LOWER MORTALITY FROM H1N1 INFLUENZA IN OLDER ARGENTINEANS: MEN MORE AFFECTED

To the Editor: Argentina was the first nation in 2009 to declare an H1N1 epidemic in the southern hemisphere.1,2 Up to the end of 2009 southern hemisphere winter, Argentina was second only to the United States in the number of reported deaths from H1N1.2 Only one pediatric study has reported H1N1 influenza mortality in Argentina.3 Conversely, several studies in North America and Europe have reported that the age distribution of the 2009 pandemic H1N1 virus differs from the populations traditionally at risk for seasonal influenza.4–6 During peak periods of seasonal influenza, most hospitalizations occur in toddlers and frail elderly people, but reports from the northern hemisphere showed that older people were at lower risk of current H1N1 infection, although they were at greater risk of hospitalization and death once infected by this virus.4–7 Consequently, H1N1 population attributable mortality risk did not differ significantly between older and younger adults during 2009 in the northern hemisphere.4–6 This letter reports H1N1 mortality risk in Argentina in 2009, stratified according to age group (Figure 1A). Cases were confirmed using reverse transcription polymerase chain reaction (RT-PCR). Mortality per 100,000 inhabitants was 0.6 for people aged 10 to 19, 2.5 for people aged 50 to 59, and 0.9 in people aged 60 and older. Except for children younger than 10, the mortality rate increased with age but started to decrease in adults aged 60 and older. The mortality of people aged 60 and older was 64% lower than in those aged 50 to 59. Possible explanations include minimal contact by older age groups with young travelers and school-aged children who amplify transmission during the early stage of the epidemic.1 Alternatively, young adults are more likely to be exposed, to exhibit fever, and to be tested for H1N1 once infected. (A) H1N1 incident mortality according to age group in Argentina, 2009. (B) 2009 H1N1 mortality in Argentina according to age group. The broken line shows expected mortality for the older age group. Expected mortality of people aged 60 and older was estimated using mathematical modeling based on previous H1N1 epidemics,8 the rhythm of increasing mortality from the age of 20 to 59 in current H1N1 pandemic and on previous seasonal influenza epidemics in Argentina (2007/08). Nevertheless, there is compelling evidence to suggest that a main reason why older Argentineans had much lower mortality is due to immune cross-protection from prior exposure to H1N1 strains circulating worldwide from 1918 (Spanish influenza) to 1957, when they were replaced by H2N2 viruses.8,9 Many of the older immigrants to Argentine are survivors of the Spanish influenza, and the highest titers of cross-reactive antibodies to H1N1 are elicited in the European population born before 1950, whereas individuals born after 1950 generally have lower titers and lack this cross-protection.10 These findings are in agreement with previous observations demonstrating that the smaller number of infections in older Americans was not simply a reflection of less testing in this group.7 In Finland, there was an age-related difference in the prevalence of neutralizing antibody titers against the 2009 H1N1 virus—96% in those born before 1919 and less than 5% in those born after 1950.10 This fact is consistent with the low frequency of the 2009 H1N1 influenza in nursing homes and the high frequency of outbreaks in schools in Argentina.2,3 Traditionally, in immunologically naive populations, mortality follows a U-shaped curve because younger adults have stronger immune responses.8 Therefore, the finding that older Argentineans have a lower mortality than middle-aged adults is unusual but explainable in terms of immunological memory acquired from 1918 to 1957, when H1N1 circulated world wide.8–10 Using mathematical modeling based on previous H1N1 epidemics,8 the tread of increasing mortality from the age of 20 to 59 in current H1N1 pandemic, and on previous seasonal influenza epidemics in Argentina (2007–2008), it can be estimated that expected mortality in people aged 60 and older would be 4.9 per 100,000 when the immune memory factor was removed from the model (Figure 1B). The actual mortality rate of 0.9 per 100.000 supports the hypothesis of cross-protection acquired in prior exposure to H1N1 strains circulating worldwide from 1918 to 1957. Unexpectedly, mortality in older Argentinean men was twice that in older women. The reasons for this difference are unknown but may involve cultural factors such as older Argentinean men leaving home to work or engaging in social activities more often than women. Another possible explanation is the difference in life expectancies between the sexes in older Argentineans (men, 72 vs women, 79). Antibodies titles against H1N1 tend to be higher in older age groups and this 7-year gap in life expectancy between the sexes might lead to a survival effect (lower levels of immunity in young-old groups). In conclusion, lower mortality was found in older Argentineans in the current H1N1 pandemic, which may have potential implications for future health policies, such as lower priority for immunization of nonfrail older people against H1N1. Only the final effect of the H1N1 epidemic upon mortality was analyzed, and reliable data on general incidence and hospitalization rates according to age group are not available from official Argentinean sources. Even though H1N1 geriatric mortality was low in Argentina, it is possible that, once infected, older Argentineans have higher risk of hospitalization and death than younger adults.4–6 In this sense, elderly people would have a lower priority for anti-H1N1 immunization campaigns but a greater need for oseltamivir indication and hospitalization than nonpregnant younger adults. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Roriz-Cruz: study concept. Roriz-Cruz, Idiane Rosset, and Montero-Odasso: obtained raw data from Argentinean Ministry of Health, interpreted and analyzed data, and wrote the manuscript. Sponsor's Role: None.

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