Effect of heterosubtypic immunity on infection with attenuated influenza ( flu ) A virus vaccines in young children.

Resistance to infection with an influenza ( flu ) A virus conferred by previous infection with an influenza ( flu ) A virus belonging to another subtype is called heterosubtypic immunity. Heterosubtypic immunity is demonstrable in laboratory animals but is believed to be weak in humans. The present study examined whether heterosubtypic immunity from previous influenza ( flu ) virus infection induced resistance to infection with an attenuated influenza ( flu ) A vaccine virus. Two groups of vaccinees consisting of young infants and children who received either influenza ( flu ) A H1N1 or H3N2 attenuated virus were studied. Influenza ( Flu ) A H3N2 virus vaccine recipients were classified by their preexisting H1N1 heterosubtypic antibody level induced by prior infection with wild-type virus, and the H1N1 vaccinees were classified by their history of infection with H3N2 vaccine virus. For both groups of vaccinees, the rates of seroconversion and virus shedding and the level of vaccine virus replication were compared in subjects with and without heterosubtypic immunity. In 48 influenza ( flu ) A H3N2 virus and 39 H1N1 virus vaccinees, heterosubtypic immunity had no demonstrable effect on infectivity, immunogenicity, or replication of attenuated vaccine virus. These observations confirm the weak nature of heterosubtypic immunity in humans and suggest that it will not limit the utility of live attenuated influenza ( flu ) A viruses in young infants and children.

An outbreak of influenza ( flu ) A in a neonatal intensive care unit.

OBJECTIVES: Investigation of an outbreak of influenza ( flu ) A in a neonatal intensive care unit (NICU) with examination of risk factors for infection and outcomes. DESIGN: Retrospective cohort study of infants admitted to the unit during the outbreak period. Prospective survey of NICU staff and mothers of infants in the cohort study. SETTING: Level III nursery in a university-affiliated tertiary referral center. RESULTS: Nineteen infants in the NICU were infected with influenza ( flu ) A There were six symptomatic cases and one death who had evidence of virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was offered to the NICU staff, and amantadine therapy was given to five of the six symptomatic infants. Mechanical ventilation, gestational age, birth weight, Clinical Risk Index for Babies score, and twin pregnancy were associated with acquisition of influenza ( flu ) A on univariate analysis. Mechanical ventilation (odds ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as significant risk factors for infection on multiple logistic regression analysis. Only 15% of respondents to the NICU staff survey were vaccinated against influenza ( flu ). There was no association between a history of an influenza ( flu )-like illness during pregnancy and acquisition of influenza ( flu ) A by infants of mothers who responded to the maternal survey (OR, 0.91; P=1.0). CONCLUSIONS: Influenza ( Flu ) A is an important pathogen in the neonatal population and is readily transmissible in the NICU setting.

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705.

We have solved the crystal structures of three HLA-B*2705-peptide complexes with the immunodominant viral peptides: EBV EBNA3C 258-266 (RRIYDLIEL), influenza ( flu ) (flu) nucleoprotein NP383-391 (SRYWAIRTR), and HIV gag 264-273 (KRWIILGLNK). Long-term non-progression during HIV infection has been associated with presentation by HLA-B*2705, and T cell recognition, of the highly immunodominant KRWIILGLNK peptide. The tight hydrogen-bonding network observed between the HLA-B*2705 B-pocket and the peptide P2 arginine guanadinium anchor explains why mutation of this residue during HIV infection results in loss of peptide binding, immune escape and progression to AIDS. Prominent, solvent-exposed structures within these peptides may participate in generating T cell responses to these immunodominant epitopes. In the HLA-B*2705 complex with flu NP383-391, the amino acid side chains of residues 4, 7 and 8 are solvent-exposed whilst in the HIV decamer, the main-chain bulges into the solvent around P7. Thus, HLA-B*2705 presents viral peptides in a range of conformations. Tetrameric complexes of HLA-B*2705 with the HIV and flu but not EBV peptides bound strongly to the killer-Ig-like receptor (KIR)3DL1. Substitution of EBV P8 glutamate to threonine allowed recognition by KIR3DL1. In the HLA-B*2705-EBV structure the P8 glutamate side chain is solvent-exposed and may inhibit KIR3DL1 binding through electrostatic forces.

Effect of computer-generated nurse/physician reminders on influenza ( flu ) immunization among seniors.

Despite long-standing recommendations by the Canadian and U.S. national immunization advisory committees that all persons aged 65 or older be vaccinated annually against influenza ( flu ), vaccination rates among North American seniors remain approximately 20%. This paper reports a study of the effect of computer-generated nurse/physician reminders to offer influenza ( flu ) vaccine to elderly patients seen during the pre-influenza ( flu ) season in a community based group family practice. The study employed a pretest-post-test design strengthened by the use of a no-intervention comparison practice and repeated pretest measures of vaccine coverage. Outcome was measured by clinical records review. The influenza ( flu ) vaccination rate increased by 165% from 10.1% to 26.8% following introduction of the computer-generated reminders. There was no increase in influenza ( flu ) immunization in the comparison practice during the corresponding time period. Over 60% of eligible patients were seen in the practice during the pre-influenza ( flu ) season; 41.6% of those received influenza ( flu ) vaccinations.

A new modified live equine influenza ( flu ) virus vaccine: phenotypic stability, restricted spread and efficacy against heterologous virus challenge.

Chambers TM, Holland RE, Tudor LR, Townsend HG, Cook A, Bogdan J, Lunn DP, Hussey S, Whitaker-Dowling P, Youngner JS, Sebring RW, Penner SJ, Stiegler GL.

Department of Veterinary Science, University of Kentucky, Lexington 40546-0099, USA.

Flu Avert IN vaccine is a new, live attenuated virus vaccine for equine influenza ( flu ). We tested this vaccine in vivo to ascertain 1) its safety and stability when subjected to serial horse to horse passage, 2) whether it spread spontaneously from horse to horse and 3) its ability to protect against heterologous equine influenza ( flu ) challenge viruses of epidemiological relevance. For the stability study, the vaccine was administered to 5 ponies. Nasal swabs were collected and pooled fluids administered directly to 4 successive groups of naive ponies by intranasal inoculation. Viruses isolated from the last group retained the vaccine's full attenuation phenotype, with no reversion to the wild-type virus phenotype or production of clinical influenza ( flu ) disease. The vaccine virus spread spontaneously to only 1 of 13 nonvaccinated horses/ponies when these were comingled with 39 vaccinates in the same field. For the heterologous protection study, a challenge model system was utilised in which vaccinated or naive control horses and ponies were exposed to the challenge virus by inhalation of virus-containing aerosols. Challenge viruses included influenza ( flu ) A/equine-2/Kentucky/98, a recent representative of the 'American' lineage of equine-2 influenza ( flu ) viruses; and A/equine-2/Saskatoon/90, representative of the 'Eurasian' lineage. Clinical signs among challenged animals were recorded daily using a standardised scoring protocol. With both challenge viruses, control animals reliably contracted clinical signs of influenza ( flu ), whereas vaccinated animals were reliably protected from clinical disease. These results demonstrate that Flu Avert IN vaccine is safe and phenotypically stable, has low spontaneous transmissibility and is effective in protecting horses against challenge viruses representative of those in circulation worldwide.

Evidence for interspecies transmission and reassortment of influenza ( flu ) A viruses in pigs in southern China.

The Asian/57, Hong Kong/68, and Russian/77 pandemics of this century appeared or reappeared in China. Interspecies transmission and genetic reassortment of influenza ( flu ) viruses have been implicated in the origin of these human pandemic influenza ( flu ) viruses. Pigs have been suspected to be the "mixing vessel" where reassortment occurs. To investigate this possibility, 104 porcine influenza ( flu ) viruses collected at random from Southern China from 1976 to 1982, including 32 H3N2 isolates and 72 H1N1 isolates, were studied using dot blot hybridization, partial sequencing, and phylogenetic analysis. There were 29 of 32 H3N2 isolates characteristic of viruses originally derived from humans; the other 3 isolates were reassortants containing genes from porcine and human influenza ( flu ) viruses. Phylogenetic analyses of the polymerase B1 (PB1) genes showed that interspecies transmission from humans to pigs has happened multiple times in pigs in Southern China. All 72 H1N1 isolates were of porcine origin characteristic of classical porcine H1N1 influenza ( flu ) virus. Analysis of 624 genes of porcine influenza ( flu ) viruses from Southern China failed to detect any evidence for avian influenza ( Flu ) virus genes. This contrasts to what is currently found in Europe, where the majority of porcine influenza ( flu ) virus isolates are of avian origin.

Use of Oseltamivir ( Tamiflu ) during influenza ( flu ) outbreaks in Ontario nursing homes, 1999-2000.

OBJECTIVES: To describe the experience of Ontario long-term care facilities that used Oseltamivir ( Tamiflu ) during influenza ( flu ) outbreaks in 1999/2000. DESIGN: Case series. SETTING: Ten Ontario long-term care facilities for older people and their residents. PARTICIPANTS: Older residents of long-term care facilities. INTERVENTION: Oseltamivir ( Tamiflu ) for treatment or prophylaxis during 11 influenza ( flu ) outbreaks in 1999/2000. MEASUREMENTS: Control of outbreaks; pneumonia, hospitalization, and death complicating acute influenza ( flu ). RESULTS: All outbreaks were due to influenza ( flu ) A//H3N2/Sydney/05/97. One facility elected to use Oseltamivir ( Tamiflu ) for treatment and amantadine for prophylaxis. The remaining nine facilities (10 outbreaks) recommended Oseltamivir ( Tamiflu ) for treatment and prophylaxis (after amantadine failure in five and as primary prophylaxis in five). Use of Oseltamivir ( Tamiflu ) was associated with termination of the outbreak in all eight evaluable outbreaks. Overall, 178/185 (96%) case-residents met the case definition of influenza ( flu ) and had complete data for evaluation. Of these, 63 (35%) were treated with antibiotics, 37 (21%) were diagnosed with pneumonia, 19 (11%) were hospitalized, and 16 (9%) died. Compared with residents receiving no therapy or who became ill while taking amantadine, residents who received Oseltamivir ( Tamiflu ) within 48 hours of the onset of symptoms were less likely to be prescribed antibiotics, to be hospitalized, or to die (P <.05 for each outcome). These differences persisted and remained statistically significant when corrected for influenza ( flu ) immunization status. A total of 730 residents received Oseltamivir ( Tamiflu ) prophylaxis for a median of 9 days (range 5-12). Of these, side effects were identified in 30 (4.1%), the most common being diarrhea (12 residents, 1.6%), cough (5, 0.7%), confusion (4, 0.5%) and nausea (4, 0.5%). CONCLUSIONS: Oseltamivir ( Tamiflu ) is safe and appears to be effective when used as treatment or prophylaxis to control outbreaks of influenza ( flu ) in older nursing home residents.

Antigenic relationship between influenza ( flu ) A (H3N2) strains circulating in Argentina and vaccine strains

Influenza ( Flu ) epidemic season occurs usually from May to September in Argentina, so that the vaccine produced in the northern hemisphere to be administered during October-November may be out of phase for Argentina. In order to determine if the locally circulating strains in Argentina are antigenically close by related to the vaccine strains administered, they were compared with the influenza ( flu ) viruses isolated from May 1994 to December 1997. Clinical samples (9866) were nasopharyngeal aspirates from children hospitalized for acute lower respiratory tract infection and nasal-pharyngeal swabs from adults with influenza ( flu ) syndrome. Initial laboratory diagnosis was performed by immunofluorescence assay, followed by isolation in MDCK cells. Influenza ( Flu ) A viruses (242) were detected and subtyped by hemagglutination inhibition (HAI) with WHO FLU Reagent Kit. A subset of the isolated viruses was antigenically analyzed by the WHO Collaborating Center at CDC, Atlanta, USA. Influenza ( Flu ) A (H3N2) viruses characterized as circulating in Argentina during the last four years matched partially with the antigens present in the vaccines administered during 1994-97 period. These antigenic variants sometimes circulate late in the year (October 1994 and 1997) initiating the following influenza ( flu ) season and becoming prevalent. They were present 2 years later in the vaccine formula administered in the southern hemisphere. The HAI results of our isolates show that they are highly specific with the homologous antiserum and much less specific with antibodies against vaccine strains. The difference is 16 to 64 fold different. These results demonstrate the need to intensify influenza ( flu ) laboratory surveillance in order to obtain the best possible vaccine.

How complete is influenza ( flu ) immunization coverage? A study in 75 nursing and residential homes for elderly people.

BACKGROUND. Elderly people in residential accommodation are particularly susceptible to outbreaks of influenza ( flu ). Up to 70% of residents can become ill and many will develop complications or die. Immunization can prevent such outbreaks and is cost-effective. AIM. A study was undertaken to measure influenza ( flu ) immunization coverage in residential accommodation for elderly people and to identify factors that might influence uptake. METHOD. In March 1992, a questionnaire survey was conducted of all 113 registered nursing and residential homes for elderly people, in South Glamorgan. It asked about the demographic characteristics of people resident on 1 October 1991, their influenza ( flu ) immunization history and the homes' arrangements for administering immunizations. RESULTS. Questionnaires were returned by respondents from 75 homes (66%). Mean influenza ( flu ) vaccine uptake was 67%. Uptake was higher in nursing homes (mean of 82% in eight nursing homes) than in homes registered as both nursing and residential homes (mean of 76% in six homes) or in residential homes (mean of 65% in 61 homes). Nearly all of those immunized (94%) had been immunized by the end of November 1991. Residents who were reported to have underlying disease that increased their risk of complications if they contracted influenza ( flu ) were no more likely to have been immunized than those without risk factors. Immunization coverage varied considerably both between homes and between general practices. Most general practices in South Glamorgan had several elderly people in residential accommodation on their list, but only nine out of 64 practices had immunized all the elderly residents on their list and 12 practices had immunized fewer than half. Routine recording of immunization status in nursing and residential homes was variable, often as a consequence of poor communication between the primary health care team and staff at the home. Even where recorded, retrieval of the data was sometimes a problem. CONCLUSION. Influenza ( Flu ) immunization coverage could be improved if general practices held a case register of all at-risk patients including elderly residents, and if nursing and residential homes were encouraged to keep better immunization records. These measures would facilitate year-on-year monitoring of influenza ( flu ) immunization coverage and the targeting of homes with low immunization coverage.

Healthcare workers and their attitudes to influenza ( flu ) vaccination.

Despite Department of Health recommendations that healthcare workers (HCWs) receive influenza ( flu ) vaccination, uptake is low. Influenza ( Flu ) vaccination has been promoted to reduce nosocomial transmission and staff absenteeism during the winter period. Our study aimed to investigate factors associated with uptake, and non-uptake, of influenza ( flu ) vaccination. In March 2001 we undertook a questionnaire-based cross-sectional survey of 604 hospital HCWs in Leicester and 11 occupational health nurses. Following multivariate analysis, uptake was associated with previous influenza ( flu ) vaccination (OR: Odds ratio 1000, 95% CI 20-3,333), age > 45 years (OR 4.45, 95% CI 1.66-11.9), and belief that influenza ( flu ) is a serious illness (OR 3.8, 95% CI 1.3-10.6). HCWs receive vaccination predominantly as a benefit for themselves. Campaigns should improve accessibility, target younger staff and stress the consequences of influenza ( flu ) infection. Simply raising awareness may not translate into increased uptake. Absenteeism was attributed to vaccine-related adverse effects by 11/83 (13%) vaccinees, resulting in 0.46 workdays lost per dose administered.