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July 29, 2005

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Avian influenza H5N1 and healthcare workers. Open link in new window

HubMed - H5N1 —
Emerg Infect Dis. 2005 Jul; 11(7): 1158-9
Schultsz C, Dong VC, Chau NV, Le NT, Lim W, Thanh TT, Dolecek C, de Jong MD, Hien TT, Farrar J

 


 
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Influenza A H5N1 replication sites in humans. Open link in new window

HubMed - H5N1 —
Emerg Infect Dis. 2005 Jul; 11(7): 1036-41
Uiprasertkul M, Puthavathana P, Sangsiriwut K, Pooruk P, Srisook K, Peiris M, Nicholls JM, Chokephaibulkit K, Vanprapar N, Auewarakul P

Tissue tropism and pathogenesis of influenza A virus subtype H5N1 disease in humans is not well defined. In mammalian experimental models, H5N1 influenza is a disseminated disease. However, limited previous data from human autopsies have not shown evidence of virus dissemination beyond the lung. We investigated a patient with fatal H5N1 influenza. Viral RNA was detected by reverse transcription-polymerase chain reaction in lung, intestine, and spleen tissues, but positive-stranded viral RNA indicating virus replication was confined to the lung and intestine. Viral antigen was detected in pneumocytes by immunohistochemical tests. Tumor necrosis factor-? mRNA was seen in lung tissue. In contrast to disseminated infection documented in other mammals and birds, H5N1 viral replication in humans may be restricted to the lung and intestine, and the major site of H5N1 viral replication in the lung is the pneumocyte.


 
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Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Open link in new window

HubMed - H5N1 —
Proc Natl Acad Sci U S A. 2005 Jul 26; 102(30): 10682-7
Hulse-Post DJ, Sturm-Ramirez KM, Humberd J, Seiler P, Govorkova EA, Krauss S, Scholtissek C, Puthavathana P, Buranathai C, Nguyen TD, Long HT, Naipospos TS, Chen H, Ellis TM, Guan Y, Peiris JS, Webster RG

Wild waterfowl, including ducks, are natural hosts of influenza A viruses. These viruses rarely caused disease in ducks until 2002, when some H5N1 strains became highly pathogenic. Here we show that these H5N1 viruses are reverting to nonpathogenicity in ducks. Ducks experimentally infected with viruses isolated between 2003 and 2004 shed virus for an extended time (up to 17 days), during which variant viruses with low pathogenicity were selected. These results suggest that the duck has become the "Trojan horse" of Asian H5N1 influenza viruses. The ducks that are unaffected by infection with these viruses continue to circulate these viruses, presenting a pandemic threat.


 
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Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein. Open link in new window

HubMed - H5N1 —
Vaccine. 2005 Jul 9;
Epstein SL, Kong WP, Misplon JA, Lo CY, Tumpey TM, Xu L, Nabel GJ

Influenza epidemic and pandemic strains cannot be predicted with certainty. Current vaccines elicit antibodies effective against specific strains, but new strategies are urgently needed for protection against unexpected strains. DNA vaccines encoding conserved antigens protect animals against diverse subtypes, but their potency needs improvement. We tested DNA prime-recombinant adenoviral boost immunization to nucleoprotein (NP). Strong antibody and T cell responses were induced. Protection against challenge was T cell-dependent and substantially more potent than DNA vaccination alone. Importantly, vaccination protected against lethal challenge with highly pathogenic H5N1 virus. Thus, gene-based vaccination with NP may contribute to protective immunity against diverse influenza viruses through its ability to stimulate cellular immunity.


 
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Characterization of a human H5N1 influenza A virus isolated in 2003. Open link in new window

HubMed - H5N1 —
J Virol. 2005 Aug; 79(15): 9926-32
Shinya K, Hatta M, Yamada S, Takada A, Watanabe S, Halfmann P, Horimoto T, Neumann G, Kim JH, Lim W, Guan Y, Peiris M, Kiso M, Suzuki T, Suzuki Y, Kawaoka Y

In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.


 
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Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic a/vietnam/1203/04 influenza virus in mice. Open link in new window

HubMed - H5N1 —
J Infect Dis. 2005 Aug 15; 192(4): 665-72
Yen HL, Monto AS, Webster RG, Govorkova EA

Background. Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in the pandemic.Methods. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; the first dose was given 4 h before inoculation with H5N1 A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens were evaluated.Results. Oseltamivir produced a dose-dependent antiviral effect against VN1203/04 in vivo (P<.01). The 5-day regimen at 10 mg/kg/day protected 50% of mice; deaths in this treatment group were delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively (P<.05). Overall, the efficacy of the 5- and 8-day regimens differed significantly (death hazard ratio, 2.658; P<.01). The new H5N1 antigenic variant VN1203/04 was more pathogenic in mice than was A/HK/156/97 virus, and a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect.Conclusions. Oseltamivir prophylaxis is efficacious against lethal challenge with VN1203/04 virus in mice. Viral virulence may affect the antiviral treatment schedule.


 
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Highly Pathogenic H5N1 Influenza Virus Infection in Migratory Birds. Open link in new window

HubMed - H5N1 —
Science. 2005 Jul 6;
Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang X, Zhang X, Zhao D, Wang G, Feng Y, Ma J, Liu W, Wang J, Gao GF

H5N1 avian influenza virus (AIV) has emerged as a pathogenic entity for a variety of species, including humans, in recent years. Here we report an outbreak among migratory birds on Lake Qinghaihu, China, in May and June 2005, in which hundreds of thousands of birds were affected. Pancreatic necrosis and abnormal neurological symptoms were the major clinical features. Sequencing of complete genomes of four H5N1 AIV strains isolated revealed to be reassortants related to a peregrine falcon isolate from Hong Kong and showed known "highly pathogenic" characteristics. Experimental animal infections reproduced typical highly pathogenic AIV-infection symptoms and pathology.


 
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Protecting human and ecological health under viral threats in Asia. Open link in new window

HubMed - H5N1 —
Water Sci Technol. 2005; 51(8): 91-7
Matsui S

Severe acute respiratory syndrome (SARS) outbroke in 2003, and the avian influenza A (H5N1) also outbroke in 2003 and continued to 2004. These pandemic viral diseases originated in South East Asia. Many human and animal lives were lost. Economic damages due to the pandemics were also very large. The question arises of why did the pandemics originate from South East Asian areas. Human influenza A consists of many sub-types of coronaviruses including the SARS virus and the avian influenza (H5N1) that are all variants of RNA of avian coronavirus. Variants are formed during infection of a coronavirus through not only birds but also mammals, including human beings. There are hot spots where viral infection rates are accelerated among birds, mammals and human beings. Suspicious areas are in South East Asia, where living conditions of birds, mammals and human beings are so close that there are always risks of viral infection. When we see the living conditions of farmers in southern China, northern Vietnam, Laos and northern Myanmar, they commonly raise ducks/chickens with pigs sharing ponds into which they discharge household wastewater, including human excreta, and pig excreta that are significant carriers of viruses. Bird faeces are also key carriers of the viruses. In the ponds, they raise ducks and conduct fish culture. Other important players are migrating birds from North Asia, which are principal vectors of avian influenza viruses. There is an urgent necessity of improving human and ecological health in South East Asia to control viral infection among birds, mammals and human beings. We can hinder the vicious cycle of virus infection through water contamination in ponds by providing good human, pig and chicken sanitation. It is easy to provide good sanitation practices for human, pigs and chickens, introducing collection and treatment of excreta. Our modern water technology can find good solutions for the problem.


 
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Avian flu: H5N1 virus outbreak in migratory waterfowl. Open link in new window

HubMed - H5N1 —
Nature. 2005 Jul 14; 436(7048): 191-2
Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, Webster RG, Peiris JS, Guan Y

 


 
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Update: Influenza activity--United States and worldwide, 2004-05 season. Open link in new window

HubMed - H5N1 —
MMWR Morb Mortal Wkly Rep. 2005 Jul 1; 54(25): 631-4
 

During the 2004-05 influenza season, influenza A (H1),* A (H3N2), and B viruses cocirculated worldwide, and influenza A (H3N2) viruses predominated. In addition, several Asian countries continued to report widespread outbreaks of avian influenza A (H5N1) among poultry; in Vietnam, Thailand, and Cambodia, these outbreaks were associated with severe illnesses and deaths among humans. In the United States, the 2004-05 influenza season peaked in February, was moderate, and was associated predominantly with influenza A (H3N2) viruses. This report summarizes influenza activity in the United States and worldwide during the 2004-05 influenza season.


 
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[Multi-epitope DNA vaccines against avian influenza in chickens] Open link in new window

HubMed - H5N1 —
Sheng Wu Gong Cheng Xue Bao. 2003 Sep; 19(5): 623-7
Peng JM, Tong GZ, Wang YF, Qiu HJ

Multiple epitopes from one or more viruses can be lined up and co-expressed in one vector to generate multi-epitopes DNA vaccines. In the study, four recombinant plasmids were constructed based on HA and NP gene of avian influenza virus (AIV) (H5N1): (1) pIRES/HA, carrying the complete HA gene; (2) pIRES/tHA, carrying a truncated HA gene fragment of major neutralizing antigenic epitopes; (3) pIRES/tHA-NPep, in which three CTL epitopes of NP gene of AIV were fused to the truncated HA from the C-terminal; and (4) pIRES/tHA-NPep-IFN-gamma, which was constructed by replacing neo gene in pIRES/ tHA-NPep with IFN-y of chicken. Fifty five SPF chickens were randomly divided into five groups and immunized with the above four constructs and control plasmid. Each chicken was intramuscally immunized with 200 microg plasmid DNA three times in a two-week interval. Two weeks after the third immunization, chickens were injected with H5N1 subtype avian influenza virus. Before the virus loading no detectable antibodies to HA were found in the chicken serum; but high levels of HI antibodies were detected in the serum of the survived chickens. The percentages of CD4+ and CD8+ T lymphocyte in peripheral blood of immunized chickens increased steadily after the vaccination. After virus loading all chickens in the control group died within three to eight days, and the survival rates of the four DNA vaccine groups were as follows: pIRES/HA, 54.5%; pIRES/tHA, 30%, pIRES/ tHA-NPep, 36.3%, pIRES/tHA-NPep-IFN-gamma, 50%. These results indicated that multi-epitopes DNA immunization can induce immune response and protect chickens from homologous virus loading.


 
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Preparing for pandemic vaccination: an international policy agenda for vaccine development. Open link in new window

HubMed - H5N1 —
J Public Health Policy. 2005 Apr; 26(1): 4-29
Fedson DS

The international use of influenza vaccine is growing, especially in developing countries. Since 1997, avian H5N1 influenza in Southeast Asia has caused several human infections and high mortality. Experts warn that the next influenza pandemic is imminent and could be severe. Prevention and control will depend on the rapid production and worldwide distribution of specific pandemic vaccines. If the vaccine supply is to be sufficient to meet global demand, issues related to the intellectual property rights for the reverse genetics technology essential for vaccine production must be resolved. In addition, candidate "pandemic-like" vaccines must be developed and tested in clinical trials to determine the most antigen sparing formulation and the best vaccination schedule. These studies must involve all vaccine companies and will require international coordination and public funding. Whether this international policy agenda for pandemic vaccine development will succeed is uncertain, but it will provide a good indication of whether "good governance" for global public health can be achieved.


 
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Analysis of synonymous codon usage in H5N1 virus and other influenza A viruses. Open link in new window

HubMed - H5N1 —
Biosystems. 2005 Jul; 81(1): 77-86
Zhou T, Gu W, Ma J, Sun X, Lu Z

In this study, we calculated the codon usage bias in H5N1 virus and performed a comparative analysis of synonymous codon usage patterns in H5N1 virus, five other evolutionary related influenza A viruses and a influenza B virus. Codon usage bias in H5N1 genome is a little slight, which is mainly determined by the base compositions on the third codon position. By comparing synonymous codon usage patterns in different viruses, we observed that the codon usage pattern of H5N1 virus is similar with other influenza A viruses, but not influenza B virus, and the synonymous codon usage in influenza A virus genes is phylogenetically conservative, but not strain-specific. Synonymous codon usage in genes encoded by different influenza A viruses is genus conservative. Compositional constraints could explain most of the variation of synonymous codon usage among these virus genes, while gene function is also correlated to synonymous codon usages to a certain extent. However, translational selection and gene length have no effect on the variations of synonymous codon usage in these virus genes.


 
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Pandemic influenza: are we ready? Open link in new window

HubMed - H5N1 —
Disaster Manag Response. 2005 Jul-Sep; 3(3): 61-7
Cinti S

An influenza pandemic is inevitable, and the H5N1 avian influenza outbreak in Southeast Asia has heightened concern that a disaster is imminent. Pandemic preparations are beginning around the world, and it is important for first responders, particularly disaster management personnel, to understand the difference between pandemic and epidemic influenza preparedness. This article will focus on distinguishing between an influenza epidemic and an influenza pandemic and, in light of these distinctions, how to manage the next pandemic with limited resources, particularly the absence of vaccine.


 
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Isolation of a genotypically unique H5N1 influenza virus from duck meat imported into Japan from China. Open link in new window

HubMed - H5N1 —
Virology. 2005 Jun 17;
Mase M, Eto M, Tanimura N, Imai K, Tsukamoto K, Horimoto T, Kawaoka Y, Yamaguchi S

An H5N1 influenza A virus was isolated from duck meat processed for human consumption, imported to Japan from Shandong Province, China in 2003. This virus was antigenically different from other H5 viruses, including the Hong Kong H5N1 viruses isolated from humans in 1997 and 2003. Sequence analysis revealed that six genes (PB1, PA, HA, NA, M, and NS) of this virus showed > 97% nucleotide identity with their counterparts from recent H5N1 viruses, but that the remaining two genes (PB2 and NP) were derived from other unknown viruses. This duck meat isolate was highly pathogenic to chickens upon intravenous or intranasal inoculation, replicated well in the lungs of mice and spread to the brain, but was not as pathogenic in mice as H5N1 human isolates (with a dose lethal to 50% of mice (MLD(50)) = 5 x 10(6) 50% egg infectious doses [EID(50)]). However, viruses isolated from the brain of mice previously infected with the virus were substantially more pathogenic (MLD(50) = approximately 10(2) EID(50)) and possessed some amino acid substitutions relative to the original virus. These results show that poultry products contaminated with influenza viruses of high pathogenic potential to mammals are a threat to public health even in countries where the virus is not enzootic and represent a possible source of influenza outbreaks in poultry.


 
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Human infection by avian influenza A H5N1. Open link in new window

HubMed - H5N1 —
Hong Kong Med J. 2005 Jun; 11(3): 189-99
Yuen KY, Wong SS

The Southeast Asian outbreak of the highly lethal avian influenza A H5N1 infection in humans is unlikely to abate because of the enormous number of backyard farms providing poultry as the main source of food protein in developing countries. This increases the risk of the emergence of a reassortant pandemic influenza virus with improved human-to-human transmissibility. Currently triage of suspected cases by epidemiological risk factors remains the only practical way of case identification for laboratory investigation and infection control. The clinical usefulness of rapid diagnostic laboratory tests requires more vigorous evaluation. The lethality of this disease may reflect systemic viral dissemination, cytokine storm, or alveolar flooding due to inhibition of cellular sodium channels. The present circulating genotype Z is intrinsically resistant to amantadine and rimantadine. Prognosis may be improved by early treatment with a neuraminidase inhibitor with good systemic drug levels, and post-exposure prophylaxis for health care workers is recommended. The role of immunomodulators and other modalities of therapy requires evaluation in randomised controlled trials, with prospective monitoring of the viral load and cytokine profiles in various clinical specimens. In view of the high fatality of the disease, a combination of contact, droplet, and airborne precautions are recommended as long as resources allow despite the fact that the relative importance of these three modes in nosocomial transmission of avian influenza is still unknown.


 
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Posted by dymaxion at July 29, 2005 05:31 PM

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