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Hospital's faced with surges in patient visits during the H1N1 pandemic and who were unable to redirect patients to community influenza clinics had a variety of response options. This article reviews the implementation and impact of an "in-hospital" Emergency Department based influenza clinic.

China had taken strict measures for pandemic 2009 H1N1 infection with enhanced surveillance and hospital isolation since April 2009. In Shenzhen, over 1200 confirmed cases of H1N1 infection were identified. Three young patients died of severe pneumonia. Among them, two boys developed neurological complications. Cytokine storm seemed an important cause.

Influenza viruses continue to cause yearly epidemics and occasional pandemics in humans. In recent years, the threat of a possible influenza pandemic arising from the avian influenza A(H5N1) virus has prompted the development of comprehensive pandemic preparedness programs in many countries. The recent emergence of the pandemic influenza A(H1N1) 2009 virus from the Americas in early 2009, although surprising in its geographic and zoonotic origins, has tested these preparedness programs and revealed areas in which further work is necessary. Nevertheless, the plethora of epidemiologic, diagnostic, mathematical and phylogenetic modeling, and investigative methodologies developed since the severe acute respiratory syndrome outbreak of 2003 and the subsequent sporadic human cases of avian influenza have been applied effectively and rapidly to the emergence of this novel pandemic virus. This article summarizes some of the findings from such investigations, including recommendations for the management of patients infected with this newly emerged pathogen.

Archival serum samples from elderly individuals with underlying chronic obstructive pulmonary disease (COPD) who were enrolled in a double-blind case-control study of seasonal influenza vaccine efficacy were assayed for cross-neutralizing antibody formation to avian influenza A (H5N1) virus. Of 118 serum samples, 58 were collected from influenza vaccinees (mean age 68.5 y), and 60 from placebo controls (mean age 68.4 y) who received vitamin B injections. Blood samples were collected before and at 1 mo after seasonal influenza vaccination from all subjects; in addition, for a longitudinal follow-up period of 1 y paired-blood samples were collected again from subjects who developed acute respiratory illness. Hemagglutination inhibition assay for antibodies to influenza A (H1N1), influenza A (H3N2), and influenza B viruses was carried out to determine the serological response to vaccination, and to diagnose influenza viral infection, while microneutralization assays were performed to detect cross-reactive antibody to H5N1 virus. Pre-existing cross-reactive H5N1 antibody at reciprocal titer 10 was found in 6 (10.3%) vaccinees and 4 (6.7%) placebo controls. There was no change in H5N1 antibody titer in these subjects after vaccination. On the other hand, 3 (5.2%) vaccinees developed seroconversion to H5N1 virus at 1 mo after vaccination, even though they had no pre-existing H5N1 antibody in their first blood samples. No cross-neutralizing antibody to H5N1 virus was detected in the placebo controls or in the 22 influenza patients, suggesting that influenza vaccination, but not influenza virus infection, induces cross-neutralizing antibody against avian influenza H5N1 virus.

Influenza is an acute respiratory disease that causes epidemics and pandemics in the human population of temperate regions. Influenza epidemics occur every year during the winter months, affecting approximately 10% of the population. The primary strategy for reducing the effect of influenza in the community is to vaccinate persons who are at risk or caring for high-risk individuals each year before seasonal increases in influenza virus circulation occur. Antiviral drugs can be used for the treatment of influenza and the prevention of seasonal and post-exposure influenza. Four antiviral drugs are available for the prevention and treatment of influenza infections: oseltamivir, zanamivir, rimantadine and amantadine. Antiviral drugs can be used for the treatment of influenza and for post-exposure and seasonal influenza prevention. The cost-effectiveness of antiviral therapies ranged from cost savings to more than US$130,000 per quality-adjusted life-year (QALY) for influenza treatment, from GB pound9000 to more than pound1 million per QALY for seasonal prevention and from cost savings to pound100,000 per QALY for post-exposure prevention. Based on the cost-effectiveness threshold of pound30,000 or $40,000 per QALY, antiviral therapies can be recommended for influenza treatment and post-exposure prevention in healthy and high-risk individuals and for seasonal prevention in high-risk individuals. Zanamivir, oseltamivir and amantadine have favorable cost-effectiveness ratios for these interventions, but amantadine should only be used in countries with a low prevalence of resistant virus. The stockpile of antiviral drugs should be maintained in developed countries because they are cost effective for the prevention and treatment of a possible influenza pandemic.

Although influenza A viruses of avian origin have long been responsible for influenza pandemics, including the "Spanish flu" pandemic of 1918, human infections caused by avian subtypes of influenza A virus, most notably H5N1, have emerged since the 1990s (H5N1 in 1997; H9N2 in 1999; and H7N7 in 2003). The wide geographic distribution of influenza A H5N1 in avian species, and the number and severity of human infections are unprecedented. Together with the ongoing genetic evolution of this virus, these features make influenza A H5N1 a likely candidate for a future influenza pandemic. This article discusses the epidemiology, pathogenesis, and diagnosis of human infections caused by influenza A H5N1 virus.

The emergence of antiviral drug-resistant strains of the influenza virus in addition to the rapid spread of the recent pandemic A(H1N1) 2009 virus highlight the importance of surveillance of influenza in identifying new variants as they appear. In this study, genetic characteristics and antiviral susceptibility patterns of influenza samples collected in Lebanon during the 2008-09 season were investigated. Forty influenza virus samples were isolated from 89 nasopharyngeal swabs obtained from patients with influenza-like illness. Of these samples, 33 (82.5%) were A(H3N2), 3 (7.5%) were A(H1N1), and 4 (10%) were B. All the H3N2 viruses were resistant to amantadine but were sensitive to oseltamivir and zanamivir; while all the H1N1 viruses were resistant to oseltamivir (possessed H275Y mutation, N1 numbering, in their NA) but were sensitive to amantadine and zanamivir. In the case of influenza B, both Victoria and Yamagata lineages were identified (three and one isolates each, respectively) and they showed decreased susceptibility to oseltamivir and zanamivir when compared to influenza A viruses. Influenza circulation patterns in Lebanon were very similar to those in Europe during the same season. Continued surveillance is important to fully elucidate influenza patterns in Lebanon and the Middle East in general, especially in light of the current influenza pandemic.

Avian influenza A (H9N2) virus is transmitted sporadically from avian species to human causing mild diseases in immunocompetent person. We report two cases of human infection in immunocompromised patients in Hong Kong between 2008 and 2009. One patient had uneventful recovery with viral shedding at day 10 after symptom onset despite her underlying acute lymphoblastic leukaemia. The other patient with post-bone marrow transplant chronic graft-versus-host disease and bronhioltis obliterans went into respiratory failure. Genetic analysis revealed that these cases were caused by different genetic variants which are circulating in poultry in this region. Review of literature identified another 9 human cases reported in Southern China since 1988. It is possible that human infection with H9N2 is more common than what has been recognized. Continuous surveillance of H9N2 influenza virus infection in human is warranted.

Influenza is an important disease in children. In April 2009, human infections caused by a novel swine H1N1 virus were reported in Mexico, followed by a pandemic. As of 14 March 2010, more than 213 countries and overseas territories or communities have reported laboratory-confirmed cases of pandemic influenza H1N1 2009, including at least 16,813 deaths. This influenza pandemic is unique in many respects. Large outbreaks occurred outside the usual season for influenza infection. The virus also caused severe illnesses and deaths in younger people, with many deaths caused by severe pneumonia. A comprehensive approach to pandemic control has been launched, including infection control interventions, antiviral drugs and vaccines. Vaccination is the most efficient way to control morbidity and mortality resulting from influenza infections in humans. For the first time, an influenza vaccine against a pandemic strain became available before the winter. However, the initially smooth influenza vaccination program was disturbed by the fear of possible adverse events following immunization. In Taiwan, mistrust of the influenza vaccination has also caused significant social impacts towards the end of 2009. Lessons learned from this pandemic influenza H1N1 2009 might help health authorities and physicians shape their preparedness for the next pandemic.

Avian influenza A viruses continue to cause disease outbreaks in humans, and extrapulmonary infection is characteristic. In vitro studies demonstrate the activity of oseltamivir against avian viruses of the H5, H7 and H9 subtypes. In animal models of lethal infection, oseltamivir treatment and prophylaxis limit viral replication and improve survival. Outcomes are influenced by the virulence of the viral strain, dosage regimen and treatment delay; it is also critical for the compound to act systemically. Observational data on oseltamivir treatment in the early stages of disease suggest it is useful for improving survival in patients infected with H5 viruses, and drug-selected resistance has only rarely been reported. The WHO strongly recommends oseltamivir for the treatment of confirmed or suspected cases of human H5 infection and prophylaxis of those at high risk of infection. In addition to oral dosing, nasogastric administration appears to be a viable option for the management of severely ill patients, as is the use of higher doses and prolonged schedules. F. Hoffmann-La Roche Ltd, the manufacturer of oseltamivir, is developing a mathematical model to allow rapid prediction of appropriate dosage regimens for any future pandemic. Roche is also funding the Avian Influenza Registry, an online database that aims to collect information from clinicians worldwide on the course of avian influenza in humans.

Influenza A virus infection occurs in many species. Wild waterfowl harbor the widest variety of influenza A viruses and serve as a constant reservoir for the emergence of new viruses. Highly pathogenic avian influenza, or “fowl plague,” has been a known poultry disease for more than 130 years. It continues to emerge and reemerge, but global changes in trade and poultry production have expanded the impact and geographic range of these outbreaks. One subtype of highly pathogenic avian influenza, H5N1, has infected poultry on several continents as well as many people, leading to a human disease that is markedly different from seasonal influenza and that is associated with high mortality.

Little is known about pandemic 2009 influenza A (H1N1) among patients with human immunodeficiency virus (HIV) infection. We report a case of 2009 influenza A (H1N1) in a patient who was newly diagnosed as having HIV. His general condition was good, and he was successfully treated in an outpatient setting. The literature was reviewed for the diagnosis, treatment, prevention, and infection control of pandemic 2009 influenza A (H1N1) among those who have HIV infection.

International audience; The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

Background Oseltamivir is considered the drug of choice for patients with pandemic influenza for whom drug treatment is recommended because adamantanes seem to be ineffective against pandemic A/H1N1 influenza virus and zanamivir is contraindicated in people with underlying respiratory conditions and difficult to administer in younger children. Objectives To increase knowledge on oseltamivir resistance emergence in pandemic A/H1N1 influenza. Study design Description of the case of an 8-year-old boy with cystic fibrosis and Pseudomonas aeruginosa infection in whom an oseltamivir-resistant pandemic A/H1N1 influenza virus was demonstrated. Results On the basis of clinical and virological failure (nasopharyngeal secretions remained positive for pandemic A/H1N1 influenza virus and appearance of 275Y mutation in 100% virus population) on fifth day of treatment, oseltamivir was replaced by zanamivir inhalation (5 mg to be inhaled twice a day). This change was associated with a rapid improvement in the patient's general condition, respiratory findings and laboratory data (including disappearance of pandemic A/H1N1 influenza virus) in the absence of any adverse event. Conclusions The emergence of oseltamivir-resistant strains is related to the administration of the drug, supporting the restriction of oseltamivir use to carefully defined high-risk groups. Infection due to pandemic virus with the H275Y mutation can be associated with a severe clinical course, supporting the systematic monitoring of antiviral susceptibility in pandemic influenza-positive high-risk patients whose influenza is not resolved by oseltamivir treatment. Zanamivir inhalation can be successfully used in patients with cystic fibrosis without causing adverse respiratory events, highlighting that the risks and benefits of this drug must be considered on a patient by patient basis.

Objective: To report an 11-year-old girl with encephalitis-associated pandemic influenza A (H1N1) 2009 virus infection. Clinical Presentation and Intervention: An 11-year-old girl presented with a 6-day history of influenza-like illness followed by an altered mental status for 1 day. She tested positive for pandemic influenza A (H1N1) 2009 virus by PCR of her nasal swab. Her CSF analysis was completely normal, including PCR for pandemic influenza A virus. Her brain MRI and EEG showed evidence suggestive of encephalitis. She was treated with oral Oseltamivir with good recovery. Conclusion: This case report shows that neurological complications can occur after respiratory tract infection with pandemic influenza A (H1N1) 2009 virus.

On 24 April 2009, the World Health Organization (WHO) reported that seven patients in the USA (five in California and two in Texas) and three patients in Mexico had become infected with a new strain of influenza, subsequently designated the new influenza A virus (H1N1/09) (1). Molecular biological testing revealed that the new influenza A virus (H1N1/09) possesses the following genes: two genes derived from the strain of avian influenza that infected the Eurasian swine population in 1979; three corresponding to classical influenza A (H1N1) from the North American swine population; two representing a triple reassortment (recombination of various gene segments present in the gene pool) from the North American swine population; and one gene homologous to the strain of human influenza A that reached the human population in 1968 with avian influenza (2). Thus, the new influenza A virus (H1N1/09) contains only a single gene segment (PB1) corresponding to the two seasonal influenza strains (H1N1 and H3N2), namely, a gene segment that entered the H3N2 virus in 1968 from an avian source and has been circulating since then. Its remaining gene segments come from swine influenza viruses of Eurasian and North American origin and from avian influenza viruses of recent decades. On 5 May 2009, 1124 cases had already been reported worldwide. In view of ongoing human-to-human transmission in multiple regions of the world, the WHO declared a phase 6 pandemic on 11 June 2009. This was the start of the new influenza A virus (H1N1/09) pandemic (3). By this time, nearly 30 000 persons had become ill with the new virus worldwide, and 144 had died in 74 countries. In Germany, the virus was found in more than 160 persons up to 13 June 2009. About half of all cases were in the state of North Rhine–Westphalia. Physicians in the Department of Gastroenterology, Hepatology, and Infectious Disease and the Department of General Pediatrics at the Dusseldorf University Hospital tested persons with suspected H1N1/09 infection for the presence of the virus. In this article, we report our experience with the new influenza virus during the first wave of the pandemic in the summer of 2009.

The direct transmission of highly pathogenic avian influenza (HPAI) viruses to humans in Eurasia and subsequent disease has sparked research efforts leading to better understanding of HPAI virus transmission and pathogenicity in mammals. There has been minimal focus on examining the capacity of circulating low pathogenic wild bird avian influenza viruses to infect mammals. We have utilized a mouse model for influenza virus infection to examine 28 North American wild bird avian influenza virus isolates that include the hemagglutinin subtypes H2, H3, H4, H6, H7, and H11. We demonstrate that many wild bird avian influenza viruses of several different hemagglutinin types replicate in this mouse model without adaptation and induce histopathologic lesions similar to other influenza virus infections but cause minimal morbidity. These findings demonstrate the potential of wild avian influenza viruses to directly infect mice without prior adaptation and support their potential role in emergence of pandemic influenza.

Background: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase)™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses. Methods and Findings: The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus. Conclusions: The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV., published_or_final_version

Swine influenza was first described in the 1918 pandemic and made a resurgence in April 2009 in the form of a triple-reassortant influenza A virus, which is composed of a combination of human, swine, and Eurasian avian strains. As evidenced with previous influenza pandemics, young adults and children aged < 24 years are the population most affected. Definitive diagnosis has largely been limited by the inability of conventional influenza testing to distinguish among influenza A subtypes; however, the surge in pandemic cases clearly emerged at the end of the annual influenza season in the northern hemisphere. The pandemic variant influenza A (H1N1) strain is typically susceptible to oseltamivir and resistant to adamantanes, unlike the 2008 to 2009 seasonal influenza A (H1N1). However, 2 cases of oseltamivir-resistant pandemic-variant influenza A (H1N1) were reported in late August 2009. The full impact of the current pandemic is not yet clear, and further reassortment with the circulating seasonal influenza strains in the upcoming 2009 fall season could potentially lead to acquisition of widespread oseltamivir resistance. Vaccination will become paramount in importance for prevention and public health safety.

The A(H5N1) influenza virus pandemic may be the result of avian H5N1 adapting to humans, leading to massive human to human transmission in a context of a lack of pre-existing immunity. As A(H1N1) and A(H5N1) share the same neuraminidase subtype, anti-N1 antibodies subsequent to H1N1 infections or vaccinations may confer some protection against A(H5N1). We analysed, by microneutralization assay, the A/Vietnam/1194/04 (H5N1) anti-N1 cross-protection acquired either during A/New-Caledonia/20/99 (H1N1) infection or vaccination. In cases with documented H1N1 infection, H5N1 cross-protection could be observed only in patients born between 1930 and 1950. No such protection was detected in the sera of vaccinated individuals.

The recent emergence of seasonal influenza A(H1N1) strains resistant to oseltamivir makes it necessary to monitoring carefully the susceptibility of human influenza viruses to neuraminidase inhibitors. We report the prevalence of the oseltamivir resistance among influenza A viruses circulating in south-western France over the past three years: seasonal influenza A(H1N1), seasonal influenza A(H3N2), and the influenza A(H1N1)v viruses associated with the ongoing 2009 pandemic. The main result of the study is the absence of oseltamivir resistance in the pandemic H1N1 strains studied so far (n=129).

Zoonotic agents challenging the world every year afresh are influenza A viruses. In the past, human pandemics caused by influenza A viruses had been occurring periodically. Wild aquatic birds are carriers of the full variety of influenza virus A subtypes, and thus, most probably constitute the natural reservoir of all influenza A viruses. Whereas avian influenza viruses in their natural avian reservoir are generally of low pathogenicity (LPAIV), some have gained virulence by mutation after transmission and adaptation to susceptible gallinaceous poultry. Those so-called highly pathogenic avian influenza viruses (HPAIV) then cause mass die-offs in susceptible birds and lead to tremendous economical losses when poultry is affected. Besides a number of avian influenza virus subtypes that have sporadically infected mammals, the HPAIV H5N1 Asia shows strong zoonotic characteristics and it was transmitted from birds to different mammalian species including humans. Theoretically, pandemic viruses might derive directly from avian influenza viruses or arise after genetic reassortment between viruses of avian and mammalian origin. So far, HPAIV H5N1 already meets two conditions for a pandemic virus: as a new subtype it has been hitherto unseen in the human population and it has infected at least 438 people, and caused severe illness and high lethality in 262 humans to date (August 2009). The acquisition of efficient human-to-human transmission would complete the emergence of a new pandemic virus. Therefore, fighting H5N1 at its source is the prerequisite to reduce pandemic risks posed by this virus. Other influenza viruses regarded as pandemic candidates derive from subtypes H2, H7, and H9 all of which have infected humans in the past. Here, we will give a comprehensive overview on avian influenza viruses in concern to their zoonotic potential.

A new strain of influenza A virus (novel influenza A H1N1) that originated in swine has rapidly spread from the initial outbreak in Mexico and the southern United States to Canada and many countries in Europe and Asia. Consequently, the World Health Organization raised the level of alert for an

The authors assessed the risk of avian influenza virus infection among humans by conducting a serologic surveillance study in Guangzhou. The findings highlight the potential risk of H9 avian influenza virus to public health.

Unexpectedly, swine-origin influenza A (H1N1) virus (S-OIV, informally known as swine flu) appeared in North America at the very end of the 2008-2009 influenza season and began to spread internationally. As the world mobilizes for a potential pandemic, this article summarizes the developments in diagnosis, treatment, and prevention.

Avian influenza A H5N1 remains the most threatening virus that may cause another devastating pandemic in the foreseeable future. In 1997, Hong Kong was the first place to detect human infections due to this virus originated from birds. The experience and lessons learnt provide important information for controlling further outbreaks caused by avian influenza viruses.

Background: Influenza infection is a global problem affecting millions of people worldwide, despite efficacious vaccines. Treatment and prophylaxis against influenza have been successful using antiviral medications such as adamantanes and neuraminidase inhibitors. Objective: To review the antiviral agents and specifically the neuraminidase inhibitor, oseltamivir, for use in treatment and prophylaxis of influenza infection. Methods: This review focuses on published literature regarding the clinical use of oseltamivir, as well as discussing emerging threats such as avian influenza, antiviral resistance, and strategies such as combination antiviral treatment to mitigate these threats. Results: Oseltamivir is effective in reducing symptom burden in those with influenza A or B infection, and is preventative against developing infection after exposure. Emergence of naturally occurring or post-treatment oseltamivir-resistant influenza as well as an avian influenza pandemic may limit its future use as a monothera...

Highly pathogenic H5N1 avian influenza virus can infect humans and is currently the most deadly influenza virus that has crossed the species barrier. As of December 2007, the spread of H5N1 virus from human to human has been rare. Nobody can predict if H5N1 may cause a pandemic. However, the number of human cases is continuously increasing and changes in virulence and epidemiology have been detected. There are specific pathogenic features of H5N1 infection. In contrast to human-adapted influenza A strains, H5N1 preferentially infects cells of the lower respiratory tract and may spread to tissues outside the respiratory tract in humans. Moreover, H5N1 replication is prolonged in target organs and results in higher viral loads and increased tissue damage. These features will have to be considered for therapeutic protocols for H5N1 infection in humans. Rapid genetic and antigenic changes observed in H5N1 virus isolates represent a challenge for the development of vaccines. In the present review, current knowledge about epidemiology, virulence factors and pathology of H5N1 infections in humans are summarised and discussed. Moreover, the possible roles of anti-influenza drugs in the pandemic situation as well as the development of effective vaccines are subject of this overview.

Influenza viruses with novel hemagglutinin and 1 or more accompanying genes derived from avian influenza viruses sporadically emerge in humans and have the potential to result in a pandemic if the virus causes disease and spreads efficiently in a population that lacks immunity to the novel hemagglutinin. Since 1997, multiple avian influenza virus subtypes have been transmitted directly from domestic poultry to humans and have caused a spectrum of human disease, from asymptomatic to severe and fatal. To assess the pandemic risk that avian influenza viruses pose, we have used multiple strategies to better understand the capacity of avian viruses to infect, cause disease, and transmit among mammals, including humans. Seroepidemiologic studies that evaluate the frequency and risk of human infection with avian influenza viruses in populations with exposure to domestic or wild birds can provide a better understanding of the pandemic potential of avian influenza subtypes. Investigations conducted in Hong Kong following the first H5N1 outbreak in humans in 1997 determined that exposure to poultry in live bird markets was a key risk factor for human disease. Among poultry workers, butchering and exposure to sick poultry were risk factors for antibody to H5 virus, which provided evidence for infection. A second risk assessment tool, the ferret, can be used to evaluate the level of virulence and potential for host-to-host transmission of avian influenza viruses in this naturally susceptible host. Avian viruses isolated from humans exhibit a level of virulence and transmissibility in ferrets that generally reflects that seen in humans. The ferret model thus provides a means to monitor emerging avian influenza viruses for pandemic risk, as well as to evaluate laboratory-generated reassortants and mutants to better understand the molecular basis of influenza virus transmissibility. Taken together, such studies provide valuable information with which we can assess the public health risk of avian influenza viruses.

H9N2 avian influenza viruses have circulated widely in domestic poultry around the world, and their outbreaks have resulted in heavy morbidity and mortality. In addition, H9N2 avian influenza viruses were transmitted directly from birds to humans in Hong Kong and mainland China during 1998 and 2003, which prompted the public health authorities to seek protective strategies to control H9N2 influenza viruses. In this study, we attempted to develop a DIVA (differentiating infected and vaccinated animals) strategy for H9N2 avian influenza viruses. This strategy does not interfere with serological monitoring and allows effective control of H9N2 avian influenza. We generated a reassortant H9N1 influenza vaccine strain by reverse genetics and employed an enzyme-linked immunosorbent assay (ELISA) with a truncated N1 antigen expressed in E. coli to differentiate between vaccinated and naturally infected animals. Immunization of BALB/c mice with the inactivated reassortant H9N1 vaccine conferred protection against lethal challenge with H9N2 viruses. Meanwhile, the ELISA can be used to distinguish between vaccination and natural infection quickly and easily. Therefore, this study has opened up a new avenue for the control of H9N2 avian influenza.

Since 1918, influenza virus has been one of the major causes of morbidity and mortality, especially among young children. Though the commonly circulating strain of the virus is not virulent enough to cause mortality, the ability of the virus genome to mutate at a very high rate may lead to the emergence of a highly virulent strain that may become the cause of the next pandemic. Apart from the influenza virus strain circulating in humans (H1N1 and H3N2), the avian influenza H5N1 H7 and H9 virus strains have also been reported to have caused human infections, H5N1 H7 and H9 have shown their ability to cross the species barrier from birds to humans and further replicate in humans. This review addresses the biological and epidemiological aspects of influenza virus and efforts to have a control on the virus globally.

Influenza A viruses are highly infectious respiratory pathogens that can infect many species. Birds are the reservoir for all known influenza A subtypes; and novel influenza viruses can emerge from birds and infect mammalian species including humans. Because swine are susceptible to infection with both avian and human influenza viruses, novel reassortant influenza viruses can be generated in this mammalian species by reassortment of influenza viral segments leading to the “mixing vessel” theory. There is no direct evidence that the reassortment events culminating in the 1918, 1957 or 1968 pandemic influenza viruses originated from pigs. Genetic reassortment among avian, human and/or swine influenza virus gene segments has occurred in pigs and some novel reassortant swine viruses have been transmitted to humans. Notably, novel reassortant H2N3 influenza viruses isolated from the US pigs, most likely infected with avian influenza viruses through surface water collected in ponds for cleaning barns and watering animals, had a similar genetic make-up to early isolates (1957) of the H2N2 human pandemic. These novel H2N3 swine viruses were able to cause disease in swine and mice and were infectious and highly transmissible in swine and ferrets without prior adaptation. The preceding example shows that pigs could transmit novel viruses from an avian reservoir to other mammalian species. Importantly, H2 viruses pose a substantial risk to humans because they have been absent from mammalian species since 1968 and people born after 1968 have little preexisting immunity to the H2 subtype. It is difficult to predict which virus will cause the next human pandemic and when that pandemic might begin. Importantly, the establishment and spread of a reassorted mammalian-adapted virus from pigs to humans could happen anywhere in the world. Therefore, both human and veterinary research needs to give more attention to potential cross-species transmission capacity of influenza A viruses.

Preventative vaccination is the most effective way to control epidemic and, perhaps, pandemic influenza viral infections. However, the immunogenicity and efficacy of influenza vaccines against epidemic strains are suboptimal among older adults. The risk of serious complications from influenza viral infection is compounded by co-morbid conditions among older adults. Furthermore, despite annual influenza vaccination campaigns, the vaccination rates in high risk populations range from 60.5 - 79.2% only [1] . In addition, H5N1 avian influenza viruses have the potential to cause a pandemic. However, H5N1 vaccines currently licensed in the US are poorly immunogenic in high doses in the absence of an adjuvant even in healthy adults.In this review, we address the current status of vaccines against epidemic and avian influenza viruses of pandemic potential.We have limited the review to the discussion of technologies and strategies that have progressed to human clinical trials and/or licensure for seasonal and pandemic influenza.Improving the immunogenicity of vaccines against avian influenza viruses, as well as aggressive programs to vaccinate high risk populations against seasonal and pandemic influenza, are crucial for our public health efforts in minimizing the impact of influenza epidemics or pandemics.

Waterfowl represent the natural reservoir of all subtypes of influenza A viruses, including H5N1. Ducks are especially considered major contributors to the spread of H5N1 influenza A viruses because they exhibit diversity in morbidity and mortality. Therefore, as a preventive strategy against endemic as well as pandemic influenza, it is important to reduce the spread of H5N1 influenza A viruses in duck populations. Here, we describe the pathogenicity of dominant clades (clades 1 and 2) of H5N1 influenza A viruses circulating in birds in Asia. Four representatives of dominant clades of the viruses cause symptomatic infection but lead to different profiles of lethality in domestic ducks. We also demonstrate the efficacy, cross-protectiveness, and immunogenicity of three different inactivated oil emulsion whole-virus H5 influenza vaccines (derived by implementing reverse genetics) to the viruses in domestic ducks. A single dose of the vaccines containing 1 μg of hemagglutinin protein provides complete protection against a lethal A/Duck/Laos/25/06 (H5N1) influenza virus challenge, with no evidence of morbidity, mortality, or shedding of the challenge virus. Moreover, two of the three vaccines achieved complete cross-clade or cross-subclade protection against the heterologous avian influenza virus challenge. Interestingly, the vaccines induce low or undetectable titers of hemagglutination inhibition (HI), cross-HI, and/or virus neutralization antibodies. The mechanism of complete protection in the absence of detectable antibody responses remains an open question.

Background: H7 and H9 subtype avian influenza viruses pose a similar threat to humans as H5 virus. Objectives: This study aims to identify the potential existence of H7 and H9 avian influenza infections in farmers and in poultry workers in northern China regions with highly pathogenic avian influenza (HPAI) H5N1 outbreaks. Study design: Sera were collected from farmers in Xinjiang Uygur autonomous region and Liaoning province and poultry workers in Shandong province. Sera from healthy residents in Shanxi province were used as the controls. H7 and H9 virus infections were examined by hemagglutination inhibition (HI) assay using horse erythrocytes. The titer equal to or greater than 1:160 was considered positive. Results: A total of 583 sera collected from farmers in Xinjiang were tested, and 10 (1.7%) were positive for H9 virus infection. Out of 200 sera collected from Liaoning, two (1.0%) were infected by H9 virus. No H7 virus infection was detected in the above serum samples. Neither H7 nor H9 virus infection was identified in 277 poultry workers of Shandong and in 407 residents of Shanxi. Conclusions: Although H9 virus infection was limited in farmers from Xinjiang and Liaoning, a public health alert is needed as novel pandemic influenza strains may develop unnoticed given the presence of subclinical infections, and the possibility of re-assortment with prevailing H5N1 virus in these regions. Published by Elsevier B.V.

An epidemic of human transmitted avian influenza could have casualties on a scale seen in the great Spanish influenza pandemic of 1918. This paper proposes that should such occur before effective vaccines and antiviral drugs are available, the outbreak could be significantly slowed by consumption of raw milk produced by herds of pathogen-free lactating cows intranasally inoculated with heat-sterilized sputa pooled from avian influenza patients, supplemented by parenteral serum immune globulin from the same cows. Efficiency of bovine antibody production could be enhanced using cholera toxin subunit b, and milk production could be rapidly accelerated using recombinant bovine somatotropin hormone. In this way, it would be possible to quickly create and distribute large quantities of milk-based and serum-based passive immune globulin active against the strains of avian influenza present in a particular geographic area and gain time for production of human convalescent plasma and other public health measures. This novel approach might also have utility for other serious respiratory infectious diseases, including non-avian influenza, SARS, hantavirus, respiratory syncytial virus, antibiotic-resistant Streptococcus pneumoniae and pneumonia-causing Staphylococcus aureus.

Reports of human cases of infection with avian influenza A(H5N1) virus have received increased public attention because of the potential for the emergence of a pandemic strain. In the end of 2005 and the beginning of 2006, avian influenza A(H5N1) virus caused outbreaks among domestic poultry and was isolated from wild swans in many European countries, including Bulgaria. Between January and March 2006, samples were collected from 26 patients who had been in close contact with ill or dead birds and developed a subsequent respiratory illness. The testing took place at the National Laboratory of Influenza in Sofia. Specific ?(H5N1) assays were applied for screening (Sacace RT-PCR and real-time kit). Avian flu ?(H5N1) virus was not detected in any of the patients tested. In three patients, human subtype ?(H1N1) influenza virus, identifiable by RT-PCR was isolated and further characterized by hemagglutination inhibition test (HIT). The reliability of the molecular assays used in this investigation was demonstrated in an International Quality Control for Human and Avian ?(H5N1) Influenza performed later in 2006 by INSTAND (Society for Promotion of Quality Assurance in the Medical Laboratories), Germany.

Avian influenza is a disease of both veterinary and public health importance. Influenza A viruses infect a range of hosts, including humans, and can cause significant morbidity and mortality. These viruses have high genetic variability, and new strains develop through both mutation and reassortment. Modes of transmission as well as the location of viral shedding may differ both by host species and by viral strain. Clinical signs of influenza A virus infection in birds vary considerably depending on the viral subtype, environmental factors, and age, health status, and species of the bird and range from decreased egg production and gastrointestinal manifestations to nervous system disorders and respiratory signs. Most commonly, peracute death with minimal clinical disease is observed in poultry infected with a highly pathogenic avian influenza virus. There are various prevention and control strategies for avian influenza, including education, biosecurity, surveillance, culling of infected animals, and vaccination. These strategies will differ by institution and current federal regulations. Each institution should have an established biosecurity protocol that can be properly instituted. Lastly, human health precautions, such as proper hand hygiene, personal protective equipment, and employee health monitoring, are imperative for at-risk individuals.

Background The H5N1 strain of avian influenza virus has been involved in severe mortality in domestic poultry, and has also been found in different species of wildlife in Europe. The Basque Country avian influenza surveillance program began sample collection and processing the fall of 2005. Results Here we report the first confirmation of the presence of highly pathogenic H5N1 strain in a Great Crested Grebe (Podiceps cristatus) found dead in a pond near Vitoria in the Basque Country on the North of Spain. Regarding the survey for generic influenza type A virus, we have obtained positive results in about 8% of more that 3500 birds examined. Conclusion We think that the self-limiting nature of our finding and others proves that certain regions have ecological, geographical and climatological features that make it difficult for the H5N1 virus to spread 1 and cause disease at least in the large scale scenario that has been worrying human and animal health authorities during the last years.

Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.

Functional and molecular techniques have both been employed to measure the production of cytokines following influenza infection. Historically, the use of functional or antibody-based techniques was employed in mammalian immunology. In avian immunology, only a few commercial antibodies are available to measure avian cytokines. However, the determination of the genomic sequence of Gallus gallus species has made it possible to measure cytokine induction without monoclonal antibody- or functional-based tests, but rather based on molecular techniques. Although these tests do not measure functionally expressed cytokines, the lack of reagents to identify and quantify avian cytokines makes them critical to extend any measure of cytokine response. Measurement of cytokine induction, based on the design of primers and probes for RT-PCR or real-time RT-PCR for the cytokine mRNA, has become one of the more recent technologies reported to measure avian cytokines. It is important to note that small nucleotide polymorphisms between different lines of birds may result in substandard results when using published primer and probe sequences. This requires empirical testing to ensure adequate results.

Pigs are an important host in influenza virus ecology since they are susceptible to infection with both avian and human influenza A viruses, often being involved in interspecies transmission, facilit

Influenza viruses are significant human respiratory pathogens that cause both seasonal, endemic infections and periodic, unpredictable pandemics. The worst pandemic on record, in 1918, killed approximately 50 million people worldwide. Human infections caused by H5N1 highly pathogenic avian influenza viruses have raised concern about the emergence of another pandemic. The histopathology of fatal influenza virus pneumonias as documented over the past 120 years is reviewed here. Strikingly, the spectrum of pathologic changes described in the 1918 influenza pandemic is not significantly different from the histopathology observed in other less lethal pandemics or even in deaths occurring during seasonal influenza outbreaks.

Introduction. Acute respiratory infections are the most common infections in the human population. Among them, virus infections, especially those caused by influenza viruses, have an important place. Type A influenza. Type A influenza virus caused three epidemics during the last century. A high percetage of deceased in pandemics of 1918, and 1919 were young, healthy persons, with many of the deaths due to an unusually severe, hemorrhagic pneumonia. At the end of 2003, and the beginning of 2004, an epidemic emerged in South East Asia of poultry influenza caused by animal (avian) virus. Later it spread to the human population, with a high death rate of 73% and with a possibility of interhuman transmission. This review article provides an overview of the clinical manifestations, laboratory findings and chest radiographs. Apart from the symptomatic and supportive therapy, there are antiviral drugs and corticosteriods. Conclusion. The use of vaccine containing subtypes of virus hemagglutinins and neuraminidase from an influenza virus currently infecting the population has a great importance. .