Avian influenza: Virchow's reminder.

Guus Rimmelzwaan and colleagues1 have contributed extremely valuable knowledge through their paper in this issue of the American Journal of Pathology regarding the ability of the highly pathogenic avian influenza H5N1 virus to replicate in domestic cats.1 Using a traditional pathogenesis approach and relatively simple techniques from the pathologist’s armamentarium, they have made substantive contributions to understanding aspects of the disease in humans. Through immunohistochemistry using a monoclonal antibody to influenza A nucleoprotein, Rimmelzwaan et al1 demonstrate that there is extensive extrarespiratory spread of the H5N1 virus in a mammalian (feline) host, with involvement of a number of tissues, including nervous, cardiovascular, urinary, digestive, lymphoid, and endocrine systems. They also demonstrated the ability of the cats to excrete H5N1 virus in feces. The authors postulate that spread from one animal to another could occur via three different potential excretory pathways—respiratory, digestive, or urinary tract. The finding of routes of excretion is particularly noteworthy and calls for vigilant biosecurity surrounding human cases. Pathological investigations of disease due to H5N1 in humans have been limited. First, the available material is often not truly representative because it presents only an end-stage of the process and is usually altered by treatment and/or secondary invaders. Second, there are numerous cultural issues that preclude the performance of autopsies in some of those countries that have experienced the largest number of cases, and so the availability of postmortem material for investigation is limited.2 Consequently, this paper sheds considerable light on what might be happening in infected humans and should help clinicians as they strive to develop the most appropriate therapies. Highly pathogenic avian influenza has become the “zoonosis” of the decade and hopefully will not become the pandemic of the century. The term “zoonosis” was coined by the German physician Rudolf Virchow exactly 150 years ago, while he was working on the public health issues of trichinosis and alveolar hydatid disease. On the subject of comparative medicine, Virchow stated, “Between animal and human medicine, there is no dividing line—nor should there be.”3 Virchow is a name familiar to all pathologists because he is widely regarded as the father of modern pathology and is heralded for elucidating the cellular nature of disease, which drastically changed the course of medicine. However, it may be his emphasis on considering diseases across species lines that will be his most lasting legacy. Guus Rimmelzwaan and colleagues remind us that the call to one medicine is more relevant today than ever. Human health and animal health are inextricably intertwined, with a steady parade of emerging zoonotic problems over the last 25 years, beginning with human immunodeficiency virus moving from an African primate to humans, creating the most critical new infectious problem facing human health in our generation. Subsequently, there have been a myriad of microbial zoonotic agents surfacing in humans: prions in beef finding their way to neurons in human teenagers; West Nile virus from Israeli geese crossing continents to cause human and equine mortalities in North America; monkeypox virus in African giant rats infecting North American prairie dogs, which then carried the virus into living rooms and human beings in four U.S. states; and severe acute respiratory syndrome coronavirus descending from bats to civet cats to a human super spreader who shared it with fellow travelers from four different continents at a hotel in Hong Kong.4 And now, avian influenza is making an inexorable march across Asia into Europe, infecting not only expected avian hosts but also potentially cats and people. The interface of human and animal health has become very blurred, and adequate public health measures for zoonotic disease control require an understanding of husbandry and ecology in the animal host. Although most influenza pandemics in history are now known to have arisen through reassortment of avian and human viruses, the ability of avian viruses to directly infect humans was not regarded as a significant danger until recently.5 Within the past 8 years, there have been many detections of avian influenza virus in humans, with four different subtypes. Beginning with the death of a three-year-old boy in Hong Kong in May of 1997, there has been a steady string of incidents involving human illness and death due to various highly pathogenic avian influenza (HPAI) viruses contracted from poultry, first in Hong Kong and China, then in the Netherlands, subsequently in Canada, and now, most frighteningly, in Southeast Asia.