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      Serological Response to the 2009 Pandemic Influenza A (H1N1) Virus for Disease Diagnosis and Estimating the Infection Rate in Thai Population

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          Abstract

          Background

          Individuals infected with the 2009 pandemic virus A(H1N1) developed serological response which can be measured by hemagglutination-inhibition (HI) and microneutralization (microNT) assays.

          Methodology/Principal Findings

          MicroNT and HI assays for specific antibody to the 2009 pandemic virus were conducted in serum samples collected at the end of the first epidemic wave from various groups of Thai people: laboratory confirmed cases, blood donors and health care workers (HCW) in Bangkok and neighboring province, general population in the North and the South, as well as archival sera collected at pre- and post-vaccination from vaccinees who received influenza vaccine of the 2006 season. This study demonstrated that goose erythrocytes yielded comparable HI antibody titer as compared to turkey erythrocytes. In contrast to the standard protocol, our investigation found out the necessity to eliminate nonspecific inhibitor present in the test sera by receptor destroying enzyme (RDE) prior to performing microNT assay. The investigation in pre-pandemic serum samples showed that HI antibody was more specific to the 2009 pandemic virus than NT antibody. Based on data from pre-pandemic sera together with those from the laboratory confirmed cases, HI antibody titers ≥40 for adults and ≥20 for children could be used as the cut-off level to differentiate between the individuals with or without past infection by the 2009 pandemic virus.

          Conclusions/Significance

          Based on the cut-off criteria, the infection rates of 7 and 12.8% were estimated in blood donors and HCW, respectively after the first wave of the 2009 influenza pandemic. Among general population, the infection rate of 58.6% was found in children versus 3.1% in adults.

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          Most cited references25

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          Emergence and pandemic potential of swine-origin H1N1 influenza virus.

          Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives of millions. The emergence of new strains will continue to pose challenges to public health and the scientific communities. A prime example is the recent emergence of swine-origin H1N1 viruses that have transmitted to and spread among humans, resulting in outbreaks internationally. Efforts to control these outbreaks and real-time monitoring of the evolution of this virus should provide us with invaluable information to direct infectious disease control programmes and to improve understanding of the factors that determine viral pathogenicity and/or transmissibility.
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            Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.

            A new pandemic influenza A (H1N1) virus has emerged, causing illness globally, primarily in younger age groups. To assess the level of preexisting immunity in humans and to evaluate seasonal vaccine strategies, we measured the antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups. Using a microneutralization assay, we measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults. Vaccination with recent seasonal nonadjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had preexisting cross-reactive antibodies. 2009 Massachusetts Medical Society
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              Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

              From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                25 January 2011
                : 6
                : 1
                : e16164
                Affiliations
                [1 ]Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
                [2 ]Bureau of Epidemiology, Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand
                [3 ]Maharat Nakhonratchasima Hospital, Ministry of Public Health, Nakhonratchasima, Thailand
                [4 ]Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
                [5 ]The National Blood Center, The Thai Red Cross Society, Bangkok, Thailand
                [6 ]Division of Preventive Medicine, Naval Medical Department, Royal Thai Navy, Chon Buri, Thailand
                [7 ]Queen Sirikit National Institute of Child Health, Ministry of Public Health, Bangkok, Thailand
                [8 ]Bamrasnaradura Infectious Disease Institute, Ministry of Public Health, Nonthaburi, Thailand
                [9 ]Faculty of Veterinary Science, Mahidol University, Nakhon Pathom, Thailand
                University of Georgia, United States of America
                Author notes

                Conceived and designed the experiments: P. Puthavathana. Performed the experiments: HL P. Pooruk SK PN. Analyzed the data: HL P. Puthavathana. Wrote the paper: P. Puthavathana HL SI. Specimen providers: CP AM SI PT UK PA KC SO WP PS TC CS SL. Processing on ethical issue: PA. Veterinarian: WW.

                Article
                PONE-D-10-02834
                10.1371/journal.pone.0016164
                3026791
                21283570
                2114ebb0-6063-4962-b8ac-7c7b1a28e1b5
                Lerdsamran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 24 September 2010
                : 7 December 2010
                Page count
                Pages: 9
                Categories
                Research Article
                Biology
                Immunology
                Immunity
                Humoral Immunity
                Immune Response
                Microbiology
                Virology
                Emerging Viral Diseases
                Viral Disease Diagnosis

                Uncategorized
                Uncategorized

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