flu
Some aspects regarding the interpretation of influenza surveillance data.

Uphoff H, Cohen JM.

Deutsches Grunes Kreuz, Schuhmarkt 4, 35039 Marburg, Germany. helmut.uphoff kilian.de

For influenza monitoring, the use of laboratory data usually in combination with morbidity data from primary care facilities is common. The estimated excess morbidity, or resulting rates and consultation incidences are the basic parameter for the estimation of influenza activity in conjunction with antigen assays of influenza in a selected sub-sample of the recorded patients. The interpretation of such data is complicated by several selection processes, confounding influences and bias. The case definition (CD) given for the selection of cases is important for the sensitivity and specificity of the registrations. For the clinical morbidity data, the lower specificity found when more general (acute respiratory tract infections) criteria are used seems to be compensated by a higher statistical sensitivity due to the larger number of cases. The relative stability of the background morbidity against the expected values is critical for the interpretation. The sub-sample of patients tested by antigen assays is usually small due to cost constraints. Testing all patients with the defined symptoms in a sub-sample of practices is rarely possible because of the workload in the GPs offices during an influenza epidemic but does allow the number of positives to be used as an indicator. Usually, a sub-sample of GPs is asked to test a limited number of patients suffering with the symptoms given as selection criteria. In this case, the rate of positives is the better indicator for the influenza activity. However, the low number of tests particularly when flu is circulating at a low level limits the statistical sensitivity of this parameter. The specificity of the criteria given for the selection of patients being swabbed and the sensitivity of the test largely determine the function between the rate of positives and the influenza activity. The virological results are mostly interpreted in a more qualitative way, to see if influenza is circulating significantly. For this interpretation, more specific selection criteria (CD) seem useful and a high sensitivity for an increasing circulation can be expected.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12458349&dopt=Abstract flu, flu medicine, tamiflu



flu
The information network of senior citizens in Geneva, Switzerland, and progress in flu vaccination coverage between 1991 and 2000.

Toscani L, Gauthey L, Robert CF.

Department of Community Medicine, Cantonal University Hospital, Geneva University Hospital, 24 r, Micheli-du-Crest, 1211 Pascal-Eric Gaberel Analyses, 4, Geneva, Switzerland. letizia.toscani hcuge.ch

Switzerland has lagged behind other industrialized countries in increasing vaccination coverage against flu in the elderly population. The information campaign "United against Flu", started in Geneva in 1993, gradually extended to other French and Italian speaking cantons in Switzerland and indirectly affected German-speaking cantons. Activities developed include the production of TV spots, press conferences, information forwarded to health professionals, an Internet site and information material such as leaflets and posters to risk groups. The campaign is evaluated by repeated surveys that measure vaccination coverage as well as network of informants, knowledge and perceptions in the geriatric population. Vaccination coverage of the geriatric population in Geneva canton has increased from 29% in 1991 to 59% in the year 2000.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12531637&dopt=Abstract flu, flu medicine, tamiflu



flu
[Practical evaluation of rapid diagnostic tests for mycobacteriosis and virus infection]

[Article in Japanese]

Nakamura H.

Division of Clinical Laboratory, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan.

Because cultures of mycobacteria and viruses take a great number of days, the results are delayed in these clinical laboratory tests. For this reason, rapid diagnostic tests without these cultures are required. Among the laboratory tests of mycobacteria, acid-fast stain as a rapid diagnostic test is the first to give significant information to laboratory staffs and physicians. There are mainly two procedures, directly smearing clinical specimens and smearing concentrated specimens treated with NALC-NaOH on slide glass. The former is performed for specimens from emergency patients. When a patient is suspected of tuberculosis, a DNA-amplification test such as COBAS AMPLICOR TEST (PCR test) is performed for directly detecting Mycobacterium tuberculosis in clinical specimens, regardless of whether the specimens show positive or negative by acid-fast stain. Sixty-one of 1,023 specimens tested in Showa University Fujigaoka Hospital in February 2000-May 2002 were found positive by both PCR and culture tests. Fourteen were found negative by PCR test and positive by culture test. Five were found positive by PCR test and negative by culture test. Alternatively, MTB-64 (Capilia TB) is a kit for rapidly identifying M. tuberculosis using colonies. The time necessary for completion of the test was approximately 15 minutes per sample. In our study, the identification test showed weak-positive for 2 strains of M. marinum (ATCC927 and one clinical isolate), compared with positive for 28 clinical isolates and strain H37Ra of M. tuberculosis. Recently, rapid diagnostic kits for detecting various pathogenic viruses have been developed. The kits for detecting influenza virus are in especially great demand with the spread of newly-developed antiviral agents. There was an epidemic of the type A virus in the winters 2001-2002. 101 (32%) of 316 clinical specimens tested in the hospital were found positive with InfluA. B-Quick [SEIKEN] (Denka) or Directigen Flu A (Becton Dickinson). These kits showed high utility. Also, Abbot TESTPACK RSV (Dainabot) for detecting RS virus and ROTALEX DRY (Orion Diagnostica) for detecting rotavirus showed high utility. However, these rapid diagnostic kits have weak points: high costs, false positives and false negatives. Thus, more improvements are required.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12542395&dopt=Abstract flu, flu medicine, tamiflu



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

Schwarzinger M, Housset B, Carrat F.

Institut National de la Sante Et de la Recherche Medicale, u444, Hopital Saint-Antoine, Paris, France. schwarzi u44.jussieu.fr

BACKGROUND: Zanamivir, a neuraminidase inhibitor, reduces the number of days of illness in influenza-positive patients. New bedside rapid flu tests (RFT) should increase the number of influenza-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-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 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-positive patients. RESULTS: During influenza epidemics, systematic zanamivir prescription provided the best health outcome (0.81 influenza 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 days and saved 14.40 US dollars per person. When the proportion of influenza-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-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 epidemics.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12558471&dopt=Abstract flu, flu medicine, tamiflu



flu
A single-nucleotide natural variation (U4 to C4) in an influenza A virus promoter exhibits a large structural change: implications for differential viral RNA synthesis by RNA-dependent RNA polymerase.

Lee MK, Bae SH, Park CJ, Cheong HK, Cheong C, Choi BS.

Department of Chemistry and National Creative Research Initiative Center, Korea Advanced Institute of Science and Technology, 373-1 Guseong-dong, Yuseong-gu, Daejon 305-701, Korea.

The influenza A virus promoter is recognized by the influenza A virus RNA-dependent RNA polymerase, and directs both transcription and replication of the viral RNA genome. Within the sequence of this promoter, flu strains exhibit a natural, unique variation, either a U or a C, at the fourth position from the 3' end. Promoters that contain a C residue (C4 promoter), which are invariably found in genome segments that encode the three RNA polymerase subunits (PB1, PB2 and PA), down-regulate transcription but activate genome replication. Here, we have determined the structure of the C4 promoter by NMR spectroscopy and compared it with the structure of the U4 promoter, which was determined previously. The structure of the internal loop in the C4 promoter is similar to that of the U4 promoter. However, the terminal stem of the C4 promoter is strikingly different from that of the U4 promoter. These structural data suggest that the internal loop is important for polymerase binding to the promoter, and the terminal stem is crucial for differential regulation of transcription and replication.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12582241&dopt=Abstract flu, flu medicine, tamiflu



flu
Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada.

Abed Y, Hardy I, Li Y, Boivin G.

Infectious Disease Research Center, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec City, Canada.

Limited information is available concerning the molecular drift of the influenza neuraminidase (NA) genes. We report on the genetic variability of the NA gene from 31 influenza A:H3N2 viruses isolated in the Province of Quebec (Canada) during the last three flu seasons (1997-2000). Amino acid substitutions within the NA protein were observed at rates of 1.01% and 0.45% between strains of the 1997-1998 and 1998-1999 seasons and between those of the 1998-1999 and 1999-2000 seasons, respectively. In most strains (28/31), amino acid changes occurred within at least one of four codons (197, 339, 370, and 401) previously implicated as antigenic sites. The 8 functional and 10 framework residues that compose the catalytic site of the NA enzyme were completely conserved over the study period. All isolates contained the seven conserved asparagine-linked glycosylation sites found in the NA of the progenitor A/Hong Kong/8/68 strain. In addition, most strains (30/31) had an eighth potential glycosylation site at position 329, whereas a ninth one was found at position 93 in 16 strains. The NA of all strains in this study was related to that of the vaccine strain A/Beijing/353/89, whereas the HA genes of these strains were related to the A/Beijing/32/92 vaccine strain. Thus, it appears that recent influenza strains continue to evolve from a reassortant produced during the cocirculation of the two above variants. Interestingly, some strains whose HA genes were closely related showed significant differences in their NA genes and conversely. This study confirms the importance of analyzing both the NA and the HA genes to assess the evolution of recent influenza epidemic strains. Copyright 2002 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12116009&dopt=Abstract flu, flu medicine, tamiflu