Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults

Couch, Robert B.; Atmar, Robert L.; Franco, Luis M.; Quarles, John; Niño, Diane; Wells, Janet; Arden, Nancy H.; Cheung, Sheree; Belmont, John W.

doi:10.1093/cid/cir809

Cited by 23 publications

(30 citation statements)

References 35 publications

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“…In our studies volunteers were treated as soon as significant symptoms or positive blood film developed, therefore only clinical features in the early phase of illness were addressed, and it remains possible that the power to distinguish between these infections clinically might be improved with a longer duration of illness. In addition the use of a non-pandemic challenge strain of influenza in this study may reduce generalisability of findings to pH1N1, which has higher pathogenicity in younger individuals 11 presumably related to reduced pre-existing immunity 12 ; yet all volunteers in our study had no detectable pre-existing immunity to the challenge strain, so in this context they might be considered more representative of a pandemic exposed population. Moreover, the pre-assessment probability of infection has a major impact on the PPV and NPV, so during a pandemic setting (where the prevalence of influenza would be significantly greater than malaria) the case definition would be expected to perform significantly better.…”

Section: Discussionmentioning

confidence: 98%

Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies

Lillie

Duncan

Sheehy

et al. 2012

Travel Medicine and Infectious Disease

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SummaryDuring the H1N1 influenza pandemic (pH1N1/09) diagnostic algorithms were developed to guide antiviral provision. However febrile illnesses are notoriously difficult to distinguish clinically. Recent evidence highlights the importance of incorporating travel history into diagnostic algorithms to prevent the catastrophic misdiagnosis of life-threatening infections such as malaria.We applied retrospectively the UK pH1N1/09 case definition to a unique cohort of healthy adult volunteers exposed to Plasmodium falciparum malaria or influenza to assess the predictive value of this case definition, and to explore the distinguishing clinical features of early phase infection with these pathogens under experimental conditions.For influenza exposure the positive predictive value of the pH1N1/09 case definition was only 0.38 (95% CI: 0.06–0.60), with a negative predictive value of 0.27 (95% CI: 0.02–0.51). Interestingly, 8/11 symptomatic malaria-infected adults would have been inappropriately classified with influenza by the pH1N1/09 case definition, while 5/8 symptomatic influenza-exposed volunteers would have been classified without influenza (P = 0.18 Fisher's exact). Cough (P = 0.005) and nasal symptoms (P = 0.001) were the only clinical features that distinguished influenza-exposed from malaria-exposed volunteers.An open mind regarding the clinical cause of undifferentiated febrile illness, particularly in the absence of upper respiratory tract symptoms, remains important even during influenza pandemic settings. These data support incorporating travel history into pandemic algorithms.

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Section: Discussionmentioning

confidence: 98%

Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies

Lillie

Duncan

Sheehy

et al. 2012

Travel Medicine and Infectious Disease

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“…Therefore, a number of investigations have focused on the protectiveness of heterologous immunity to pH1N1 infection, conferred from previous exposure to circulating influenza strains or vaccines (19, 27, 28). Human studies and mouse models have demonstrated that cross-reactive T cells and cross-reactive non-neutralizing antibody defenses can limit viral load and protect from a lethal heterologous influenza infection (10, 19, 21, 30).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, seasonal influenza A-specific memory T cells from humans (naïve to pH1N1) are capable of recognizing pH1N1 epitopes and can directly lyse pH1N1-infected target cells (19). Therefore, the ability of cross-protective memory T cells to control pH1N1 infection could explain the relatively benign symptoms experienced by a majority of those infected (19, 28). However, cross-reactive antibody protection to pH1N1 cannot be ignored.…”

Section: Introductionmentioning

confidence: 99%

Diet-Induced Obese Mice Exhibit Altered Heterologous Immunity during a Secondary 2009 Pandemic H1N1 Infection

Milner

Sheridan

Karlsson

et al. 2013

The Journal of Immunology

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During the 2009 pandemic H1N1 (pH1N1) influenza outbreak, obese individuals were at greater risk for morbidity and mortality to pandemic infection. However, the mechanisms contributing to greater infection severity in obese individuals remain unclear. Although most individuals lacked pre-existing, neutralizing antibody protection to the novel pH1N1 virus, heterologous defenses conferred from exposure to circulating strains or vaccination have been shown to impart protection against pH1N1 infection in humans and mice. Because obese humans and mice have impaired memory T-cell and antibody responses following influenza vaccination or infection, we investigated the impact of obesity on heterologous protection to pH1N1 infection using a mouse model of diet-induced obesity. Lean and obese mice were infected with influenza A/PR/8/34 and five weeks later challenged with a lethal dose of heterologous pH1N1 (A/Cal/04/09). Cross-neutralizing antibody protection was absent in this model, but obese mice exhibited a significantly lower level of non-neutralizing, cross-reactive pH1N1 nucleoprotein antibodies following the primary PR/8 infection. Further, obese mice had elevated viral titers, greater lung inflammation, lung damage, and an increased number of cytotoxic memory CD8+ T cells in the lung airways. Although obese mice had more regulatory T cells (Tregs) in the lung airways compared with lean controls during the pH1N1 challenge, Tregs isolated from obese mice were 40% less suppressive than Tregs isolated from lean mice. Taken together, excessive inflammatory responses to pH1N1 infection, potentially due to greater viral burden and impaired Treg function, may be a novel mechanism by which obesity contributes to greater pH1N1 severity.

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“…[6], [18], [19] In contrast with this, some degree of cross protection from severe illness by prior seasonal vaccination was suggested in some studies. [20], [21], [22] Prior infection with an influenza A virus can reduce morbidity and mortality caused by an infection with an antigenically divergent influenza A virus because of heterosubtypic immunity, both within and between subtypes. [23] Both natural infection and seasonal vaccination can induce heterosubtypic neutralizing antibodies, but our data suggest skewing against such antibodies in persons with a history of seasonal vaccination.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Humoral Response to Influenza A(H1N1)pdm09 Infection and Vaccination Measured by a Protein Microarray in Persons with and without History of Seasonal Vaccination

et al. 2013

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BackgroundThe influence of prior seasonal influenza vaccination on the antibody response produced by natural infection or vaccination is not well understood.MethodsWe compared the profiles of antibody responses of 32 naturally infected subjects and 98 subjects vaccinated with a 2009 influenza A(H1N1) monovalent MF59-adjuvanted vaccine (Focetria®, Novartis), with and without a history of seasonal influenza vaccination. Antibodies were measured by hemagglutination inhibition (HI) assay for influenza A(H1N1)pdm09 and by protein microarray (PA) using the HA1 subunit for seven recent and historic H1, H2 and H3 influenza viruses, and three avian influenza viruses. Serum samples for the infection group were taken at the moment of collection of the diagnostic sample, 10 days and 30 days after onset of influenza symptoms. For the vaccination group, samples were drawn at baseline, 3 weeks after the first vaccination and 5 weeks after the second vaccination.ResultsWe showed that subjects with a history of seasonal vaccination generally exhibited higher baseline titers for the various HA1 antigens than subjects without a seasonal vaccination history. Infection and pandemic influenza vaccination responses in persons with a history of seasonal vaccination were skewed towards historic antigens.ConclusionsSeasonal vaccination is of significant influence on the antibody response to subsequent infection and vaccination, and further research is needed to understand the effect of annual vaccination on protective immunity.

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Prior Infections With Seasonal Influenza A/H1N1 Virus Reduced the Illness Severity and Epidemic Intensity of Pandemic H1N1 Influenza in Healthy Adults

Abstract: The 2009 A/H1N1 epidemic among healthy adults was relatively mild, most likely because of immunity from prior infections with A/H1N1 viruses.

Cited by 23 publications

References 35 publications

Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies

Distinguishing malaria and influenza: Early clinical features in controlled human experimental infection studies

Diet-Induced Obese Mice Exhibit Altered Heterologous Immunity during a Secondary 2009 Pandemic H1N1 Infection

Profiling of Humoral Response to Influenza A(H1N1)pdm09 Infection and Vaccination Measured by a Protein Microarray in Persons with and without History of Seasonal Vaccination

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