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Incidence and Epidemiology of Hospitalized Influenza Cases in Rural Thailand during the Influenza A (H1N1)pdm09 Pandemic, 2009–2010  [PDF]
Henry C. Baggett, Malinee Chittaganpitch, Somsak Thamthitiwat, Prabda Prapasiri, Sathapana Naorat, Pongpun Sawatwong, Darunee Ditsungnoen, Sonja J. Olsen, James M. Simmerman, Prasong Srisaengchai, Somrak Chantra, Leonard F. Peruski, Pathom Sawanpanyalert, Susan A. Maloney, Pasakorn Akarasewi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048609
Abstract: Background Data on the burden of the 2009 influenza pandemic in Asia are limited. Influenza A(H1N1)pdm09 was first reported in Thailand in May 2009. We assessed incidence and epidemiology of influenza-associated hospitalizations during 2009–2010. Methods We conducted active, population-based surveillance for hospitalized cases of acute lower respiratory infection (ALRI) in all 20 hospitals in two rural provinces. ALRI patients were sampled 1:2 for participation in an etiology study in which nasopharyngeal swabs were collected for influenza virus testing by PCR. Results Of 7,207 patients tested, 902 (12.5%) were influenza-positive, including 190 (7.8%) of 2,436 children aged <5 years; 86% were influenza A virus (46% A(H1N1)pdm09, 30% H3N2, 6.5% H1N1, 3.5% not subtyped) and 13% were influenza B virus. Cases of influenza A(H1N1)pdm09 first peaked in August 2009 when 17% of tested patients were positive. Subsequent peaks during 2009 and 2010 represented a mix of influenza A(H1N1)pdm09, H3N2, and influenza B viruses. The estimated annual incidence of hospitalized influenza cases was 136 per 100,000, highest in ages <5 years (477 per 100,000) and >75 years (407 per 100,000). The incidence of influenza A(H1N1)pdm09 was 62 per 100,000 (214 per 100,000 in children <5 years). Eleven influenza-infected patients required mechanical ventilation, and four patients died, all adults with influenza A(H1N1)pdm09 (1) or H3N2 (3). Conclusions Influenza-associated hospitalization rates in Thailand during 2009–10 were substantial and exceeded rates described in western countries. Influenza A(H1N1)pdm09 predominated, but H3N2 also caused notable morbidity. Expanded influenza vaccination coverage could have considerable public health impact, especially in young children.
Dynamic Patterns of Circulating Seasonal and Pandemic A(H1N1)pdm09 Influenza Viruses From 2007–2010 in and around Delhi, India  [PDF]
Shobha Broor, Anand Krishnan, Dipanjan S. Roy, Shivram Dhakad, Samander Kaushik, Muneer A. Mir, Yashpal Singh, Ann Moen, Mandeep Chadha, Akhilesh C. Mishra, Renu B. Lal
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029129
Abstract: Influenza surveillance was carried out in a subset of patients with influenza-like illness (ILI) presenting at an Employee Health Clinic (EHS) at All India Institute of Medical Sciences (AIIMS), New Delhi (urban) and pediatric out patients department of civil hospital at Ballabhgarh (peri-urban), under the Comprehensive Rural Health Services Project (CRHSP) of AIIMS, in Delhi region from January 2007 to December 2010. Of the 3264 samples tested, 541 (17%) were positive for influenza viruses, of which 221 (41%) were pandemic Influenza A(H1N1)pdm09, 168 (31%) were seasonal influenza A, and 152 (28%) were influenza B. While the Influenza viruses were detected year-round, their types/subtypes varied remarkably. While there was an equal distribution of seasonal A(H1N1) and influenza B in 2007, predominance of influenza B was observed in 2008. At the beginning of 2009, circulation of influenza A(H3N2) viruses was observed, followed later by emergence of Influenza A(H1N1)pdm09 with co-circulation of influenza B viruses. Influenza B was dominant subtype in early 2010, with second wave of Influenza A(H1N1)pdm09 in August-September, 2010. With the exception of pandemic H1N1 emergence in 2009, the peaks of influenza activity coincided primarily with monsoon season, followed by minor peak in winter at both urban and rural sites. Age group analysis of influenza positivity revealed that the percent positivity of Influenza A(H1N1)pdm09 influenza virus was highest in >5–18 years age groups (OR 2.5; CI = 1.2–5.0; p = 0.009) when compared to seasonal influenza. Phylogenetic analysis of Influenza A(H1N1)pdm09 from urban and rural sites did not reveal any major divergence from other Indian strains or viruses circulating worldwide. Continued surveillance globally will help define regional differences in influenza seasonality, as well as, to determine optimal periods to implement influenza vaccination programs among priority populations.
Burden of Seasonal and Pandemic Influenza-Associated Hospitalization during and after 2009 A(H1N1)pdm09 Pandemic in a Rural Community in India  [PDF]
Mandeep S. Chadha, Siddhivinayak Hirve, Fatimah S. Dawood, Pallavi Lele, Avinash Deoshatwar, Somnath Sambhudas, Sanjay Juvekar, Kathryn E. LaFond, Joshua A. Mott, Renu B. Lal, Akhilesh C. Mishra
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055918
Abstract: Background Influenza is vaccine-preventable; however, the burden of severe influenza in India remains unknown. We conducted a population-based study to estimate the incidence of laboratory confirmed influenza-associated hospitalizations in a rural community in western India. Methods We conducted active surveillance for hospitalized patients with acute medical illnesses or acute chronic disease exacerbations in Pune during pandemic and post pandemic periods (May 2009–April 2011). Nasal and throat swabs were tested for influenza viruses. A community health utilization survey estimated the proportion of residents hospitalized with respiratory illness at non-study facilities and was used to adjust incidence estimates from facility-based surveillance. Results Among 9,426 hospitalizations, 3,391 (36%) patients were enrolled; 665 of 3,179 (20.9%) tested positive for influenza. Of 665 influenza positives, 340 (51%) were pandemic A(H1N1)pdm09 and 327 (49%) were seasonal, including A/H3 (16%), A/H1 (3%) and influenza B (30%). The proportion of patients with influenza peaked during August 2009 (39%) and 2010 (42%). The adjusted annual incidence of influenza hospitalizations was 46.8/10,000 during pandemic and 40.5/10,000 during post-pandemic period with comparable incidence of A(H1N1)pdm09 during both periods (18.8 and 20.3, respectively). The incidence of both pH1N1 and seasonal hospitalized influenza disease was highest in the 5–29 year olds. Conclusions We document the previously unrecognized burden of influenza hospitalization in a rural community following the emergence of influenza A(H1N1)pdm09 viruses in India. During peak periods of influenza activity circulation i.e during the monsoon period, 20% of all hospital admissions in the community had influenza positivity. These findings can inform development of influenza prevention and control strategies in India.
Reconstruction of the Evolutionary Dynamics of the A(H1N1)pdm09 Influenza Virus in Italy during the Pandemic and Post-Pandemic Phases  [PDF]
Gianguglielmo Zehender, Elena Pariani, Antonio Piralla, Alessia Lai, Elena Gabanelli, Alberto Ranghiero, Erika Ebranati, Antonella Amendola, Giulia Campanini, Francesca Rovida, Massimo Ciccozzi, Massimo Galli, Fausto Baldanti, Alessandro Remo Zanetti
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0047517
Abstract: The aim of this study was to reconstruct the evolutionary dynamics of the A(H1N1)pdm09 influenza virus in Italy during two epidemic seasons (2009/2010 and 2010/2011) in the light of the forces driving the evolution of the virus. Nearly six thousands respiratory specimens were collected from patients with influenza-like illness within the framework of the Italian Influenza Surveillance Network, and the A(H1N1)pdm09 hemagglutinin (HA) gene was amplified and directly sequenced from 227 of these. Phylodynamic and phylogeographical analyses were made using a Bayesian Markov Chain Monte Carlo method, and codon-specific positive selection acting on the HA coding sequence was evaluated. The global and local phylogenetic analyses showed that all of the Italian sequences sampled in the post-pandemic (2010/2011) season grouped into at least four highly significant Italian clades, whereas those of the pandemic season (2009/2010) were interspersed with isolates from other countries at the tree root. The time of the most recent common ancestor of the strains circulating in the pandemic season in Italy was estimated to be between the spring and summer of 2009, whereas the Italian clades of the post-pandemic season originated in the spring of 2010 and showed radiation in the summer/autumn of the same year; this was confirmed by a Bayesian skyline plot showing the biphasic growth of the effective number of infections. The local phylogeography analysis showed that the first season of infection originated in Northern Italian localities with high density populations, whereas the second involved less densely populated localities, in line with a gravity-like model of geographical dispersion. Two HA sites, codons 97 and 222, were under positive selection. In conclusion, the A(H1N1)pdm09 virus was introduced into Italy in the spring of 2009 by means of multiple importations. This was followed by repeated founder effects in the post-pandemic period that originated specific Italian clades.
Association of Killer Cell Immunoglobulin-Like Receptor Genes with Pandemic Influenza A (H1N1)pdm09 Infection in Critically Ill Macedonian Patients
Aleksandar Petlichkovski,Zvonko Milenkovic,Eli Djulejic,Bisera Jefremovska
Macedonian Journal of Medical Sciences , 2012,
Abstract: Background: Infection by the pandemic influenza A (H1N1)pdm09 virus results in significant pathology disease in many cases in different populations worldwide. The natural killer (NK) cells are among the major effectors important in early innate immune responses to viral infections, interacting with host cells through their activating or inhibiting receptors. Aim: The aim of this study was to analyze Killer Ig-Like Receptor (KIR) gene polymorphisms in critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection. Material and Methods: The studied sample consists of 63 critically ill Macedonian patients with pandemic influenza A (H1N1)pdm09 infection. The population genetics analysis package, Arlequin, was used for analysis of the data. Results: We found that all 16 KIR genes were observed in the studied individuals and framework genes (KIR3DL3, KIR3DP1, KIR2DL4, and KIR3DL2) were present in all individuals. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. Comparison of KIR gene frequencies between critically ill H1N1/09 Macedonian patients and healthy subjects reveals statistically significant difference for frequency of KIR2DL1 (F=1 in the patients group, and 0.94 in the control group, p=0.045).Conclusion: We did not found any significant association of all 16 KIR genes or KIR genotypes with critically ill (H1N1)pdm09 Macedonian patients, except for the KIR2DL1.
The Spread of Influenza A(H1N1)pdm09 in Victorian School Children in 2009: Implications for Revised Pandemic Planning  [PDF]
James E. Fielding, Isabel Bergeri, Nasra Higgins, Heath A. Kelly, Julian Meagher, Emma S. McBryde, Rodney Moran, Margaret E. Hellard, Rosemary A. Lester
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057265
Abstract: Background Victoria was the first state in Australia to experience community transmission of influenza A(H1N1)pdm09. We undertook a descriptive epidemiological analysis of the first 1,000 notified cases to describe the epidemic associated with school children and explore implications for school closure and antiviral distribution policy in revised pandemic plans. Methods Records of the first 1,000 laboratory-confirmed cases of influenza A(H1N1)pdm09 notified to the Victorian Government Department of Health between 20 May and 5 June 2009 were extracted from the state’s notifiable infectious diseases database. Descriptive analyses were conducted on case demographics, symptoms, case treatment, prophylaxis of contacts and distribution of cases in schools. Results Two-thirds of the first 1,000 cases were school-aged (5–17 years) with cases in 203 schools, particularly along the north and western peripheries of the metropolitan area. Cases in one school accounted for nearly 8% of all cases but the school was not closed until nine days after symptom onset of the first identified case. Amongst all cases, cough (85%) was the most commonly reported symptom followed by fever (68%) although this was significantly higher in primary school children (76%). The risk of hospitalisation was 2%. The median time between illness onset and notification of laboratory confirmation was four days, with only 10% of cases notified within two days of onset and thus eligible for oseltamivir treatment. Nearly 6,000 contacts were followed up for prophylaxis. Conclusions With a generally mild clinical course and widespread transmission before its detection, limited and short-term school closures appeared to have minimal impact on influenza A(H1N1)pdm09 transmission. Antiviral treatment could rarely be delivered to cases within 48 hours of symptom onset. These scenarios and lessons learned from them need to be incorporated into revisions of pandemic plans.
Pandemic Influenza A(H1N1)pdm09 Seroprevalence in Sweden before and after the Pandemic and the Vaccination Campaign in 2009  [PDF]
Andreas M?rner, Andreas Br?ve, Anna-Maria Kling, Sharon Kühlmann-Berenzon, Katarina Krook, Mona Hedenskog, Irene Silhammar, Margaretha Ljungman, ?ke ?rtqvist, S?ren Andersson, Maria Brytting, Rigmor Thorstensson, Annika Linde
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0053511
Abstract: The immunity to pandemic influenza A(H1N1)pdm09 in Sweden before and after the outbreaks in 2009 and 2010 was investigated in a seroepidemiological study. Serum samples were collected at four time points: during 2007 (n = 1968), in October 2009 (n = 2218), in May 2010 (n = 2638) and in May 2011 (n = 2513) and were tested for hemagglutination inhibition (HI) antibodies. In 2007, 4.9% of the population had pre-existing HI titres ≥40, with the highest prevalence (20.0%) in 15–24 year-olds, followed by ≥80 year-olds (9.3%). The overall prevalence of HI titres ≥40 had not changed significantly in October 2009. In May 2010 the prevalence had increased to 48.6% with the highest percentages in 5–14 year-olds (76.2%) andlowest in 75–79 year-olds (18.3%). One year later the prevalence of HI titres ≥40 had increased further to 52.2%. Children 5–14 years had the highest incidence of infection and vaccine uptake as well as the highest post-pandemic protective antibody levels. In contrast, the elderly had high vaccine uptake and low attack rate but low levels of protective antibodies, underlining that factors other than HI antibodies are involved in protection against influenza A(H1N1)pdm09. However, for all age-groups the seroprevalence was stable or increasing between 2010 and 2011, indicating that both vaccine- and infection-induced antibodies were long-lived.
Usefulness of health registries when estimating vaccine effectiveness during the influenza A(H1N1)pdm09 pandemic in Norway
Bernardo Guzmán Herrador, Preben Aavitsland, Berit Feiring, Marianne A Riise Bergsaker, Katrine Borgen
BMC Infectious Diseases , 2012, DOI: 10.1186/1471-2334-12-63
Abstract: We conducted a population-based retrospective cohort study, linking MSIS and SYSVAK with pandemic influenza vaccination as exposure and laboratory-confirmed pandemic influenza as outcome. We measured VE by week and defined two thresholds for immunity; eight and 15 days after vaccination.The weekly VE ranged from 77% to 96% when considering 15 days or more after vaccination as the threshold of immunity and from 73% to 94% when considering eight days or more. Overall, 157 individuals contracted pandemic influenza eight or more days after vaccination (8.4/100,000 vaccinated), of these 58 had onset 15 days or more after vaccination (3.0/100,000 vaccinated). Most of the vaccine failures occurred during the first weeks of the vaccination campaign. More than 30% of the vaccine failures were found in people below 10 years of age.Having available health registries with data regarding cases of specific disease and vaccination makes it feasible to estimate VE in a simple and rapid way. VE was high regardless the immunity threshold chosen. We encourage public health authorities in other countries to set up such registries. It is also important to consider including information on underlying diseases in registries already existing, in order to make it feasible to conduct more complete VE estimations.During the 2009-2010 influenza pandemic, surveillance for influenza in Norway was enhanced: laboratory-confirmed infection with the new A(H1N1)pdm09 virus was defined as a mandatory notifiable disease on a case based level. During the pandemic, doctors from all health care settings were encouraged to swab patients with suspected influenza and submit the samples to their nearest clinical microbiology laboratory. Each laboratory-confirmed case had to be notified to the Norwegian Institute of Public Health (NIPH), where it was registered in the Norwegian Surveillance System for Communicable Diseases (MSIS) with the unique personal identification number (PIN). Criteria for sampling suspe
Polymorphisms at Residue 222 of the Hemagglutinin of Pandemic Influenza A(H1N1)pdm09: Association of Quasi-Species to Morbidity and Mortality in Different Risk Categories  [PDF]
Paola Cristina Resende, Fernando C. Motta, Maria de Lourdes A. Oliveira, Tatiana S. Gregianini, Sandra B. Fernandes, Ana Luisa F. Cury, Maria do Carmo D. Rosa, Thiago Moreno L. Souza, Marilda M. Siqueira
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092789
Abstract: The D222G substitution in the hemagglutinin (HA) gene of the pandemic influenza A(H1N1)pdm09 virus has been identified as a potential virulence marker, because this change allows for virus invasion deeper into the respiratory tract. In this study, we analyzed D, G and N polymorphisms at residue 222 by pyrosequencing (PSQ). We initially analyzed 401 samples from Brazilian patients. These were categorized with respect to clinical conditions due to influenza infection (mild, serious or fatal) and sub-stratified by risky factors. The frequency of mixed population of virus, with more than one polymorphism at residue 222, was significantly higher in serious (10.6%) and fatal (46.7%) influenza cases, whereas those who showed mild influenza infections were all infected by D222 wild-type. Mixtures of quasi-species showed a significant association of mortality, especially for those with risk factors, in special pregnant women. These results not only reinforce the association between D222G substitution and influenza A(H1N1)pdm09-associated morbidity and mortality, but also add the perspective that a worse clinical prognosis is most likely correlated with mixtures of quasi-species at this HA residue. Therefore, quasi-species may have a critical and underestimated role in influenza-related clinical outcomes.
Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses  [PDF]
Jeff Butler,Kathryn A. Hooper,Stephen Petrie,Raphael Lee,Sebastian Maurer-Stroh,Lucia Reh,Teagan Guarnaccia,Chantal Baas,Lumin Xue,Sophie Vitesnik,Sook-Kwan Leang,Jodie McVernon,Anne Kelso,Ian G. Barr,James M. McCaw,Jesse D. Bloom,Aeron C. Hurt
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004065
Abstract: Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide.
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