Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses

Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH4Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC50 of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents

Human and animal integrated influenza surveillance: a novel sampling approach for an additional transmission way in the aquatic bird reservoir.

Background: infectious low pathogenic avian influenza viruses (LPAIVs) have been recently detected on feathers of wild ducks. Laboratory trial results suggested that the preen oil gland secretion, covering waterbirds\u2019 feathers, may attract and concentrate virus particles from AIV-contaminated waters to birds\u2019 bodies. We evaluated whether ducks can become infected by the ingestion of preen oil-associated viral particles, experimentally smeared on their plumage. In addition, we compared virologic and serologic results obtained from mallards whose feathers were experimentally infected, with those from wild mallards naturally carrying AIVs on feathers. Methods: we experimentally coated 7 mallards (Anas plathyrynchos) using preen oil mixed with a LPAIV (H10N7 subtype), and housed them for 45 days with a control, uncoated duck. Cloacal, oropharyngeal and feather swabs were collected from all birds and examined for AIV molecular detection and isolation. Blood samples were also taken to detect influenza specific antibodies. In addition, sera from 10 wild mallards, carrying on feathers infectious LPAIV H10N7, were examined. Results: virologic and serologic results indicated that through self- and allopreening all the birds experimentally coated with the preen oil/AIV mix and the control duck ingested viruses covering feathers and became infected. Virus isolation from feathers was up to 32 days post-coating treatment. One out of 8 wild mallards showing antibodies against type A influenza virus was seropositive for H10 subtype too. Conclusions: our experimental and field results show evidences suggesting that uninfected birds carrying viruses on their feathers, including immune ones, might play an active role in spreading AIV infection in nature. For this reason, routine AIV surveillance programs, aimed at detecting intestinal and/or respiratory viruses, should include the collection of samples, such as feather swabs, enabling the detection of viruses sticky to preened birds\u2019 bodies

Personal Protective Equipment and Risk for Avian Influenza (H7N3)

An outbreak of avian influenza (H7N3) among poultry resulted in laboratory-confirmed disease in 1 of 103 exposed persons. Incomplete use of personal protective equipment (PPE) was associated with conjunctivitis and influenza-like symptoms. Rigorous use of PPE by persons managing avian influenza outbreaks may reduce exposure to potentially hazardous infected poultry materials

Transmission of Hemagglutinin D222G Mutant Strain of Pandemic (H1N1) 2009 Virus

A pandemic (H1N1) 2009 virus strain carrying the D222G mutation was identified in a severely ill man and was transmitted to a household contact. Only mild illness developed in the contact, despite his obesity and diabetes. The isolated virus reacted fully with an antiserum against the pandemic vaccine strain

Integrating influenza antigenic dynamics with molecular evolution.

Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001

Co-circulation of the two influenza B lineages during 13 consecutive influenza surveillance seasons in Italy, 2004-2017

BACKGROUND: Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season. METHODS: From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene. RESULTS: Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for >\u200920% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains. CONCLUSIONS: This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004-2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases

Limiting worker exposure to highly pathogenic avian influenza a (H5N1): a repeat survey at a rendering plant processing infected poultry carcasses in the UK

<p>Abstract</p> <p>Background</p> <p>Current occupational and public health guidance does not distinguish between rendering plant workers and cullers/poultry workers in terms of infection risk in their respective roles during highly pathogenic avian influenza poultry outbreaks. We describe an operational approach to human health risk assessment decision making at a large rendering plant processing poultry carcasses stemming from two separate highly pathogenic avian influenza A (H5N1) outbreaks in England during 2007.</p> <p>Methods</p> <p>During the first incident a uniform approach assigned equal exposure risk to all rendering workers in or near the production line. A task based exposure assessment approach was adopted during the second incident based on a hierarchy of occupational activities and potential for infection exposure. Workers assessed as being at risk of infection were offered personal protective equipment; pre-exposure antiviral prophylaxis; seasonal influenza immunisation; hygiene advice; and health monitoring. A repeat survey design was employed to compare the two risk assessment approaches, with allocation of antiviral prophylaxis as the main outcome variable.</p> <p>Results</p> <p>Task based exposure assessment during the second incident reduced the number of workers assessed at risk of infection from 72 to 55 (24% reduction) when compared to the first incident. No cases of influenza like illness were reported in workers during both incidents.</p> <p>Conclusions</p> <p>Task based exposure assessment informs a proportionate public health response in rendering plant workers during highly pathogenic avian influenza H5N1 outbreaks, and reduces reliance on extensive antiviral prophylaxis.</p