The Shortridge paper

In oral presentations, in print and in personal conversation Dr. Peter Palese, a highly regarded senior flu researcher at the Mount Sinai School of Medicine, has expressed reservations about the likelihood that H5N1 will become a pandemic strain. Wendy Orent has also implied (correctly, I think) that he is a bird flu nay-sayer, although when you push him, even a little, he backs off quickly. He is frank to say his view is just a hunch, based primarily on data he has seen that H5N1 may have been around and infecting humans far longer than we are aware and it had yet to adapt to humans in a virulent form. The basis for his opinion (and a slide in his presentations) are data of seroprevalence to various hemagglutinin subtypes reported by Shortridge in a 1992 paper, "Pandemic influenza: a zoonosis?" Seminars in Respiratory Infections 7(1):11-25. I have tried to get a copy of this paper a couple of times without success. The journal is uncommon and I couldn't find it in several major medical center collections.

Now Dr. Juliet R. C. Pulliam, Dept. of Ecology & Evolutionary Biology, Princeton, University, has tracked it down and given a rough synopsis of the relevant data, distributed in a ProMed email (and is presumably on the website as well). Here is Dr. Pulliam's communication:

I looked up the articles that were cited as implying that approximately 35 million Chinese citizens have antibodies to H5N1 influenza.

The article referenced in the RFI [ProMed Request for Information] is Palese, P. 2004. Influenza: old and new threats. Nature Medicine 10(12): S82-S87. This article states that: "...seroepidemiological studies conducted among the rural population in China suggest that millions of people have been infected with influenza viruses of the H4-to-H15 subtypes. Specifically, seroprevalence levels of 2-7 percent for H5 viruses alone have been reported...".

The reference given for this claim is Shortridge, K.F. 1992. Pandemic influenza: a zoonosis? Seminars in Respiratory Infections 7(1):11-25. This paper reports seroprevalence ("presumptive antibody detected by single radial hemolysis using antigenic material from avian virus only") of 13 HA subtypes (H1 to H13) in 4 human populations. H5 antibodies were detected in 2 percent of samples from the Pearl River Delta (n=400), 7 percent of samples from Jiangsu Province (n=300), 2 percent of samples from Taichung, Taiwan (n=150), and[nearly] 0 percent of samples from Urban Hong Kong (n=100). There are no corresponding data reported for N subtypes, so a conclusion that these antibodies indicate prior presence of H5N1 in the human population is unfounded, and there is no support for an estimate of 35 million Chinese citizens with H5N1 antibodies.

This same paper reports the results of a study of ducks (8737), geese (1353), and chickens (1708) originating from southern China and Hong Kong over a 5-year period (Nov 1975-Oct 1980) at a poultry-dressing plant in Hong Kong. Of 586 viral isolates obtained from this survey, 23 had HA subtype H5: 22 of these isolates were H5N3 (one from a goose, and 21 from ducks), and one isolate was H5N2 (from a duck). No H5N1 virus was found.

Thus the Shortridge et al. paper only identifies antibodies to influenza/A (H5) viruses, not specifically to H5N1. As H5N2 is a common Low Pathogenic Avian Influenza (LPAI) virus we do not know whether the H5 prevalence was a result of High Pathogenic Avian Influenza H5N1 or LPAI H5N2, or perhaps LPAI H5N1.

In the sample, overall H5 seroprevalence in rural China was just over 3.6% and 0% in urban Hong Kong. The 35 million figure cannot be dervied from either China's total population in 1992 (1.17 billion) or its rural population (848 million; data here), although using the rural population figure, we note that 3.6% of 848 million is 30.5 million. Perhaps the 35 million was a typo for 30.5 million.

In any event, these data seem weak reasons for Dr. Palese's hesitation about the threat from H5N1 as a pandemic strain. We thank Dr. Pulliam for her diligence in digging up these data.

Meanwhile the fifth officially acknowledged human case of bird flu was announced in China yesterday.