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Lone Simonsen

Publications and source records attributed to Lone Simonsen.

At least 19 recordsLinked to original sources
PubMed2006

Influenza-related mortality in the Italian elderly: no decline associated with increasing vaccination coverage.

We investigated trends in influenza-related mortality among the elderly population in Italy associated with increased vaccination coverage. Using Italian vital statistics data, we studied monthly death rates for pneumonia and influenza and all-cause for persons >/=65 years of age by 5-year age groups for 1970-2001. Using a classic seasonal regression modelling approach, we estimated the age-specific seasonal excess mortality rates among Italian elderly as a measure of influenza-related deaths. We studied trends in excess mortality after adjusting for population aging and analyzing separately seasons dominated by the severe A/H3N2 subtype and those dominated by other circulating influenza subtypes. After the late 1980s, no decline in age-adjusted excess mortality was associated with increasing influenza vaccination distribution primarily targeted for the elderly. These findings suggest that either the vaccine failed to protect the elderly against mortality (possibly due to immune senescence), and/or the vaccination efforts did not adequately target the frailest elderly. As in the US, our study challenges current strategies to best protect the elderly against mortality, warranting the need for better controlled trials with alternative vaccination strategies.

Aged↗
PubMed2006

Transmissibility and mortality impact of epidemic and pandemic influenza, with emphasis on the unusually deadly 1951 epidemic.

There are important gaps in our current understanding of the influenza virus behavior. In particular, it remains unclear why some inter-pandemic seasons are associated with unusually high mortality impact, sometimes comparable to that of pandemics. Here we compare the epidemiological patterns of the unusually deadly 1951 influenza epidemic (A/H1N1) in England and Wales and Canada with those of surrounding epidemic and pandemic seasons, in terms of overall mortality impact and transmissibility. Based on the statistical and mathematical analysis of vital statistics and morbidity epidemic curves in these two countries, we show that the 1951 epidemic was associated with both higher mortality impact and higher transmissibility than the 1957 and 1968 pandemics. Surprisingly in Liverpool, considered the 'epicenter' of the severe 1951 epidemic, the mortality impact and transmissibility even surpassed the 1918 pandemic.

Communicable Disease Control↗
PubMed2006

Synchrony, waves, and spatial hierarchies in the spread of influenza.

Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints.

Adult↗
PubMed2006

Stochastic processes are key determinants of short-term evolution in influenza a virus.

Understanding the evolutionary dynamics of influenza A virus is central to its surveillance and control. While immune-driven antigenic drift is a key determinant of viral evolution across epidemic seasons, the evolutionary processes shaping influenza virus diversity within seasons are less clear. Here we show with a phylogenetic analysis of 413 complete genomes of human H3N2 influenza A viruses collected between 1997 and 2005 from New York State, United States, that genetic diversity is both abundant and largely generated through the seasonal importation of multiple divergent clades of the same subtype. These clades cocirculated within New York State, allowing frequent reassortment and generating genome-wide diversity. However, relatively low levels of positive selection and genetic diversity were observed at amino acid sites considered important in antigenic drift. These results indicate that adaptive evolution occurs only sporadically in influenza A virus; rather, the stochastic processes of viral migration and clade reassortment play a vital role in shaping short-term evolutionary dynamics. Thus, predicting future patterns of influenza virus evolution for vaccine strain selection is inherently complex and requires intensive surveillance, whole-genome sequencing, and phenotypic analysis.

Antigenic Variation↗
PubMed2006

1951 influenza epidemic, England and Wales, Canada, and the United States.

Influenza poses a continuing public health threat in epidemic and pandemic seasons. The 1951 influenza epidemic (A/H1N1) caused an unusually high death toll in England; in particular, weekly deaths in Liverpool even surpassed those of the 1918 pandemic. We further quantified the death rate of the 1951 epidemic in 3 countries. In England and Canada, we found that excess death rates from pneumonia and influenza and all causes were substantially higher for the 1951 epidemic than for the 1957 and 1968 pandemics (by > or =50%). The age-specific pattern of deaths in 1951 was consistent with that of other interpandemic seasons; no age shift to younger age groups, reminiscent of pandemics, occurred in the death rate. In contrast to England and Canada, the 1951 epidemic was not particularly severe in the United States. Why this epidemic was so severe in some areas but not others remains unknown and highlights major gaps in our understanding of interpandemic influenza.

Adolescent↗
PubMed2005

Mortality due to influenza in the United States--an annualized regression approach using multiple-cause mortality data.

Influenza is an important cause of mortality in temperate countries, but there is substantial controversy as to the total direct and indirect mortality burden imposed by influenza viruses. The authors have extracted multiple-cause death data from public-use data files for the United States from 1979 to 2001. The current research reevaluates attribution of deaths to influenza, by use of an annualized regression approach: comparing measures of excess deaths with measures of influenza virus prevalence by subtype over entire influenza seasons and attributing deaths to influenza by a regression model. This approach is more conservative in its assumptions than is earlier work, which used weekly regression models, or models based on fitting baselines, but it produces results consistent with these other methods, supporting the conclusion that influenza is an important cause of seasonal excess deaths. The regression model attributes an annual average of 41,400 (95% confidence interval: 27,100, 55,700) deaths to influenza over the period 1979-2001. The study also uses regional death data to investigate the effects of cold weather on annualized excess deaths.

Cause of Death↗
PubMed2005

Antibody response to influenza vaccination in the elderly: a quantitative review.

We performed a quantitative review of 31 vaccine antibody response studies conducted from 1986 to 2002 and compared antibody responses to influenza vaccine in groups of elderly versus younger adults. We did a weighted analysis of the probability of vaccine response (measured as seroconversion and seroprotection) for each vaccine component (H1, H3 and B antigens). Using a multiple regression model, we adjusted for factors that might affect the vaccine response. The adjusted odds-ratio (OR) of responses in elderly versus young adults ranged from 0.24 to 0.59 in terms of seroconversion and seroprotection to all three antigens. The CDC estimates of 70-90% clinical vaccine efficacy in young adults and these estimates suggest a corresponding clinical efficacy in the elderly of 17-53% depending on circulating viruses. We conclude that the antibody response in the elderly is considerably lower than in younger adults. This highlights the need for more immunogenic vaccine formulations for the elderly.

Adolescent↗
PubMed2005

A hexavalent human rotavirus-bovine rotavirus (UK) reassortant vaccine designed for use in developing countries and delivered in a schedule with the potential to eliminate the risk of intussusception.

There is an urgent need for a rotavirus vaccine, because up to 592,000 infants and young children <5 years old die each year from rotavirus diarrhea, predominantly in the developing countries. We have developed a tetravalent human-bovine rotavirus (UK) reassortant vaccine with VP7 (G) specificity for serotypes 1, 2, 3, and 4, which has been shown to be safe, immunogenic, and effective in preventing severe rotavirus diarrhea. However, because of the emergence of VP7 (G) serotype 9 as an epidemiologically important serotype and the importance of VP7 (G) serotype 8 in focal areas, we are planning to add human-bovine (UK) reassortants with G8 and G9 specificity to the tetravalent vaccine, thereby formulating a "designed" hexavalent vaccine for universal use. In addition, we propose that the vaccine be administered orally in a 2-dose schedule, with the first dose given at 0-4 weeks of age and the second dose given at 4-8 weeks of age, when infants are relatively refractory to developing intussusception, thereby avoiding the age period when naturally occurring intussusception is most prevalent (i.e., ages 3-4 months through age 9 months). In this way, there may be the potential to eliminate or at least significantly decrease the risk of intussusception associated with rotavirus vaccination.

Administration, Oral↗
PubMed2005

Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City.

The 1918 "Spanish flu" was the fastest spreading and most deadly influenza pandemic in recorded history. Hypotheses of its origin have been based on a limited collection of case and outbreak reports from before its recognized European emergence in the summer of 1918. These anecdotal accounts, however, remain insufficient for determining the early diffusion and impact of the pandemic virus. Using routinely collected monthly age-stratified mortality data, we show that an unmistakable shift in the age distribution of epidemic deaths occurred during the 1917/1918 influenza season in New York City. The timing, magnitude, and age distribution of this mortality shift provide strong evidence that an early wave of the pandemic virus was present in New York City during February-April 1918.

Adolescent↗
PubMed2005

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.

Disease Outbreaks↗
PubMed2005

Impact of influenza vaccination on seasonal mortality in the US elderly population.

BACKGROUND: Observational studies report that influenza vaccination reduces winter mortality risk from any cause by 50% among the elderly. Influenza vaccination coverage among elderly persons (> or =65 years) in the United States increased from between 15% and 20% before 1980 to 65% in 2001. Unexpectedly, estimates of influenza-related mortality in this age group also increased during this period. We tried to reconcile these conflicting findings by adjusting excess mortality estimates for aging and increased circulation of influenza A(H3N2) viruses. METHODS: We used a cyclical regression model to generate seasonal estimates of national influenza-related mortality (excess mortality) among the elderly in both pneumonia and influenza and all-cause deaths for the 33 seasons from 1968 to 2001. We stratified the data by 5-year age group and separated seasons dominated by A(H3N2) viruses from other seasons. RESULTS: For people aged 65 to 74 years, excess mortality rates in A(H3N2)-dominated seasons fell between 1968 and the early 1980s but remained approximately constant thereafter. For persons 85 years or older, the mortality rate remained flat throughout. Excess mortality in A(H1N1) and B seasons did not change. All-cause excess mortality for persons 65 years or older never exceeded 10% of all winter deaths. CONCLUSIONS: We attribute the decline in influenza-related mortality among people aged 65 to 74 years in the decade after the 1968 pandemic to the acquisition of immunity to the emerging A(H3N2) virus. We could not correlate increasing vaccination coverage after 1980 with declining mortality rates in any age group. Because fewer than 10% of all winter deaths were attributable to influenza in any season, we conclude that observational studies substantially overestimate vaccination benefit.

Age Distribution↗