Self-Interest versus Group-Interest in Antiviral Control.

PLoS ONE. 2008;3(2):e1558

Authors: van Boven M, Klinkenberg D, Pen I, Weissing FJ, Heesterbeek H

Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs.

PMID: 19050769 [PubMed - in process]

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Anti-influenza drugs: the development of sialidase inhibitors.

Handb Exp Pharmacol. 2009;(189):111-54

Authors: Itzstein M, Thomson R

Viruses, particularly those that are harmful to humans, are the 'silent terrorists' of the twenty-first century. Well over four million humans die per annum as a result of viral infections alone. The scourge of influenza virus has plagued mankind throughout the ages. The fact that new viral strains emerge on a regular basis, particularly out of Asia, establishes a continual socio-economic threat to mankind. The arrival of the highly pathogenic avian influenza H5N1 heightened the threat of a potential human pandemic to the point where many countries have put in place 'preparedness plans' to defend against such an outcome. The discovery of the first designer influenza virus sialidase inhibitor and anti-influenza drug Relenza(TM), and subsequently Tamiflu(TM), has now inspired a number of continuing efforts towards the discovery of next generation anti-influenza drugs. Such drugs may act as 'first-line-of-defence' against the spread of influenza infection and buy time for necessary vaccine development particularly in a human pandemic setting. Furthermore, the fact that influenza virus can develop resistance to therapeutics makes these continuing efforts extremely important.An overview of the role of the virus-associated glycoprotein sialidase (neuraminidase) and some of the most recent developments towards the discovery of anti-influenza drugs based on the inhibition of influenza virus sialidase is provided in this chapter.

PMID: 19048199 [PubMed - in process]

Knowledge about Avian Influenza, European Region.

Emerg Infect Dis. 2008 Dec;14(12):1956-7

Authors: Mossialos E, Rudisill C

To the Editor: Since the first identifications of avian influenza (H5N1) in Europe in late 2005 and early 2006, Eurobarometer survey data obtained during April-May 2006 have provided a unique opportunity to examine the knowledge of respondents across the European Union, Croatia, and Turkey about the risks and transmission of avian influenza. The H5N1 strain of avian influenza virus has caused >240 human deaths in central and Southeast Asia, the Middle East, and Africa (1). Four of these deaths occurred in Turkey in 2006. Understanding gaps in the public's knowledge about avian influenza risks and transmission provides guidance on which issues future public health information campaigns may wish to focus. From a public health perspective, a more informed general public will be less likely to unnecessarily alter their travel and food consumption behavior and more likely to take appropriate preventive actions.

PMID: 19046535 [PubMed - in process]

Avian Influenza Outbreaks in Chickens, Bangladesh.

Emerg Infect Dis. 2008 Dec;14(12):1909-1912

Authors: Biswas PK, Christensen JP, Ahmed SS, Barua H, Das A, Rahman MH, Giasuddin M, Hannan AS, Habib MA, Ahad A, Rahman AS, Faruque R, Debnath NC

To determine the epidemiology of outbreaks of avian influenza A virus (subtypes H5N1, H9N2) in chickens in Bangladesh, we conducted surveys and examined virus isolates. The outbreak began in backyard chickens. Probable sources of infection included egg trays and vehicles from local live bird markets and larger live bird markets.

PMID: 19046518 [PubMed - as supplied by publisher]

Influenza Infection in Wild Raccoons.

Emerg Infect Dis. 2008 Dec;14(12):1842-1848

Authors: Hall JS, Bentler KT, Landolt G, Elmore SA, Minnis RB, Campbell TA, Barras SC, Root JJ, Pilon J, Pabilonia K, Driscoll C, Slate D, Sullivan H, McLean RG

Raccoons (Procyon lotor) are common, widely distributed animals that frequently come into contact with wild waterfowl, agricultural operations, and humans. Serosurveys showed that raccoons are exposed to avian influenza virus. We found antibodies to a variety of influenza virus subtypes (H10N7, H4N6, H4N2, H3, and H1) with wide geographic variation in seroprevalence. Experimental infection studies showed that raccoons become infected with avian and human influenza A viruses, shed and transmit virus to virus-free animals, and seroconvert. Analyses of cellular receptors showed that raccoons have avian and human type receptors with a similar distribution as found in human respiratory tracts. The potential exists for co-infection of multiple subtypes of influenza virus with genetic reassortment and creation of novel strains of influenza virus. Experimental and field data indicate that raccoons may play an important role in influenza disease ecology and pose risks to agriculture and human health.

PMID: 19046505 [PubMed - as supplied by publisher]

Highly Pathogenic Avian Influenza Virus (H5N1) Infection in Red Foxes Fed Infected Bird Carcasses.

Emerg Infect Dis. 2008 Dec;14(12):1835-41

Authors: Reperant LA, van-Amerongen G, van-de-Bildt MW, Rimmelzwaan GF, Dobson AP, Osterhaus AD, Kuiken T

Eating infected wild birds may put wild carnivores at high risk for infection with highly pathogenic avian influenza (HPAI) virus (H5N1). To determine whether red foxes (Vulpes vulpes) are susceptible to infection with HPAI virus (H5N1), we infected 3 foxes intratracheally. They excreted virus pharyngeally for 3-7 days at peak titers of 103.5-105.2 median tissue culture infective dose (TCID50) per mL and had severe pneumonia, myocarditis, and encephalitis. To determine whether foxes can become infected by the presumed natural route, we fed infected bird carcasses to 3 other red foxes. These foxes excreted virus pharyngeally for 3-5 days at peak titers of 104.2-104.5 TCID50/mL, but only mild or no pneumonia developed. This study demonstrates that red foxes fed bird carcasses infected with HPAI virus (H5N1) can excrete virus while remaining free of severe disease, thereby potentially playing a role in virus dispersal.

PMID: 19046504 [PubMed - in process]

[National plan for the prevention and control "influenza pandemic"]

Rev Prat. 2008 Oct 15;58(15):1687-93

Authors: Henry S, Manuguerra JC, Escourolle D, Bessette D, Camus D, Houssin D

France has developed a national plan for the prevention and control of an influenza pandemic with the aim of reducing its health impact and its consequences on the economic and social life of the country. The main objectives of the plan are to prepare the country to face an epizootic of avian influenza due to a highly pathogenic virus, to detect the first manifestation of a new flu virus, to curb its spread by adopting early and appropriate public health measures and to protect the French population, as well as French citizens abroad. Ensuring that the population has the best possible access to prevention and care, through the organisation and adaptation of the health system facing a pandemic, is one of the major goals of the plan. The plan, and organisation associated to it, forms the foundation of a coherent and adaptable system which every citizen should feel ownership of.

PMID: 19044053 [PubMed - in process]

[New pandemic influenza: what are the risks?]

Rev Prat. 2008 Oct 15;58(15):1679-86

Authors: Lina B

Influenza pandemics result from the introduction of a new influenza A subtype from the avian reservoir. This reservoir is vast but the introductions are seldom. To be adapted for human infection, they have to undergo major changes. Two mechanisms have been described, allowing this adaptation: direct adaptation after accumulation of mutations, or genetic exchange between human and avian viruses (reassortant virus). Today, we are facing a pandemic threat due to A(H5N1). Already 382 cases have been detected, including 241 death cases. However, this virus is not adapted to man. On the other hand, the large epizootic clusters observed, the cases observed after exposition to infected poultry and the lack of control of the A(H5N1) infection in wild and domestic birds make this virus the best candidate for the next pandemic.

PMID: 19044052 [PubMed - in process]

[Natural history of influenza]

Rev Prat. 2008 Oct 15;58(15):1645-54

Authors: Hannoun C

Influenza is known as a human disease, but many influenza viruses can be found in several other animal species. In some it induces a disease similar to man's infection with a major respiratory tropism. In others the disease is quite different, like the systemic infection of fowl plague. In others, it can be totally asymptomatic. The main species concerned are birds, horse, pig, felines, canines, marine mammals and mustelids. The mechanisms of interspecies transmission of the virus are now better understood and they condition influenza epidemiology. Lessons from the study of past pandemics and other manifestations of influenza during 20th century help to design the tools and procedures for managing an eventual new pandemic.

PMID: 19044047 [PubMed - in process]

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Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

Vaccine. 2008 Nov 26;

Authors: Pavlova SP, Veits J, Keil GM, Mettenleiter TC, Fuchs W

Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived without showing any clinical signs. Real-time RT-PCR indicated limited challenge virus replication after vaccination with H5-ILTV only, which was completely blocked after coimmunization with N1-ILTV. Thus, chickens can be protected from H5N1 HPAIV-induced disease by live vaccination with an attenuated hemagglutinin-expressing ILTV recombinant, and efficacy can be further increased by coadministration of an ILTV mutant expressing neuraminidase. Furthermore, chickens vaccinated with ILTV vectors can be easily differentiated from influenza virus-infected animals by the absence of serum antibodies against the AIV nucleoprotein.

PMID: 19041677 [PubMed - as supplied by publisher]

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Passive immunization against highly pathogenic Avian Influenza Virus (AIV) strain H7N3 with antiserum generated from viral polypeptides protect poultry birds from lethal viral infection.

Virol J. 2008 Nov 28;5(1):144

Authors: Shahzad MI, Naeem K, Mukhtar M, Khanum A

ABSTRACT: Our studies were aimed at developing a vaccination strategy that could provide protection against highly pathogenic avian influenza virus (AIV), H7N3 or its variants outbreaks. A purified viral stock of highly pathogenic H7N3 isolate was lysed to isolate viral proteins by electrophresing on 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by their elution from gel through trituration in phosphate buffered saline (PBS). Overall, five isolated viral polypeptides/proteins upon characterization were used to prepare hyperimmune monovalent serum against respective polypeptides independently and a mixture of all five in poultry birds, and specificity confirmation of each antiserum through dot blot and Western blotting. Antiserum generated from various group' birds was pooled and evaluated in 2-weeks old broiler chicken for its protection against viral challenge. To evaluate in-vivo protection of each antiserum against viral challenges six groups of 2-week old broiler chicken were injected with antiserum and a seventh control group received normal saline. Each group was exposed to purified highly pathogenic AIV H7N3 strain at a dose 106 embryo lethal dose (ELD50). We observed that nucleoprotein (NP) antiserum significantly protected birds from viral infection induced morbidity, mortality and lowered viral shedding compared with antiserum from individual viral proteins or mixed polypeptides/proteins inclusive of NP component. The capability of individual viral polypeptide specific antisera to protect against viral challenges in decreasing order was nucleoprotein (NP) > heamagglutinin (HA) > neuraminidase (NA) > Viral proteins mix > viral polymerase. Our data provide proof of concept for potential utilization of passive immunization in protecting poultry industry during infection outbreaks. Furthermore conserved nature of avian NP makes it an ideal candidate to produce antiserum protective against viral infection.

PMID: 19040734 [PubMed - as supplied by publisher]