh, and her colleagues in the Netherlands and Gabon then vaccinated the children and found that rural children had a weaker immune response than children living in a semiurban environment. Rural children have both a higher rate of infection with worms - which, Yazdanbakhsh said, "skews the immune response" in a way that makes the response to vaccines less effective - and on the average a poorer nutritional status overall. The researchers believe that both factors contribute to their weaker immune response to the vaccine.

Yazdanbakhsh concluded that effectively fighting influenza in Africa will necessitate greater awareness that the disease is a problem in the first place and interventions that take into account the poor general health of the population and an "urban rural gradient in vaccine effectiveness," in addition to just the vaccine.

"If you want to combat poverty, you need a healthy body," she concluded. "And a healthy body is maintained by a well-balanced immune system."

In the Oct. 17, 2007, issue of PNAS, researchers from the Baylor College of Medicine and Rice University take a more cellular approach to understanding influenza. They used X-ray crystallography to study influenza B's hemagglutinin, which is the key surface protein on the virus that binds to host cells.

Compared to influenza A, much less is known about how influenza B binds to cells. In particular, it is unclear why influenza B is so much more specific to humans than influenza A, which affects birds and pigs as well as humans. The task is further complicated by the fact that influenza viruses often are cultured in eggs, and the culturing itself changes the influenza B hemagglutinin in ways that make it more similar to bird flu strains.

When the researchers studied influenza B bound both to human-like and bird-like receptors, they found that a single amino acid - number 222, which is occupied by a lysine in influenza B - is "a key and likely a universal determinant for the different binding modes of human receptor analogues by different [hemagglutinin] molecules."

The researchers hope that their work on influenza B will give clues to the sorts of changes that influenza A strains, especially H5N1, have to undergo to infect humans more easily, which is a key prerequisite for a pandemic strain.