Characterization of avian H5N1 influenza ( flu ) viruses from poultry in Hong Kong.

The transmission of avian H5N1 influenza ( flu ) viruses to 18 humans in Hong Kong in 1997 with six deaths established that avian influenza ( Flu ) viruses can transmit to and cause lethal infection in humans. This report characterizes the antigenic and biological properties of the H5N1 influenza ( flu ) viruses isolated from chickens, ducks, and geese from farms and poultry markets in Hong Kong during 1997 and compares them with those of virus isolated from the index human case. Each of the H5N1 viruses from Hong Kong poultry markets that were tested were lethal in chickens, possessed polybasic amino acids at the carboxy-terminus of HA1, and by definition were highly pathogenic in poultry. The available nonpathogenic H5 influenza ( flu ) viruses and the pathogenic H5N1 virus from Hong Kong were analyzed with monoclonal antibodies prepared to A/chicken/Pennsylvania/1370/83 (H5N2). The analysis revealed limited antigenic drift in 15 years and established that monoclonal antibodies are useful reagents for identification and antigenic analysis of avian strains that may transmit to humans in the future. One of the monoclonal antibodies permitted separation of the H5N1 influenza ( flu ) viruses from poultry into two groups that correlated with the presence or absence of a carbohydrate at residue 158 adjacent to the receptor binding site on HA. The H5N1 viruses examined replicated in geese, pigs, rats, and mice, but to only a very limited extent in ducks. It is noteworthy that all infected geese shed virus and that the H5N1 viruses caused disease signs and death in a portion (3 of 16) of the geese, with evidence of systemic spread to the brain. The tropism for geese is unusual and may provide insight into the origin of these viruses. In mice, the H5N1 virus caused lethal pneumonia and spread systemically to the brain. Mice would thus provide an ideal model system for studying immune responses and pathogenesis. Transmission experiments in chickens revealed that the H5N1 viruses are spread by fecal-oral transmission rather than by aerosol, and that the viruses are inactivated by drying of feces at ambient temperature. However, infectivity is maintained for at least 4 days in wet feces at 25 degreesC. There were differences in the morphology of the H5N1 viruses isolated from birds and humans. The perpetuation of H5N1 influenza ( flu ) viruses in the poultry markets in Hong Kong and the transmission of these viruses to humans emphasize the importance of these markets in the epidemiology of influenza ( flu ). The poultry markets are of critical importance in the perpetuation and transmission of influenza ( flu ) viruses to other avian species and to mammals, including humans.

Precursor genes of future pandemic influenza ( flu ) viruses are perpetuated in ducks nesting in Siberia.

Influenza ( Flu ) A viruses of different subtypes were isolated from fecal samples of ducks in their nesting areas in Siberia in summer from 1996 to 1998. Phylogenetic analysis of the NP genes of the isolates in Siberia and those in Hokkaido, Japan on their flyway of migration from Siberia to the south in autumn revealed that they belong to the Eurasian lineage of avian influenza ( Flu ) viruses. It is noted that the genes of the isolates in Siberia are closely related to those of H5N1 influenza ( flu ) virus strains isolated from chickens and humans in Hong Kong in 1997 as well as to those of isolates from domestic birds in southern China. The results indicate that influenza ( flu ) viruses perpetuated in ducks nesting in Siberia should have contributed genes in the emergence of the H5N1 virus in Hong Kong. Vaccine prepared from avirulent A/duck/Hokkaido/4/96 (H5N3) influenza ( flu ) virus was potent enough to protect mice from challenge with lethal dose of the pathogenic H5N1 virus [19]. Intensive surveillance study of aquatic birds especially in Siberia is, therefore, stressed to provide information on the future pandemic influenza ( flu ) virus strains and for vaccine preparation.

Contribution of influenza ( flu ) and respiratory syncytial virus to community cases of influenza ( flu )-like illness: an observational study.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of lower-respiratory-tract infection in children and elderly people, but its effect in other age-groups is uncertain. We did a community-based observational study of RSV infection in community-dwelling individuals of all ages who presented to general practices in the UK with influenza ( flu )-like illnesses during three successive winters (1995-96, 1996-97, and 1997-98). METHODS: Nasopharyngeal swabs routinely submitted for virological surveillance were examined by multiplex reverse transcription PCR for influenza ( flu ) A and B viruses and RSV A and B, and findings were related to the clinical incidence of influenza ( flu )-like illness and acute bronchitis at that time. RSV strains identified were compared with those obtained from hospital admissions. FINDINGS: 480 RSV and 709 influenza ( flu ) viruses were identified from a total of 2226 swabs submitted. Both types of virus were found in all age-groups for between 12 and 20 weeks in each winter. RSV A accounted for 60% of RSV detections. Similar strains of RSV were present in hospital and community patients within the same year, but there were different lineages each year. INTERPRETATION: In individuals diagnosed with influenza ( flu )-like illness, there is a substantial potential for confusion between illnesses caused by influenza ( flu ) and those caused by RSV. The burden of illness attributable to each needs to be clarified to define optimum management routines.

Influenza ( Flu ) and pneumococcal vaccination as a model to assess C-reactive protein response to mild inflammation.

This study was set up to examine whether an influenza ( flu ) vaccine or an influenza ( flu ) vaccine in combination with pneumococcal vaccine can be used as a model to study responses to mild stimulation of the inflammatory system. In this study, 19 subjects received the influenza ( flu ) vaccine, 20 subjects the combination of influenza ( flu ) and pneumococcal vaccine. CRP and prothrombin fragment 1 and 2 (F1+2) were measured at baseline, and two times after vaccination. Influenza ( Flu ) vaccination increased CRP by 0.20 mg/L, and influenza ( flu ) in combination with pneumococcal vaccine increased CRP by 0.60 mg/L. F1+2 increased 0.15 nmol/L after the combined vaccination; an increase in response to the influenza ( flu ) vaccination was not statistically significant. Our findings show that the influenza ( flu ) vaccine alone as well as the combination of the influenza ( flu ) and pneumococcal vaccine increases CRP-levels with a peak 2 days after vaccination.

Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza ( flu ) season.

OBJECTIVES: A population-based assessment of maternal and perinatal morbidity related to respiratory illness during influenza ( flu ) season among pregnant women has not been published. The objectives of this investigation were to describe and quantify the impact of respiratory hospitalization during pregnancy on serious maternal and perinatal morbidity. STUDY DESIGN: A matched cohort study using an administrative database of pregnant women enrolled in the Tennessee Medicaid population to determine pregnancy outcomes associated with respiratory hospitalizations during influenza ( flu ) season. Pregnant women aged 15 to 44 years with a respiratory hospitalization during influenza ( flu ) seasons 1985-1993 were matched by gestational age and presence of comorbidity with pregnant control subjects without a respiratory hospitalization. RESULTS: During the eight influenza ( flu ) seasons studied, 293 women with singleton pregnancies had respiratory disease hospitalizations (5.1:1000). Women with asthma had high rates of such hospitalization (59.7:1000). Compared with matched controls, women with respiratory hospitalizations had similar modes of delivery, delivery length of stay, and episodes of preterm labor. The prevalence of prematurity and low birth weight among infants born to such women was likewise similar between the two groups. CONCLUSION: In this population of pregnant women, those with asthma accounted for half of all respiratory-related hospitalizations during influenza ( flu ) seasons, with 6% of pregnant women with asthma requiring respiratory hospitalization during influenza ( flu ) season, (odds ratio 10.63, 95% CI, 8.18-13.83, compared with women without a medical comorbidity). We detected no significant increase in adverse perinatal outcomes associated with respiratory hospitalizations during influenza ( flu ) season.

Is influenza ( flu ) vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial.

The aim of this study was to determine the cost effectiveness of influenza ( flu ) vaccination for healthy people aged 65-74 years living in the UK. People without risk factors for influenza ( flu ) (chronic heart, lung or renal disease, diabetic, immunosuppressed or those living in an institution) were identified from 20 general practitioner (GP) practices in Liverpool in September 1999. 729/5875 (12.4%) eligible individuals were recruited and randomised to receive either influenza ( flu ) vaccine or placebo (ratio 3:1), with all participants receiving 23-valent-pneumococcal polysaccharide vaccine unless already administered. The primary analysis was the frequency of influenza ( flu ) as recorded by a GP diagnosis of pneumonia or influenza ( flu ) like illness. In 2000, the UK vaccination policy was changed with influenza ( flu ) vaccine becoming available for all people aged 65 years and over irrespective of risk. As a consequence of this policy change, the study had to be fundamentally restructured and only results obtained over a one rather than the originally planned two-year randomised controlled trial framework were used. Results from 1999/2000 demonstrated no significant difference between groups for the primary outcome (relative risk 0.8, 95% CI 0.16-4.1). In addition, there were no deaths or hospitalisations for influenza ( flu ) associated respiratory illness in either group. The subsequent analysis, using both national and local sources of evidence, estimated the following cost effectiveness indicators: (1) incremental NHS cost per GP consultation avoided = 2000 pound sterling; (2) incremental NHS cost per hospital admission avoided = 61,000 pound sterling; (3) incremental NHS cost per death avoided = 1,900,000 pound sterling and (4) incremental NHS cost per QALY gained = 304,000 pound sterling. The analysis suggested that influenza ( flu ) vaccination in this population would not be cost effective.

Immunokinetics in severe pneumonia due to influenza ( flu ) virus and bacteria coinfection in mice.

Coinfections of bacteria and influenza ( flu ) are a major cause of excessive mortality during influenza ( flu ) epidemics. However, the mechanism of the synergy between influenza ( flu ) virus and bacteria are poorly understood. In this study, mice were inoculated with influenza ( flu ) virus, followed 2 days later by inoculation with Streptococcus pneumoniae. The kinetics of viral titres, bacterial numbers and the immune response (cytokine and chemokine production) were also analysed. Short-term survival correlated with pathological changes in the lungs of infected mice. Influenza ( Flu ) virus or S. pneumoniae infection alone induced moderate pneumonia; however, severe bronchopneumonia with massive haemorrhage in coinfected mice, which caused death of these mice approximately 2 days after inoculation with S. pneumoniae, was noted. Intrapulmonary levels of inflammatory cytokines/chemokines, type-1 T-helper cell cytokines and Toll-like receptors, and the related mitogen-activated protein kinase signalling molecules (phosphorylated extracellular signal-regulated kinase -1 and - 2, p38 and c-Jun N-terminal kinase), were increased in coinfected mice. These results suggest that immune mediators, including cytokines and chemokines, through Toll-like receptors/mitogen-activated protein kinase pathways, play important roles in the pathology of coinfection caused by influenza ( flu ) virus and Streptococcus pneumoniae.

Isolation from turkey breeder hens of a reassortant H1N2 influenza ( flu ) virus with swine, human, and avian lineage genes.

Type A influenza ( flu ) viruses can infect a wide range of birds and mammals, but influenza ( flu ) in a particular species is usually considered to be species specific. However, infection of turkeys with swine H1N1 viruses has been documented on several occasions. This report documents the isolation of an H1N2 influenza ( flu ) virus from a turkey breeder flock with a sudden drop in egg production. Sequence analysis of the virus showed that it was a complex reassortant virus with a mix of swine-, human-, and avian-origin influenza ( flu ) genes. A swine influenza ( flu ) virus with a similar gene complement was recently reported from pigs in Indiana. Isolation and identification of the virus required the use of nonconventional diagnostic procedures. The virus was isolated in embryonated chicken eggs by the yolk sac route of inoculation rather than by the typical chorioallantoic sac route. Interpretation of hemagglutination-inhibition test results required the use of turkey rather than chicken red blood cells, and identification of the neuraminidase subtype required the use of alternative reference sera in the neuraminidase-inhibition test. This report provides additional evidence that influenza ( flu ) viruses can cross species and cause a disease outbreak, and diagnosticians must be aware that the variability of influenza ( flu ) viruses can complicate the isolation and characterization of new isolates.

Bedside rapid flu test and zanamivir prescription in healthy working adults: a cost-benefit analysis.

BACKGROUND: Zanamivir, a neuraminidase inhibitor, reduces the number of days of illness in influenza ( flu )-positive patients. New bedside rapid flu tests (RFT) should increase the number of influenza ( flu )-positive patients whom receive zanamivir appropriately. OBJECTIVE: To estimate the economic effects of implementing RFT and zanamivir among unvaccinated healthy working adults who consult within 2 days of the onset of influenza ( flu )-like symptoms. METHODS: We constructed a decision tree to perform a cost-benefit analysis from a societal perspective. Clinical outcome, i.e. number of influenza ( flu ) days averted, and societal costs were compared for three strategies: RFT and conditional zanamivir prescription;systematic zanamivir prescription; and no zanamivir. A two-way sensitivity analysis was performed including the proportion of influenza ( flu )-positive patients. RESULTS: During influenza ( flu ) epidemics, systematic zanamivir prescription provided the best health outcome (0.81 influenza ( flu ) days averted) and minimised societal costs (reduced by 29.80 US dollars per person compared with no zanamivir; 1999 values). RFT with conditional zanamivir averted 0.65 influenza ( flu ) days and saved 14.40 US dollars per person. When the proportion of influenza ( flu )-positive patients was under 39%, the no zanamivir strategy yielded the greatest societal savings; otherwise, systematic zanamivir was the dominant strategy. Medical costs associated with no zanamivir were 88.70 US dollars per patient consulting with influenza ( flu )-like illness, and increased to 125.50 US dollars with systematic zanamivir and to 127.60 US dollars with RFT and conditional zanamivir. CONCLUSIONS: Due to poor sensitivity of current RFT, systematic zanamivir prescription without RFT for unvaccinated healthy working adults should be recommended during influenza ( flu ) epidemics.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza ( flu ) A virus without affecting cytolytic activity in the lung.

The immune response to influenza ( flu ) virus is exquisitely sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); however, the cellular mechanisms underlying the suppressive effects of TCDD are unknown. Mice exposed to TCDD exhibited a dose-responsive increase in mortality following an otherwise non-lethal influenza ( flu ) virus infection. Given that cytotoxic T lymphocytes (CTL) are generally thought to resolve primary infections in the lung, we tested the hypothesis that exposure to TCDD suppresses T-cell responsiveness, leading to decreased CTL in the lung. After infection with influenza ( flu ) virus, naive CD8+ lymphocytes are activated and differentiate in the mediastinal lymph node (MLN). In mice exposed to TCDD and infected with influenza ( flu ) virus, the number of CD8+ MLN cells was reduced 60% compared to vehicle-treated mice. Moreover, MLN cells from TCDD-treated mice failed to develop cytolytic activity, and the production of interleukin (IL)-2 and interferon (IFN)-gamma was suppressed. Exposure to TCDD also altered the production of virus-specific antibodies, decreased the recruitment of CD8+ cells to the lung, reduced the percentage and number of bronchoalveolar lavage cells bearing a CTL phenotype (CD8+CD44hiCD62L(l) degrees ), and suppressed IL-12 levels in the lung. Despite our findings that exposure to TCDD suppressed T cell-dependent functions, the cytolytic activity of lung lavage cells from TCDD and vehicle treated mice was equivalent, and IFN gamma levels in the lungs of mice treated with TCDD were enhanced 10-fold. Thus, while exposure to TCDD suppressed a number of responses associated with the development of adaptive immunity to influenza ( flu ) virus, a direct link between these effects and enhanced susceptibility to influenza ( flu ) remains unclear.