In January 2004, the most serious outbreak of avian influenza in terms of the number of human deaths (22 deaths out of a total of 33 cases in Vietnam and Thailand) began. This outbreak was caused by the viral subtype H5N1 (H (haemoagglutinin) and N (neuraminidase) are viral surface proteins that define specific subtypes) and, to date, constitutes the largest epidemic in commercial poultry,^1,2 affecting a number of Asian countries (that is, Cambodia, China, Indonesia, Japan, Lao People’s Democratic Republic, and the Republic of Korea, in addition to Thailand and Vietnam), where more than 100 million birds either died or were culled in the first two months of 2004.^3,4 The high case fatality rate, together with the potential occurrence of human epidemics, have created great public health concern, given the viruses’ high pathogenicity in humans. The question that remains unanswered, and that is the basic cause of such concern, is: “Will this avian virus be able to cause a large scale epidemic among humans after mutation or reassortment?”

To answer this question, we have to consider what we already know. The natural reservoir of avian influenza viruses is wild aquatic birds, which may be infected with “avirulent” or “low pathogenic” strains of the virus and present with only mild symptoms or no symptoms at all. Low pathogenic viruses can infect domestic poultry and other intermediate hosts and develop into highly pathogenic viruses (usually the H5N1 subtype), which cause a highly lethal disease, once defined as “fowl plague” (fowl plague was first identified in 1878 by an Italian scientist, Edoardo Perroncito, who described …