Highly Pathogenic Avian Influenza H5N1 Virus Infection Research Articles

Outbreak of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in cats, Poland, June to July 2023.

BackgroundOver a 3-week period in late June/early July 2023, Poland experienced an outbreak caused by highly pathogenic avian influenza (HPAI) A(H5N1) virus in cats.AimThis study aimed to characterise the identified virus and investigate possible sources of infection.MethodsWe performed next generation sequencing and phylogenetic analysis of detected viruses in cats.ResultsWe sampled 46 cats, and 25 tested positive for avian influenza virus. The identified viruses belong to clade 2.3.4.4b, genotype CH (H5N1 A/Eurasian wigeon/Netherlands/3/2022-like). In Poland, this genotype was responsible for several poultry outbreaks between December 2022 and January 2023 and has been identified only sporadically since February 2023. Viruses from cats were very similar to each other, indicating one common source of infection. In addition, the most closely related virus was detected in a dead white stork in early June. Influenza A(H5N1) viruses from cats possessed two amino acid substitutions in the PB2 protein (526R and 627K) which are two molecular markers of virus adaptation in mammals. The virus detected in the white stork presented one of those mutations (627K), which suggests that the virus that had spilled over to cats was already partially adapted to mammalian species.ConclusionThe scale of HPAI H5N1 virus infection in cats in Poland is worrying. One of the possible sources seems to be poultry meat, but to date no such meat has been identified with certainty. Surveillance should be stepped up on poultry, but also on certain species of farmed mammals kept close to infected poultry farms.

MicroRNA expression profiling in the lungs of genetically different Ri chicken lines against the highly pathogenic avian influenza H5N1 virus.

The highly pathogenic avian influenza (HPAI) virus triggers infectious diseases, resulting in pulmonary damage and high mortality in domestic poultry worldwide. This study aimed to analyze miRNA expression profiles after infection with the HPAI H5N1 virus in resistant and susceptible lines of Ri chickens.For this purpose, resistant and susceptible lines of Vietnamese Ri chicken were used based on the A/G allele of Mx and BF2 genes. These genes are responsible for innate antiviral activity and were selected to determine differentially expressed (DE) miRNAs in HPAI-infected chicken lines using small RNA sequencing. A total of 44 miRNAs were DE after 3 days of infection with the H5N1 virus. Computational program analysis indicated the candidate target genes for DE miRNAs to possess significant functions related to cytokines, chemokines, MAPK signaling pathway, ErBb signaling pathway, and Wnt signaling pathway. Several DE miRNA-mRNA matches were suggested to play crucial roles in mediating immune functions against viral evasion. These results revealed the potential regulatory roles of miRNAs in the immune response of the two Ri chicken lines against HPAI H5N1 virus infection in the lungs.

Public Health Response to Outbreaks of Highly Pathogenic Avian Influenza (H5N1)

Abstract Aim Human infections from highly pathogenic avian influenza (HPAI) H5N1 are associated with significant morbidity and mortality internationally. This study aimed to use routinely available data to examine key strategies to prevent H5N1 transmission to humans during outbreaks in poultry in residents in Cavan, Louth, Meath and Monaghan. Study design Cross-sectional based study. Methods Data were obtained from Health Protection Team (HPT) in the Department of Public Health (DPH), HSE North-East and Department of Agriculture, Food, and the Marine (DAFM). Data entry and analyses were conducted using Microsoft Excel 2016. Results The public health response focussed on contact tracing, monitoring, and follow-up for household, farm-workers, and DAFM staff exposed on the affected farms. A total of 157 contact episodes were identified. Contacts received advice about active monitoring from their last exposure. A total of 111 (80%) were recommended chemoprophylaxis for exposure to HPAI H5N1. During the active monitoring period, two contacts developed acute respiratory symptoms, and parainfluenza 3 and rhino/enterovirus were identified in these individuals respectively. Conclusions The findings of this study, using routinely gathered data, highlighted that collaboration between public health and DAFM at regional and national level was key to rapid response to these outbreaks of HPAI in domesticated poultry. In addition, the public health response was successful in preventing H5N1 transmission from domesticated birds to humans. Key messages • HPAI H5N1 virus infections transmissions from poultry to humans is low. • Effective public health measures are crucial to further mitigate the risks to an absolute minimum.

Wild ducks excrete highly pathogenic avian influenza virus H5N8 (2014–2015) without clinical or pathological evidence of disease

Highly pathogenic avian influenza (HPAI) is essentially a poultry disease. Wild birds have traditionally not been involved in its spread, but the epidemiology of HPAI has changed in recent years. After its emergence in southeastern Asia in 1996, H5 HPAI virus of the Goose/Guangdong lineage has evolved into several sub-lineages, some of which have spread over thousands of kilometers via long-distance migration of wild waterbirds. In order to determine whether the virus is adapting to wild waterbirds, we experimentally inoculated the HPAI H5N8 virus clade 2.3.4.4 group A from 2014 into four key waterbird species—Eurasian wigeon (Anas penelope), common teal (Anas crecca), mallard (Anas platyrhynchos), and common pochard (Aythya ferina)—and compared virus excretion and disease severity with historical data of the HPAI H5N1 virus infection from 2005 in the same four species. Our results showed that excretion was highest in Eurasian wigeons for the 2014 virus, whereas excretion was highest in common pochards and mallards for the 2005 virus. The 2014 virus infection was subclinical in all four waterbird species, while the 2005 virus caused clinical disease and pathological changes in over 50% of the common pochards. In chickens, the 2014 virus infection caused systemic disease and high mortality, similar to the 2005 virus. In conclusion, the evidence was strongest for Eurasian wigeons as long-distance vectors for HPAI H5N8 virus from 2014. The implications of the switch in species-specific virus excretion and decreased disease severity may be that the HPAI H5 virus more easily spreads in the wild-waterbird population.

Physician's knowledge, attitudes, and practices regarding seasonal influenza, pandemic influenza, and highly pathogenic avian influenza A (H5N1) virus infections of humans in Indonesia.

Indonesia has reported highest number of fatal human cases of highly pathogenic avian influenza (HPAI) A (H5N1) virus infection worldwide since 2005. There are limited data available on seasonal and pandemic influenza in Indonesia. During 2012, we conducted a survey of clinicians in two districts in western Java, Indonesia, to assess knowledge, attitudes, and practices (KAP) of clinical diagnosis, testing, and treatment of patients with seasonal influenza, pandemic influenza, or HPAI H5N1 virus infections. Overall, a very low percentage of physician participants reported ever diagnosing hospitalized patients with seasonal, pandemic, or HPAI H5N1 influenza. Use of influenza testing was low in outpatients and hospitalized patients, and use of antiviral treatment was very low for clinically diagnosed influenza patients. Further research is needed to explore health system barriers for influenza diagnostic testing and availability of antivirals for treatment of influenza in Indonesia.

Evaluation of elution methods for recovery of highly pathogenic avian influenza (H5N1) virus from infected duck feathers

In view of the tenacity of viruses in the feathers, many workers have suggested the importance of using feathers as the diagnostic material for epidemiological surveillance of highly pathogenic avian influenza (HPAI) H5N1 virus infections. In this study, we have compared the efficiency of two different processing methods, immersion method and trituration method for elution of HPAI H5N1 virus from the feathers of avian influenza negative ducks in terms of virus isolation in 9-to 11-day-old embryonated specific pathogen free chicken eggs and viral RNA detection by haemagglutinin gene based real-time RTPCR. The recovery of virus by immersion method in terms of percent infectivity in 3 replicates was 96.67, 93.33 and 96.67, whereas in trituration method, percent infectivity was 26.67, 20 and 16.67. In real-time RTPCR, viral RNA could be detected in 17 out of 18 samples by immersion method and from only 2 out of 18 samples by trituration method. The study revealed that the immersion method gave higher viral infectivity percentage and could also be easily detected by real-time RTPCR. We conclude that immersion method of virus elution could be useful for processing of shed duck feathers present in the environment for epidemiological screening against HPAI H5N1 virus infections.

ID: 201: Live cell imaging-based studies of dynamics of antiviral signaling

Highly pathogenic avian influenza (HPAI) H5N1 virus is posing a continuous threat by frequent human infections with mortality of 60%. The dysregulation of cytokine-mediated host antiviral responses are suggested to be the reason for the severe pathology behind the H5N1 infection. Studying the infective H5N1 virus is challenging in the BSL-3 facilities. Sample preparation for the biochemical analyses is laborious and demands lots of handwork with infective material. Thus, we have sought other, safer approaches to elucidate the temporal control of antiviral activation by H5N1 infection. We have established a live-cell fluorescence microscopy facility in our BSL-3 laboratory for the analysis of HPAI H5N1 virus infection at the single-cell level. As many attempts have failed to create an influenza virus carrying a fluorescence protein, we will construct reporter cells where we fuse IRF3, RelA and STAT1 into a fluorescent moiety. With these reporters we will elucidate the nuclear translocation dynamics of these transcription factors reflecting their activation state during infection. In addition, we will construct reporters where cytokine gene promoter drives the expression of fluorescent protein and with these we are able to visualize the activation of cytokine gene expression. The virus replication reporters will be constructed by transducing a fluorescence protein-encoding influenza virus-like RNA under the control of human RNA polymerase I promoter and terminator similarly as in recombinant influenza system. These studies will establish completely new aspects to the infection studies of H5N1 virus and lead to more comprehensive understanding of the molecular mechanisms underlying the H5N1 infection.

The East Jakarta Project: surveillance for highly pathogenic avian influenza A(H5N1) and seasonal influenza viruses in patients seeking care for respiratory disease, Jakarta, Indonesia, October 2011-September 2012.

Indonesia has reported the most human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus worldwide. We implemented enhanced surveillance in four outpatient clinics and six hospitals for HPAI H5N1 and seasonal influenza viruses in East Jakarta district to assess the public health impact of influenza in Indonesia. Epidemiological and clinical data were collected from outpatients with influenza-like illness (ILI) and hospitalized patients with severe acute respiratory infection (SARI); respiratory specimens were obtained for influenza testing by real-time reverse transcription-polymerase chain reaction. During October 2011-September 2012, 1131/3278 specimens from ILI cases (34·5%) and 276/1787 specimens from SARI cases (15·4%) tested positive for seasonal influenza viruses. The prevalence of influenza virus infections was highest during December-May and the proportion testing positive was 76% for ILI and 36% for SARI during their respective weeks of peak activity. No HPAI H5N1 virus infections were identified, including hundreds of ILI and SARI patients with recent poultry exposures, whereas seasonal influenza was an important contributor to acute respiratory disease in East Jakarta. Overall, 668 (47%) of influenza viruses were influenza B, 384 (27%) were A(H1N1)pdm09, and 359 (25%) were H3. While additional data over multiple years are needed, our findings suggest that seasonal influenza prevention efforts, including influenza vaccination, should target the months preceding the rainy season.

Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses.

Highly pathogenic avian influenza (HPAI) H5N1 viruses cause severe infection in chickens at near complete mortality, but corresponding infection in ducks is typically mild or asymptomatic. To understand the underlying molecular differences in host response, primary chicken and duck lung cells, infected with two HPAI H5N1 viruses and a low pathogenicity avian influenza (LPAI) H2N3 virus, were subjected to RNA expression profiling. Chicken cells but not duck cells showed highly elevated immune and pro-inflammatory responses following HPAI virus infection. HPAI H5N1 virus challenge studies in chickens and ducks corroborated the in vitro findings. To try to determine the underlying mechanisms, we investigated the role of signal transducer and activator of transcription-3 (STAT-3) in mediating pro-inflammatory response to HPAIV infection in chicken and duck cells. We found that STAT-3 expression was down-regulated in chickens but was up-regulated or unaffected in ducks in vitro and in vivo following H5N1 virus infection. Low basal STAT-3 expression in chicken cells was completely inhibited by H5N1 virus infection. By contrast, constitutively active STAT-3 detected in duck cells was unaffected by H5N1 virus infection. Transient constitutively-active STAT-3 transfection in chicken cells significantly reduced pro-inflammatory response to H5N1 virus infection; on the other hand, chemical inhibition of STAT-3 activation in duck cells increased pro-inflammatory gene expression following H5N1 virus infection. Collectively, we propose that elevated pro-inflammatory response in chickens is a major pathogenicity factor of HPAI H5N1 virus infection, mediated in part by the inhibition of STAT-3.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-014-0118-3) contains supplementary material, which is available to authorized users.

Seasonal patterns in human A (H5N1) virus infection: analysis of global cases.

BackgroundHuman cases of highly pathogenic avian influenza (HPAI) A (H5N1) have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods.MethodsWe performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Köppen-Geiger climate classification.FindingsWe identified 617 human cases (611 with complete seasonal data) occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03) than summer (n = 64), and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season.InterpretationAcross diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.

Demographic and Clinical Predictors of Mortality from Highly Pathogenic Avian Influenza A (H5N1) Virus Infection: CART Analysis of International Cases

BackgroundHuman infections with highly pathogenic avian influenza (HPAI) A (H5N1) viruses have occurred in 15 countries, with high mortality to date. Determining risk factors for morbidity and mortality from HPAI H5N1 can inform preventive and therapeutic interventions.MethodsWe included all cases of human HPAI H5N1 reported in World Health Organization Global Alert and Response updates and those identified through a systematic search of multiple databases (PubMed, Scopus, and Google Scholar), including articles in all languages. We abstracted predefined clinical and demographic predictors and mortality and used bivariate logistic regression analyses to examine the relationship of each candidate predictor with mortality. We developed and pruned a decision tree using nonparametric Classification and Regression Tree methods to create risk strata for mortality.FindingsWe identified 617 human cases of HPAI H5N1 occurring between December 1997 and April 2013. The median age of subjects was 18 years (interquartile range 6–29 years) and 54% were female. HPAI H5N1 case-fatality proportion was 59%. The final decision tree for mortality included age, country, per capita government health expenditure, and delay from symptom onset to hospitalization, with an area under the receiver operator characteristic (ROC) curve of 0.81 (95% CI: 0.76–0.86).InterpretationA model defined by four clinical and demographic predictors successfully estimated the probability of mortality from HPAI H5N1 illness. These parameters highlight the importance of early diagnosis and treatment and may enable early, targeted pharmaceutical therapy and supportive care for symptomatic patients with HPAI H5N1 virus infection.

Evaluation of heterosubtypic cross-protection against highly pathogenic H5N1 by active infection with human seasonal influenza A virus or trivalent inactivated vaccine immunization in ferret models

The threat of highly pathogenic avian influenza (HPAI) H5N1 viruses to cause the next pandemic remains a major concern. Here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (TIV) against HPAI H5N1 (A/Vietnam/1203/2004) virus in ferrets. Groups were treated with PBS (group A), infected with H1N1 (group B) or H3N2 (group C) virus, or immunized with TIV (group D). Twelve weeks after the last treatment, serological assays revealed that groups B and C, but not group D, sustained moderate immunogenicity against homologous viruses; cross-reactivity against the H5N1 virus was not detected in any group. Following challenge with A/Vietnam/1203/2004 (H5N1) virus, only groups B and C exhibited attenuated viral loads leading to 100 % survival. Our data suggest that natural infection with human seasonal strains could potentially provide better heterosubtypic protection against HPAI H5N1 virus infection compared to TIV immunization.

Mammalian Innate Resistance to Highly Pathogenic Avian Influenza H5N1 Virus Infection Is Mediated through Reduced Proinflammation and Infectious Virus Release

Respiratory epithelial cells and macrophages are the key innate immune cells that play an important role in the pathogenesis of influenza A virus infection. We found that these two cell types from both human and pig showed comparable susceptibilities to initial infection with a highly pathogenic avian influenza (HPAI) H5N1 virus (A/turkey/Turkey/1/05) and a moderately pathogenic human influenza H1N1 virus (A/USSR/77), but there were contrasting differences in host innate immune responses. Human cells mounted vigorous cytokine (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and chemokine (CXCL9, CXCL10, and CXCL11) responses to H5N1 virus infection. However, pig epithelial cells and macrophages showed weak or no TNF-α and chemokine induction with the same infections. The apparent lack of a strong proinflammatory response, corroborated by the absence of TNF-α induction in H5N1 virus-challenged pigs, coincided with greater cell death and the reduced release of infectious virus from infected pig epithelial cells. Suppressor of cytokine signaling 3 (SOCS3), a protein suppressor of the JAK-STAT pathway, was constitutively highly expressed and transcriptionally upregulated in H5N1 virus-infected pig epithelial cells and macrophages, in contrast to the corresponding human cells. The overexpression of SOCS3 in infected human macrophages dampened TNF-α induction. In summary, we found that the reported low susceptibility of pigs to contemporary Eurasian HPAI H5N1 virus infections coincides at the level of innate immunity of respiratory epithelial cells and macrophages with a reduced output of viable virus and an attenuated proinflammatory response, possibly mediated in part by SOCS3, which could serve as a target in the treatment or prevention of virus-induced hypercytokinemia, as observed for humans.

Host regulatory network response to infection with highly pathogenic H5N1 avian influenza virus.

During the last decade, more than half of humans infected with highly pathogenic avian influenza (HPAI) H5N1 viruses have died, yet virus-induced host signaling has yet to be clearly elucidated. Airway epithelia are known to produce inflammatory mediators that contribute to HPAI H5N1-mediated pathogenicity, but a comprehensive analysis of the host response in this cell type is lacking. Here, we leveraged a system approach to identify and statistically validate signaling subnetworks that define the dynamic transcriptional response of human bronchial epithelial cells after infection with influenza A/Vietnam/1203/2004 (H5N1, VN1203). Importantly, we validated a subset of transcripts from one subnetwork in both Calu-3 cells and mice. A more detailed examination of two subnetworks involved in the immune response and keratinization processes revealed potential novel mediators of HPAI H5N1 pathogenesis and host response signaling. Finally, we show how these results compare to those for a less virulent strain of influenza virus. Using emergent network properties, we provide fresh insight into the host response to HPAI H5N1 virus infection and identify novel avenues for perturbation studies and potential therapeutic interventions for fatal HPAI H5N1 disease.

Risk for Highly Pathogenic Avian Influenza H5N1 Virus Infection in Chickens in Small-Scale Commercial Farms, in a High-Risk Area, Bangladesh, 2008

Small-scale commercial chicken farms (FAO-defined system 3) with poor biosecurity predominate in developing countries including Bangladesh. By enroling fifteen highly pathogenic avian influenza (HPAI) cases occurring in such farms - (February - April 2008) and 45 control farms (March-May 2008) with similar set up, we conducted a case-control study to evaluate the risk factors associated with HPAI H5N1 virus infections in chickens reared in small-scale commercial farms in a spatially high-risk area in Bangladesh. Data collected by a questionnaire from the selected farms were analysed by univariable analysis and multivariable conditional logistic regression. The risk factors independently associated were 'dead crow seen at or near farm' [odds ratio (OR) 47.4, 95% confidence interval (CI) 4.7-480.3, P = 0.001], 'exchanging eggtrays with market vendors' (OR 20.4, 95% CI 1.9-225.5, P = 0.014) and 'mortality seen in backyard chicken reared nearby' (OR 19.4, 95% CI 2.8-131.9, P = 0.002). These observations suggest that improved biosecurity might reduce the occurrence of HPAI outbreaks in small-scale commercial farms in Bangladesh.

Captive Rearing and Release of Bar-headed Geese (Anser indicus) in China: A Possible HPAI H5N1 Virus Infection Route to Wild Birds

In April–June 2005, more than 6,000 birds, including more than 3,000 Barheaded Geese Anser indicus, died at Lake Qinghai, northern China, during an outbreak of highly pathogenic avian influenza (HPAI) H5N1 (Chen et al., 2006). In spring 2006, more waterbirds, again mainly Bar-headed Geese (939 recorded at three Qinghai sites but not counted at others), died at four sites in Qinghai province and three in Tibet. Two virus isolations, from a Bar-headed Goose and a Great Black-headed Gull (Larus ichthyaetus), were reported from Lake Qinghai in 2007 (Li et al., 2010) and in May 2009, more wild birds (species not recorded) died at two sites in Qinghai province (Wang et al., 2008; World Organisation for Animal Health [OIE], 2010). In May 2010, dead wild birds, including Barheaded Geese, were reported from Nagqu province, Tibet (OIE, 2010). In 2005, 2006, 2009, and 2010 outbreaks on the Qinghai-Tibet plateau were contemporaneous with or followed by outbreaks in wild birds in Mongolia and southern Russia (OIE, 2010). Virus isolation from dead wild birds at Lake Qinghai in 2005 revealed a new strain of HPAI H5N1, designated Clade 2.2 (World Health Organization/World Organisation for Animal Health/Food and Agriculture Organization, 2008), which has subsequently spread to Europe and Asia (Feare, 2007). Although there had been outbreaks in poultry in Lanzhou, approximately 300 km from Lake Qinghai, and in the vicinity of Lhasa, Tibet (OIE, 2010), the evolution of HPAI H5N1 viruses was not studied in northern China (Smith et al., 2006), and the origin of the Qinghai stain remains a mystery. After the 2005 HPAI H5N1 outbreak at Lake Qinghai, one of the authors (T.K.) discovered Chinese-language internet media bulletins that described captive rearing of Bar-headed Geese on China’s central high plateau. These reports lack detail but describe practices that promote contact between captive-bred geese and domesticated and wild birds. Our aim here is to summarize the salient information from these reports because they present a possible scenario for emergence of the Qinghai Clade 2.2 viruses and its occurrence in wild birds. Captive breeding of Bar-headed Geese began in 2003 at Yamzho Yumco Lake, about 100 km south of Lhasa, Tibet, by the ‘‘Lhasa Nida Natural Ecology Development Bar-headed Goose Artificial Breeding Company.’’ Several hundred abandoned Bar-headed Goose eggs were collected from a declining colony, claimed to comprise 30,000 birds, at the lake and were artificially incubated, with 99% reared to fledging. The enterprise was extended to Xaina County, Nagqu Prefecture (about 300 km NE of Lhasa), where 500 Bar-headed Geese were successfully raised ‘‘to meet market demand.’’ The company also contracted production to a villager in Gonggar (Meldrogonkar) County, south of Lhasa. In 2006 another breeding unit was established in the same town, at a wetland and reservoir suitable

Comparative Pathology of Select Agent Influenza A Virus Infections

Influenza A virus infections may spread rapidly in human populations and cause variable mortality. Two of these influenza viruses have been designated as select agents: 1918 H1N1 virus and highly pathogenic avian influenza (HPAI) virus. Knowledge of the pathology of these virus infections in humans, other naturally infected species, and experimental animals is important to understand the pathogenesis of influenza, to design appropriate models for evaluation of medical countermeasures, and to make correct diagnoses. The most important complication of influenza in humans is viral pneumonia, which often occurs with or is followed by bacterial pneumonia. Viremia and extrarespiratory disease are uncommon. HPAI viruses, including HPAI H5N1 virus, cause severe systemic disease in galliform species as well as in anseriform species and bird species of other orders. HPAI H5N1 virus infection also causes severe disease in humans and several species of carnivores. Experimental animals are used to model different aspects of influenza in humans, including uncomplicated influenza, pneumonia, and virus transmission. The most commonly used experimental animal species are laboratory mouse, domestic ferret, and cynomolgus macaque. Experimental influenza virus infections are performed in various other species, including domestic pig, guinea pig, and domestic cat. Each of these species has advantages and disadvantages that need to be assessed before choosing the most appropriate model to reach a particular goal. Such animal models may be applied for the development of more effective antiviral drugs and vaccines to protect humans from the threat of these virus infections.

Influenza A H5N1 Clade 2.3.4 Virus with a Different Antiviral Susceptibility Profile Replaced Clade 1 Virus in Humans in Northern Vietnam

BackgroundPrior to 2007, highly pathogenic avian influenza (HPAI) H5N1 viruses isolated from poultry and humans in Vietnam were consistently reported to be clade 1 viruses, susceptible to oseltamivir but resistant to amantadine. Here we describe the re-emergence of human HPAI H5N1 virus infections in Vietnam in 2007 and the characteristics of the isolated viruses.Methods and FindingsRespiratory specimens from patients suspected to be infected with avian influenza in 2007 were screened by influenza and H5 subtype specific polymerase chain reaction. Isolated H5N1 strains were further characterized by genome sequencing and drug susceptibility testing. Eleven poultry outbreak isolates from 2007 were included in the sequence analysis. Eight patients, all of them from northern Vietnam, were diagnosed with H5N1 in 2007 and five of them died. Phylogenetic analysis of H5N1 viruses isolated from humans and poultry in 2007 showed that clade 2.3.4 H5N1 viruses replaced clade 1 viruses in northern Vietnam. Four human H5N1 strains had eight-fold reduced in-vitro susceptibility to oseltamivir as compared to clade 1 viruses. In two poultry isolates the I117V mutation was found in the neuraminidase gene, which is associated with reduced susceptibility to oseltamivir. No mutations in the M2 gene conferring amantadine resistance were found.ConclusionIn 2007, H5N1 clade 2.3.4 viruses replaced clade 1 viruses in northern Vietnam and were susceptible to amantadine but showed reduced susceptibility to oseltamivir. Combination antiviral therapy with oseltamivir and amantadine for human cases in Vietnam is recommended.

Control Versus No Control: Options for Avian Influenza H5N1 in Nigeria

In January 2006, an outbreak of a highly pathogenic avian influenza (HPAI) was recorded in Nigeria for the first time. This present work describes an estimation of possible costs associated with a vaccination-based control policy added to other measures to restrict HPAI H5N1 virus infections. The evaluations used epidemiological and production data, including budgets necessary for the vaccine acquisition, distribution and administration in arriving at the final costs. Using decision tree and cost benefit analysis the economical benefits for Nigeria and countries with similar veterinary infrastructures, biosecurity and farming systems are calculated. The result indicated that a halting in the continued spread of the virus through effective control measure will be 52 times better than taking no action. This should help policy makers in deciding in favour of vaccination combined with other tools as an effective means of controlling avian influenza H5N1. * Control of HPAI H5N1 will best be understood by policy makers in financial terms. * Effective control through vaccination of poultry is much cheaper and reduces the chances of human zoonoses. * Poultry vaccination combined with other control measures will be the most effective means of control in most developing economies.