Influenza Research and Treatment

Point-of-Care Testing as an Influenza Surveillance Tool: Methodology and Lessons Learned from Implementation

Thu, 11 Apr 2013 10:41:29 +0000

Objectives. Disease surveillance combines data collection and analysis with dissemination of findings to decision makers. The timeliness of these activities affects the ability to implement preventive measures. Influenza surveillance has traditionally been hampered by delays in both data collection and dissemination. Methods. We used statistical process control (SPC) to evaluate the daily percentage of outpatient visits with a positive point-of-care (POC) influenza test in the University of Utah Primary Care Research Network. Results. Retrospectively, POC testing generated an alert in each of 4 seasons (2004–2008, median 16 days before epidemic onset), suggesting that email notification of clinicians would be 9 days earlier than surveillance alerts posted to the Utah Department of Health website. In the 2008-09 season, the algorithm generated a real-time alert 19 days before epidemic onset. Clinicians in 4 intervention clinics received email notification of the alert within 4 days. Compared with clinicians in 6 control clinics, intervention clinicians were 40% more likely to perform rapid testing () and twice as likely to vaccinate for seasonal influenza () after notification. Conclusions. Email notification of SPC-generated alerts provided significantly earlier notification of the epidemic onset than traditional surveillance. Clinician preventive behavior was not significantly different in intervention clinics.

Monoclonal Antibody Targeting Neutralizing Epitope on H5N1 Influenza Virus of Clade 1 and 0 for Specific H5 Quantification

Fang He and Jimmy Kwang — Tue, 05 Mar 2013 13:25:52 +0000

H5N1 influenza viruses cause high mortality in avian and mammalian species, including humans. Antigenic drift in H5 sequence poses challenges in the development of vaccine and therapeutic antibody. In this study, a monoclonal antibody 11G12 was produced from inactivated H5N1 immunized mice. Results from IFA, ELISA, HI, and virus neutralization indicated that Mab 11G12 can specifically recognize and neutralize H5 type hemagglutinin from clade 1 and 0 without any cross-reaction to any other clades of H5N1 viruses. Mab 11G12 was used to differentiate and quantify the expression of H5N1 strain A/VietNam/1203/04 from a trivalent vaccine mix in ELISA. Sequencing of escape mutants identified that Mab 11G12 targets a major neutralizing epitope of influenza H5 hemagglutinin. The study indicated that some major neutralizing epitopes in H5s of early strains were mutated due to antigenic drift.

Comparing Deaths from Influenza H1N1 and Seasonal Influenza A: Main Sociodemographic and Clinical Differences between the Most Prevalent 2009 Viruses

Sun, 30 Dec 2012 16:09:27 +0000

Background. During the 2009 spring epidemic outbreak in Mexico, an important research and policy question faced was related to the differences in clinical profile and population characteristics of those affected by the new H1N1 virus compared with the seasonal virus. Methods and Findings. Data from clinical files from all influenza A deaths in Mexico between April 10 and July 13, 2009 were analyzed to describe differences in clinical and socioeconomic profile between H1N1 and non-H1N1 cases. A total of 324 influenza A mortality cases were studied of which 239 presented rt-PCR confirmation for H1N1 virus and 85 for seasonal influenza A. From the differences of means and multivariate logistic regression, it was found that H1N1 deaths occurred in younger and less educated people, and among those who engage in activities where there is increased contact with other unknown persons (OR 4.52, 95% CI 1.56–13.14). Clinical symptoms were similar except for dyspnea, headache, and chest pain that were less frequently found among H1N1 cases. Conclusions. Findings suggest that age, education, and occupation are factors that may be useful to identify risk for H1N1 among influenza cases, and also that patients with early dyspnea, headache, and chest pain are more likely to be non-H1N1 cases.

Genetic Analysis of Avian Influenza Viruses: Cocirculation of Avian Influenza Viruses with Allele A and B Nonstructural Gene in Northern Pintail (Anas acuta) Ducks Wintering in Japan

Tue, 25 Dec 2012 13:46:15 +0000

The pandemic influenza virus strains of 1918 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1) have genes related to avian influenza viruses (AIVs). The nonstructural (NS) gene of AIVs plays a significant role in host-viral interaction. However, little is known about the degree of diversity of this gene in Northern pintail (Anas acuta) ducks wintering in Japan. This study describes characteristics of pintail-originated H1N1, H1N2, H1N3, H5N2, H5N3, H5N9, and H7N7 viruses. Most of the viruses were revealed to be avian strains and not related to pandemic and seasonal flu strains. Nevertheless, the NP genes of 62.5% (5/8) viruses were found closely related to a A/swine/Korea/C12/08, indicating exchange of genetic material and ongoing mammalian-linked evolution of AIVs. Besides, all the viruses, except Aomori/422/07 H1N1, contain PSIQSR*GLF motif usually found in avian, porcine, and human H1 strains. The Aomori/422/07 H1N1 has a PSVQSR*GLF motif identical to a North American strain. This findings linked to an important intercontinental, Asian-American biogeographical interface. Phylogenetically all the viruses were clustered in Eurasian lineage. Cocirculation of allele A and B (NS gene) viruses was evident in the study implying the existence of a wide reservoir of influenza A viruses in pintail wintering in Japan.

Myocarditis Associated with Influenza A H1N1pdm2009

Akira Ukimura, Hidetoshi Satomi, Yukimasa Ooi, and Yumiko Kanzaki — Mon, 17 Dec 2012 09:15:21 +0000

Acute myocarditis is a well-known complication of influenza infection. The frequency of myocardial involvement in influenza infection varies widely, with the clinical severity ranging from asymptomatic to fulminant varieties. The worst cases can result in death due to impaired cardiac function, although such fulminant myocarditis associated with influenza infection is rare, as shown by previous papers. Following the 2009 influenza pandemic, we reported on the clinical features of a cohort of 15 patients in Japan with H1N1pdm2009 myocarditis. In our subsequent survey of the literature for case reports or series of patients with myocarditis associated with H1N1pdm2009, we identified 58 detailed cases. We discuss here the high prevalence of fulminant myocarditis (36/58, 62%) among patients reported to have myocarditis associated with H1N1pdm2009. Mechanical circulatory support was required in 17 of the patients with fulminant myocarditis, 13 of whom recovered. We stress the need for increased awareness of influenza-associated myocarditis; such knowledge will facilitate earlier diagnosis and treatment of this fatal complication during future influenza pandemics.

Factors Affecting Medical Students’ Uptake of the 2009 Pandemic Influenza A (H1N1) Vaccine

Wed, 28 Nov 2012 09:53:04 +0000

Background. Pandemic influenza vaccination rate amongst healthcare workers in England 2009/2010 was suboptimal (40.3%). Targeting medical students before they enter the healthcare workforce is an attractive future option. This study assessed the H1N1 vaccine uptake rate amongst medical students and factors that influenced this. Methods. Anonymised, self-administered questionnaire at a medical school. Results. The uptake rate amongst 126 medical students offered the vaccine was 49.2% and intended uptake amongst 77 students was 63.6%. Amongst those offered the vaccine, the strongest barriers to acceptance were fear of side effects (67.9%), lack of vaccine information (50.9%), lack of perceived risk (45.3%), and inconvenience (35.8%). Having a chronic illness (OR 3.4 (95% CI 1.2–10.2)), 4th/5th year of study (OR 3.0 (95% CI 1.3–7.1)), and correct H1N1 knowledge (OR 2.6 (95% CI 1.1–6.0)) were positively associated with uptake. Non-white ethnicity was an independent negative predictor of uptake (OR 0.4 (95% CI 0.2–0.8)). Students who accepted the H1N1 vaccine were three times more likely (OR 3.1 (95% CI 1.2–7.7)) to accept future seasonal influenza vaccination. Conclusion. Efforts to increase uptake should focus on routine introduction of influenza vaccine and creating a culture of uptake during medical school years, evidence-based education on vaccination, and improving vaccine delivery.

Factors Affecting Acceptance and Intention to Receive Pandemic Influenza A H1N1 Vaccine among Primary School Children: A Cross-Sectional Study in Birmingham, UK

Wed, 17 Oct 2012 09:41:41 +0000

UK pandemic influenza strategy focused on vaccination of high risk groups, although evidence shows that school-age children have the highest infection rates. Vaccination of children might be an additional strategy. We undertook a cross-sectional study amongst 149 parents of primary school children aged 4–7 years in Birmingham, UK to quantify intention to accept pandemic influenza vaccine and identify factors affecting uptake. Ninety-one (61.1%, 95% CI 52.8, 68.9) had or would accept vaccine for their child. The most common reasons for declining vaccine were concerns about safety (58.6% reported this), side effects (55.2%), or believing their child had already had swine flu (12.1%). Parents of nonwhite ethnicity (OR 2.4 (1.1, 5.0)) and with asthmatic children (OR 6.6 (1.4, 32.1)) were significantly more likely to accept pandemic vaccine, as were those whose children had ever received seasonal vaccine and those who believed swine flu to be a serious threat (OR 4.2 (1.9, 9.1)). Parents would be more likely to accept vaccination if they received a letter of invite, if the government strongly encouraged them, if it were administered at school, and if it were more thoroughly tested. Accurate media portrayal of safety of the vaccine during future pandemics will be essential.

Persistence of Avian Influenza Viruses in Various Artificially Frozen Environmental Water Types

Dany Shoham, Alam Jahangir, Sakchai Ruenphet, and Kazuaki Takehara — Thu, 04 Oct 2012 13:21:55 +0000

Background. This study investigates the viable persistence of avian influenza viruses (AIVs) in various types of artificially frozen environmental water and evaluates the feasibility of similar occurrence taking place in nature, and allowing for prolonged abiotic virus survival, with subsequent biotic viral recirculation. Methods. Fresh, brackish, and salty water, taken in Japan from aquatic biotopes regularly visited by migratory waterfowl, were seeded with AIVs. We monthly monitored the viability of the seeded viruses in the frozen state at −20°C and −30°C, for 12 months. We also monitored virus viability following repeatedly induced freezing and thawing. Results. The viruses exhibited considerable viable persistence all along that period of time, as well as during freezing-thawing cycles. Appreciable, yet noncrucial variances were observed in relation to some of the parameters examined. Conclusions. As typical waterborne pathogens of numerous northerly aquatic birds, AIVs are innately adapted to both the body temperature of their hosts (40°C to 42°C) and, presumably, to subzero temperatures of frozen lakes (down to −54°C in parts of Siberia) occupied and virus-seeded by subclinically infected birds, prior to freezing. Marked cryostability of AIVs appears to be evident. Preservation in environmental ice has significant ecophylogenetic and epidemiological implications, potentially, and could account for various unexplained phenomena.

Pediatric Influenza-Associated Deaths in New York State: Death Certificate Coding and Comparison to Laboratory-Confirmed Deaths

Dina Hoefer, Bryan Cherry, Marilyn Kacica, Kristi McClamroch, and Kimberly Kilby — Tue, 25 Sep 2012 19:18:58 +0000

Introduction. Surveillance for laboratory-confirmed influenza-associated deaths in children is used to monitor the severity of influenza at the population level and to inform influenza prevention and control policies. The goal of this study was to better estimate pediatric influenza mortality in New York state (NYS). Methods. Death certificate data were requested for all passively reported deaths and any pneumonia and influenza (P&I) coded pediatric deaths occurring between October 2004 and April 2010, excluding New York City (NYC) residents. A matching algorithm and capture-recapture analysis were used to estimate the total number of influenza-associated deaths among NYS children. Results. Thirty-four laboratory-confirmed influenza-associated pediatric deaths were reported and 67 death certificates had a P&I coded death; 16 deaths matched. No laboratory-confirmed influenza-associated death had a pneumonia code and no pneumonia coded deaths had laboratory evidence of influenza infection in their medical record. The capture-recapture analysis estimated between 38 and 126 influenza-associated pediatric deaths occurred in NYS during the study period. Conclusion. Passive surveillance for influenza-associated deaths continues to be the gold standard methodology for characterizing influenza mortality in children. Review of death certificates can complement but not replace passive reporting, by providing better estimates and detecting any missed laboratory-confirmed deaths.

Situation-Based Survey of Avian Influenza Viruses in Possible “Bridge” Species of Wild and Domestic Birds in Nigeria

Sun, 02 Sep 2012 08:26:04 +0000

The highly pathogenic avian influenza (H5N1 subtype) recurred in Nigeria after 9 months period of no reported case. A critical look at possible sources of the re-occurrence was desirable. The objective of this study was to determine whether avian influenza viruses were present at reasonably detectable levels (0.5%) in possible “bridge” species of wild and domestic birds. The study was conducted in 8 Nigerian states. A total of 403 birds from 40 species were sampled. Virus isolation was done in embryonated chicken eggs according to standard protocols. The test results were all negative for avian influenza viruses. The overall confidence interval (CI) calculated in R using the exact binomial confidence interval function was 0–0.007406. Tawny Eagle (Aquila rapax) was the lowest sampled 0.3% (1/403) and Red-billed Firefinch (Lagonosticta senegala) the highest 11.7% (47/403). The limitations of the sample size and possibly designing effects on the study, as to make concrete conclusions were acknowledged. Species of wild birds, so identified in the study could be useful in future surveys. Furthermore, multidisciplinary and community oriented approach, blending targeted and passive surveillances was suggested. This approach was envisaged to bring about wider coverage of “bridge” species and clearer insight of their possible roles in avian influenza re-occurrences and spread in Nigeria.

Influenza-Associated Mortality in Georgia (2009–2011)

Wed, 15 Aug 2012 12:52:02 +0000

We analyzed data from NCDCPH Georgia where samples from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory syndrome (SARI) are referred for testing on influenza virus using PCR analysis. During 2009-2010 and 2010-2011 influenza pandemics total number of the laboratory-confirmed influenza cases were 1286 with 33 deaths (all of them influenza type A) and 1203 (51.4% type A) with 44 deaths, respectively. At least one underlying medical condition was reported in 70.7% (for pandemic influenza strain) and 96% (for influenza type B) of deaths. Predominating preexisting condition was coronary heart disease.

Comparison of Human-Like H1 (𝛿-Cluster) Influenza A Viruses in the Swine Host

Sun, 03 Jun 2012 11:49:04 +0000

Influenza A viruses cause acute respiratory disease in swine. Viruses with H1 hemagglutinin genes from the human seasonal lineage (𝛿-cluster) have been isolated from North American swine since 2003. The objective of this work was to study the pathogenesis and transmission of 𝛿-cluster H1 influenza viruses in swine, comparing three isolates from different phylogenetic subclusters, geographic locations, and years of isolation. Two isolates from the 𝛿2 subcluster, A/sw/MN/07002083/07 H1N1 (MN07) and A/sw/IL/00685/05 H1N1 (IL05), and A/sw/TX/01976/08 H1N2 (TX08) from the 𝛿1 sub-cluster were evaluated. All isolates caused disease and were transmitted to contact pigs. Respiratory disease was apparent in pigs infected with MN07 and IL05 viruses; however, clinical signs and lung lesions were reduced in severity as compared to TX08. On day 5 following infection MN07-infected pigs had lower virus titers than the TX08 pigs, suggesting that although this H1N1 was successfully transmitted, it may not replicate as efficiently in the upper or lower respiratory tract. MN07 and IL05 H1N1 induced higher serum antibody titers than TX08. Greater serological cross-reactivity was observed for viruses from the same HA phylogenetic sub-cluster; however, antigenic differences between the sub-clusters may have implications for disease control strategies for pigs.

Influenza Vaccine Coverage among Pregnant Women in a Public Hospital System during the 2009-2010 Pandemic Influenza Season

Dean V. Coonrod, Blanca-Flor Jimenez, Amber N. Sturgeon, and David Drachman — Mon, 07 May 2012 14:18:43 +0000

The purpose of this study was to compare influenza vaccination rates of pregnant women in a public safety-net health system to national coverage rates during the 2009-2010 pandemic influenza season. A chart review of a random sample of deliveries was undertaken to determine rates of coverage and predictors of vaccine coverage of women who obtained prenatal care and delivered in our health system. Rates were calculated from deliveries from when the vaccine was first available through April 30, 2010. Coverage rates were 54% for the seasonal influenza vaccine and 51% for the H1N1 vaccine. Race/ethnicity, insurance status and language spoken did not predict the receipt of either vaccine. When we included only births which occurred through March 12, 2010, as was done in a large population-based study, the rates were 61% and 59%, respectively. Our rates are about 10% higher than the rates reported in that study. Our comprehensive strategy for promoting vaccine coverage achieved higher vaccination rates in a safety-net health system, which serves groups historically less likely to be vaccinated, than those reported for the pregnant population at large.

Clinical and Epidemiologic Characteristics of Hospitalized Patients with 2009 H1N1 Influenza Infection

Mon, 23 Apr 2012 10:47:54 +0000

Objective. 2009 H1N1 virus is a new virus that was firstly detected in April 2009. This virus spreads from human to human and causes a worldwide disease. This paper aimed to review the clinical and epidemiological properties of patients with 2009 H1N1 influenza who were hospitalized and monitored at Eskisehir Osmangazi University Faculty of Medicine Hospital. Setting. A 1000-bed teaching hospital in Eskisehir, Turkey. Patients-Methods. Between 05 November 2009–01 February 2010, 106 patients with 2009 H1N1 influenza, who were hospitalized, were prospectively evaluated. Results. Out of 106 patients who were hospitalized and monitored, 99 (93.4%) had fever, 86 (81.1%) had cough, 48 (45.3%) had shortness of breath, 47 (44.3%) had sore throat, 38 (35.8%) had body pain, 30 (28.3%) had rhinorrhea, 17 (16%) had vomiting, 15 (14.2%) had headache, and 14 (13.2%) had diarrhea. When the patients were examined in terms of risk factors for severe disease, 83 (78.3%) patients had at least one risk factor. During clinical monitoring, pneumonia was the most frequent complication with a rate of 66%. While 47.2% of the patients were monitored in intensive care unit, 34% of them required mechanical ventilation support. Conclusion. Patients with 2009 H1N1 influenza, who were hospitalized and monitored, should be carefully monitored and treated.

Influenza Vaccination in the Face of Immune Exhaustion: Is Herd Immunity Effective for Protecting the Elderly?

Sun, 29 Jan 2012 08:19:38 +0000

At the start of the 21st century, seasonal influenza virus infection is still a major public health concern across the world. The recent body of evidence confirms that trivalent inactivated influenza vaccines (TIVs) are not optimal within the population who account for approximately 90% of all influenza-related death: elderly and chronically ill individuals regardless of age. With the ever increasing aging of the world population and the recent fears of any pandemic influenza rife, great efforts and resources have been dedicated to developing more immunogenic vaccines and strategies for enhancing protection in these higher-risk groups. This paper describes the mechanisms that shape immune response at the extreme ages of life and how they have been taken into account to design more effective immunization strategies for these vulnerable populations. Furthermore, consideration will be given to how herd immunity may provide an effective strategy in preventing the burden of seasonal influenza infection within the aged population.

A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection

Thu, 12 Jan 2012 08:18:48 +0000

Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (𝑃<0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.

A Time Course for Susceptibility to Staphylococcus aureus Respiratory Infection during Influenza in a Swine Model

Wed, 11 Jan 2012 16:20:59 +0000

Bacterial superinfections following influenza A virus (IAV) are predominant causes of morbidity in humans. The recent emergence of methicillin-resistant Staphylococcus aureus (MRSA) and highly virulent IAV strains has reduced treatment options. Development of an appropriate animal model to study secondary S. aureus infections may provide important information regarding disease pathogenesis. Pigs are natural hosts to both IAV and S. aureus and have respiratory physiology and immune response comparable to humans. To establish a time course of susceptibility to S. aureus after IAV infection, nursery pigs infected intranasally with IAV were challenged with MRSA at different time points. Lung pathology scores and MRSA CFU were evaluated in dual-infected animals after IAV infection. Flow cytometric analysis of bronchoalveolar lavage fluid indicated differences between treatments. These results demonstrate the appropriateness of an intranasal challenge model in nursery pigs for studying the pathogenesis of IAV and S. aureus coinfection and provide insights into the timeframe for susceptibility of IAV-infected pigs to secondary S. aureus infection.

Experiences after Twenty Months with Pandemic Influenza A (H1N1) 2009 Infection in the Naïve Norwegian Pig Population

Tue, 03 Jan 2012 10:22:54 +0000

Pandemic (H1N1) 2009 influenza A virus was detected in Norwegian pigs in October 2009. Until then, Norway was regarded free of swine influenza. Intensified screening revealed 91 positive herds within three months. The virus was rapidly transmitted to the susceptible population, including closed breeding herds with high biosecurity. Humans were important for the introduction as well as spread of the virus to pigs. Mild or no clinical signs were observed in infected pigs. Surveillance of SIV in 2010 revealed that 41% of all the Norwegian pig herds had antibodies to pandemic (H1N1) 2009 virus. Furthermore, this surveillance indicated that pigs born in positive herds after the active phase did not seroconvert, suggesting no ongoing infection in the herds. However, results from surveillance in 2011 show a continuing spread of the infection in many herds, either caused by new introduction or by virus circulation since 2009.

Clinical Impact of Infection with Pandemic Influenza (H1N1) 2009 Virus in Naïve Nucleus and Multiplier Pig Herds in Norway

Thu, 22 Dec 2011 08:56:49 +0000

The Norwegian pig population has been free from influenza viruses until 2009. The pandemic influenza outbreak during the autumn 2009 provided an opportunity to study the clinical impact of this infection in an entirely naïve pig population. This paper describes the results of a case-control study on the clinical impact of pandemic influenza (H1N1) 2009 infection in the nucleus and multiplier herds in Norway. The infection spread readily and led to seroconversion of 42% of the Norwegian nucleus and multiplier herds within a year. Positive and negative herds were identified based on surveillance data from the Norwegian Veterinary Institute. Telephone interviews were conducted with pig herd owners or managers between November 2010 and January 2011. Pigs with clinical signs were reported from 40% of the case herds with varying morbidity and duration of respiratory disease and reduced reproductive performance. Clinical signs were reported in all age groups.

Pathological Findings and Distribution of Pandemic Influenza A (H1N1) 2009 Virus in Lungs from Naturally Infected Fattening Pigs in Norway

Mette Valheim, Hans Gamlem, Britt Gjerset, Anna Germundsson, and Bjørn Lium — Tue, 20 Dec 2011 08:59:43 +0000

The Norwegian pig population was considered free from influenza A virus infections until the first case of porcine pandemic influenza A (H1N1) 2009 virus infection in October 2009. Human to pig transmission of virus was suspected. Unusual lung lesions were observed in fattening pigs, with red, lobular, multifocal to coalescing consolidation, most frequently in the cranial, middle, and accessory lobes. The main histopathological findings were epithelial degeneration and necrosis, lymphocyte infiltration in the epithelial lining and lamina propria of small bronchi and bronchioles, and peribronchial and peribronchiolar lymphocyte infiltrations. Infection with pandemic influenza A (H1N1) 2009 virus was confirmed by real-time RT-PCR and immunohistochemical detection of influenza A virus nucleoprotein in the lesions. This investigation shows that natural infection with the pandemic influenza A (H1N1) 2009 virus induces lung lesions similar to lesions described in experimental studies and natural infections with other swine-adapted subtypes of influenza A viruses.

The Modes of Evolutionary Emergence of Primal and Late Pandemic Influenza Virus Strains from Viral Reservoir in Animals: An Interdisciplinary Analysis

Dany Shoham — Tue, 15 Nov 2011 13:53:28 +0000

Based on a wealth of recent findings, in conjunction with earliest chronologies pertaining to evolutionary emergences of ancestral RNA viruses, ducks, Influenzavirus A (assumingly within ducks), and hominids, as well as to the initial domestication of mallard duck (Anas platyrhynchos), jungle fowl (Gallus gallus), wild turkey (Meleagris gallopavo), wild boar (Sus scrofa), and wild horse (Equus ferus), presumed genesis modes of primordial pandemic influenza strains have multidisciplinarily been configured. The virological fundamentality of domestication and farming of those various avian and mammalian species has thereby been demonstrated and broadly elucidated, within distinctive coevolutionary paradigms. The mentioned viral genesis modes were then analyzed, compatibly with common denominators and flexibility that mark the geographic profile of the last 18 pandemic strains, which reputedly emerged since 1510, the antigenic profile of the last 10 pandemic strains since 1847, and the genomic profile of the last 5 pandemic strains since 1918, until present. Related ecophylogenetic and biogeographic aspects have been enlightened, alongside with the crucial role of spatial virus gene dissemination by avian hosts. A fairly coherent picture of primary and late evolutionary and genomic courses of pandemic strains has thus been attained, tentatively. Specific patterns underlying complexes prone to generate past and future pandemic strains from viral reservoir in animals are consequentially derived.

Efficacy and Safety of CVT-E002, a Proprietary Extract of Panax quinquefolius in the Prevention of Respiratory Infections in Influenza-Vaccinated Community-Dwelling Adults: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

Janet E. McElhaney, Andrew E. Simor, Shelly McNeil, and Gerald N. Predy — Wed, 20 Jul 2011 08:13:57 +0000

CVT-E002 (a proprietary extract) was found to be effective in the prevention of upper respiratory infections (URIs) in healthy adults, and institutionalized and community-dwelling seniors. A multicenter, randomized, double-blind, placebo-controlled trial was carried out to determine effects of CVT-E002 in the prevention of URIs in influenza-vaccinated community-dwelling adults. 783 community-dwelling adults were randomized to receive placebo, 400 mg or 800 mg treatment/d (1 : 1 : 1) for 6 months. Primary analysis on the incidence of laboratory-confirmed-clinical URIs (LCCUs), including influenza A and B, was performed on those receiving at least one dose. Secondary analysis was performed on study completers and included incidence, severity, and duration of URIs meeting a Jackson-based criteria and safety of CVT-E002. The incidence of LCCUs in the ITT group was 5.5%, 5.2%, and 4.6% in the placebo, 400 mg and 800 mg groups, respectively (𝑃=0.89). Jackson-confirmed URIs were significantly lower in the treated groups (𝑃<0.04). CVT-E002 supplementation reduced the severity and duration of Jackson-confirmed URIs. The results indicate that CVT-E002 can be safely used by similar groups and may prevent symptoms of URIs; larger sample size is warranted.

Predictive and Reactive Distribution of Vaccines and Antivirals during Cross-Regional Pandemic Outbreaks

Andrés Uribe-Sánchez and Alex Savachkin — Sun, 05 Jun 2011 09:48:36 +0000

As recently pointed out by the Institute of Medicine, the existing pandemic mitigation models lack the dynamic decision support capability. We develop a large-scale simulation-driven optimization model for generating dynamic predictive distribution of vaccines and antivirals over a network of regional pandemic outbreaks. The model incorporates measures of morbidity, mortality, and social distancing, translated into the cost of lost productivity and medical expenses. The performance of the strategy is compared to that of the reactive myopic policy, using a sample outbreak in Fla, USA, with an affected population of over four millions. The comparison is implemented at different levels of vaccine and antiviral availability and administration capacity. Sensitivity analysis is performed to assess the impact of variability of some critical factors on policy performance. The model is intended to support public health policy making for effective distribution of limited mitigation resources.

Characterization of a Low Pathogenic Avian Influenza Virus (H6N1) Isolated from Turkeys

I. Shkoda, E. Lapin, E. Rosenbluth, S. Perk, Z. Geva, A. Inbar, and I. Davidson — Thu, 30 Dec 2010 16:06:35 +0000

An avian influenza virus (AIV), A/turkey/Israel/09 subtype H6N1, was isolated from turkey poults exhibiting typical pathology associated with AIV infection. The virus was characterized by RT-PCR using AIV subtype-specific primers and by the haemagglutination inhibition test using AIV subtype-specific antisera. The virus has an intravenous pathogenicity index of 0 and possessed a nucleotide sequence at the cleavage site of the hemagglutinin gene, PQIETR*GLF, associated with avian influenza viruses of low pathogenicity. Unlike the two previous H6N2 isolates originating from domestic ducks and mallard, the A/turkey/Israel/09 (H6N1) was isolated from turkeys. The gene sequences of the A/turkey/Israel/09 (H6N1) virus show divergence from the former Israeli H6 isolates.

Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan

Tue, 28 Dec 2010 12:08:49 +0000

The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan. Epidemic outbreaks have been occurring in Southeast Asia, with the most recent in 2010. Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive. Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year. In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses.

Shedding of the Pandemic Swine-Origin Influenza A Virus (H1N1) after Oseltamivir Administration

Tue, 14 Dec 2010 11:21:43 +0000

We analyzed the virus shedding of an oseltamivir-treated patient who had been infected with the pandemic swine-origin influenza A (H1N1) virus which had an oseltamivir-sensitive neuraminidase. The virus was isolated from the pharyngeal swabs of the patient using MDCK cells, and the virus genome RNA was detected in the same samples both by real-time RT-PCR and RT-PCR. The virus was isolated until 44 h after oseltamivir administration although the virus genome was detected until one day after oseltamivir treatment was stopped. Due to their high sensitivity, RT-PCR and real-time RT-PCR may cause misdiagnosis by detection of viral genome which does not infect, and classical virus isolation and clinical symptoms are recommended for the evaluation of oseltamivir treatment.

Changing Patterns of H6 Influenza Viruses in Hong Kong Poultry Markets

Hiroichi Ozaki, Yi Guan, Malik Peiris, Robert Webster, and Richard Webby — Mon, 18 Oct 2010 10:07:46 +0000

Until 2001, H6N1 influenza viruses in the Hong Kong bird markets were represented by a single stable A/teal/Hong Kong/W312/97-like lineage. Beginning in 2001, despite a reduction in overall prevalence, an increase was observed in the number of H6 viruses isolated from chickens and other hosts. To assess any changes in H6 viruses, we characterized 18 H6 viruses isolated in the Hong Kong bird markets from 2001 to 2003. Experimental data showed that the 2003 H6 viruses had similar infectivity for chickens as did A/teal/HK/W312/97, and they were unable to transmit. Although all hemagglutinin genes were closely related to A/teal/HK/W312/97, 7 isolates were reassortant viruses containing similar gene segments of co-circulating H9N2 or H5N1 viruses. The receptor specificity was different from that of A/teal/Hong Kong/W312/97. Interestingly, similar observations have been documented in H9N2 viruses in Hong Kong. This evolution strongly suggests that some change in the ecology of influenza in the region selected for these changes. Taken together, these findings suggest that the H6 influenza viruses isolated in the Hong Kong markets are not well adapted to chickens and that the likely continued source of these viruses are other “minor” poultry species in which they are undergoing genetic and biologic evolution.

Factors Associated with Increased Risk Perception of Pandemic Influenza in Australia

Tue, 20 Jul 2010 12:59:21 +0000

The aim of this study was to assess factors associated with increased risk perception of pandemic influenza in Australia. The sample consisted of 2081 Australian adults aged 16 years and older who completed a short three item pandemic influenza question module which was incorporated into the NSW Health Adult Population Health Survey during the first quarter of 2007. After adjusting for covariates, multivariate analysis indicated that those living in rural regions were significantly more likely to perceive a high risk that a pandemic influenza would occur, while those with poor self-rated health perceived both a high likelihood of pandemic and high concern that self/family would be directly affected were such an event to occur. Those who spoke a language other than English at home and those on low incomes and younger people (16–24 years) were significantly more likely to have changed the way they lived their lives due to the possibility of pandemic influenza, compared to those who spoke only English at home, middle-high income earners, and older age groups, respectively. This data provides an Australian population baseline against which the risk perceptions of demographic subgroups regarding the current, and potential future pandemics, can be compared and monitored.

Evaluation of a Subunit H5 Vaccine and an Inactivated H5N2 Avian Influenza Marker Vaccine in Ducks Challenged with Vietnamese H5N1 Highly Pathogenic Avian Influenza Virus

Sun, 27 Jun 2010 14:27:15 +0000

The protective efficacy of a subunit avian influenza virus H5 vaccine based on recombinant baculovirus expressed H5 haemagglutinin antigen and an inactivated H5N2 avian influenza vaccine combined with a marker antigen (tetanus toxoid) was compared with commercially available inactivated H5N2 avian influenza vaccine in young ducks. Antibody responses, morbidity, mortality, and virus shedding were evaluated after challenge with a Vietnamese clade 1 H5N1 HPAI virus [A/VN/1203/04 (H5N1)] that was known to cause a high mortality rate in ducks. All three vaccines, administered with water-in-oil adjuvant, provided significant protection and dramatically reduced the duration and titer of virus shedding in the vaccinated challenged ducks compared with unvaccinated controls. The H5 subunit vaccine was shown to provide equivalent protection to the other two vaccines despite the H5 antibody responses in subunit vaccinated ducks being significantly lower prior to challenge. Ducks vaccinated with the H5N2 marker vaccine consistently produced antitetanus toxoid antibody. The two novel vaccines have attributes that would enhance H5N1 avian influenza surveillance and control by vaccination in small scale and village poultry systems.

Ten-Year (1999–2009) Epidemiological and Virological Surveillance of Influenza in South Italy (Apulia)

Tue, 22 Jun 2010 08:20:48 +0000

Clinical and epidemiological surveillance of influenza and other Acute Respiratory Infections (ARI) are currently a major objective of Public Health. The aim was to describe the epidemiology of influenza using the Italian surveillance system. Vaccination Coverage (VC) rates were calculated during 1999-2009 influenza seasons. Molecular studies of influenza virus isolated, from patients with ILI, living in Apulia, are described. 1269 nasal-pharyngeal swabs were taken from patients with ILI and ARI in order to isolate and identify viruses using PCR. Influenza isolates are typed as being types A and B and influenza A isolates are A/H1 and A/H3. The progression of the ILI cases registered in Apulia was similar to the data recorded on a national level. The VC data recorded in Apulia showed a progressive increase in the vaccine doses administered to subjects over 65 years old. The virological surveillance showed a major circulation of the type A/H3N2 influenza virus during the peak incidence of the illness in seasons 1999-2000, 2002-2003, 2004-2005 and 2008-2009. During the same period, the lowest incidence was registered when the type A/H1N1 and B viruses were in circulation. In contrast, during the other seasons the lowest incidence was reported with A/H3N2 and B viruses.