There are two circulating strains of avian influenza that have infected large numbers of humans recently with devastating effects in those infected. Both strains have pandemic potential, as there had been no human experience with either of the hemagglutinins, H5 or H7. There have been more than 600 documented cases of avian influenza A(H5N1) since December 2003 and more than 130 cases of avian A(H7N9) influenza from February to May 2013. Although these are both avian influenza strains, there have been remarkable differences in the epidemiology of influenza A(H5N1) compared with influenza A(H7N9). Both started in China and have the potential to spread to multiple countries. This has, in fact, happened with A(H5N1) during a decade or more, but to our knowledge has not yet occurred with A(H7N9). The one exception is one case of A(H7N9) imported to Taiwan from China.

Vectors of disease differ

The differences are in the major locations of the poultry involved as vectors, the patient population, probably the mortality rate and the control measures that have been used. Influenza A(H5N1) is a high pathogenicity strain for poultry, meaning that many poultry become ill and many die. Therefore, outbreaks in poultry rapidly become apparent. In contrast, A(H7N9) is a low pathogenicity strain and poultry do not become sick. However, infection is therefore not apparent. Furthermore, contact with A(H5N1) has often if not primarily occurred with backyard flocks of poultry.

In contrast, A(H7N9) seems to have been “recognized” primarily in poultry in live or “wet” animal markets. The emphasis is on the word “recognized,” as no large surveys have been reported on backyard flocks or other birds. Of interest is that H5N1 has infected a multitude of animals, but at present we have little information on the ability of H7N9 to naturally infect species other than birds and humans.

The backyard flocks are primarily cared for by older children and young adults and children playing in the yards, whereas most of the people in the live markets are adults. This may in part help to explain differences in age populations between infections with the two viruses. Influenza A(H5N1) has infected mainly healthy people aged younger than 50 years; infection in older individuals has been uncommon, and when it occurs, it is milder.

In contrast, infection with A(H7N9) occurs mainly in older male adults (median, older than 60 years) with underlying diseases. When it occasionally infects children, they tend to have mild or asymptomatic disease. Some have attributed the paucity of human cases of A(H5N1) in older individuals to previous experience with the N1 antigen, but this is questionable.

Possible genetic predisposition

Clusters of cases have occurred with A(H5N1) but have not been reported with A(H7N9). Of interest is that the clusters with A(H5N1), whether from exposure to the same source or human-to-human spread, seem to be restricted to blood-related individuals — ie, parent and child or brother and sister, rather than husband to wife. This has suggested a genetic predisposition to A(H5N1) infection. Although it is still early in the game, there is no evidence for either person-to-person spread with A(H7N9) or a genetic predisposition.

The mortality rate in documented cases is high for both strains of avian influenza, about 60% for H5N1 and about 30% for H7N9. However, the 30% mortality for H7N9 is probably too high because in contrast to H5N1, asymptomatic as well as mildly symptomatic cases of H7N9 have been observed. Therefore, cases are underreported.

Control of spread of influenza in poultry has depended mainly on destruction of infected flocks, although vaccines have been used preventively, but they are expensive and difficult to maintain. Identification of infected flocks is easy with H5N1 but difficult with H7N9 because there is no illness in the birds. Public health measures, such as warning people not to come in contact with sick poultry in the case of H5N1, and closing live poultry markets in the case of H7N9, are important. In fact, the mass closing of live poultry markets has apparently stopped the H7N9 outbreak dead in its tracks for now. Some have speculated that the disappearance of H7N9 may be due to “seasonal factors,” as the disappearance of H7N9 has been more or less coincident with the decline of H1N1, H3N2 and B influenza in China and elsewhere in the Northern Hemisphere.

Regardless of cause of its disappearance, the virus is probably circulating in asymptomatic poultry and perhaps other birds or animals in China.

Pandemic potential of H7N9

Both H5N1 and H7N9 have pandemic potential with either mutation to a form more transmissible from person to person or recombination with a human influenza virus to a more transmissible form.

H5N1 has been circulating in wild water birds, as well as poultry, for many years over a large land mass with huge numbers of poultry and people (Asia, the Middle East and Africa) and has not caused a pandemic. It probably never will.

H7N9 is potentially more dangerous as it circulates asymptomatically in poultry and is therefore not obvious when it infects a flock. In the United States and other highly industrialized countries, there are relatively few backyard flocks and H5N1 would be rapidly identified and contained in a commercial poultry farm. With H7N9, it would not be nearly as easy to identify its presence in a flock.

Furthermore, the experience with H7N9 has been much more limited than with H5N1. We just don’t know enough about its evolution yet to breathe a sigh of relief, despite the apparent control of the current outbreak.

Disclosure: Kaye reports no relevant financial disclosures.