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Epidemiological Characterization of Influenza A(H1N1)pdm09 Cases from 2009 to 2010 in Baguio City, the Philippines  [PDF]
Rochelle R. Pamaran, Taro Kamigaki, Teresita T. Hewe, Korrine Madeleine C. Flores, Edelwisa S. Mercado, Portia P. Alday, Alvin G. Tan, Hitoshi Oshitani, Remigio M. Olveda, Veronica L. Tallo
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079916
Abstract: Background Baguio City, Philippines experienced its first influenza A(H1N1)pdm09 [A(H1)pdm09] case in May 2009. In spite of numerous reports describing the epidemiological and clinical features of A(H1)pdm09 cases, there are no studies about A(H1)pdm09 epidemiology in the Philippines, where year-round influenza activity was observed. Objectives We aimed to investigate the epidemiological and clinical features of A(H1)pdm09 in pandemic and post-pandemic periods. Methods Data were collected under enhanced surveillance of influenza-like illness (ILI) and severe acute respiratory infection (SARI) from January 2009 to December 2010. RT-PCR was used to detect A(H1)pdm09, following the protocol of the United States Centers for Disease Control and Prevention. The reproduction number was computed as a simple exponential growth rate. Differences in proportional and categorical data were examined using chi-square test or Fishers’ exact test. Results and Conclusions The outbreak was observed from week 25 to 35 in 2009 and from week 24 to 37 in 2010. The highest proportion of cases was among children aged 5–14 years. The number of ILI outpatients was 2.3-fold higher in 2009 than in 2010, while the number of inpatients was 1.8-fold higher in 2009. No significant difference in gender was observed during the two periods. The clinical condition of all patients was generally mild and self-limiting, with only 2 mortalities among inpatients in 2009. The basic reproduction number was estimated as 1.16 in 2009 and 1.05 in 2010 in the assumption of mean generation time as 2.6 days. School children played a significant role in facilitating influenza transmission.
Serological Response of Patients with Influenza A (H1N1) pdm09-Associated Pneumonia: An Observational Study  [PDF]
Nasikarn Angkasekwinai, Bualan Kaewnapha, Duangdao Waywa, Peerawong Werarak, Sasima Tongsai, Kulkanya Chokephaibulkit, Visanu Thamlikitkul, Sontana Siritantikorn
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081436
Abstract: Background Little is known about the dynamics or magnitude of antibody response in patients with influenza A (H1N1) pdm09-associated pneumonia. We described and compared the antibody response to influenza A (H1N1) pdm09 in patients with and without pneumonia. Methods We collected serum samples and determined antibody titers by the hemagglutination inhibition (HI) and microneutralization (mNT) assays from patients with RT-PCR confirmed influenza A (H1N1) pdm09 virus at baseline, 1, 2 and 6 months after onset of illness. Results Fifty-nine patients were enrolled, 45 (76.3%) were between 15 and 60 years of age, 49 (83.1%) were hospitalized and 25 (42.4%) had complications with pneumonia. Ninety-four percent of patients had HI titers ≥ 1: 40 and 90% had mNT titers ≥ 1: 160 at 2 months after illness. Geometric mean titers (GMT) of HI and mNT increased significantly (p<0.001) between baseline and months 1 or 2, then declined significantly (p<0.001) at month 6 by the HI assay, but dropped to an insignificant level (p=0.24) by the mNT assay. The mNT-GMT was at least twice as high as corresponding HI antibodies over a 6 month period. The GMT of HI and mNT in those with pneumonia (1 mo) peaked earlier than that of those without pneumonia (2 mo). When adjusted by age and gender, those with pneumonia had a higher HI-GMT than those without pneumonia at 1 month (264 vs. 117, p=0.007), 2 months (212 vs. 159, p=0.013), and 6 months (160 vs. 82, p=0.018). Conclusions The patients recovered from influenza A (H1N1) pdm09-associated pneumonia, clearly developed an earlier and more robust antibody response until 6 months after onset of illness. The results in our study are useful to determine an appropriate donor and timing to obtain convalescent plasma for adjunctive treatment of seriously ill patients with pandemic H1N1 influenza.
Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies  [PDF]
Ruth Lynfield, Richard Davey, Dominic E. Dwyer, Marcelo H. Losso, Deborah Wentworth, Alessandro Cozzi-Lepri, Kathy Herman-Lamin, Grazyna Cholewinska, Daniel David, Stefan Kuetter, Zelalem Ternesgen, Timothy M. Uyeki, H. Clifford Lane, Jens Lundgren, James D. Neaton, for the INSIGHT Influenza Study Group
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101785
Abstract: Background Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. Methods and Findings Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1–3) and 6 days (IQR 4–10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4–7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5–26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. Conclusions Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. Trial Registration ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185.
The Association between Serum Biomarkers and Disease Outcome in Influenza A(H1N1)pdm09 Virus Infection: Results of Two International Observational Cohort Studies  [PDF]
Richard T. Davey, Ruth Lynfield, Dominic E. Dwyer, Marcello H. Losso, Alessandro Cozzi-Lepri, Deborah Wentworth, H. Clifford Lane, Robin Dewar, Adam Rupert, Julia A. Metcalf, Sarah L. Pett, Timothy M. Uyeki, Jose Maria Bruguera, Brian Angus, Nathan Cummins, Jens Lundgren, James D. Neaton, INSIGHT FLU 002 & 003 Study Groups
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057121
Abstract: Background Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. Methods Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. Results In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3rd versus 1st tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3rd versus 1st tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. Conclusions In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome.
Effectiveness of MF59? Adjuvanted Influenza A(H1N1)pdm09 Vaccine in Risk Groups in the Netherlands  [PDF]
Leonoor Wijnans, Jeanne Dieleman, Bettie Voordouw, Miriam Sturkenboom
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063156
Abstract: Background The aim of the present study was to estimate the effectiveness of the MF59?-adjuvanted influenza A(H1N1)pdm09 vaccine against medically attended influenza-like illness and RT-PCR confirmed influenza in the at-risk population and persons over 60 in the Netherlands. Methods We conducted a retrospective cohort study in a Dutch based GP medical record database between 30 November 2009 and 1 March 2010 to estimate the vaccine effectiveness against influenza-like illness. Within the cohort we nested a test negative case-control study to estimate the effectiveness against laboratory confirmed influenza. Results The crude effectiveness in preventing diagnosed or possible influenza-like illness was 17.3% (95%CI: ?8.5%–36.9%). Of the measured covariates, age, the severity of disease and health seeking behaviour through devised proxies confounded the association between vaccination and influenza-like illness. The adjusted vaccine effectiveness was 20.8% (95%CI: ?5.4%, 40.5%) and varied significantly by age, being highest in adults up to 50 years (59%, 95%CI: 23%, 78%), and non-detectable in adults over 50 years. The number of cases in the nested case control study was too limited to validly estimate the VE against confirmed influenza. Conclusions With our study we demonstrated that the approach of combining a cohort study in a primary health care database with field sampling is a feasible and useful option to monitor VE of influenza vaccines in the future.
Effectiveness of A(H1N1)pdm09 Influenza Vaccine in Adults Recommended for Annual Influenza Vaccination  [PDF]
Giedre Gefenaite, Margot Tacken, Jens Bos, Irina Stirbu-Wagner, Joke C. Korevaar, Ronald P. Stolk, Bert Wolters, Marc Bijl, Maarten J. Postma, Jan Wilschut, Kristin L. Nichol, Eelko Hak
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066125
Abstract: Introduction Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. Methods VE against influenza and/or pneumonia was assessed in the cohort study (n>25000), and vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza was assessed in a matched case-control study (16 pairs). Odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated by using multivariate logistic regression; vaccine effectiveness was estimated as (1-odds ratio)*100%. Results Vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia was 98% (84–100%) and 33% (2–54%) respectively. The vaccine did not prevent influenza and/or pneumonia in 18–59 years old subjects, and was 49% (16–69%) effective in 60 years and older subjects. Conclusions Even though we cannot entirely rule out that selection bias, residual confounding and/or cross-protection has played a role, the present results indicate that the MF59-adjuvanted A(H1N1)pdm09 influenza vaccine has been effective in preventing laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia, the latter notably in 60 years and older subjects.
Analysis of fatal outcomes from influenza A(H1N1)pdm09 in Mongolia  [cached]
Jantsansengeegiin Baigalmaa,Tseesurengiin Tuul,Badarchyn Darmaa,Erdenebaatariin Soyolmaa
Western Pacific Surveillance and Response , 2012,
Abstract: Introduction: While influenza A(H1N1)pdm09 usually causes mild illness in the majority of people, there have been reports of severe cases and deaths. As there is no documented evidence on fatal outcomes from influenza in Mongolia previously, we aimed to describe the epidemiology of fatal influenza A(H1N1)pdm09 cases to provide recommendations to assist the national influenza prevention and control strategy.Methods: We selected influenza A(H1N1)pdm09-confirmed deaths in hospitals between 12 October 2009 and 31 January 2010 in Mongolia from the national influenza surveillance system. The mortality rate and case fatality rate (CFR) of influenza A(H1N1)pdm09-hospitalized deaths were calculated. Using country prevalence of pregnancy and chronic diseases, we calculated the relative risk of death from influenza A(H1N1)pdm09.Results: There were 29 deaths with a mortality rate of 1.0 per 100 000 population during the study period, which was highest in children under five and the middle-aged population. Crude CFR was 2.2%. Of all fatal cases, 62% had at least one underlying condition. Most (62%) were provided antivirals, although none received these within 48 hours of symptom onset. Prevalence for pregnancy, cardiovascular and chronic liver diseases was five to 50 times higher in fatal cases compared to country prevalence.Discussion: Mortality and crude CFR in our study was higher than in other studies. However, due to the diagnostic policy change during the epidemic, this estimate is likely to have overestimated actual case fatalities. Pregnancy, cardiovascular and chronic liver diseases were suggestive risk factors for death from influenza A(H1N1)pdm09. Strengthening hospital-based influenza surveillance is important in predicting severity of an epidemic and responding to influenza epidemics in a timely and appropriate manner.
Influenza A(H1N1)pdm09-Associated Pneumonia Deaths in Thailand  [PDF]
Charatdao Bunthi, Somsak Thamthitiwat, Henry C. Baggett, Pasakorn Akarasewi, Ruchira Ruangchira-urai, Susan A. Maloney, Kumnuan Ungchusak
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054946
Abstract: Background The first human infections with influenza A(H1N1)pdm09 virus were confirmed in April 2009. We describe the clinical and epidemiological characteristics of influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand from May 2009-January 2010. Methods We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance system and performed detailed reviews of a subset. Results Of 198 deaths reported, 49% were male and the median age was 37 years; 146 (73%) were 20–60 years. Among 90 deaths with records available for review, 46% had no identified risk factors for severe influenza. Eighty-eight patients (98%) received antiviral treatment, but only 16 (18%) initiated therapy within 48 hours of symptom onset. Conclusions Most influenza A(H1N1)pdm09 pneumonia fatalities in Thailand occurred in adults aged 20–60 years. Nearly half lacked high-risk conditions. Antiviral treatment recommendations may be especially important early in a pandemic before vaccine is available. Treatment should be considered as soon as influenza is suspected.
Reproductive Number and Serial Interval of the First Wave of Influenza A(H1N1)pdm09 Virus in South Africa  [PDF]
Brett N. Archer, Stefano Tempia, Laura F. White, Marcello Pagano, Cheryl Cohen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049482
Abstract: Background/Objective Describing transmissibility parameters of past pandemics from diverse geographic sites remains critical to planning responses to future outbreaks. We characterize the transmissibility of influenza A(H1N1)pdm09 (hereafter pH1N1) in South Africa during 2009 by estimating the serial interval (SI), the initial effective reproductive number (initial Rt) and the temporal variation of Rt. Methods We make use of data from a central registry of all pH1N1 laboratory-confirmed cases detected throughout South Africa. Whenever date of symptom onset is missing, we estimate it from the date of specimen collection using a multiple imputation approach repeated 100 times for each missing value. We apply a likelihood-based method (method 1) for simultaneous estimation of initial Rt and the SI; estimate initial Rt from SI distributions established from prior field studies (method 2); and the Wallinga and Teunis method (method 3) to model the temporal variation of Rt. Results 12,360 confirmed pH1N1 cases were reported in the central registry. During the period of exponential growth of the epidemic (June 21 to August 3, 2009), we simultaneously estimate a mean Rt of 1.47 (95% CI: 1.30–1.72) and mean SI of 2.78 days (95% CI: 1.80–3.75) (method 1). Field studies found a mean SI of 2.3 days between primary cases and laboratory-confirmed secondary cases, and 2.7 days when considering both suspected and confirmed secondary cases. Incorporating the SI estimate from field studies using laboratory-confirmed cases, we found an initial Rt of 1.43 (95% CI: 1.38–1.49) (method 2). The mean Rt peaked at 2.91 (95% CI: 0.85–2.91) on June 21, as the epidemic commenced, and Rt>1 was sustained until August 22 (method 3). Conclusions Transmissibility characteristics of pH1N1 in South Africa are similar to estimates reported by countries outside of Africa. Estimations using the likelihood-based method are in agreement with field findings.
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.
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