TL;DR: It is shown that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions and subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7n7 lineage.
Abstract: A novel H7N9 influenza A virus first detected in March 2013 has since caused more than 130 human infections in China, resulting in 40 deaths. Preliminary analyses suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza viruses, and carries some amino acids associated with mammalian receptor binding, raising concerns of a new pandemic. However, neither the source populations of the H7N9 outbreak lineage nor the conditions for its genesis are fully known. Using a combination of active surveillance, screening of virus archives, and evolutionary analyses, here we show that H7 viruses probably transferred from domestic duck to chicken populations in China on at least two independent occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2 viruses to generate the H7N9 outbreak lineage, and a related previously unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large geographic region and is prevalent in chickens at live poultry markets, which are thought to be the immediate source of human infections. Whether the H7N9 outbreak lineage has, or will, become enzootic in China and neighbouring regions requires further investigation. The discovery here of a related H7N7 influenza virus in chickens that has the ability to infect mammals experimentally, suggests that H7 viruses may pose threats beyond the current outbreak. The continuing prevalence of H7 viruses in poultry could lead to the generation of highly pathogenic variants and further sporadic human infections, with a continued risk of the virus acquiring human-to-human transmissibility.
TL;DR: To assess the potential treatment efficacy of convalescent plasma in reducing mortality in current patients with H5N1 influenza, a review of studies from the Spanish influenza era that used influenza-convalescent human blood products to treat patients with Spanish influenza complicated by pneumonia was conducted.
Abstract: Background: Studies from the Spanish influenza era reported that transfusion of influenza-convalescent human blood products reduced mortality in patients with influenza complicated by pneumonia. Treatments for H5N1 influenza are unsatisfactory, and convalescent human plasma containing H5N1 antibodies could be an effective therapy during outbreaks and pandemics. Purpose: To determine whether transfusion with influenza-convalescent human blood products reduced the risk for death in patients with Spanish influenza pneumonia. Data Sources: Manual search of English-language journals from 1918 to 1925. Citations from retrieved studies were also searched. Study Selection: Published English-language studies that had at least 10 patients in the treatment group, used convalescent blood products to treat Spanish influenza pneumonia in a hospital setting, and reported on a control or comparison group. Data Extraction: Two investigators independently extracted data on study characteristics, outcomes, adverse events, and quality. Data Synthesis: Eight relevant studies involving 1703 patients were found. Treated patients, who were often selected because of more severe illness, were compared with untreated controls with influenza pneumonia in the same hospital or ward. The overall crude case-fatality rate was 16% (54 of 336) among treated patients and 37% (452 of 1219) among controls. The range of absolute risk differences in mortality between the treatment and control groups was 8% to 26% (pooled risk difference, 21% [95% Cl, 15% to 27%]). The overall crude case-fatality rate was 19% (28 of 148) among patients who received early treatment (after <4 days of pneumonia complications) and 59% (49 of 83) among patients who received late treatment (after ≥4 days of pneumonia complications). The range of absolute risk differences in mortality between the early treatment group and the late treatment group was 26% to 50% (pooled risk difference, 41 % [Cl, 29% to 54%]). Adverse effects included chill reactions and possible exacerbations of symptoms in a few patients. Limitations: Studies were few and had many methodologic limitations. No study was a blinded, randomized, or placebo-controlled trial. Some pertinent studies may have been missed. Conclusions: Patients with Spanish influenza pneumonia who received influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death. Convalescent human H5N1 plasma could be an effective, timely, and widely available treatment that should be studied in clinical trials.
TL;DR: Recommendations are made to improve the control of aerosol-transmitted infections in hospitals as well as in the design and construction of future isolation facilities.
Abstract:
Summary
The epidemics of severe acute respiratory syndrome (SARS) in 2003 highlighted both short- and long-range transmission routes, i.e. between infected patients and healthcare workers, and between distant locations. With other infections such as tuberculosis, measles and chickenpox, the concept of aerosol transmission is so well accepted that isolation of such patients is the norm. With current concerns about a possible approaching influenza pandemic, the control of transmission via infectious air has become more important. Therefore, the aim of this review is to describe the factors involved in: (1) the generation of an infectious aerosol, (2) the transmission of infectious droplets or droplet nuclei from this aerosol, and (3) the potential for inhalation of such droplets or droplet nuclei by a susceptible host. On this basis, recommendations are made to improve the control of aerosol-transmitted infections in hospitals as well as in the design and construction of future isolation facilities.
TL;DR: Using newly assembled data sets of the locations of 8,943 live-poultry markets in China and maps of environmental correlates, a statistical model is developed that accurately predicts the risk of H7N9 market infection across Asia.
Abstract: Two epidemic waves of an avian influenza A (H7N9) virus have so far affected China. Most human cases have been attributable to poultry exposure at live-poultry markets, where most positive isolates were sampled. The potential geographic extent of potential re-emerging epidemics is unknown, as are the factors associated with it. Using newly assembled data sets of the locations of 8,943 live-poultry markets in China and maps of environmental correlates, we develop a statistical model that accurately predicts the risk of H7N9 market infection across Asia. Local density of live-poultry markets is the most important predictor of H7N9 infection risk in markets, underscoring their key role in the spatial epidemiology of H7N9, alongside other poultry, land cover and anthropogenic predictor variables. Identification of areas in Asia with high suitability for H7N9 infection enhances our capacity to target biosurveillance and control, helping to restrict the spread of this important disease.
TL;DR: Both sources in the Yangtze River Delta region and the Pearl RiverDelta region have been established and found to be responsible for the H7N9 outbreaks in mainland China, posing a long-term threat of H7n9 infection in humans.
Abstract: Due to enzootic infections in poultry and persistent human infections in China, influenza A (H7N9) virus has remained a public health threat. The Yangtze River Delta region, which is located in eastern China, is well recognized as the original source for H7N9 outbreaks. Based on the evolutionary analysis of H7N9 viruses from all three outbreak waves since 2013, we identified the Pearl River Delta region as an additional H7N9 outbreak source. H7N9 viruses are repeatedly introduced from these two sources to the other areas, and the persistent circulation of H7N9 viruses occurs in poultry, causing continuous outbreak waves. Poultry movements may contribute to the geographic expansion of the virus. In addition, the AnH1 genotype, which was predominant during wave 1, was replaced by JS537, JS18828, and AnH1887 genotypes during waves 2 and 3. The establishment of a new source and the continuous evolution of the virus hamper the elimination of H7N9 viruses, thus posing a long-term threat of H7N9 infection in humans. Therefore, both surveillance of H7N9 viruses in humans and poultry and supervision of poultry movements should be strengthened.
IMPORTANCE Since its occurrence in humans in eastern China in spring 2013, the avian H7N9 viruses have been demonstrating the continuing pandemic threat posed by the current influenza ecosystem in China. As the viruses are silently circulated in poultry, with potentially severe outcomes in humans, H7N9 virus activity in humans in China is very important to understand. In this study, we identified a newly emerged H7N9 outbreak source in the Pearl River Delta region. Both sources in the Yangtze River Delta region and the Pearl River Delta region have been established and found to be responsible for the H7N9 outbreaks in mainland China.
TL;DR: A new stochastic model of the spread of influenza across a large population is developed, which has realistic social contact networks, and transmission and infections are based on the current state of knowledge of the natural history of influenza.
Abstract: Mathematical and computer models of epidemics have contributed to our understanding of the spread of infectious disease and the measures needed to contain or mitigate them. To help prepare for future influenza seasonal epidemics or pandemics, we developed a new stochastic model of the spread of influenza across a large population. Individuals in this model have realistic social contact networks, and transmission and infections are based on the current state of knowledge of the natural history of influenza. The model has been calibrated so that outcomes are consistent with the 1957/1958 Asian A(H2N2) and 2009 pandemic A(H1N1) influenza viruses. We present examples of how this model can be used to study the dynamics of influenza epidemics in the United States and simulate how to mitigate or delay them using pharmaceutical interventions and social distancing measures. Computer simulation models play an essential role in informing public policy and evaluating pandemic preparedness plans. We have made the source code of this model publicly available to encourage its use and further development.
TL;DR: The frequency of variants with decreased sensitivity to the NAIs did not increase significantly during this period, but continued surveillance is required, especially in regions with higher NAI use.
Abstract: Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) develops at a low level following drug treatment, and person-to-person transmission of resistant virus has not been recognized to date. The Neuraminidase Inhibitor Susceptibility Network (NISN) was established to follow susceptibility of isolates and occurrence of NAI resistance at a population level in various parts of the world. Isolates from the WHO influenza collaborating centers were screened for susceptibilities to oseltamivir and zanamivir by a chemiluminescent enzyme inhibition assay, and those considered potentially resistant were analyzed by sequence analysis of the neuraminidase genes. During the first 3 years of NAI use (1999 to 2002), 2,287 isolates were tested. Among them, eight (0.33%) viruses had a >10-fold decrease in susceptibility to oseltamivir, one (0.22%) in 1999 to 2000, three (0.36%) in 2000 to 2001, and four (0.41%) in 2001 to 2002. Six had unique changes in the neuraminidase gene compared to neuraminidases of the same subtype in the influenza sequence database. Although only one of the mutations had previously been recognized in persons receiving NAIs, none were from patients who were known to have received the drugs. During the 3 years preceding NAI use, no resistant variants were detected among 1,054 viruses. Drug use was relatively stable during the period, except for an approximate 10-fold increase in oseltamivir use in Japan during the third year. The frequency of variants with decreased sensitivity to the NAIs did not increase significantly during this period, but continued surveillance is required, especially in regions with higher NAI use.
TL;DR: Influenza A virus-induced IFN-alpha/beta is essential in host's antiviral defence by activating the expression of antiviral Mx, PKR and oligoadenylate synthetase genes.
TL;DR: The A/Chick/Penn/83 (H5N2) influenza virus that appeared in chickens in Pennsylvania in April 1983 and subsequently became virulent in October 1983, was examined for plaque-forming ability and cleavability of the hemagglutinin (HA) molecule.
TL;DR: Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.
Abstract: Background There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings. Methods We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses. Results Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for t...
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"Influenza virus surveillance in mig..." refers background or methods in this paper
...27, 28 Fisher's exact test and chi-squared tests were used to compare count data including occurrence of side effects, laboratory confirmed, and clinically defined influenza infections....
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...27, 28 Elevated ProCT levels were not observed in patients with purulent sputum and clear CXR....
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...Viral microneutralization (VN) using standard methods was found to be more sensitive than HAI in detecting antibody response against A ⁄ California ⁄ 04 ⁄ 2009(H1N1) in another study conducted by our group 27 and was, therefore, used in this study....
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...Although real time RT-PCR targeting the HA gene has been used for specific diagnosis of pdmH1N1 with high sensitivity, [22] [23] [24] [25] [26] [27] it is a method that requires manipulation of the sample to extract viral RNA, and it is prone to crosscontamination during the PCR steps....