Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a smoldering pandemic.

BACKGROUND The first pandemic season of A/H3N2 influenza virus (1968/1969) resulted in significant mortality in the United States, but it was the second pandemic season of A/H3N2 influenza virus (1969/1970) that caused the majority of deaths in England. We further explored the global pattern of mortality caused by the pandemic during this period. METHODS We estimated the influenza-related excess mortality in 6 countries (United States, Canada, England and Wales, France, Japan, and Australia) using national vital statistics by age for 1967-1978. Geographical and temporal pandemic patterns in mortality were compared with the genetic drift of the influenza viruses by analyzing hemagglutinin and neuraminidase sequences from GenBank. RESULTS In North America, the majority of influenza-related deaths in 1968/1969 and 1969/1970 occurred during the first pandemic season (United States, 70%; Canada, 54%). Conversely, in Europe and Asia, the pattern was reversed: 70% of deaths occurred during the second pandemic season. The second pandemic season coincided with a drift in the neuraminidase antigen. CONCLUSION We found a consistent pattern of mortality being delayed until the second pandemic season of A/H3N2 circulation in Europe and Asia. We hypothesize that this phenomenon may be explained by higher preexisting neuraminidase immunity (from the A/H2N2 era) in Europe and Asia than in North America, combined with a subsequent drift in the neuraminidase antigen during 1969/1970.