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Effect of passive maternal antibody on influenza illness in children: a prospective study of influenza A in mother-infant pairs.

Reuman PD, Ayoub EM, Small PA.

To determine the effect of passive antibody on the incidence of influenza in infants, infants born to mothers with serum antibody to influenza A (immune) and those born to mothers without evidence for this serum antibody (non-immune) were followed during the influenza H1N1 epidemic of 1979. Immune mothers had higher H1-specific antibody titers before the epidemic (P less than 0.001), were less frequently culture positive, showed fewer titer rises (P less than 0.001) and were less symptomatic than were nonimmune mothers. Infants of immune mothers had higher H1-specific passive antibody titers that correlated with their mother's antibody titers. Although infants of both groups showed no difference in incidence of influenza infection, infants of immune mothers had influenza symptoms that were delayed in onset (P = 0.02) and were of shorter mean duration compared with infants of nonimmune mothers. These findings suggest that passive maternal antibody delays the onset and decreases the severity of influenza disease in young infants.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3588113&dopt=Abstract flu, influenza



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Effect of vaccination by community pharmacists among adult prescription recipients.

Grabenstein JD, Guess HA, Hartzema AG, Koch GG, Konrad TR.

US Army Medical Command, Falls Church, Virginia, USA. Grabenstein mindspring.com

BACKGROUND: Millions of doses of influenza vaccine are administered each year in the United States at nontraditional sites and by nontraditional vaccine providers. Pharmacists are increasingly becoming vaccine providers. OBJECTIVES: To measure association between availability of pharmacist-immunizers and immunization delivery to adult prescription recipients, and the relative contributions of various types of vaccine providers. RESEARCH DESIGN: Mailed survey in spring 1999, contrasting adults in urban Washington State, where pharmacists administer vaccines, to adults in urban Oregon, where pharmacists did not. SUBJECTS: Cluster sample based on October 1998 prescription records suggesting need for influenza vaccine, derived from 24 community pharmacies belonging to one pharmacy chain. MEASURES: Vaccination status and choice of vaccine provider. RESULTS: Influenza vaccination rates among respondents 65 years or older increased 4.7% more in Washington than in Oregon between 1997 and 1998 (P = 0.20). The net increase in influenza vaccination rate among younger respondents taking indicator medications for chronic diseases for which influenza vaccination is recommended was 10.6% (P = 0.05). Among respondents unvaccinated against influenza in 1997, the 1998 influenza vaccination rate was 34.7% in Washington, compared with 23.9% in Oregon (P = 0.01). CONCLUSIONS: Vaccine delivery by pharmacists is associated with higher rates of vaccination among those younger than 65 taking indicator medications medications for chronic diseases, as well as prescription recipients unvaccinated against influenza in the previous year.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11329521&dopt=Abstract flu, influenza



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Clinical manifestations and consequences of influenza.

Cate TR.

The spread of influenza virus through a community typically causes large increases in medical visits for febrile respiratory disease. Increased school absenteeism occurs early in the epidemic, and school children appear to be important for disseminating the virus. Industrial absenteeism, hospitalizations of adults and infants for pneumonia, and deaths due to pneumonia-influenza all tend to peak later in the epidemic. Although influenza infection rates are highest in persons of school age, hospitalizations and deaths occur primarily in infants and in the elderly, particularly among those with pulmonary, cardiovascular, or other debilitating disorders. Influenza viruses can be spread by aerosol or contact. The primary target cells are those of the respiratory epithelium. In healthy adults, the typical influenza syndrome includes fever, cough, and general aches for three to seven days, but lassitude, cough, and evidence of small-airways disease may persist for weeks. Laryngotracheobronchitis, pneumonia, and unexplained fever are prominent manifestations of influenza that lead to hospitalization of young children. Adults are more likely to have complications of bacterial pneumonia and worsening of chronic pulmonary disease or congestive heart failure. Less frequent complications include myositis, various neurologic disorders, and Reye's syndrome. These consequences of influenza clearly justify strenuous efforts at prevention and control.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3591813&dopt=Abstract flu, influenza



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Influenza: quantifying morbidity and mortality.

Monto AS.

Because of their dramatic impact, morbidity and mortality associated with influenza have been recognized since at least the time of Elizabeth I of England. Excess mortality has been documented since 1889, and the infamous 1918 outbreak confirmed that influenza was truly one of the last major plagues. Despite the clear recognition of large clusters of influenza activity, it is still difficult to quantify precisely the total impact of influenza morbidity and mortality, since laboratory confirmation is required for exact diagnosis. Many methods have been developed to provide estimates of the mortality associated with influenza. These methods are usually predicated on establishing expected baseline rates of mortality. Deaths in excess of these rates are then calculated--and attributed to the circulating influenza virus. In this way, groups at high risk of mortality have been defined as the elderly and those with chronic conditions. Special-risk groups, such as those in institutions, have also been identified. The quantification of morbidity has required different approaches, and here community and family studies have made major contributions. In contrast to mortality, morbidity is most pronounced in children and young adults, and the diseases, although self-limited, are often quite severe. Although the size of the outbreaks varies, influenza infection can be documented annually. Thus, each year must be considered an influenza year.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3591814&dopt=Abstract flu, influenza



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Prevention and control of influenza. Role of vaccine.

Ruben FL.

A major component in the prevention and control of influenza should be the use of killed influenza vaccines. These vaccines became possible after the first discovery of human strains of influenza virus in the 1930s. The ensuing decades have seen marked improvement in the available inactivated vaccines. Current vaccines have excellent reliability and assured potency, and they contain the proper antigens to match the frequent changes in circulating influenza viruses. Killed vaccines work by inducing serum antibodies against the hemagglutinin and neuraminidase of the vaccine strains, with sufficient antibodies ensuring protection against infection. The antibody responses to current vaccines appear to be adequate in all age groups. Although antibody responses are depressed in patients receiving chemotherapy or immunosuppressants, current vaccines do provide protection for most populations. Vaccines prevent the manifestations of disease by about 30 to 70 percent in all populations, and they reduce deaths in high-risk individuals by about 60 to 87 percent. Local adverse reactions to vaccine are quite common, but not severe. Fever, also somewhat common, usually does not last beyond 48 hours. Neurologic complications have not been observed since the use of the swine influenza vaccine of 1976. Killed vaccines should be given annually in the fall, but they can be given up to and during an outbreak. Target groups for vaccines have been defined by the Centers for Disease Control. In recent years, these groups have included physicians and nurses who give care to patients at risk for complications of influenza.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3591815&dopt=Abstract flu, influenza



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[The 1985 influenza epidemic in a pediatric practice]

[Article in German]

Doller G, Tjhen KY, Doller PC, Gerth HJ.

Because it is not possible to distinguish clinically influenza from other respiratory infections, virological methods have to be used to establish the influenza etiology. Nasopharyngeal swabs from 202 children with respiratory symptoms were taken. Influenza A virus (H3N2) was isolated from 44 children, influenza A virus (H1N1) from 61 children and influenza B virus from 13 children. The maximal activity of the two influenza A virus subtypes was different. The following features permitted the classification of 3 groups; monophasic fever greater than or equal to 38.5 degrees C (81.35%), biphasic fever (14.41%), and pseudocroup (4.24%). 16.1% of the children with fever also had gastrointestinal symptoms. No relation between influenza type/subtype and type of manifestation could be established.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3600670&dopt=Abstract flu, influenza



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The surface receptor is a major determinant of the cell tropism of influenza C virus.

Herrler G, Klenk HD.

N-Acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) has been shown to be a high-affinity receptor determinant for attachment of influenza C virus to erythrocytes (G. N. Rogers, G. Herrler, J. C. Paulson, and H-D. Klenk, 1986, J. Biol. Chem. 261, 5947-5951). In this report the nature of the cell surface receptor for influenza C virus on tissue culture cells was analyzed. Pretreatment with either neuraminidase or neuraminate 9-O-acetylesterase was found to render LLC-MK2 cells resistant to infection by influenza C virus as evidenced by the failure to detect virus release into the medium by hemagglutination titration. Susceptibility to infection was fully restored after incubation of neuraminidase-treated cells with bovine brain gangliosides known to contain Neu5,9Ac2. These results indicate that (i) Neu5,9Ac2 is the primary receptor determinant required for influenza C virus to attach to tissue culture cells and to initiate infection and (ii) gangliosides containing this type of sialic acid are potential receptors for influenza C virus. Several cell lines which are resistant to infection by this virus were able to release influenza C virus into the medium provided they were incubated with bovine brain gangliosides prior to virus infection. This result indicates that lack of appropriate receptors on the cell surface is a major reason for the restricted cell tropism of influenza C virus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3604057&dopt=Abstract flu, influenza



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Primary structure of the polymerase acidic (PA) gene of an influenza B virus (B/Sing/222/79).

Akoto-Amanfu E, Sivasubramanian N, Nayak DP.

A DNA copy of influenza B/Singapore/222/79 viral RNA segment 3 containing the gene coding for the polymerase acidic (PA) protein has been cloned in Escherichia coli plasmid pBR322, and its nucleotide sequence has been determined. The cDNA clone was incomplete and contained 1810 nucleotides (nt 396 to 2205). The remaining nucleotide sequence at both 5' and 3' ends of B PA gene was obtained by sequencing the viral RNA (minus sense) and messenger RNA (plus sense) using oligonucleotide primers. The influenza B PA gene contains 2304 nucleotides and codes for a protein of 725 amino acids with a molecular weight of 83,000. The predicted influenza B PA protein is less acidic than the influenza A PA protein. Computer alignment of the influenza B PA amino acid sequence with that of influenza A PA (A/PR/8/34) revealed an overall 38% direct homology which increases to 45% in the carboxyl terminus half of the protein. In addition, comparison of the secondary structural elements, hydropathy profile, and isofunctional amino acid changes between B PA and A PA proteins demonstrated a strong structural and possibly functional conservation between these two proteins. These data suggest that PA genes of influenza A and B viruses arose from a common ancestor gene.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3604058&dopt=Abstract flu, influenza



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Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent heterosubtypic cross-protection against lethal influenza A H5N1 virus infection.

Tumpey TM, Renshaw M, Clements JD, Katz JM.

Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Influenza vaccines that induce greater cross-reactive or heterosubtypic immunity (Het-I) may overcome limitations in vaccine efficacy imposed by the antigenic variability of influenza A viruses. We have compared mucosal versus traditional parenteral administration of inactivated influenza vaccine for the ability to induce Het-I in BALB/c mice and evaluated a modified Escherichia coli heat-labile enterotoxin adjuvant, LT(R192G), for augmentation of Het-I. Mice that received three intranasal (i.n.) immunizations of H3N2 vaccine in the presence of LT(R192G) were completely protected against lethal challenge with a highly pathogenic human H5N1 virus and had nasal and lung viral titers that were at least 2,500-fold lower than those of control mice receiving LT(R192G) alone. In contrast, mice that received three vaccinations of H3N2 vaccine subcutaneously in the presence or absence of LT(R192G) or incomplete Freund's adjuvant were not protected against lethal challenge and had no significant reductions in tissue virus titers observed on day 5 post-H5N1 virus challenge. Mice that were i.n. administered H3N2 vaccine alone, without LT(R192G), displayed partial protection against heterosubtypic challenge. The immune mediators of Het-I were investigated. The functional role of B and CD8+ T cells in Het-I were evaluated by using gene-targeted B-cell (IgH-6(-/-))- or beta2-microglobulin (beta2m(-/-))-deficient mice, respectively. beta2m(-/-) but not IgH-6(-/-) vaccinated mice were protected by Het-I and survived a lethal infection with H5N1, suggesting that B cells, but not CD8+ T cells, were vital for protection of mice against heterosubtypic challenge. Nevertheless, CD8+ T cells contributed to viral clearance in the lungs and brain tissues of heterotypically immune mice. Mucosal but not parenteral vaccination induced subtype cross-reactive lung immunoglobulin G (IgG), IgA, and serum IgG anti-hemagglutinin antibodies, suggesting the presence of a common cross-reactive epitope in the hemagglutinins of H3 and H5. These results suggest a strategy of mucosal vaccination that stimulates cross-protection against multiple influenza virus subtypes, including viruses with pandemic potential.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11333895&dopt=Abstract flu, influenza



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Epidemiologic particularities of influenza in 1986 in a large urban centre of Romania.

Magureanu E, Busuioc C, Ionescu V, Guguianu E, Stoicescu A, Horhogea G, Murgoci R, Coban V, Dobrescu A.

Chair of Epidemiology, Institute of Medicine and Pharmacy, Bucharest, Romania.

The study presents the evolutive peculiarities of the epidemiologic influenza process in 1986 in a large urban centre in Romania, inferrable from the active control by a complex methodology based on clinical, epidemiologic and laboratory investigations. The prevalent part of A (H1N1 and H3N2) and B influenza viruses in causing seasonal morbidity risings is being stressed. A (H3N2) and B influenza viruses determined an epidemic rising during the first trimester and A (H1N1) and A (H3N2) during the fourth trimester in 1986. The epidemiologic influenza impact in 1986 is discussed from the point of view of the complex relationships between the antigenic structure of circulating influenza viruses and the antiinfluenza immune structure of the population.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3660584&dopt=Abstract flu, influenza



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Decreased pulmonary clearance of S. pneumoniae following influenza A infection in mice.

LeVine AM, Koeningsknecht V, Stark JM.

Department of Pulmonary Biology, Childrens Hospital Medical Center, Cincinnati, OH, USA.

In children, the incidence of complicated pneumonias (including empyemas and lung abscesses) associated with Streptococcus pneumoniae infection has increased in recent years. In many cases, these complicated pneumonias followed flu-like illnesses. To determine mechanisms behind this association, a murine model of sequential pulmonary infection has been developed. BALB/cJ mice infected with influenza A had mild pulmonary inflammation that resolved within 5-7 days. Seven days following their initial 'treatment' (mock infection or influenza exposure), mice were challenged with 10(6) cfu of S. pneumoniae, and their lungs were harvested at intervals for analysis. Lungs of influenza-exposed mice demonstrated greater colony counts 24 and 48 h following S. pneumoniae exposure compared to control mice. In addition, neutrophil numbers were significantly increased in the influenza/S. pneumoniae sequentially-infected animals compared to S. pneumoniae infection alone (1.4+/-0.6 x 10(6) vs. 0.06+/-0.07 x 10(6) cells, P < 0.05, 24 h). Influenza-exposed animals had greater levels of IL-1beta and TNF-alpha in lung homogenates following S. pneumoniae inoculation. These data demonstrate that mice exposed to influenza have enhanced inflammatory responses and increased bacterial burden following S. pneumoniae exposure than do control mice. This model will be useful in defining mechanisms behind the enhanced susceptibility to S. pneumoniae that occurs after influenza exposure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11337052&dopt=Abstract flu, influenza