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.