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

Stewart-Jones GB, di Gleria K, Kollnberger S, McMichael AJ, Jones EY, Bowness P.

The Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, Oxford, UK.

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) 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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15657948&dopt=Abstract flu, flu medicine, tamiflu



flu
Establishment of vaccination clinics; user fees for investigational new drug (IND) influenza vaccine services and vaccines. Interim final rule and request for comments.

Centers for Disease Control and Prevention (CDC), Department of Health and Human Services (HHS).

We are amending 42 CFR part 70 to establish vaccination clinics and a user fee in connection with the administration of vaccination services and vaccine. On December 7, 2004, HHS Secretary Tommy G. Thompson announced the purchase of 1.2 million doses of GlaxoSmithKline (GSK) influenza vaccine, Fluarix, for distribution to areas most in need as determined by State public health authorities. The Fluarix vaccine has been approved in seventy-eight foreign countries, and FDA has recently reviewed extensive manufacturing and summary clinical information and conducted an inspection of the GSK manufacturing facility in Germany to determine that this vaccine, although not licensed in the United States, is suitable for use under an Investigational New Drug application (IND). The Food and Drug Administration (FDA) reviewed GSK's IND application as well as the clinical protocol and manufacturing data. CDC and CDC's Institutional Review Board approved the GSK flu vaccine response protocol including the informed consent document. To ensure that the vaccine is properly administered to individuals identified to be most at risk and facilitate compliance with IND requirements, CDC is establishing vaccination clinics. CDC is proceeding without delay because of the unprecedented nature of this season's influenza vaccine shortage caused by contamination problems with Chiron Corporation's production facility in the United Kingdom, which effectively cut in half the expected United States supply of inactivated influenza vaccine. A user fee is being established in order to recoup the costs associated with administering the vaccine and for the vaccine itself. All individuals, other than those who are enrolled in Medicare Part B, will be required to pay the user fee.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15669145&dopt=Abstract flu, flu medicine, tamiflu



flu
[Epidemics of acute respiratory infections in Madagascar in 2002: from alert to confirmation]

[Article in French]

Soares JL, Ratsitorahina M, Rakoto Andrianarivelo M, Robinson R, Rousset D, Rasoazanamiarana LN, Rabarijaona LP, Manuguerra JC, Migliani R.

Institut Pasteur de Madagascar, Antananarivo.

An epidemiological investigation (Ministry of Health/Institut Pasteur de Madagascar (IPM)) was conducted in July 2002, in two districts of a same province (Fianarantsoa: Fianarantsoa II and Ikongo) considering the high frequency of deaths linked with acute respiratory infection (ARI). Morbidity and mortality data was collected in the Centre de Sante de Base (CSB) which gave the alert (village of Sahafata, district Fianarantsoa II). Analysis of monthly activity reports (MAR) allowed calculation of incidence rates of ARI/pneumonia in Fianarantsoa province. Virological data was based on the analysis of nasopharyngeal samples collected during the investigations. Clinical symptoms and homogeneity of laboratory results are consistent with an origin of these epidemics being related to the circulation of an influenza virus A subtype H3N2. Attack rates were very high. CFR was significantly higher in individuals of less than 1 year and more than 65 years. This data was confirmed by posterior investigations of teams from MoH/WHO. Surprisingly, this large epidemic was due to a known influenza virus that previously circulated in countries of northern hemisphere (the year before) and even in Antananarivo weeks before. Different hypothesis could be proposed to explain such phenomenon: great restriction of exchanges between different geographical zones, nutritional status.... Conclusion: The epidemic episodes of acute respiratory infections in Madagascar in July 2002 were due to an influenza virus A subtype H3N2 without any genotypic or phenotypic features. Various factors, could explain the importance of the epidemic and particular high lethality found in some age groups. This epidemic illustrates the relative incapacity for a developing country, to face and manage a flu epidemic caused by a classical influenza virus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15678810&dopt=Abstract flu, flu medicine, tamiflu



flu
When animal viruses attack: SARS and avian influenza.

Lee PJ, Krilov LR.

Division of Pediatric Infectious Diseases, Winthrop University Hospital, Mineola, NY, USA.

SARS and avian influenza have many common features. They both arose in Asia and originated from animal viruses. They both have the potential to become pandemics because human beings lack antibodies to the animal-derived antigens present on the viral surface and rapid dissemination can occur from the relative ease and availability of high speed and far-reaching transportation methods. Pediatricians, in particular, should remain alert about the possibility of pandemic illnesses in their patients. Annual rates of influenza in children may be 1.5 to 3 times those in the adult population, and infection rates during a community epidemic may exceed 40% in preschool-aged children and 30% in school-aged children. Infected children also play a central role in disseminating influenza, as they are the major point of entry for the virus into the household, from which adults spread disease into the community. Of course, children younger than 24 months also are at high risk for complications from influenza. A 1999 Centers for Disease Control and Prevention projection of an influenza pandemic in the US paints a grim picture: 89,000 to 207,000 deaths, 314,000 to 734,000 hospitalizations, 18 million to 42 million outpatient visits, and 20 million to 47 million additional illnesses, at a cost to society of at least dollars 71.3 billion to dollars 166.5 billion. High-risk patients (15% of the population) would account for approximately 84% of all deaths. Although SARS has been kind to the pediatric population so far, there are no guarantees that future outbreaks would be as sparing. To aid readers in remaining up-to-date with SARS and avian influenza, some useful websites are listed in the Sidebar. Two masters of suspense, Alfred Hitchcock and Stephen King, may have been closer to the truth than they ever would have believed. Both birds and a super flu could bring about the end of civilization as we know it. But all is not lost--to paraphrase Thomas Jefferson, the price of health is eternal vigilance. Although we may not be able to prevent future pandemics, mankind has the ability to recognize new diseases and outbreaks as they occur, to study these infections and find ways to contain and treat them, and to implement the necessary measures to defeat them.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15693215&dopt=Abstract flu, flu medicine, tamiflu



flu
Determinants of influenza vaccination timing.

Yoo BK, Frick K.

Center for Health Policy, Stanford University, USA.

New guidelines recommend different influenza vaccination timing for different subpopulations due to the limited availability of flu shots (FS). This study's objectives are to develop a theoretical model to demonstrate why some individuals choose to receive an early FS while others choose a late FS and to empirically explore the determinants of vaccination timing. Empirical results generally supported the theoretical results. Individuals vary their FS timing in response to variations in perceived risks, chronic condition levels reflecting their risk of influenza infection, and opportunity costs, measured by the presence of medical care other than an FS. Copyright (c) 2005 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15700301&dopt=Abstract flu, flu medicine, tamiflu



flu
Genetic characterization of H5N1 avian influenza viruses isolated in southern China during the 2003-04 avian influenza outbreaks.

Wan XF, Ren T, Luo KJ, Liao M, Zhang GH, Chen JD, Cao WS, Li Y, Jin NY, Xu D, Xin CA.

Digital Biology Laboratory, Department of Computer Science, University of Missouri, Columbia, MO, U.S.A..

The recent H5N1 avian influenza outbreaks in Asia spread over more than 8 countries. It has caused enormous economic loss and grand challenges for the public health. During these breakouts we isolated three strains of H5N1 Avian Influenza Virus (AIV) from chickens and one from duck in different farms of Southern China. We completely sequenced these four AIVs. Molecular characterization demonstrated that these strains retain the reported H5N1 AIV sequence properties relevant to virus virulence and host adaptation. Phylogeny results demonstrated that three of these isolates (except A/Chicken/Guangdong/174/04) were closely linked to other H5N1 AIVs isolated from the recent H5N1 outbreaks in Asia. Six of 8 segments (except PA and M) of A/Chicken/Guangdong/174/04 also shares a close linkage to other H5N1 AIVs isolated from the recent H5N1 outbreaks. However, the PA gene of A/Chicken/Guangdong/174/04 and another H5N1 strain forms a distinct subgroup along with an H6N1 AIV, and the M gene of A/Chicken/Guangdong/174/04 shows a close linkage to some H5N1 AIVs from aquatic species in China. Our findings suggest that a new genotype of AIV (in addition to previous reported ones) was present during the 2003-04 Asian bird flu outbreaks and that continuing virus surveillance of AIVs be conducted to monitor the evolutionary paths of the A/Chicken/Guangdong/174/04-like AIVs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15717120&dopt=Abstract flu, flu medicine, tamiflu