Environmental Contamination during Influenza A Virus (H5N1) Outbreaks, Cambodia, 2006

To determine potential risk for bird-to-human transmission during influenza A virus (H5N1) outbreaks among backyard poultry in rural Cambodia, we collected environmental specimens. Viral RNA was detected in 27 (35%) of 77 specimens of mud, pond water, water plants, and soil swabs. Our results underscore the need for regular disinfection of poultry areas

The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children.

BACKGROUND: In a 2012 Phase II clinical trial, 300 Bangladeshi children aged 24 to 59 months with no prior influenza vaccine exposure were randomized to receive a single intranasally-administered dose of either trivalent, Russian-backbone, live, attenuated influenza vaccine (LAIV) or placebo. Protocol-defined analyses, presented in the companion manuscript, demonstrate decreased viral detection and immunogenicity for A/H1N1pdm09, relative to the A/H3N2 and B strains. This post hoc analysis of the trial data aims to investigate the LAIV strain differences by testing the hypothesis that preexisting humoral and mucosal immunity may influence viral recovery and immune responses after LAIV receipt. METHODS: We used logistic regressions to evaluate the relations between markers of preexisting immunity (ie, hemagglutination inhibition [HAI], microneutralization, and immunoglobulin G and immunoglobulin A (both serum and mucosal antibodies) and LAIV viral recovery in the week post-vaccination. We then tested for potential effect modification by baseline HAI titers (ie, <10 versus ≥10) and week 1 viral recovery on the LAIV-induced serum and mucosal immune responses, measured between days 0 and 21 post-vaccination. RESULTS: Higher levels of preexisting immunity to influenza A/H3N2 and B were strongly associated with strain-specific prevention of viral shedding upon LAIV receipt. While evidence of LAIV immunogenicity was observed for all 3 strains, the magnitudes of immune responses were most pronounced in children with no evidence of preexisting HAI and in those with detectable virus. CONCLUSIONS: The results provide evidence for a bidirectional association between viral replication and immunity, and underscore the importance of accounting for preexisting immunity when evaluating virologic and immunologic responses to LAIVs. CLINICAL TRIALS REGISTRATION: NCT01625689

Seasonal Oscillation of Human Infection with Influenza A/H5N1 in Egypt and Indonesia

As of June 22, 2011, influenza A/H5N1 has caused a reported 329 deaths and 562 cases in humans, typically attributed to contact with infected poultry. Influenza H5N1 has been described as seasonal. Although several studies have evaluated environmental risk factors for H5N1 in poultry, none have considered seasonality of H5N1 in humans. In addition, temperature and humidity are suspected to drive influenza in temperate regions, but drivers in the tropics are unknown, for H5N1 as well as other influenza viruses. An analysis was conducted to determine whether human H5N1 cases occur seasonally in association with changes in temperature, precipitation and humidity. Data analyzed were H5N1 human cases in Indonesia (n = 135) and Egypt (n = 50), from January 1, 2005 (Indonesia) or 2006 (Egypt) through May 1, 2008 obtained from WHO case reports, and average daily weather conditions obtained from NOAA's National Climatic Data Center. Fourier time series analysis was used to determine seasonality of cases and associations between weather conditions and human H5N1 incidence. Human H5N1 cases in Indonesia occurred with a period of 1.67 years/cycle (p<0.05) and in Egypt, a period of 1.18 years/cycle (p≅0.10). Human H5N1 incidence in Egypt, but not Indonesia, was strongly associated with meteorological variables (κ2≥0.94) and peaked in Egypt when precipitation was low, and temperature, absolute humidity and relative humidity were moderate compared to the average daily conditions in Egypt. Weather conditions coinciding with peak human H5N1 incidence in Egypt suggest that human infection may be occurring primarily via droplet transmission from close contact with infected poultry

Can Preening Contribute to Influenza A Virus Infection in Wild Waterbirds?

Wild aquatic birds in the Orders Anseriformes and Charadriiformes are the main reservoir hosts perpetuating the genetic pool of all influenza A viruses, including pandemic viruses. High viral loads in feces of infected birds permit a fecal-oral route of transmission. Numerous studies have reported the isolation of avian influenza viruses (AIVs) from surface water at aquatic bird habitats. These isolations indicate aquatic environments have an important role in the transmission of AIV among wild aquatic birds. However, the progressive dilution of infectious feces in water could decrease the likelihood of virus/host interactions. To evaluate whether alternate mechanisms facilitate AIV transmission in aquatic bird populations, we investigated whether the preen oil gland secretions by which all aquatic birds make their feathers waterproof could support a natural mechanism that concentrates AIVs from water onto birds' bodies, thus, representing a possible source of infection by preening activity. We consistently detected both viral RNA and infectious AIVs on swabs of preened feathers of 345 wild mallards by using reverse transcription–polymerase chain reaction (RT-PCR) and virus-isolation (VI) assays. Additionally, in two laboratory experiments using a quantitative real-time (qR) RT-PCR assay, we demonstrated that feather samples (n = 5) and cotton swabs (n = 24) experimentally impregnated with preen oil, when soaked in AIV-contaminated waters, attracted and concentrated AIVs on their surfaces. The data presented herein provide information that expands our understanding of AIV ecology in the wild bird reservoir system

Spread of Avian Influenza Viruses by Common Teal (Anas crecca) in Europe

Since the recent spread of highly pathogenic (HP) H5N1 subtypes, avian influenza virus (AIV) dispersal has become an increasing focus of research. As for any other bird-borne pathogen, dispersal of these viruses is related to local and migratory movements of their hosts. In this study, we investigated potential AIV spread by Common Teal (Anas crecca) from the Camargue area, in the South of France, across Europe. Based on bird-ring recoveries, local duck population sizes and prevalence of infection with these viruses, we built an individual-based spatially explicit model describing bird movements, both locally (between wintering areas) and at the flyway scale. We investigated the effects of viral excretion duration and inactivation rate in water by simulating AIV spread with varying values for these two parameters. The results indicate that an efficient AIV dispersal in space is possible only for excretion durations longer than 7 days. Virus inactivation rate in the environment appears as a key parameter in the model because it allows local persistence of AIV over several months, the interval between two migratory periods. Virus persistence in water thus represents an important component of contamination risk as ducks migrate along their flyway. Based on the present modelling exercise, we also argue that HP H5N1 AIV is unlikely to be efficiently spread by Common Teal dispersal only

Method for screening influenza neutralizing antibodies in crude human plasma and its derivatives using SPR

We applied Surface Plasmon Resonance (SPR) technology to develop a method for potency screening and quantification of anti-influenza antibodies in minimally processed human plasma samples and intravenous immunoglobulin (IGIV) products. We found that specific antibodies in human plasma or IGIV capable of inhibiting binding of influenza hemagglutinin to receptor-analogous glycans do so in concentration-dependent manner. We ranked the inhibitory activity of plasma samples from multiple donors and found a good correlation (r = 0.87) of SPR assay measurements and conventional hemagglutination inhibition (HAI) assay results. This method was also applied to screen for specific anti-influenza antibodies in IGIV lots manufactured pre- and post-2009 H1N1 pandemic. The SPR method was also applied to study binding inhibition of the intact A/California/04/2009 H1N1 and B/Victoria/504/2000 influenza viruses to α2,6 or α2,3-linked synthetic glycans. In contrast to recombinant H1 hemagglutinin, which was found to interact primarily with α2,6-linked terminal sialic acids, intact H1N1 or influenza B virus recognized both types of receptor analogs with different observed dissociation rates and the inhibitory activity of plasma antibodies was dependent on the type of sialic acid link. The SPR method can provide a high-throughput, time-saving and semi-automated alternative to conventional assays such as HAI or microneutralization in situations where screening of large numbers of plasma donations to identify high titer units is needed to product highly potent immunoglobulins

The influence of underdense polymer target with/without high-Z nanoparticles on laser radiation absorption and energy transport

Fabrication methods for low-density fine-structure (cell size $<$1 $\mu$m) 3-D networks of cellulose triacetate (TAC) are developed. Target densities ranged 4-20 mg/cc, similar polymer structures were produced both with no load and with high-Z cluster dopant with concentration up to 30%. Foams of varying density down to 0.25 plasma critical density at the third harmonic of iodine laser wavelength are supplied for laser shots. Experiments with underdense foam targets with and without clusters irradiated on the PALS laser facility are analyzed preliminary, showing strong influence of target structure on process of laser light absorption. Heat and radiation transport in such targets are considered