Cross-immunity and age patterns of influenza A(H5N1) infection

Kucharski, Adam J.; Edmunds, W. John

doi:10.1017/s0950268814001976

Cited by 10 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This value agrees well with published estimates of population susceptibility (Table 3), with cross-immunity coming from the smallpox vaccination campaigns that ended in the two decades preceding the outbreaks [5]. We also found evidence of pre-existing immunity to influenza A(H5N1) in older individuals; it has previously been suggested that such immunity could result either from prior exposure to H5N1, or from cross-immunity from previous infection with influenza A(H1N1) [27]. In contrast, we estimated that both age groups had similar levels of susceptibility to MERS and influenza A(H7N9).…”

Section: Discussionsupporting

confidence: 91%

“…We found that the 95% confidence interval of the joint Table 3. Comparison of our parameter estimates and previously published estimates of R, from studies using single-type models, and S, from studies of vaccination history [5] and seroprevalence [28,29] and models of immune acquisition [27]. distribution of R 0 and S was very broad (S8 Fig.).…”

Section: Application To Real Outbreaksmentioning

confidence: 72%

See 1 more Smart Citation

Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks

Kucharski

Edmunds

2015

PLoS Comput Biol

View full text Add to dashboard Cite

The transmission potential of a novel infection depends on both the inherent transmissibility of a pathogen, and the level of susceptibility in the host population. However, distinguishing between these pathogen- and population-specific properties typically requires detailed serological studies, which are rarely available in the early stages of an outbreak. Using a simple transmission model that incorporates age-stratified social mixing patterns, we present a novel method for characterizing the transmission potential of subcritical infections, which have effective reproduction number R<1, from readily available data on the size of outbreaks. We show that the model can identify the extent to which outbreaks are driven by inherent pathogen transmissibility and pre-existing population immunity, and can generate unbiased estimates of the effective reproduction number. Applying the method to real-life infections, we obtained accurate estimates for the degree of age-specific immunity against monkeypox, influenza A(H5N1) and A(H7N9), and refined existing estimates of the reproduction number. Our results also suggest minimal pre-existing immunity to MERS-CoV in humans. The approach we describe can therefore provide crucial information about novel infections before serological surveys and other detailed analyses are available. The methods would also be applicable to data stratified by factors such as profession or location, which would make it possible to measure the transmission potential of emerging infections in a wide range of settings.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Application To Real Outbreaksmentioning

confidence: 72%

Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks

Kucharski

Edmunds

2015

PLoS Comput Biol

View full text Add to dashboard Cite

show abstract

“…To formally assess the HA imprinting hypothesis alongside previous explanations (1,3–7) for observed H5N1 and H7N9 age distributions, we developed a set of multinomial models. These models related the probability that a case occurred in a given birth cohort to country- and year-specific demography, and risk factors including age-based risk of exposure to poultry, age-based risk of severe disease or case ascertainment, and reconstructed patterns of first exposure (and hence potential immunological imprinting) to HA or NA subtypes (Table S1).…”

Section: Ha Imprinting Explains Age Distributionsmentioning

confidence: 99%

“…Despite commonalities in their reservoir hosts and epidemiology, these viruses show puzzling differences in age distribution of observed human cases (1,2). Existing explanations, including possible protection against H5N1 among older birth-year cohorts exposed to the neuraminidase of H1N1 as children (3,4) or age biases in exposure to infected poultry (5–7), cannot fully explain these opposing patterns of severe disease and mortality. Another idea is that severity of H5N1 and H7N9 differs by age, leading to case ascertainment biases (1), but no explanatory mechanism has been proposed.…”

mentioning

confidence: 99%

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting

Gostic

Ambrose

Worobey

et al. 2016

Science

400

368

View full text Add to dashboard Cite

Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual’s first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows protective HA imprinting is the crucial explanatory factor, providing 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain’s pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.

show abstract

“…Despite commonalities in their reservoir hosts and epidemiology, these viruses show puzzling differences in age distribution of observed human cases (2,3). Explanations proposed to date, including possible protection against H5N1 from past exposure to the neuraminidase of H1N1 (4,5) and human behavioral factors (such as age bias in exposure to infected poultry) (6)(7)(8), cannot fully explain these opposing patterns of severe disease and mortality. Another idea is that severity of H5N1 and H7N9 differs by age class, leading to case ascertainment bias (2), but no explanatory mechanism has been proposed.…”

Section: Main Textmentioning

confidence: 99%

Potent Protection Against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting

Gostic

Ambrose

Worobey

et al. 2016

Preprint

147

View full text Add to dashboard Cite

Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit puzzling differences in age distribution of human cases. Previous explanations cannot fully account for these patterns. We analyze data from all known human cases of H5N1 and H7N9 and show that an individual's first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes of the same phylogenetic group. Statistical modeling reveals protective HA imprinting to be the crucial explanatory factor, providing 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and to demonstrate that a novel strain's pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment. Main TextThe spillover of novel influenza A virus (IAV) strains is a persistent threat to global public health. Current thinking assumes a central role for an immunologically naïve human population in the emergence of pandemic IAVs (1) . H5N1 and H7N9 are particularly concerning avian-origin IAVs, each having caused hundreds of severe or fatal human cases (2) . Despite commonalities in their reservoir hosts and epidemiology, these viruses show puzzling differences in age distribution of observed human cases (2,3). Explanations proposed to date, including possible protection against H5N1 from past exposure to the neuraminidase of H1N1 (4,5) and human behavioral factors (such as age bias in exposure to infected poultry) (6-8), cannot fully explain these opposing patterns of severe disease and mortality. Another idea is that severity of H5N1 and H7N9 differs by age class, leading to case ascertainment bias (2), but no explanatory mechanism has been proposed.The key determinants for IAV susceptibility are the virus's two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), where different numbered subtypes canonically indicate no cross-immunity. However, recent experiments have revealed that broadly crossprotective immune responses can provide immunity between different HA subtypes, typically within the same phylogenetic group (9-15). H5 belongs to HA group 1 (which also includes H1 and H2), while H7 is in group 2 (which includes H3). We hypothesized that the 1968 pandemic, which marked the transition from an era of group 1 HA circulation to . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/061598 doi: bioRxiv preprint first posted online Jul. 5, 2016; 2 an era dominated by a group 2 HA virus (1968-present) (Fig. 1A), caused a major shift in population susceptibility that explains why H5N1 cases are generally detected in younger people than H7N9 (3,(16)(17)(18). We found strong evidence that HA group-matched primary exposur...

show abstract

Cross-immunity and age patterns of influenza A(H5N1) infection

Cited by 10 publications

References 18 publications

Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks

Characterizing the Transmission Potential of Zoonotic Infections from Minor Outbreaks

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting

Potent Protection Against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting

Contact Info

Product

Resources

About