- Email: [email protected]
How common was 2009 pandemic influenza A H1N1?
Comment
How common was 2009 pandemic influenza A H1N1? By contrast with the well described clinical and laboratory aspects of 2009 pandemic influenza A H1N1, the true infection rate after the first wave of the pandemic is unknown. Such information is important to plan for future pandemics and to develop vaccine strategies. Because laboratory confirmation of acute pandemic H1N1 infection was not universal and asymptomatic or mild infection was common, serosurveys are the best available measure of rates of pandemic H1N1 infection. Serosurveys have estimated pandemic H1N1 prevalence after the first wave of infection by various methods.1–9 For definitive serological diagnosis of infection, seroconversion or a four-times or greater rise between pandemic H1N1-specific antibody titres before and after infection is needed;2,3 one high titre is only suggestive of infection. However, serum samples collected before and after infection are not always available in retrospective population-based studies, thus investigators can report only titres after the first wave of infection.7,8 So far, three studies have recorded pandemic H1N1 rates based on individual seroconversion.2,3,9 Other investigations have subtracted pre-pandemic wave from post-wave antibody titres of different populations—not always matched by geographical location or age—to estimate true infection rates.1,4–6,9 However, this method is not indicative of individual seroconversion.9 Various studies have defined seropositivity with different cutoffs: 1/10 or higher,7 1/20 or higher,6 1/32 or higher,5 and 1/40 or higher.1–5,8,9 When one sample is tested, definition of seropositivity in the absence of known clinical illness is difficult. For example, a low positive haemagglutination-inhibition titre of 1/40 or higher might not suggest recent infection. We recorded2 seroconversion in only 21% and 52% of individuals with positive haemagglutination-inhibition titres of 1/40 and 1/80, respectively, when samples collected before and after the initial wave of infection were examined in parallel. Of more relevance is interpretation of what a low positive pandemic H1N1-specific haemagglutinationinhibition (or neutralisation) titre truly represents, because data for the seroprotective titre against pandemic H1N1 are scarce. In seasonal and pandemic H1N1 influenza vaccine trials, a haemagglutinationinhibition titre of 1/40 or higher was judged protective,10 although vaccine efficacy is best measured by clinical www.thelancet.com/infection Vol 11 June 2011
effectiveness (which is rarely assessed), rather than by laboratory markers. Many reasons account for pandemic H1N1-specific antibody titre differences from reported serosurveys, including the various serological methods used, different or ill defined study periods (ie, time between sample collection and the peak or end of pandemic activity), populations tested, proportions of individuals tested within various age groups (eg, some studies have not included children2–4,7,8), geographical locations (eg, urban vs rural), and extent of local influenza activity. Different influenza antigens (A/California/4/2009, A/California/7/2009,A/Tennessee/1560/2009,A/England/ 195/2009, and A/Finland/554/2009 have been used1,5,7,9,11) can affect pandemic H1N1-specific haemagglutinationinhibition titres. Haemagglutination-inhibition assays are less sensitive than microneutralisation, and might underestimate the true prevalence.5,9 Validation of influenza subtype-specific serology is difficult without interlaboratory comparisons and international quality assurance programmes. Studies that report pandemic H1N1-specific antibody results should exclude cross-reactions to seasonal strains of influenza A H1N1 or influenza A H3N2, or both. Some serosurveys have presented cross-reaction data,1,3–6 but others have not.2,7–9 In 2010, Gilbert and colleagues1 suggested a scarcity of cross-reaction, whereas in 2009, Loeb and colleagues11 proposed that cross-reactive antibodies could result in higher seroconversion rates. In the investigation by Loeb and colleagues, the unexpected pandemic H1N1 seroconversion rate of 10% pre-dated the region’s first laboratory confirmed case of pandemic H1N1; the expectation was that pandemic H1N1 would have circulated widely for some weeks before seroconversion rates of 10% were recorded. The ideal time to collect serum samples after the initial wave of infection was the period between the first laboratory confirmed pandemic H1N1 case and vaccine introduction. Antibody titres fall between actual infection and sample collection. Monovalent or trivalent pandemic H1N1 vaccine programmes will affect future serosurveys, although vaccine uptake varies in different countries and age groups. Seroprevalence and seroconversion rates were higher in younger people compared with elderly populations worldwide;1–3,5,9,11
This online publication has been corrected. The corrected version first appeared at thelancet.com/infection on June 20, 2011
423
Comment
cross-reactive antibodies from presumed childhood infection with 1918 influenza A H1N1-like viruses could be the cause.12 This idea needs to be confirmed with tests against 1918-like or other older influenza A H1N1 viruses. Although subsequent waves of infections in previous pandemics have been severe, pandemic H1N1 incidence should decrease because of herd immunity from recent pandemic H1N1 infection, pre-existing cross-protective antibodies in older individuals, and vaccination. This notion was reported during the southern hemisphere’s 2010 winter, when there was a substantial reduction in the number of laboratory confirmed pandemic H1N1 cases. To properly understand pandemic influenza infection rates, individual samples should be collected before and after the initial wave of infection to measure seroconversion as part of appropriately designed multinational population-based studies, after resolution of methodological differences in tests for pandemic H1N1-specific antibodies. *Jen Kok, Dominic E Dwyer Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia [email protected]
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Gilbert GL, Cretikos MA, Hueston L, et al. Influenza A (H1N1) 2009 antibodies in residents of New South Wales, Australia, after the first pandemic wave in the 2009 southern hemisphere winter. PLoS ONE 2010; 5: e12562. Kok J, Tudo K, Blyth CC, et al. Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected individuals. J AIDS 2011; 56: 91–94. Chen MI, Lee VJ, Lim W, et al. 2009 Influenza A(H1N1) seroconversion rates and risk factors among distinct adult cohorts in Singapore. JAMA 2010; 303: 1383–91. McVernon J, Laurie K, Nolan T, et al. Seroprevalence of 2009 pandemic influenza A(H1N1) virus in Australian blood donors, October–December 2009. Euro Surveill 2010; 15: pii=19678. Miller E, Hoschler K, Hardelid P, et al. Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet 2010; 375: 1100–08. Waalen K, Kilander A, Dudman SG, et al. High prevalence of antibodies to the 2009 pandemic influenza A(H1N1) virus in the Norwegian population following a major epidemic and a large vaccination campaign in autumn 2009. Euro Surveill 2010; 15: pii=19633. Aho M, Lyytikaïnen O, Nyholm JE, et al. Outbreak of 2009 pandemic influenza A(H1N1) in a Finnish garrison—a serological survey. Euro Surveill 2010; 15: pii=19709. Adamson WE, Maddi S, Robertson C, et al. 2009 pandemic influenza A(H1N1) virus in Scotland: geographically variable immunity in Spring 2010, following the winter outbreak. Euro Surveill 2010; 15: pii=19590. Wu JT, Ma ES, Lee CK, et al. The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis 2010; 51: 1184–91. U.S. Department of Health and Human Service Food and Drug Administration Center for Biologics Evaluation and Research. Guidance for industry: clinical data needed to support licensure of pandemic influenza vaccines. May, 2007. http://www.fda.gov/downloads/ BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ Guidances/Vaccines/ucm091985.pdf (accessed Dec 8, 2010). Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs N95 respirator for preventing influenza among health care workers. JAMA 2009; 302: 1865–71. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009; 361: 1945–52.
We declare that we have no conflicts of interest.
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www.thelancet.com/infection Vol 11 June 2011
How common was 2009 pandemic influenza A H1N1? By contrast with the well described clinical and laboratory aspects of 2009 pandemic influenza A H1N1, the true infection rate after the first wave of the pandemic is unknown. Such information is important to plan for future pandemics and to develop vaccine strategies. Because laboratory confirmation of acute pandemic H1N1 infection was not universal and asymptomatic or mild infection was common, serosurveys are the best available measure of rates of pandemic H1N1 infection. Serosurveys have estimated pandemic H1N1 prevalence after the first wave of infection by various methods.1–9 For definitive serological diagnosis of infection, seroconversion or a four-times or greater rise between pandemic H1N1-specific antibody titres before and after infection is needed;2,3 one high titre is only suggestive of infection. However, serum samples collected before and after infection are not always available in retrospective population-based studies, thus investigators can report only titres after the first wave of infection.7,8 So far, three studies have recorded pandemic H1N1 rates based on individual seroconversion.2,3,9 Other investigations have subtracted pre-pandemic wave from post-wave antibody titres of different populations—not always matched by geographical location or age—to estimate true infection rates.1,4–6,9 However, this method is not indicative of individual seroconversion.9 Various studies have defined seropositivity with different cutoffs: 1/10 or higher,7 1/20 or higher,6 1/32 or higher,5 and 1/40 or higher.1–5,8,9 When one sample is tested, definition of seropositivity in the absence of known clinical illness is difficult. For example, a low positive haemagglutination-inhibition titre of 1/40 or higher might not suggest recent infection. We recorded2 seroconversion in only 21% and 52% of individuals with positive haemagglutination-inhibition titres of 1/40 and 1/80, respectively, when samples collected before and after the initial wave of infection were examined in parallel. Of more relevance is interpretation of what a low positive pandemic H1N1-specific haemagglutinationinhibition (or neutralisation) titre truly represents, because data for the seroprotective titre against pandemic H1N1 are scarce. In seasonal and pandemic H1N1 influenza vaccine trials, a haemagglutinationinhibition titre of 1/40 or higher was judged protective,10 although vaccine efficacy is best measured by clinical www.thelancet.com/infection Vol 11 June 2011
effectiveness (which is rarely assessed), rather than by laboratory markers. Many reasons account for pandemic H1N1-specific antibody titre differences from reported serosurveys, including the various serological methods used, different or ill defined study periods (ie, time between sample collection and the peak or end of pandemic activity), populations tested, proportions of individuals tested within various age groups (eg, some studies have not included children2–4,7,8), geographical locations (eg, urban vs rural), and extent of local influenza activity. Different influenza antigens (A/California/4/2009, A/California/7/2009,A/Tennessee/1560/2009,A/England/ 195/2009, and A/Finland/554/2009 have been used1,5,7,9,11) can affect pandemic H1N1-specific haemagglutinationinhibition titres. Haemagglutination-inhibition assays are less sensitive than microneutralisation, and might underestimate the true prevalence.5,9 Validation of influenza subtype-specific serology is difficult without interlaboratory comparisons and international quality assurance programmes. Studies that report pandemic H1N1-specific antibody results should exclude cross-reactions to seasonal strains of influenza A H1N1 or influenza A H3N2, or both. Some serosurveys have presented cross-reaction data,1,3–6 but others have not.2,7–9 In 2010, Gilbert and colleagues1 suggested a scarcity of cross-reaction, whereas in 2009, Loeb and colleagues11 proposed that cross-reactive antibodies could result in higher seroconversion rates. In the investigation by Loeb and colleagues, the unexpected pandemic H1N1 seroconversion rate of 10% pre-dated the region’s first laboratory confirmed case of pandemic H1N1; the expectation was that pandemic H1N1 would have circulated widely for some weeks before seroconversion rates of 10% were recorded. The ideal time to collect serum samples after the initial wave of infection was the period between the first laboratory confirmed pandemic H1N1 case and vaccine introduction. Antibody titres fall between actual infection and sample collection. Monovalent or trivalent pandemic H1N1 vaccine programmes will affect future serosurveys, although vaccine uptake varies in different countries and age groups. Seroprevalence and seroconversion rates were higher in younger people compared with elderly populations worldwide;1–3,5,9,11
This online publication has been corrected. The corrected version first appeared at thelancet.com/infection on June 20, 2011
423
Comment
cross-reactive antibodies from presumed childhood infection with 1918 influenza A H1N1-like viruses could be the cause.12 This idea needs to be confirmed with tests against 1918-like or other older influenza A H1N1 viruses. Although subsequent waves of infections in previous pandemics have been severe, pandemic H1N1 incidence should decrease because of herd immunity from recent pandemic H1N1 infection, pre-existing cross-protective antibodies in older individuals, and vaccination. This notion was reported during the southern hemisphere’s 2010 winter, when there was a substantial reduction in the number of laboratory confirmed pandemic H1N1 cases. To properly understand pandemic influenza infection rates, individual samples should be collected before and after the initial wave of infection to measure seroconversion as part of appropriately designed multinational population-based studies, after resolution of methodological differences in tests for pandemic H1N1-specific antibodies. *Jen Kok, Dominic E Dwyer Centre for Infectious Diseases and Microbiology Laboratory Services, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia [email protected]
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Gilbert GL, Cretikos MA, Hueston L, et al. Influenza A (H1N1) 2009 antibodies in residents of New South Wales, Australia, after the first pandemic wave in the 2009 southern hemisphere winter. PLoS ONE 2010; 5: e12562. Kok J, Tudo K, Blyth CC, et al. Pandemic (H1N1) 2009 influenza virus seroconversion rates in HIV-infected individuals. J AIDS 2011; 56: 91–94. Chen MI, Lee VJ, Lim W, et al. 2009 Influenza A(H1N1) seroconversion rates and risk factors among distinct adult cohorts in Singapore. JAMA 2010; 303: 1383–91. McVernon J, Laurie K, Nolan T, et al. Seroprevalence of 2009 pandemic influenza A(H1N1) virus in Australian blood donors, October–December 2009. Euro Surveill 2010; 15: pii=19678. Miller E, Hoschler K, Hardelid P, et al. Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet 2010; 375: 1100–08. Waalen K, Kilander A, Dudman SG, et al. High prevalence of antibodies to the 2009 pandemic influenza A(H1N1) virus in the Norwegian population following a major epidemic and a large vaccination campaign in autumn 2009. Euro Surveill 2010; 15: pii=19633. Aho M, Lyytikaïnen O, Nyholm JE, et al. Outbreak of 2009 pandemic influenza A(H1N1) in a Finnish garrison—a serological survey. Euro Surveill 2010; 15: pii=19709. Adamson WE, Maddi S, Robertson C, et al. 2009 pandemic influenza A(H1N1) virus in Scotland: geographically variable immunity in Spring 2010, following the winter outbreak. Euro Surveill 2010; 15: pii=19590. Wu JT, Ma ES, Lee CK, et al. The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin Infect Dis 2010; 51: 1184–91. U.S. Department of Health and Human Service Food and Drug Administration Center for Biologics Evaluation and Research. Guidance for industry: clinical data needed to support licensure of pandemic influenza vaccines. May, 2007. http://www.fda.gov/downloads/ BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/ Guidances/Vaccines/ucm091985.pdf (accessed Dec 8, 2010). Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs N95 respirator for preventing influenza among health care workers. JAMA 2009; 302: 1865–71. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 2009; 361: 1945–52.
We declare that we have no conflicts of interest.
424
www.thelancet.com/infection Vol 11 June 2011