Zoonotic Influenza Viruses Research Articles

Propagation of vaccine strain of duck enteritis virus in a cell line of duck origin as an alternative production system to propagation in embryonated egg

Duck virus enteritis (DVE) also known as duck plague, is a viral infection of ducks caused by duck enteritis virus (DEV). The control of the disease is mainly done by vaccination with a chicken embryo-adapted live virus that is known to be poorly immunogenic and affords partial protection. Further, the risk of harboring other infectious agents in the embryo particularly the deadly and zoonotic avian influenza virus is also high. In this paper, we report propagation of a chicken embryo-adapted vaccine strain of duck enteritis virus in duck embryo fibroblast (DEF) cell line. Thirty serial passages were done in DEF cell that made the vaccine virus further attenuated which was tested in ducks. The growth behaviors of the virus in DEF cells were studied and at 30th passage level the virus titre was found to be 10 6.8 TCID 50/ml. Ducks were immunized with this virus and challenged after 21 days with high dose of virulent DEV. All the immunized ducks withstood challenge with no clinical symptoms in any of the ducks while all the control ducks died. DEF cell which is free from other infectious agents appears to be a good system for cultivation of duck enteritis virus vaccine strain.

Antiviral Role of Toll-Like Receptor-3 Agonists Against Seasonal and Avian Influenza Viruses

The divergence and antigenic shifts in influenza viruses represent significant challenges for the development of effective vaccines and antiviral drugs against influenza viruses. In view of current challenges and/or deficiencies in the influenza pandemic influenza preparedness, novel antiviral strategies which are robust and can respond to constant viral mutations, are particularly needed to combat future pandemic threats. Toll-like receptor-3 (TLR-3) is an integral part of the host's innate immune system and serves as an important signaling pathway for the recognition of dsRNA for the triggering of antiviral and inflammatory responses to combat viral infections. This review examines dsRNA including Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) as TLR-3 agonists for their antiviral activity against seasonal and highly pathogenic avian influenza (HPAI) viruses. Furthermore, their roles in attenuating the antiviral and inflammatory cytokines in the host will also be explored. Preclinical studies in experimental animals suggest Poly ICLC and liposome-encapsulated Poly ICLC are safe and offer broad-spectrum protection against both seasonal and HPAI viruses, as well as other respiratory viruses including respiratory syncytial virus and SARS. Preliminary results from recent studies suggest these drugs up-regulate the production of interferons (-alpha, -beta, and -gamma), and tumor necrosis factor (TNF-alpha) but downregulate some proinflammatory cytokines including IL-2 and IL-4. Taken together, these results suggest these TLR-3 agonists have a promising role to play as safe, effective and broad-spectrum anti-influenza drugs that could complement other antiviral drugs to combat seasonal, zoonotic and pandemic influenza viruses. The clinical safety of these drugs and their efficacy in pre-clinical studies may provide sufficient justification for regulatory agencies to consider their fast track development for use in future outbreaks of pandemic influenza or of other emerging respiratory pathogens.

Facing pandemic influenza threats: The importance of including poultry and swine workers in preparedness plans

Recent research has shown that poultry and swine workers, especially those with intense exposures, are at increased risk of zoonotic influenza virus infections. In multiple studies, US poultry workers and poultry veterinarians have evidence of previous infections with avian influenza virus. Similarly, US swine workers have strong evidence of previous and acute infections with swine influenza viruses. Mathematical modeling has demonstrated that such workers may accelerate the spread of pandemic viruses in their rural communities. Because these workers may contribute to the novel generation of viruses and serve as a bridging population in the cross-species sharing of influenza viruses, it seems prudent to include poultry and swine workers in influenza preparedness programs. Possible preventive and control interventions include special education programs to increase workers' use of personal protective equipment such as gloves, increased surveillance for influenza viruses among workers and their animals, recommendations that workers seek medical attention should they develop influenza-like illness, and workers' priority receipt of annual and pandemic influenza vaccines.

Swine Workers and Swine Influenza Virus Infections

In 2004, 803 rural Iowans from the Agricultural Health Study were enrolled in a 2-year prospective study of zoonotic influenza transmission. Demographic and occupational exposure data from enrollment, 12-month, and 24-month follow-up encounters were examined for association with evidence of previous and incident influenza virus infections. When proportional odds modeling with multivariable adjustment was used, upon enrollment, swine-exposed participants (odds ratio [OR] 54.9, 95% confidence interval [CI] 13.0-232.6) and their nonswine-exposed spouses (OR 28.2, 95% CI 6.1-130.1) were found to have an increased odds of elevated antibody level to swine influenza (H1N1) virus compared with 79 nonexposed University of Iowa personnel. Further evidence of occupational swine influenza virus infections was observed through self-reported influenza-like illness data, comparisons of enrollment and follow-up serum samples, and the isolation of a reassortant swine influenza (H1N1) virus from an ill swine farmer. Study data suggest that swine workers and their nonswine-exposed spouses are at increased risk of zoonotic influenza virus infections.

Detecting human-to-human transmission of avian influenza A (H5N1).

Highly pathogenic avian influenza A (HPAI) subtype H5N1 has caused family case clusters, mostly in Southeast Asia, that could be due to human-to-human transmission. Should this virus, or another zoonotic influenza virus, gain the ability of sustained human-to-human transmission, an influenza pandemic could result. We used statistical methods to test whether observed clusters of HPAI (H5N1) illnesses in families in northern Sumatra, Indonesia, and eastern Turkey were due to human-to-human transmission. Given that human-to-human transmission occurs, we estimate the infection secondary attack rates (SARs) and the local basic reproductive number, R0. We find statistical evidence of human-to-human transmission (p = 0.009) in Sumatra but not in Turkey (p = 0.114). For Sumatra, the estimated household SAR was 29% (95% confidence interval [CI] 15%-51%). The estimated lower limit on the local R0 was 1.14 (95% CI 0.61-2.14). Effective HPAI (H5N1) surveillance, containment response, and field evaluation are essential to monitor and contain potential pandemic strains.

Detecting Human-to-Human Transmission of Avian Influenza A (H5N1)

Highly pathogenic avian influenza A (HPAI) subtype H5N1 has caused family case clusters, mostly in Southeast Asia, that could be due to human-to-human transmission. Should this virus, or another zoonotic influenza virus, gain the ability of sustained human-to-human transmission, an influenza pandemic could result. We used statistical methods to test whether observed clusters of HPAI (H5N1) illnesses in families in northern Sumatra, Indonesia, and eastern Turkey were due to human-to-human transmission. Given that human-to-human transmission occurs, we estimate the infection secondary attack rates (SARs) and the local basic reproductive number, R0. We find statistical evidence of human-to-human transmission (p = 0.009) in Sumatra but not in Turkey (p = 0.114). For Sumatra, the estimated household SAR was 29% (95% confidence interval [CI] 15%-51%). The estimated lower limit on the local R0 was 1.14 (95% CI 0.61-2.14). Effective HPAI (H5N1) surveillance, containment response, and field evaluation are essential to monitor and contain potential pandemic strains.

Pandemic influenza planning: Shouldn’t swine and poultry workers be included?

Recent research has demonstrated that swine and poultry professionals, especially those who work in large confinement facilities, are at markedly increased risk of zoonotic influenza virus infections. In serving as a bridging population for influenza virus spread between animals and man, these workers may introduce zoonotic influenza virus into their homes and communities as well as expose domestic swine and poultry to human influenza viruses. Prolonged and intense occupational exposures of humans working in swine or poultry confinement buildings could facilitate the generation of novel influenza viruses, as well as accelerate human influenza epidemics. Because of their potential bridging role, we posit that such workers should be recognized as a priority target group for annual influenza vaccines and receive special training to reduce the risk of influenza transmission. They should also be considered for increased surveillance and priority receipt of pandemic vaccines and antivirals.

Cases of Swine Influenza in Humans: A Review of the Literature

As the threat of a pandemic looms, improvement in our understanding of interspecies transmission of influenza is necessary. Using the search terms "swine," "influenza," and "human," we searched the PubMed database in April 2006 to identify publications describing symptomatic infections of humans with influenza viruses of swine origin. From these reports, we extracted data regarding demographic characteristics, epidemiological investigations, and laboratory results. We found 50 cases of apparent zoonotic swine influenza virus infection, 37 of which involved civilians and 13 of which involved military personnel, with a case-fatality rate of 14% (7 of 50 persons). Most civilian subjects (61%) reported exposure to swine. Although sporadic clinical cases of swine influenza occur in humans, the true incidence of zoonotic swine influenza virus infection is unknown. Because prior studies have shown that persons who work with swine are at increased risk of zoonotic influenza virus infection, it is prudent to include them in pandemic planning efforts.

Are Swine Workers in the United States at Increased Risk of Infection with Zoonotic Influenza Virus?

Pandemic influenza strains originate in nonhuman species. Pigs have an important role in interspecies transmission of the virus. We examined multiple swine-exposed human populations in the nation's number 1 swine-producing state for evidence of previous swine influenza virus infection. We performed controlled, cross-sectional seroprevalence studies among 111 farmers, 97 meat processing workers, 65 veterinarians, and 79 control subjects using serum samples collected during the period of 2002-2004. Serum samples were tested using a hemagglutination inhibition assay against the following 6 influenza A virus isolates collected recently from pigs and humans: A/Swine/WI/238/97 (H1N1), A/Swine/WI/R33F/01 (H1N2), A/Swine/Minnesota/593/99 (H3N2), A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and A/Nanchang/933/95 (H3N2). Using multivariable proportional odds modeling, all 3 exposed study groups demonstrated markedly elevated titers against the H1N1 and H1N2 swine influenza virus isolates, compared with control subjects. Farmers had the strongest indication of exposure to swine H1N1 virus infection (odds ratio [OR], 35.3; 95% confidence interval [CI], 7.7-161.8), followed by veterinarians (OR, 17.8; 95% CI, 3.8-82.7), and meat processing workers (OR, 6.5; 95% CI, 1.4-29.5). Similarly, farmers had the highest odds for exposure to swine H1N2 virus (OR, 13.8; 95% CI, 5.4-35.4), followed by veterinarians (OR, 9.5; 95% CI, 3.6-24.6) and meat processing workers (OR, 2.7; 95% CI, 1.1-6.7). Occupational exposure to pigs greatly increases workers' risk of swine influenza virus infection. Swine workers should be included in pandemic surveillance and in antiviral and immunization strategies.