Avian Influenza H5N1 Outbreaks Research Articles

Eco-virological approach for assessing the role of wild birds in the spread of avian influenza H5N1 along the Central Asian Flyway.

A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this ‘thoroughfare’. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005–2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations.

JOINT SUB-CLASSIFIERS ONE CLASS CLASSIFICATION MODEL FOR AVIAN INFLUENZA OUTBREAK DETECTION

H5N1 avian influenza outbreak detection is a significant issue for early warning of epidemics. This paper proposes domain knowledge-based joint one class classification model for avian influenza outbreak. Instead of focusing on manipulations of the one class classification model, we delve into the one class avian influenza dataset, divide it into sub-classes by domain knowledge, train the sub-class classifiers and unify the result of each classifier. The proposed joint method solves the one class classification and features selection problems together. The experiment results demonstrate that the proposed joint model definitely outperforms the normal one class classification model on the animal avian influenza dataset.

Limiting worker exposure to highly pathogenic avian influenza a (H5N1): a repeat survey at a rendering plant processing infected poultry carcasses in the UK

BackgroundCurrent occupational and public health guidance does not distinguish between rendering plant workers and cullers/poultry workers in terms of infection risk in their respective roles during highly pathogenic avian influenza poultry outbreaks. We describe an operational approach to human health risk assessment decision making at a large rendering plant processing poultry carcasses stemming from two separate highly pathogenic avian influenza A (H5N1) outbreaks in England during 2007.MethodsDuring the first incident a uniform approach assigned equal exposure risk to all rendering workers in or near the production line. A task based exposure assessment approach was adopted during the second incident based on a hierarchy of occupational activities and potential for infection exposure. Workers assessed as being at risk of infection were offered personal protective equipment; pre-exposure antiviral prophylaxis; seasonal influenza immunisation; hygiene advice; and health monitoring. A repeat survey design was employed to compare the two risk assessment approaches, with allocation of antiviral prophylaxis as the main outcome variable.ResultsTask based exposure assessment during the second incident reduced the number of workers assessed at risk of infection from 72 to 55 (24% reduction) when compared to the first incident. No cases of influenza like illness were reported in workers during both incidents.ConclusionsTask based exposure assessment informs a proportionate public health response in rendering plant workers during highly pathogenic avian influenza H5N1 outbreaks, and reduces reliance on extensive antiviral prophylaxis.

Elevated 17β-Estradiol Protects Females from Influenza A Virus Pathogenesis by Suppressing Inflammatory Responses

Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load.

(A183) Umbrella” in a Small, Developing Country - A Case Report on Pandemic Influenza Preparedness in Bosnia and Herzegovina

Cooperation between veterinary and public health authorities in Bosnia and Herzegovina and their respective field services has historically been weak and inefficient. As is the case in many countries, animal health and public health fall under separate ministries with animal health the responsibility of the ministry of agriculture and public health the ministry of health. This model has promoted interagency competition for funding for disease surveillance and control. It has also resulted in poor information exchange, lack of efficient utilization of diagnostic resources, and poor harmonization of policies. Political decentralization, established in Bosnia after the Dayton peace agreement, resulted in the lack of a national-level responsibility for animal or public health. This was instead placed at mid-governmental levels. A state (national) veterinary office was created in 2000, but there still remains no national public health agency. The H5N1 Avian Influenza (AI) outbreak which began in Southeast Asia in 2003 and reached Europe in 2005 raised concerns about Bosnia and Herzegovina's (BiH) preparedness to combat pandemic disease. Accordingly, the state (national) veterinary service of Bosnia and Herzegovina (BiH) conducted exercises which resulted in increased monitoring of wild and domestic bird populations and the drafting and adoption of a contingency plan (CP) for AI. The activities prescribed by the CP were implemented in February 2006 when the H5N1 virus was diagnosed in wild swans. However, no cooperation was established with public health authorities during this incident, further underscoring the need for a one health approach to disease control activities. Adoption of the One Health concept is challenging, and there is no simple plan that can be applied across all cultures. To prevent it from simply existing as an idealistic theory, some revision is needed and practical guidelines must be developed. The authors will include suggestions as to how this might be achieved.

VIRULENCE OF H5N1 INFLUENZA VIRUS IN CATTLE EGRETS (BUBULCUS IBIS)

In Vietnam, Cattle Egrets (Bubulcus ibis) are common in a variety of habitats, such as freshwater marshes, beaches, and paddy fields. They are also found associated with cattle (Bos spp.) and occasionally with pigs (Sus scrofa), goats (Capra hircus), and horses (Equus caballus) and are kept for insect control in households. In this study, six Cattle Egrets were experimentally infected intranasally with highly pathogenic avian influenza (AI) A/duck/Vietnam/40D/04 (H5N1) to investigate a possible epidemiologic role for Cattle Egrets in outbreaks of H5N1 AI in Vietnam. The Cattle Egrets were highly susceptible to the infection and either died within a week or had to be euthanized. Five uninfected chickens housed with the inoculated Cattle Egrets from day 1 to day 8 postinfection showed no signs of disease or mortality. This observation was most probably due to the low-level virus shedding by the Cattle Egrets. We concluded that Cattle Egrets are not significant reservoir hosts for H5N1 AI virus.

Prevalence of infectious bronchitis and Newcastle disease virus among domestic and wild birds in H5N1 outbreaks areas

The first H5N1 outbreak in Burkina Faso was reported to the World Organization for Animal Health on 3 April 2006. This study aimed to determine the prevalence of avian influenza virus, infectious bronchitis virus, and Newcastle disease virus among domestic and wild birds in highly pathogenic avian influenza (HPAI) H5N1 outbreaks areas. We collected paired tracheal and cloacal swabs from 283 birds including 278 domestic and five wild birds (three vultures, one sparrowhawk and one Western Grey Plantain-eater) in the Central Region (Ouagadougou) and the Western Region (Bobo-Dioulasso and Sokoroni) of Burkina Faso. Total RNA extracted from samples were subjected to reverse transcription and resulting cDNA amplified by PCR using specific primers for detection of Avian Influenza Virus (AIV mainly highly pathogenic H5N1), Infectious Bronchitis Virus (IBV), and Newcastle Disease Virus (NDV) for the first time in Burkina Faso. Our results show that 13.8% (39/283) samples were reactive for NDV, and the prevalence of IBV was 3.9% (11/283). None of the 283 birds were co-infected by AIV, IBV and/or NDV in our study areas. The prevalence of influenza A virus was 3.2% (95% CI: 0-6.6) with a 1.7% (95% CI: 0-3.2) prevalence of H5N1 being detected. Positive cases of H5N1 virus were found in two out of three vultures in Ouagadougou, and in three out of 203 local chickens in the Western Region. These results confirm the presence of influenza A H5N1 virus, IBV and NDV in domestic and wild birds in Burkina Faso.

Blow Flies Were One of the Possible Candidates for Transmission of Highly Pathogenic H5N1 Avian Influenza Virus during the 2004 Outbreaks in Japan

The 2003-2004 H5N1 highly pathogenic avian influenza (HPAI) outbreaks in Japan were the first such outbreaks in 79 years in Japan. Epidemic outbreaks have been occurring in Southeast Asia, with the most recent in 2010. Knowledge of the transmission route responsible for the HPAI outbreaks in these countries remains elusive. Our studies strongly suggested that field and laboratory studies focusing on mechanical transmission by blow flies should be considered to control H5N1 avian influenza outbreaks, in particular in epidemic areas, where there are high densities of different fly species throughout the year. In this paper, we review these field and laboratory entomological studies and discuss the possibility of blow flies transmitting H5N1 viruses.

Spatio–temporal analyses of highly pathogenic avian influenza H5N1 outbreaks in the Mekong River Delta, Vietnam, 2009

This paper presents the results of spatio–temporal analyses and epidemic modelling of HPAI H5N1 outbreaks that occurred in four provinces of the Mekong River Delta, Vietnam between January and March 2009. Significant spatio–temporal interaction of disease risk was observed within a distance of 10 km and 12 days following the detected onset of clinical signs. We estimate that the household-to-household infection rate within a commune was approximately 50 times greater than the household-to-household infection rate between communes. Our findings show that the predominant mechanism of infection transfer was local spread. A comparison of disease control procedures and veterinary capacity in communes with relatively high and low infection rates should help to identify procedures essential for effective outbreak management in this area of Vietnam.

Movement patterns of Bar-headed Geese Anser indicus during breeding and post-breeding periods at Qinghai Lake, China

The highly pathogenic avian influenza (HPAI) H5N1 outbreak at Qinghai Lake, China, in 2005 caused the death of over 6,000 migratory birds, half of which were Bar-headed Geese Anser indicus. Understanding the movements of this species may inform monitoring of outbreak risks for HPAI viruses; thus, we investigated the movement patterns of 29 Bar-headed Geese at Qinghai Lake, China during 2007 and 2008 by using high resolution GPS satellite telemetry. We described the movements and distribution of marked Bar-headed Geese during the pre-nesting, nesting, and moulting periods. Of 21 Bar-headed Geese with complete transmission records, 3 moved to other areas during the nesting period: 2 to Jianghe wetland (50 km northwest of Qinghai Lake) and 1 to Cuolongka Lake (220 km northwest of Qinghai Lake) during the nesting period. We identified nesting attempts of 7 of the marked geese at Qinghai Lake. Four completed successful nesting attempts according to our rules of judgment for the breeding status, and 2 geese lost broods soon after hatching (hereafter referred to as unsuccessful breeders). Of 18 geese present at Qinghai Lake during the nesting period, 9 (6 non-breeders, 2 successful breeders and 1 unsuccessful breeder) remained at Qinghai Lake during the moulting period; and 9 (5 non-breeders, 4 unsuccessful breeders) left Qinghai Lake for moulting. Kuhai Lake, Donggeicuona Lake, Alake Lake, Zhaling-Eling Lake area and Huangheyuan wetland area were used as moulting sites. Geese that moulted at Qinghai Lake, Cuolongka Lake, Kuhai Lake, Donggeicuona Lake and Alake Lake also moved to Zhaling-Eling Lake area or Huangheyuan wetland area and stayed there for several days prior to autumn migration. Mean home range and core area estimates did not differ significantly by sex, year and between breeders and non-breeders.

Risk factors and clusters of Highly Pathogenic Avian Influenza H5N1 outbreaks in Bangladesh

Between March 2007 and July 2009, 325 Highly Pathogenic Avian Influenza (HPAI, subtype H5N1) outbreaks in poultry were reported in 154 out of a total of 486 sub-districts in Bangladesh. This study analyzed the temporal and spatial patterns of HPAI H5N1 outbreaks and quantified the relationship between several spatial risk factors and HPAI outbreaks in sub-districts in Bangladesh. We assessed spatial autocorrelation and spatial dependence, and identified clustering sub-districts with disease statistically similar to or dissimilar from their neighbors. Three significant risk factors associated to HPAI H5N1 virus outbreaks were identified; the quadratic log-transformation of human population density [humans per square kilometer, P = 0.01, OR 1.15 (95% CI: 1.03–1.28)], the log-transformation of the total commercial poultry population [number of commercial poultry per sub-district, P < 0.002, OR 1.40 (95% CI: 1.12–1.74)], and the number of roads per sub-district [ P = 0.02, OR 1.07 (95% CI: 1.01–1.14)]. The distinct clusters of HPAI outbreaks and risk factors identified could assist the Government of Bangladesh to target surveillance and to concentrate response efforts in areas where disease is likely to occur. Concentrating response efforts may help to combat HPAI more effectively, reducing the environmental viral load and so reducing the number of disease incidents.

First Year of the Highly Pathogenic Avian Influenza H5N1 Outbreak in Egypt: Rapid Antigenic/Molecular Diagnosis and Virus Isolation

First Year of the Highly Pathogenic Avian Influenza H5N1 Outbreak in Egypt: Rapid Antigenic/Molecular Diagnosis and Virus Isolation

Economic Effect of the Highly Pathogenic Avian Influenza H5N1 Outbreaks Among Turkey Producers, 2005–06, Turkey

This research assessed the direct economic effects of the 2005-06 HPAI outbreaks on contracted turkey producers in Turkey in 2007. The data were obtained from 71 randomly selected, contracted turkey farms (producing 23% of the national turkey meat in Turkey in 2005) from five provinces for four integrated firms, which account for 67% of the national turkey production. Each farm was visited once for an oral interview conducted by the authors in 2007, using a questionnaire survey. The financial data before and after highly pathogenic avian influenza (HPAI) H5N1 outbreak periods were obtained from available financial records. Changes in production and economics parameters before and after the HPAI H5N1 outbreak periods were compared. In the analyses, the "before the HPAI H5N1 outbreak" period was stated as October 1, 2004, to May 31, 2005, whereas the "after the HPAI H5N1 outbreak" period was stated as the 8-mo between October 1, 2005, and May 31, 2006. The research revealed that changes in the technical parameters (number of hired labor, feed conversion rate, mortality rate, and the length of fattening period) were not found to be statistically significant at P > 0.05. However, there were severe effects of the HPAI H5N1 outbreaks on the economic parameters of the turkey production. The contracted turkey producers lost on average 0.9 cycles (38%) of production, and their management fees were reduced by 9.3% in the 8 mo after the outbreaks. As a result, the production level and enterprise income declined by 36% and 39%, respectively. About 93% of the producers did not do any other supplementary work during the idle production period; 59% of the producers had to use on average 4970TL (US$3200) from their personnel saving during the HPAI H5N1 outbreaks. About 62% of the producers stated that they had been considering expanding their businesses, but suspended the idea because of the outbreak, and 80% of the producers increased the biosecurity measures after the outbreaks. The futures of the contracted turkey producers are fully dependent on those of the integrated firms. Any negative effects on the latter appear to be directly transferred to the former. However, the government neglected contracted producers in the HPAI compensation programs.

The space–time clustering of highly pathogenic avian influenza (HPAI) H5N1 outbreaks in Bangladesh

Bangladesh faced two epidemic waves of highly pathogenic avian influenza (HPAI) H5N1 in two consecutive years. The peaks of the waves were observed in February-July 2007 and January-April 2008, respectively. We examined the spatial and temporal patterns of the 293 outbreaks in 143 subdistricts in 2007 and 2008. Global clustering assessed by K-function was seen at distances 150-300 km between subdistricts. Significant local clusters were detected by space-time scan statistics. In both waves, significant primary clusters of HPAI outbreaks were identified in the central part of the country dominated by commercial production systems and in the northwestern part primarily in backyard production systems. Secondary clusters varied from the northwestern part in 2007 and the southern part in 2008. The findings are highly relevant for the successful planning and implementation of control, prevention and surveillance strategies by highlighting areas where detailed investigations should be initiated.

A description of the management of itinerant grazing ducks in the Mekong River Delta of Vietnam

A cross-sectional survey of management practices of itinerant grazing ducks (known as field running ducks) was conducted during March 2008 in four districts of Can Tho and Bac Lieu provinces in the Mekong River Delta, Vietnam. The objective was to characterize the demographic structure of the itinerant grazing duck population and the management practices which might be related to the continuing outbreaks of H5N1 avian influenza in this region. Broiler duck flocks were owned by 55% of survey respondents, and layer flocks by 53%. Greater than 80% of ducks within 93% of villages and 99% of duck flocks were reported to have been vaccinated against H5N1 avian influenza, whereas only 19% of villages and 60% of chicken flocks had greater than 80% of chickens vaccinated. Fifty-nine percent of duck owners moved their ducks outside their home communes, whilst 37% and 28% of owners moved their ducks outside their home district and province, respectively. Larger flocks were more likely to be run outside their home district compared with smaller flocks. After adjusting for the effect of flock production type and district, the odds of an out-of-district field running duck flock movement was increased by a factor of 7.24 (95% CI 2.89–19.24) for households with flocks of more than 800 ducks, compared with flocks of less than 250. Most households sold ducks to traders (72%) or to neighbours (33%), whereas less than 20% sold their birds through markets. The findings of this study suggest that surveillance strategies for field running duck flocks should focus on layer flocks as well as larger flocks as they are more likely to be moved outside of their home district, facilitating long-distance disease spread.

Changes in Poultry Handling Behavior and Poultry Mortality Reporting among Rural Cambodians in Areas Affected by HPAI/H5N1

BackgroundSince 2004, 21 highly pathogenic avian influenza H5N1 outbreaks in domestic poultry and eight human cases have been confirmed in Cambodia. As a result, a large number of avian influenza education campaigns have been ongoing in provinces in which H5N1outbreaks have occurred in humans and/or domestic poultry.Methodology/Principal FindingsData were collected from 1,252 adults >15 years old living in two southern provinces in Cambodia where H5N1 has been confirmed in domestic poultry and human populations using two cross-sectional surveys conducted in January 2006 and in November/December 2007. Poultry handling behaviors, poultry mortality occurrence and self-reported notification of suspect H5N1 poultry cases to animal health officials in these two surveys were evaluated. Our results demonstrate that although some at risk practices have declined since the first study, risky contact with poultry is still frequent. Improved rates of reporting poultry mortality were observed overall, but reporting to trained village animal health workers decreased by approximately 50%.Conclusions/SignificanceAlthough some improvements in human behavior have occurred, there are still areas—particularly with respect to the handling of poultry among children and the proper treatment of poultry and the surrounding household environment—that need to be addressed in public health campaigns. Though there were some differences in the sampling methods of the 2006 and 2007 surveys, our results illustrate the potential to induce considerable, potentially very relevant, behavioral changes over a short period of time.

Farm- and flock-level risk factors associated with Highly Pathogenic Avian Influenza outbreaks on small holder duck and chicken farms in the Mekong Delta of Viet Nam

After 11 consecutive months of control, the Mekong Delta in Viet Nam experienced a wave of Highly Pathogenic Avian Influenza (HPAI) H5N1 outbreaks on small holder poultry farms from December 2006 to January 2007. We conducted a retrospective matched case–control study to investigate farm- and flock-level risk factors for outbreak occurrence during this period. Twenty-two case farms were selected from those where clinical signs consistent with HPAI H5N1 had been present and HPAI H5N1 had been confirmed with a positive real-time PCR test from samples obtained from affected birds. For every case farm enrolled, two control farms were selected matched on time of outbreak occurrence, farm location and species. Veterinarians conducted interviews with farmers, to collect information on household demographics, farm characteristics, husbandry practices, trading practices, poultry health, vaccination and biosecurity. Exact stratified logistic regression models were used to assess putative risk factors associated with a flock having or not having a HPAI outbreak. Nested analyses were also performed, restricted to subsets of farms using scavenging, confinement or supplementary feeding practices. Risk of an outbreak of HPAI H5N1 was increased in flocks that had received no vaccination (odds ratio (OR)=20.2; 95% confidence interval (CI): 1.0, +infinity) or only one vaccination (OR=85.2; 95% CI: 6.5, +infinity) of flocks compared to two vaccinations, and in flocks on farms that had family and friends visiting (OR=8.2; 95% CI: 1.0, +infinity) and geese present (OR=11.5; 95% CI: 1.1, +infinity). The subset analysis using only flocks that scavenged showed that sharing of scavenging areas with flocks from other farms was associated with increased risk of an outbreak (OR=10.9; 95% CI: 1.4, 492.9). We conclude that none or only one vaccination, visitors to farms, the presence of geese on farms and sharing of scavenging areas with ducks from other farms increase the risk of HPAI H5N1 outbreaks in poultry flocks in Viet Nam.

Evaluation of Student Abilities to Respond to a “Real-World” Question about an Emerging Infectious Disease

Veterinarians play an important role in educating the public about emerging animal and zoonotic diseases. This article investigates the ability of third-year veterinary students (N=31), from a veterinary school in the USA, to respond to an actual client's question about an emerging disease. In an open-book, take-home examination, students were asked to respond to a nurse's concern that she could bring home influenza from work and infect her macaw. While 75% of the students answered the question correctly, only 51% demonstrated that they understood that this question came from the ongoing publicity about the highly pathogenic H5N1 avian influenza outbreak in Asia, Africa, and Europe. Additional information that would have decreased the client's concern and provided the client with a better understanding of this disease outbreak was lacking in many of the answers. The results of this study suggest that greater emphasis should be applied to exercises requiring veterinary students to research, carefully study, and formulate answers to applied topics that are novel to them.

Television exposure is related to fear of avian flu, an Ecological Study across 23 member states of the European Union.

Background: A pandemic outbreak of H5N1 avian influenza is believed to coincide with large-scale panic. Even without an outbreak fear of infection may be widespread. Mass media coverage of the risks of a pandemic may lead to higher levels of fear. Methods: An ecological study looked at data from 23 member states of the European Union and controlled for population size, level of education, age distribution and income and wealth. Results: When the findings for Cyprus were excluded each additional hour of average TV viewing was associated with a 15.6% increase in the proportion of people worrying about the virus. TV viewing explained 52% of the variance. Conclusion: Fear of a pandemic precedes any real pandemic and may have to be dealt with separately. Exposure to television is highly associated with worrying about the virus. This relationship merits further study.

Avian influenza A H5N1 infections in Bali province, Indonesia: a behavioral, virological and seroepidemiological study

Bali Province was affected by avian influenza H5N1 outbreaks in birds in October 2003. Despite ongoing circulation of the virus, no human infection had been identified by December 2005. To assess behavioral patterns associated with poultry rearing in Bali, and to identify potential risk factors for H5N1 infection in humans and in household chickens, ducks and pigs. A behavioral, virological and seroepidemiologic survey in 38 villages and three live bird markets was completed in December 2005. A multi-stage cluster design was used to select 291 households with 841 participants from all nine districts in Bali. Specimens were collected from participants as well as a maximum of three pigs, chickens and ducks from each household. Eighty-seven market vendors participated, where specimens were collected from participants as well as chickens and ducks. Twenty out of the 38 villages sampled had H5N1 outbreaks. Despite exposure to H5N1 outbreaks, none of the participants from villages or markets were seropositive for H5N1. None of the pigs tested were positive for H5N1. Virus isolation rate in ducks and chicken in markets was higher than in households. Transport of poultry in or out of villages was a risk factor for outbreaks in household chickens and ducks. The study highlighted that the market chain and associated behaviors may play a role in maintaining the virus in household flocks. The study adds evidence that transmission of H5N1 to humans remains a rare event despite high level handling of both healthy and sick birds.