Search

We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.

The NucliSens easyMAG and BioRot 9604 automated nucleic acid extraction systems were evaluated and compared with the manual QIAamp (Qiagen) extraction method for their abilities to extract nucleic acid from nasopharyngeal aspirate samples for the detection of RNA and DNA respiratory viruses. The nucleic acids recovered by all three methods gave comparable sensitivities in PCR tests, and the three methods gave comparable viral loads. There was no evidence of residual PCR inhibitors and no evidence of PCR cross-contamination.

There has long been controversy over the potential for asymptomatic cases of the influenza virus to have the capacity for onward transmission, but recognition of asymptomatic transmission of COVID-19 stimulates further research into this topic. Here, we develop a Bayesian methodology to analyze detailed data from a large cohort of 727 households and 2515 individuals in the 2009 pandemic influenza A(H1N1) outbreak in Hong Kong to characterize household transmission dynamics and to estimate the relative infectiousness of asymptomatic versus symptomatic influenza cases. The posterior probability that asymptomatic cases [36% of cases; 95% credible interval (CrI): 32%, 40%] are less infectious than symptomatic cases is 0.82, with estimated relative infectiousness 0.57 (95% CrI: 0.11, 1.54). More data are required to strengthen our understanding of the contribution of asymptomatic cases to the spread of influenza. [ABSTRACT FROM AUTHOR]

Influenza vaccination is an important intervention to prevent influenza virus infection. Our previous analysis suggested that indirect protection is limited in an influenza B epidemic in Hong Kong. We further analyzed six influenza A epidemics to determine such potential. We applied a statistical model to estimate household transmission dynamics in the 3 influenza A(H3N2) and 3 pandemic influenza A(H1N1) epidemics. Then, we estimated the reduction in infection risk among unvaccinated household members when all children in households are vaccinated, with different assumptions on vaccine efficacy (VE). In the optimal scenario that VE was 70%, the reduction to the total probability of infection was only marginal, with relative probabilities ranged from 0.91–0.94 when all children in households were vaccinated because community was by far the main source of infection during the six epidemics in our study. The proportion of cases attributed to household transmission was 10% (95% CrI: 7%, 13%). Individual influenza vaccination is important even when other household members are vaccinated, given the degree of indirect protection is small. [ABSTRACT FROM AUTHOR]

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not lead to increased mortality. Using a combination of immunohistochemistry and transmission electron microscopy, we showed that the epithelium of the conducting airways of hamsters was the primary target for viral infection within the first 5 days of infection, with little evidence of productive infection of pneumocytes. At 6 days postinfection, antigen was cleared but parenchymal damage persisted, and the major pathological changes resolved by day 14. These findings are similar to those previously reported for hamsters with SARS-CoV-1 infection. In contrast, infection of K18-hACE2 transgenic mice resulted in pneumocyte damage, with viral particles and replication complexes in both type I and type II pneumocytes together with the presence of convoluted or cubic membranes; however, there was no evidence of virus replication in the conducting airways. The Syrian hamster is a useful model for the study of SARS-CoV-2 transmission and vaccination strategies, whereas infection of the K18-hCE2 transgenic mouse results in lethal disease with fatal neuroinvasion but with sparing of conducting airways. [ABSTRACT FROM AUTHOR]

To determine the effects of nonpharmaceutical interventions (NPIs) for coronavirus disease on pediatric hospitalizations for infection with respiratory viruses other than severe acute respiratory syndrome coronavirus 2, we analyzed hospital data for 2017-2021. Compared with 2017-2019, age-specific hospitalization rates associated with respiratory viruses greatly decreased in 2020, when NPIs were in place. Also when NPIs were in place, rates of hospitalization decreased among children of all ages for infection with influenza A and B viruses, respiratory syncytial virus, adenovirus, parainfluenza viruses, human metapneumovirus, and rhinovirus/enterovirus. Regression models adjusted for age and seasonality indicated that hospitalization rates for acute febrile illness/respiratory symptoms of any cause were reduced by 76% and by 85%-99% for hospitalization for infection with these viruses. NPIs in Hong Kong were clearly associated with reduced pediatric hospitalizations for respiratory viruses; implementing NPIs and reopening schools were associated with only a small increase in hospitalizations for rhinovirus/enterovirus infections. [ABSTRACT FROM AUTHOR]

Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009–2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons. [ABSTRACT FROM AUTHOR]

Background: Neutrophil is of the most abundant number in human immune system. During acute influenza virus infection, neutrophils are already active in the early phase of inflammation - a time in which clinical biopsy or autopsy material is not readily available. However, the role of neutrophil in virus infection is not well understood. Here, we studied the role of neutrophil in host defense during influenza A virus infection, specifically assessing if it contributes to the differential pathogenesis in H5N1 disease.Methods: Neutrophils were freshly isolated from healthy volunteers and subjected to direct influenza H1N1 and H5N1 virus infection in vitro. The ability of the naïve neutrophils to infiltrate from the basolateral to the apical phase of the influenza virus infected alveolar epithelium was assessed. The viral replication, innate immune responses and Neutrophil extracellular trap (NET) formation of neutrophils upon influenza virus infection were evaluated.Results: Our results demonstrated that influenza virus infected alveolar epithelium allowed neutrophil transmigration. Significantly more neutrophils migrated across the H5N1 influenza virus infected the epithelium than the counterpart infected by the seasonal influenza H1N1 virus infected. Neutrophils were equally susceptible to H5N1 and H1N1 virus infection with similar viral gene transcription. Productive replication was observed in H5N1 infected neutrophils. H5N1 induced higher cytokine and chemokine gene transcription than H1N1 infected neutrophils, including TNF-α, IFN-β, CXCL10, MIP-1α and IL-8. This inferred a more intense inflammatory response posed by H5N1 than H1N1 virus. Strikingly, NADPH oxidase-independent NET formation was only observed in H1N1 infected neutrophils at 6 hpi while no NET formation was observed upon H5N1 infection.Conclusion: Our data is the first to demonstrate that NET formation is abrogated in H5N1 influenza virus infection and might contribute to the severity of H5N1 disease. [ABSTRACT FROM AUTHOR]

Background: Poisson model has been widely applied to estimate the disease burden of influenza, but there has been little success in providing reliable estimates for other respiratory viruses. Methods: We compared the estimates of excess hospitalization rates derived from the Poisson models with different combinations of inference methods and virus proxies respectively, with the aim to determine the optimal modeling approach. These models were validated by comparing the estimates of excess hospitalization attributable to respiratory viruses with the observed rates of laboratory confirmed paediatric hospitalization for acute respiratory infections obtained from a population based study. Results: The Bayesian inference method generally outperformed the classical likelihood estimation, particularly for RSV and parainfluenza, in terms of providing estimates closer to the observed hospitalization rates. Compared to the other proxy variables, age-specific positive counts provided better estimates for influenza, RSV and parainfluenza, regardless of inference methods. The Bayesian inference combined with age-specific positive counts also provided valid and reliable estimates for excess hospitalization associated with multiple respiratory viruses in both the 2009 H1N1 pandemic and interpandemic period. Conclusions: Poisson models using the Bayesian inference method and virus proxies of age-specific positive counts should be considered in disease burden studies on multiple respiratory viruses. [ABSTRACT FROM AUTHOR]

Compared with the average transmissibility of human influenza A virus, much less attention has been paid to the potential variability in its transmissibility. We considered viral shedding as a proxy for infectiousness and explored the heterogeneity of infectiousness among patients with medically attended seasonal influenza A virus infection. The analysis revealed that viral shedding is more heterogeneous in children than in adults. The top 20% most infectious children and adults were estimated to be responsible for 89%–96% and 78%–82%, respectively, of the total infectiousness in each age group. Further investigation is required to correlate the substantial variations in viral shedding with heterogeneity in actual transmissibility. [ABSTRACT FROM AUTHOR]

Background. Volunteer challenge studies have provided detailed data on viral shedding from the respiratory tract before and through the course of experimental influenza virus infection. There are no comparable quantitative data to our knowledge on naturally acquired infections. Methods. In a community-based study in Hong Kong in 2008, we followed up initially healthy individuals to quantify trends in viral shedding on the basis of cultures and reverse-transcription polymerase chain reaction (RT-PCR) through the course of illness associated with seasonal influenza A and B virus infection. Results. Trends in symptom scores more closely matched changes in molecular viral loads measured with RT-PCR for influenza A than for influenza B. For influenza A virus infections, the replicating viral loads determined with cultures decreased to undetectable levels earlier after illness onset than did molecular viral loads. Most viral shedding occurred during the first 2-3 days after illness onset, and we estimated that 1%-8% of infectiousness occurs prior to illness onset. Only 14% of infections with detectable shedding at RT-PCR were asymptomatic, and viral shedding was low in these cases. Conclusions. Our results suggest that "silent spreaders" (ie, individuals who are infectious while asymptomatic or presymptomatic) may be less important in the spread of influenza epidemics than previously thought. [ABSTRACT FROM AUTHOR]

Objectives: The influenza virus (IFV) infection models commonly used to evaluate antiviral agents (e.g. MDCK cell line and mice) are limited by physiological differences from the human respiratory tract in vivo. Here we report the pharmacodynamics of DAS181, a sialidase fusion protein that inhibits influenza infection, in the model systems of well-defined human airway epithelium (HAE) culture and ex vivo culture of fresh human bronchial tissue, both of which are close mimics of the human respiratory tract in vivo. [ABSTRACT FROM PUBLISHER]

From January 2004 through June 2008, surveillance of dead wild birds in Hong Kong, People's Republic of China, periodically detected highly pathogenic avian influenza (HPAI) viruses (H5N1) in individual birds from different species. During this period, no viruses of subtype H5N1 were detected in poultry on farms and in markets in Hong Kong despite intensive surveillance. Thus, these findings in wild birds demonstrate the potential for wild birds to disseminate HPAI viruses (H5N1) to areas otherwise free from the viruses. Genetic and antigenic characterization of 47 HPAI (H5N1) viruses isolated from dead wild birds in Hong Kong showed that these isolates belonged to 2 antigenically distinct virus groups: clades 2.3.4 and 2.3.2. Although research has shown that clade 2.3.4 viruses are established in poultry in Asia, the emergence of clade 2.3.2 viruses in nonpasserine birds from Hong Kong, Japan, and Russia raises the possibility that this virus lineage may have become established in wild birds. [ABSTRACT FROM AUTHOR]

Background. Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed. Methods. Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice. Results. A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized. One of these MAbs, 13D4, has been demonstrated to protect mice against lethal challenge by 4 H5N1 strains representing the current major genetic populations, clades 1, 2.1, 2.2, and 2.3, even at a stage of infection when H5N1 virus has disseminated beyond the pulmonary system. Complete neutralization of virus in lung tissue of infected animals was observed 24 h after treatment with 13D4. Mapping of this MAb with escape mutants showed it to bind to 2 conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. Conclusion. Generation of broadly cross-protective MAbs against H5N1 influenza virus may be optimized by selecting MAbs that target conserved sites in hemagglutinin. H5 MAbs such as 13D4 may prove to have therapeutic value in controlling infection due to current and future H5N1 variants. [ABSTRACT FROM AUTHOR]

Samples of drinking water from poultry cages, which can be collected conveniently and noninvasively, provide higher rates of influenza (H9N2) virus isolation than do samples of fecal droppings. Studies to confirm the usefulness of poultry drinking water for detecting influenza (H5N1) should be conducted in disease-endemic areas. [ABSTRACT FROM AUTHOR]

The interaction of human social behaviour and transmission is an intriguing aspect of the life cycle of respiratory viral infections. Although age-specific mixing patterns are often assumed to be the key drivers of the age-specific heterogeneity in transmission, the association between social contacts and biologically confirmed infection has not previously been tested at the individual level. We administered a questionnaire to participants in a longitudinal cohort survey of influenza in which infection was defined by longitudinal paired serology. Using a variety of statistical approaches, we found overwhelming support for the inclusion of individual age in addition to contact variables when explaining odds of infection: the best model not including age explained only 15.7% of the deviance, whereas the best model with age explained 23.6%. However, within age groups, we did observe an association between contacts, locations and infection: median numbers of contacts (or locations) reported by those infected were higher than those from the uninfected group in every age group other than the youngest. Further, we found some support for the retention of location and contact variables in addition to age in our regression models, with excess odds of infection of approximately 10% per additional 10 contacts or one location. These results suggest that, although the relationship between age and incidence of respiratory infection at the level of the individual is not driven by self-reported social contacts, risk within an age group may be. [ABSTRACT FROM AUTHOR]

The 2009 pandemic influenza H1N1 (H1N1pdm) virus was generated by reassortment of swine influenza viruses of different lineages. This was the first influenza pandemic to emerge in over 4 decades and the first to occur after the realization that influenza pandemics arise from influenza viruses of animals. In order to understand the biological determinants of pandemic emergence, it is relevant to compare the tropism of different lineages of swine influenza viruses and reassortants derived from them with that of 2009 pandemic H1N1 (H1N1pdm) and seasonal influenza H1N1 viruses in ex vivo cultures of the human nasopharynx, bronchus, alveoli, and conjunctiva. We hypothesized that virus which can transmit efficiently between humans replicated well in the human upper airways. As previously reported, H1N1pdm and seasonal H1N1 viruses replicated efficiently in the nasopharyngeal, bronchial, and alveolar epithelium. In contrast, representative viruses from the classical swine (CS) (H1N1) lineage could not infect human respiratory epithelium; Eurasian avian-like swine (EA) (H1N1) viruses only infected alveolar epithelium and North American triple-reassortant (TRIG) viruses only infected the bronchial epithelium albeit inefficiently. Interestingly, a naturally occurring triple-reassortant swine virus, A/SW/HK/915/04 (H1N2), with a matrix gene segment of EA swine derivation (i.e., differing from H1N1pdm only in lacking a neuraminidase [NA] gene of EA derivation) readily infected and replicated in human nasopharyngeal and bronchial epithelia but not in the lung. A recombinant sw915 with the NA from H1N1pdm retained its tropism for the bronchus and acquired additional replication competence for alveolar epithelium. In contrast to H1N1pdm, none of the swine viruses tested nor seasonal H1N1 had tropism in human conjunctiva. Recombinant viruses generated by swapping the surface proteins (hemagglutinin and NA) of H1N1pdm and seasonal H1N1 virus demonstrated that these two gene segments together are key determinants of conjunctival tropism. Overall, these findings suggest that ex vivo cultures of the human respiratory tract provide a useful biological model for assessing the human health risk of swine influenza viruses. [ABSTRACT FROM AUTHOR]