Showing papers on "Avian Influenza A Virus published in 2005"

Influenza: lessons from past pandemics, warnings from current incidents

Abstract: Recent outbreaks of highly pathogenic avian influenza A virus infections (H5 and H7 subtypes) in poultry and in humans (through direct contact with infected birds) have had important economic repercussions and have raised concerns that a new influenza pandemic will occur in the near future. The eradication of pathogenic avian influenza viruses seems to be the most effective way to prevent influenza pandemics, although this strategy has not proven successful so far. Here, we review the molecular factors that contribute to the emergence of pandemic strains.

Influenza A H5N1 replication sites in humans.

Abstract: 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-α 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.

p38 Mitogen-Activated Protein Kinase-Dependent Hyperinduction of Tumor Necrosis Factor Alpha Expression in Response to Avian Influenza Virus H5N1

Abstract: Avian influenza A virus subtype H5N1 can infect humans to cause a severe viral pneumonia with mortality rates of more than 30%. The biological basis for this unusual disease severity is not fully understood. We previously demonstrated that in contrast to human influenza A virus subtypes including H1N1 or H3N2, the H5N1 virus associated with the "bird flu" outbreak in Hong Kong in 1997 (H5N1/97) hyperinduces proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in primary human macrophages in vitro. To delineate the molecular mechanisms involved, we analyzed the role of transcription factor NF-kappaB and cellular kinases in TNF-alpha dysregulation. H5N1 and H1N1 viruses did not differ in the activation of NF-kappaB or degradation of IkappaB-alpha in human macrophages. However, we demonstrated that unlike H1N1 virus, H5N1/97 strongly activates mitogen-activated protein kinase (MAPK), including p38 MAPK and extracellular signal-regulated kinases 1 and 2. Specific inhibitors of p38 MAPK significantly reduced the H5N1/97-induced TNF-alpha expression in macrophages. Taken together, our findings suggest that H5N1/97-mediated hyperinduction of cytokines involves the p38 MAPK signaling pathway. These results may provide insights into the pathogenesis of H5N1 disease and rationales for the development of novel therapeutic strategies.

Characterization of a Human H5N1 Influenza A Virus Isolated in 2003

Abstract: 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

Lack of H5N1 Avian Influenza Transmission to Hospital Employees, Hanoi, 2004

Abstract: To establish whether human-to-human transmission of influenza A H5N1 occurred in the healthcare setting in Vietnam, we conducted a cross-sectional seroprevalence survey among hospital employees exposed to 4 confirmed and 1 probable H5N1 case-patients or their clinical specimens. Eighty-three (95.4%) of 87 eligible employees completed a questionnaire and provided a serum sample, which was tested for antibodies to influenza A H5N1. Ninety-five percent reported exposure to >1 H5N1 casepatients; 59 (72.0%) reported symptoms, and 2 (2.4%) fulfilled the definition for a possible H5N1 secondary case-patient. No study participants had detectable antibodies to influenza A H5N1. The data suggest that the H5N1 viruses responsible for human cases in Vietnam in January 2004 are not readily transmitted from person to person. However, influenza viruses are genetically variable, and transmissibility is difficult to predict. Therefore, persons providing care for H5N1 patients should continue to take measures to protect themselves.

Human-to-human transmission of avian influenza A/H7N7, The Netherlands, 2003

Abstract: An outbreak of highly pathogenic avian influenza A virus subtype H7N7 began in poultry farms in the Netherlands in 2003. Virus infection was detected by RT-PCR in 86 poultry workers and three household contacts of PCR-positive poultry workers, mainly associated with conjunctivitis. To determine the magnitude of and risk factors for human-to-human transmission of influenza A/H7N7 in the Netherlands, a retrospective cohort study among household members of infected poultry workers was undertaken. In total, 33 (58.9%) of 56 (among 62) participants who provided blood samples had positive H7 serology, using single convalescent serum samples obtained at least 3 weeks after onset of symptoms of the index case. Eight household members (12.9%) reported symptoms (conjunctivitis and/or ILI), of which four of five (80.0%) tested seropositive. On univariate analysis, significant risk factors for seropositivity included having at least two toilets, a pet bird, and using cloth handkerchiefs. It was not possible to obtain a stable model for binomial regression for the outcome of A/H7N7 infection. Further seroprevalence studies among contacts of asymptomatic H7 cases should be conducted.

Avian influenza H5N1 and healthcare workers

Abstract: To the Editor: Since January 2004, 35 human cases of avian influenza A virus H5N1 have been reported in Vietnam. Human-to-human transmission of H5N1 is a major concern, particularly because of reported family clustering (1). Two probable cases of human-to-human transmission were recently reported from Thailand (2), and evidence for human-to-human transmission was found in the 1997 Hong Kong outbreak (3). We evaluated healthcare workers exposed to 2 patients (patients 5 and 6 [1], referred to as patients A and B, respectively, in this article) with H5N1 infection, confirmed by polymerase chain reaction (PCR), to determine the potential risk for nosocomial human-to-human transmission of H5N1. Patient A was admitted to a general ward of a pediatric hospital in Ho Chi Minh City on January 15, 2004, on day 8 of illness; no infection control measures were taken at that time. On January 18, 2004, she was transferred to the intensive care unit (ICU). Eight hours after ICU admission, limited infection control measures were implemented: the patient was transferred to a single room, and healthcare workers were required to use disposable surgical masks and gloves and wear nondisposable gowns. However, because resources were limited, each healthcare worker wore only 1 glove. On January 23, patient A was transferred to another hospital. Patient B was admitted to the infectious diseases ward of the pediatric hospital on January 19, 2004, on day 6 of illness; he was transferred to the ICU after 4 hours and stayed there until he died on January 23. Infection control measures were implemented 2 days after ICU admission; these measures were similar to those taken for patient A except that no single room was available. From January 25 to 27, 2004, a nasal swab specimen and baseline serum sample were collected from healthcare workers at the hospital; each worker also completed a questionnaire. On February 9 and 10, follow-up serum samples were collected. Nasal swab samples were tested by reverse transcription (RT)-PCR to detect the H5 gene (1). Paired serum samples were subjected to enzyme-linked immunosorbent assay (ELISA) (Virion/Serion, Wurzburg, Germany) to detect immunoglobulin G against the nucleoprotein of influenza A; samples were also subjected to an H5-specific microneutralization assay (4). Of 62 healthcare workers involved in caring for patient A, patient B, or both, 60 (97%) provided both samples and questionnaires: 16 who cared for patient A on the general ward, 33 who cared for patients A and B in the ICU, and 11 who cared for patient B on the infectious diseases ward or who were consulted for diagnostic or clinical procedures involving either patient. Characteristics of the workers and their exposures are shown in the Table. Table Characteristics of 60 healthcare workers exposed to avian influenza patient A, patient B, or both The median time between last exposure and collection of the nasal swab and the baseline serum samples was 7 days (range 2–12 days). The median time between last exposure and collection of the follow-up serum sample was 21 days (range 17–26 days). All 60 nasal swab samples were negative by RT-PCR. Paired serum samples were available from 46 healthcare workers, and 42 were negative in the influenza A–specific ELISA, 2 reacted with a negative-to-borderline response, 1 had a borderline-to-positive response, and 1 had 2 positive responses. A positive response indicates recent infection. All paired serum samples, 12 additional baseline samples, and 2 additional follow-up samples were negative in the H5-specific microneutralization assay. None of the paired samples from 4 healthcare workers that were reactive in the ELISA showed 4-fold or greater changes in titer in H1- and H3-specific hemagglutination inhibition and microneutralization assays, which indicates they had not recently been infected with human influenza. None of these 4 healthcare workers reported any illness or potential exposure to H5N1 other than to patient A or B. The ELISA results were considered nonspecific. Paired serum samples from patient A showed clear seroconversion in both ELISA and H5 microneutralization. Serum specimens were not available from patient B. We found no transmission of H5N1 to healthcare workers, despite the lack of infection control measures, which suggests inefficient human-to-human H5N1 transmission; similar results were found in Hanoi (5). Droplet and contact transmission are considered the most effective means of transmitting influenza A in hospitals, and the clinical importance of airborne transmission has not been fully elucidated (6). Diarrhea in H5N1-infected patients potentially contains viable virus (1,7) and may affect the H5N1 transmission route. While these results appear reassuring, the limited options that were available to prevent nosocomial infection are worrisome. If reassortment between avian and human influenza A virus were to occur, resulting in a virus with pandemic potential, nosocomial transmission would be a concern. Infection control measures are crucial in all cases of avian influenza, and resources to prevent nosocomial infection must be made available in affected countries.

In vitro demonstration of neural transmission of avian influenza A virus

Abstract: Neural involvement following infections of influenza viruses can be serious. The neural transport of influenza viruses from the periphery to the central nervous system has been indicated by using mouse models. However, no direct evidence for neuronal infection has been obtained in vitro and the mechanisms of neural transmission of influenza viruses have not been reported. In this study, the transneural transmission of a neurotropic influenza A virus was examined using compartmentalized cultures of neurons from mouse dorsal root ganglia, and the results were compared with those obtained using the pseudorabies virus, a virus with well-established neurotransmission. Both viruses reached the cell bodies of the neurons via the axons. This is the first report on axonal transport of influenza A virus in vitro. In addition, the role of the cytoskeleton (microtubules, microfilaments and intermediate filaments) in the neural transmission of influenza virus was investigated by conducting cytoskeletal perturbation experiments. The results indicated that the transport of avian influenza A virus in the neurons was independent of microtubule integrity but was dependent on the integrity of intermediate filaments, whereas pseudorabies virus needed both for neural spread.

A retrospective description of a highly pathogenic avian influenza A virus (H7N1/Carduelis/Germany/72) in a free-living siskin (Carduelis spinus Linnaeus, 1758) and its accidental transmission to yellow canaries (Serinus canaria Linnaeus, 1758).

Abstract: A haemagglutinating virus was isolated in summer 1972 from a single free-living siskin (Carduelis spinus Linnaeus, 1758) in embryonated chicken eggs. Additional cases of morbidity or mortality were not observed in the area were the sick siskin was found. The virus was characterized as an avian influenza A virus of the subtype H7N1 and designated H7N1/Carduelis/Germany/72. The virus induced following experimental inoculation of chicken embryos a high rate mortality (mean death time approximately 24 hours), formed plaques in chicken embryo fibroblast cultures without addition of trypsin and has an intracerebral pathogenicity index (ICPI) of 1.80. Therefore, this virus is considered as a highly pathogenic avian influenza A virus. Canaries (Serinus canarius Linnaeus, 1758), that were housed in the same room with the siskin were accidentially exposed by contact to the sick siskin which resulted in virus transmission followed by conjunctivitis, apathy, anorexia and a high rate mortality.

Process for detecting H5N1 hypotype Avian influenza virus and special-purpose reagent kit

Abstract: The invention disclosed a detection method for H5N1 subtype avian influenza virus and special purpose reagent case thereof. The reagent case comprises avian influenza A virus general primer NPF and NPL, specificity primer H5F and H5L of H5 subtype avian influenza virus hemagglutinin and specificity primer N1F and N1L of N1 subtype avian influenza virus neuraminidase; said NPF processes nucleotide sequence of sequence1 in the sequence table, said NPL processes nucleotide sequence of sequence2 in the sequence table, said H5F processes nucleotide sequence of sequence3 in the sequence table, said H5L processes nucleotide sequence of sequence4 in the sequence table, said N1F processes nucleotide sequence of sequence5 in the sequence table, said N1F processes nucleotide sequence of sequence6 in the sequence table. The invention can be used not only for laboratory diagnosis and scientific research, but also for large-scale epidemiology survey.

Avian influenza in humans : A practical review for clinicians

Abstract: Human outbreaks of avian influenza in Southeast Asia in recent years have raised concerns about the potential for a pandemic. The highly pathogenic avian influenza A virus (subtype H5N1) has caused high mortality in previously healthy children and young adults and has demonstrated characteristics that suggest a potential for pandemic spread. It is important that front-line physicians be able to recognize cases of avian influenza, to be aware of atypical symptoms, to institute proper isolation precautions, and to start appropriate therapy. Current influenza vaccines provide no protection against avian influenza, but vaccination of at-risk persons may help decrease the likelihood of genetic recombination that could lead to efficiently transmitted strains. Amantadine and rimantadine are considered ineffective for treatment of infection with the highly pathogenic H5N1 strain, but oseltamivir may play an important role in prevention and control of avian influenza outbreaks among humans.