bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis G infection: role in cryptogenic chronic liver disease and primary liver cell cancer in the UK
Authors: Hollingsworth R. C. , Minton E. J. , Fraser‐Moodie C. , Metivier E. , Rizzi P. M. , Irving W. L. , Jenkins D. , Ryder S. D.
Published: March 2003

Hepatitis G virus (HGV) is a flavivirus that can cause acute hepatitis and persistent infection but its role in chronic liver disease or primary liver cancer is unproven. In this study we have examined the prevalence of HGV RNA in the serum of patients with hepatitis C virus (HCV) infection and in patients with cryptogenic chronic liver disease, including non‐alcoholic steatohepatitis (NASH), and in patients with HCV‐related hepatocellular carcinoma (HCC) and HCC arising in patients with cryptogenic liver disease. One‐hundred and thirty patients who were positive for antibody to HCV (anti‐HCV), 54 patients with cryptogenic chronic liver disease (including 17 patients with NASH) and 46 patients with hepatitis C‐related (n=27) or cryptogenic liver disease‐related HCC (n=19) were studied. HGV RNA was detected using nested reverse transcriptase–polymerase chain reaction (RT–PCR) and was found in 16.1% of patients with HCV infection. HGV RNA was not detected in any patient with cryptogenic liver disease. In patients with HCC, 7/34 samples were positive for HGV RNA and six out of seven HGV‐positive subjects also had HCV infection. Only one patient with HCC in cryptogenic liver disease was positive for HGV RNA. Hence, cryptogenic liver disease in the UK is not caused by HGV/GBVc infection. It seems unlikely that HGV plays a significant role in hepatocarcinogenesis.
The long‐term effect of treatment with interferon‐α2a in chronic hepatitis B
Authors: Krogsgaard Kim ,   the Long‐term Follow‐up Investigator Group,   Executive Team on Anti‐Viral Treatment
Published: March 2003

This study was performed to evaluate the long‐term effects of interferon‐α2a (IFN‐α2a) vs no treatment in patients with chronic hepatitis B and to determine whether viral clearance, following therapy or occurring spontaneously, was sustained. Patients originating from three previously published multicentre, randomized, controlled trials were analysed. Information about survival and response during long‐term follow‐up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA and loss of hepatitis B e antigen (HBeAg) and improvement in alanine aminotransferase level. Scheduled treatment‐free follow‐up was 12 months in all studies. Median long‐term follow‐up time after inclusion in the individual studies was 4.7 years (range: 0.2–7.5 years). Viral clearance after IFN‐α2a, or occurring spontaneously, was sustained in 70 out of 80 evaluable patients (88%) who were responders at the end of the original trials and 21 (30%) lost hepatitis B surface antigen (HBsAg). A total of 80 patients received (re)treatment during the long‐term follow‐up period and 33% of them responded, irrespective of previous treatment category. Overall response rate was not significantly affected by gender, sexual inclination or ethnic origin. Durability of response did not depend upon ethnic origin or presence of cirrhosis. At the end of the original trial periods, 253 patients were histologically evaluated and 22 (9%) had histologically confirmed progression to cirrhosis. During long‐term follow‐up an additional five patients developed cirrhosis. Hepatocellular carcinoma developed in three patients (1%): in one patient during the follow‐up period of the original trial and in two patients (one untreated) during the long‐term follow‐up period. Ten of 25 deaths were liver‐related (hepatocellular carcinoma in three, gastrointestinal bleeding in two and liver failure in five). The distribution of clinical events (progression to cirrhosis, hepatocellular carcinoma and liver‐related deaths) was unrelated to original treatment category and response to treatment. Hence, 90% of responding patients will, irrespective of treatment category, have a sustained response. At least 30% of responding patients will eventually lose HBsAg. For a number of reasons, the present patient population and observation period are insufficient to establish a presumed beneficial effect of IFN‐α2a on disease progression and survival.
Hepatitis B third‐generation vaccines: improved response and conventional vaccine non‐response – evidence for genetic basis in humans
Authors: McDermott A. B. , Cohen S. B. A. , Zuckerman J. N. , Madrigal J. A.
Published: March 2003

The lack of response to hepatitis B vaccination remains a problem for those individuals directly at risk of hepatitis B infection, particularly those who work in the health care industry. The factors associated with non‐response to hepatitis B vaccination have been investigated in 86 non‐responder health care workers who had received multiple ‘S’ vaccinations without sustained production of anti‐HBs. This group received a recently developed hepatitis B vaccine, HepageneTM, which included proteins derived from the envelope region of HBV, not present in currently licensed vaccines. The pre‐S1 and pre‐S2 proteins were included in HepageneTM in order to circumvent anti‐HBs non‐responsiveness which had previously been demonstrated in the inbred mouse model. The inclusion of these additional proteins in HepageneTM enabled some seroconverion, from non‐responder to responder; however, a proportion of the vaccinees remained non‐responders and the reasons for this have been investigated here, with reference to HLA alleles and the demographic predisposition. Here the mechanisms that underlie hepatitis B vaccine non‐response have considered the distribution of HLA alleles, age, sex, height and weight in addition to the T‐cell responses to HepageneTM derived antigens.
Hepatitis G virus infections in Iceland
Authors: Löve A. , Stanzeit B. , Gudmundsson S. , Widell A.
Published: March 2003

This study describes the prevalence of hepatitisG virus (HGV) in Iceland, in blood donors and in persons with parenteral risk factors. Among 370 randomly selected Icelandic blood donors, the prevalence of HGV viraemia was 3.8%, whereas the prevalence of HGV antibodies in the same donor group was found to be 13.2%, thus indicating that at least 17% of blood donors in Iceland had previously been exposed to HGV. Previous exposure was seen in all age groups and also in older blood donors. Among intravenous drug users (IVDUs), the prevalence of HGV was much higher. Among 109 hepatitisC virus (HCV) antibody‐positive serum samples collected in the years 1992–1997, 33.9% were polymerase chain reaction (PCR)‐positive for HGV and 48.6% had HGV antibodies. Thus, the pattern of HGV in IVDUs was similar to findings among IVDUs in other western countries. HGV viraemia was detected neither in 10 patients with haemophilia nor in five dialysis patients. However, six of the 10 haemophilic patients and one of the five dialysis patients had HGV antibody. In conclusion, unlike hepatitisC, which seems to have been introduced into Iceland relatively recently and has remained virtually confined to IVDUs, exposure to HGV is common among all age groups in the general population, suggesting that the virus has been prevalent in Iceland for much longer, making additional routes of transmission probable.
Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates
Authors: Vranckx R. , Alisjahbana A. , Meheus A.
Published: March 2003

The high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in pregnant women is considered to be the most important factor contributing to the high carrier rate of HBsAg in some populations. Several factors, including the age at which infection occurs, predispose to the acquisition and frequency of the carrier state. The proportion of infected people who become chronic carriers ranges from about 80 to 95% for babies born to HBsAg/HBeAg‐positive mothers. In this study of Indonesian infants receiving only active immunization against HBV, we measured the HBV markers passively acquired from their HBsAg‐positive mothers. The relationship of these markers with vaccination response and with HBV infection status was studied longitudinally in the infants. In the exposed neonates from the HBsAg‐positive mothers (n=61), the seroconversion rate to hepatitis B surface antibody (HBsAb) positivity was 95% after the first booster vaccination, with a geometric mean titre (GMT) of 2017IUl–1. After 60months, the GMT in this group decreased to 50IUl–1. Four newborns in this group became HBsAg carriers. Of the four vaccination failures, three newborns were HBsAg/HBeAg positive at birth, suggesting that they had been infected in utero. No vaccination strategy (active alone, or passive/active) can prevent this transmission from occurring. One carrier was HBsAg negative at birth and up to month 4 but was HBsAg positive at month 12 and subsequently, suggesting a postnatal infection. Vaccination early in life can, to a large extent, prevent perinatal transmission and hepatitis B virus (HBV) infection later in infancy and childhood. In this study, the protective efficacy of the vaccination was 85% in the subcohort of neonates from HBeAg‐positive mothers and 100% in the subcohort of neonates from HBeAg‐negative mothers. Lack of maternal antibodies to hepatitis B core antigen (HBcAb) correlated strongly with transmission of HBV infection.
Hepatitis G virus/GBV‐C persistence: absence of hypervariable E2 region and genetic analysis of viral quasispecies in serum and lymphocytes
Authors: Zampino R. , Pickering J. , Iqbal M. , Gaud U. , Thomas H. C. , Karayiannis P.
Published: March 2003

Persistent infection with hepatitis G virus (HGV) or GB virus‐C (GBV‐C) is common and may last for years. In addition, the principal site of virus replication remains undefined. Sequencing studies of E2 in four patients showed that a hypervariable region equivalent to that of hepatitis C virus (HCV) was absent and that viral quasispecies were less frequent than in HCV infection, particularly with respect to amino acid variation. Recurrence of viraemia following interferon treatment did not result in the emergence of new quasispecies. Virus persistence therefore does not appear to be related to immune escape by strains bearing a hypervariable E2 region. We also investigated whether virus replication occurred in peripheral blood mononuclear cells. The positive‐RNA strand of the virus, but no negative strand, was detected in both serum and lymphocytes. The lymphocytes harbouring the virus were CD4 and CD19 positive. Direct sequencing and cloning of amplicons from the region of the non‐structural 3 (NS3) protein showed that the nucleotide sequences in lymphocytes were different from those in serum and did not represent any of the minor serum quasispecies. Although evidence of replication in lymphocytes has not been forthcoming, the differences in sequences between serum and lymphocytes suggest that circulating virus originates from a non‐hepatic site, other than lymphocytes.
A novel primer‐extension assay for the detection of a G to A mutation in the distal precore region of hepatitis B virus DNA
Authors: Chung J. P. , Han K. H. , Kim K. S. , Yeh B. I. , Kim S. T. , Lee K. S. , Chon C. Y. , Moon Y. M. , Kang J. K. , Park I. S.
Published: March 2003

The roles of genetic heterogeneity of the hepatitis B virus (HBV) precore gene in the pathogenesis of HBV infection are unclear. Various methods have been used to detect nucleotide (nt) 1896 precore mutants. We established a new primer‐extension assay to facilitate the detection of these mutants. This assay is based upon the fact that there is no adenine in the distal precore region of wild‐type HBV. Polymerase chain reaction (PCR)‐amplified template DNA was denatured and annealed to the [γ‐32P]‐labelled primer. During primer extension in the presence of DNA polymerase and dCTP, dGTP, dTTP and ddATP, the reaction terminates if there is a nucleotide A. When mixtures of different ratios of wild‐type and nt 1896 precore mutants were analysed in the primer‐extension assay, correlation between the percentage known amounts and the percentage measured amounts of nt 1896 precore mutants was excellent (r2=0.9669). When the primer‐extension assay and direct sequencing were compared in hepatitis B e antigen (HBeAg)‐positive and ‐negative chronic active hepatitis B patients, the primer‐extension assay detected a greater number of nt 1896 precore mutants than direct sequencing and thus most HBV infections were found to be mixed infections. In conclusion, the primer‐extension assay is a reliable and sensitive method for the detection of nt 1896 precore mutants.
Flaviviridae polymerase and RNA replication
Authors: Bartholomeusz A. , Thompson P.
Published: March 2003

Sequence motifs within the non‐structural protein NS5 or NS5B of the members of the family Flaviviridae suggest that this protein is the RNA‐dependent RNA polymerase. This protein has now been expressed in various in vitro systems and used in polymerase assays. To understand the role of the RNA polymerase in RNA replication, this review will examine not only the polymerase protein but also the other proteins in the RNA replication complex. To date, several groups have investigated the interaction of these proteins both in vitro and in vivo and also the interaction of these proteins with the RNA signals at the 3’ terminus of the RNA. Infectious clones and replicons containing the non‐structural proteins have now been generated and these will be useful tools in understanding the processes of initiation and elongation of both positive and negative RNA synthesis.
Clinical, virological and histological implications of GB virus‐C/hepatitis G virus infection in patients with chronic hepatitis C virus infection: a multicentre study based on 671 patients
Authors: Slimane  , Albrecht  , Fang  , Goodman  , Mizokami  , Qian  , Lau  ,   the Hepatitis Interventional Therapy Group
Published: March 2003

To determine the prevalence, as well as the clinical, virological and histological implications of GB virus C/hepatitis G virus (GBC‐C/HGV) infection in patients with chronic hepatitis C virus (HCV) infection, sera from 671 well‐characterized patients with chronic HCV infection were tested for GBV‐C/HGV RNA using a sensitive and specific reverse transcription ‘nested’ polymerase chain reaction (RT–nPCR). GBV‐C/HGV RNA was detected in 65 of 671 (9.7%) patients with chronic HCV infection. Importantly, GBV‐C/HGV co‐infection was not associated with any changes in indices of liver diseases, including serum alanine transaminase levels, Knodell score or histology activity index (HAI). In this cohort, GBV‐C/HGV co‐infection was weakly associated with a shorter mean estimated duration of HCV infection and a higher median HCV viraemia level. We conclude that GBV‐C/HGV has minimal or no impact on liver disease activity in patients with chronic HCV infection. This data supports the notion that GBV‐C/HGV may not be a hepatitis virus.
Molecular analysis of hepatitis D virus infection in Miyako Island, a small Japanese island
Authors: Arakawa  , Moriyama  , Taira  , Hayashi  , Tanaka  , Okubo  , Sugitani  , Arakawa
Published: March 2003

The present investigation attempted to determine the exact prevalence of hepatitis D virus (HDV) infection among inhabitants of Miyako Island (a remote island in the Okinawa Prefecture) and the molecular characteristics of the HDV genome that was isolated. Among the 4728 inhabitants, 375 (7.9%) were hepatitis B surface antigen (HBsAg) positive. Antibody to HDV (anti‐HDV) was present in 32 (8.5%) of these 375 subjects, and liver function tests were normal in most subjects. The presence of HDV RNA was analysed by nested polymerase chain reaction (PCR). Thirteen out of the 32 anti‐HDV antibody‐positive subjects were HDV RNA positive. Thus, 3.5% of HBsAg‐positive subjects on Miyako Island were HDV RNA positive. Among the HDV RNA‐positive subjects, liver function tests were within normal limits or were mildly abnormal. Nucleotide sequence analysis revealed that the HDV genomes on Miyako Island were similar to the Japanese and Taiwan isolates of HDV genotype II. Taiwan is geographically close to Miyako Island. Even though the races are different, a geographical factor was revealed to be significant with regard to HDV infection, which was spread in a closed environment.
Clinical characteristics of patients with chronic hepatitis C showing biochemical remission, without hepatitis C virus eradication, as a result of interferon therapy
Authors: Kasahara  , Hayashi  , Mochizuki  , Hiramatsu  , Sasaki  , Kakumu  , Kiyosawa  , Okita  ,   the Osaka Liver Disease Study Group
Published: March 2003

During long‐term follow‐up of patients chronically infected with the hepatitis C virus (HCV) and treated with interferon (IFN), we identified some who had persistent normalization of serum alanine aminotransferase (ALT) but remained positive for HCV RNA. The aims of this study were to clarify the characteristics of these patients and to examine their clinical outcome after treatment. Nine hundred and ninety‐eight patients treated with IFN were followed‐up biochemically and virologically, and by liver ultrasound, for 13–95 months. A short‐term biochemical sustained response, where ALT remained within the normal range for 6 months after the completion of IFN therapy, was found in 296 patients; in 240 of these patients serum HCV RNA remained undetectable during long‐term follow‐up. The rate of HCV RNA persistence was 7.09 times greater in short‐term biochemical sustained responders with a high viral load than in those with a low viral load (P=0.0001, odds ratio [OR]=7.09), and 3.70‐fold lower in those treated with a large dose of IFN than in those treated with a small dose (P=0.02, OR=0.27). Thirty‐three (59%) of 56 patients without HCV eradication showed continuous ALT normalization for 26–80 months after cessation of IFN therapy. Short‐term biochemical sustained responders who were older (P=0.009, OR=10.43) and who were male (P=0.03, OR=6.98) had a significantly greater probability of maintaining a normal ALT level, even when serum HCV RNA was positive. When the incidence of HCC was investigated during long‐term follow‐up in patients without HCV eradication, it was found to be significantly lower in patients with persistently normal ALT levels than in those with abnormal ALT levels (P=0.03). Hence, when HCV is not eradicated as a result of IFN therapy, it may induce a long‐term carrier state of HCV infection with normal ALT levels in older or male patients, in whom the cumulative incidence of HCC is markedly decreased.
The HCV National Register: towards informing the natural history of hepatitis C infection in the UK
Authors: Harris H. E. , Ramsay M. E. , Heptonstall J. , Soldan K. , Eldridge K. P. ,   on behalf of the HCV National Register Steering Group
Published: March 2003

The aim of this paper is to describe the development of a national hepatitis C register and the completeness of the data it contains. This is a descriptive report of the structure and function of the register, including case definitions, registration and follow‐up procedures, and methods used to maximize data quality and to obtain comparative data sources. The register contains data on HCV‐infected individuals who acquired their infections on a known date and by a known route; to date all are transfusion recipients identified during the UK lookback exercise, who tested positive or indeterminate for anti‐HCV after receiving ‘infected’ blood issued before the introduction of routine testing of the blood supply for anti‐HCV. By 31 December 1999, 871 (87%) of 996 eligible transfusion recipients had been registered, and 984 (99%) flagged in the NHS Central Registers. Registered patients had been infected for an average of 11.1 years (SEM 0.1); around half were being cared for by clinicians with a specialist interest in liver disease. Except for the information on tobacco use, current alcohol use, and hepatitis B status, data were more than 80% complete, and for most variables, more than 90% complete. The consistency of data abstraction was found to be 98% (SEM 0.5). In conclusion, the Register contains high quality anonymised data on one of the largest cohorts of individuals with HCV infections acquired on a known date and by a known route. It could serve as a model for other chronic disease registers; developers may find the structure, design, and methodological issues addressed useful.
Management of recurrent hepatitis C after liver transplantation
Authors: Teixeira R. , Papatheodoridis G. V. , Burroughs A. K.
Published: March 2003

Hepatitis C virus (HCV) reinfection is almost universal in patients transplanted for HCV‐related cirrhosis. The medium‐term survival after orthotopic liver transplantation (OLT) is similar to other transplanted patients, but the long‐term survival remains uncertain. The prevention and an effective treatment of progressive liver disease are the primary aims in HCV recurrence. Interferon and ribavirin, as monotherapy or in combination, have been tried to treat or prevent HCV recurrence. Preliminary studies suggest a better chance of initial HCV clearance and better results in preventing HCV recurrence with combination therapy. IFN or ribavirin, as monotherapy, may normalize liver enzymes, but only gives rise to a transient virological response, without histological improvement. Combination IFN and ribavirin may be able to prevent progression of HCV‐related graft disease, but indications and duration of treatment need further evaluation.

No clear association between type and dose of immunosuppressive and outcome of post‐transplant HCV recurrence has been found. Strategies to minimize the effects of immunosuppressive drugs include dose reduction of all agents and the selective discontinuation of individual agents. Initial immunosuppression with a single drug may inhibit or delay the severe fibrosis, and further investigation with a single immunosuppressive regimen to evaluate the outcome of recurrent hepatitis C should be performed. The recent evidence that mycophenolate may have an antiviral effect needs a clinical confirmation.

Retransplantation survival is better with early retransplantation, and for indications not directly related to viral recurrence.
Biochemical markers of liver fibrosis in patients infected by hepatitis C virus: longitudinal validation in a randomized trial
Authors: Poynard T. , Imbert‐Bismut F. , Ratziu V. , Chevret S. , Jardel C. , Moussalli J. , Messous D. , Degos F. ,   for the GERMED cyt04 group
Published: March 2003

A liver fibrosis index was recently prospectively validated in a cross‐sectional study where patients infected by hepatitis C virus (HCV) had only one biopsy and no longitudinal follow‐up. The aim of this study was to retrospectively assess the diagnostic value of this index in patients included in a randomized trial of interferon (IFN) using repeated measurements, two biopsies and hyaluronic acid as a comparative reference. One‐hundred and sixty‐five patients who had had two interpretable liver biopsies and at least one stored serum sample before IFN treatment were selected. Seventy‐eight patients received 3 MU of IFN‐α thrice weekly for 24 weeks and 87 followed a reinforced regimen for 48 weeks. A fibrosis index combining five biochemical markers (α2‐macroglobulin, haptoglobin, apolipoprotein A1, γ‐glutamyl transpeptidase (GGT) and total bilirubin adjusted for gender and age) as well as hyaluronic acid was assessed on 461 samples available at baseline, at the end of treatment and at the end of follow‐up (72 weeks).

There was a significant decrease of the fibrosis index score among the 17 sustained virologic responders, from 0.33 ± 0.06 (mean ± SE) at baseline to 0.18 ± 0.06 at 72 weeks in comparison with 92 nonresponders (from 0.41 ± 0.03 at baseline to 0.44 ± 0.03 at 72 weeks; P < 0.001) and in comparison with 56 relapsers (from 0.36 ± 0.03 at baseline to 0.32 ± 0.03 at 72 weeks; P=0.05). No significant differences were observed for hyaluronic acid.

Hence, this fibrosis index could be used as a surrogate marker of the antifibrotic effect of treatments in patients with chronic hepatitis C.
Seroprevalences of hepatitis B and C among health care workers in Turkey
Authors: Ozsoy M. F. , Oncul O. , Cavuslu S. , Erdemoglu A. , Emekdas G. , Pahsa A.
Published: March 2003

summary. We determined the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among health care workers (HCWs) at Gülhane Military Medical Academy, Haydarpasa Training Hospital in Istanbul, Turkey. Between April 1998 and September 2000, 702 HCWs were included in the study. The blood samples were tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti‐HBs) and HCV antibody (anti‐HCV) using third‐generation tests, with confirmation by reverse transcriptase‐polymerase chain reaction. Seroprevalence rates were compared with those detected in 5670 blood donors during the same period. HBsAg, anti‐HBs and anti‐HCV were detected in 21 (3.0%), in 480 (68.4%) and in 2 (0.3%) of 702 HCWs respectively. HBsAg and anti‐HCV rates were 2.1 and 0.4% in blood donors, respectively. These data show that the prevalence rates of HBV and HCV were similar with prevalence rates detected in randomized blood donors showing that universal infection‐control precautions and encouraging HBV vaccination reduces HCW infection with hepatotropic viruses.
Mutations in the NS5A and E2‐PePHD region of hepatitis C virus type 1b and correlation with the response to combination therapy with interferon and ribavirin
Authors: Hung C.‐H. , Lee C.‐M. , Lu S.‐N. , Lee J.‐F. , Wang J.‐H. , Tung H.‐D. , Chen T.‐M. , Hu T.‐H. , Chen W.‐J. , Changchien C.‐S.
Published: March 2003

summary. Nonstructural 5A (NS5A) and the second envelope (E2) proteins of hepatitis C virus (HCV) have the potential to block interferon (IFN)‐induced RNA‐dependent protein kinase (PKR) and may therefore interfere with the response to IFN therapy, but controversy still exists regarding the relevance of this. This study aimed to assess whether mutations in these regions correlated with the response to combination therapy, IFN and ribavirin. Pretreatment parameters were analysed in 57 HCV‐1b patients who had received IFN‐α2b (3 or 5 MU three times weekly) and ribavirin (800–1200 mg per day) for 24 weeks. The amino acid sequences of the NS5A and PKR‐eIF2α phosphorylation homology domain (E2‐PePHD) were deduced from the corresponding coding sequence, which were determinated by direct sequencing of the HCV genome amplified by the polymerase chain reaction. Twenty (36%) patients achieved a sustained virological response (SVR). The mean number of amino acid substitutions in the NS5A–PKR binding domain (2209–2274), interferon sensitivity‐determining region (ISDR) (2209–2248), and E2‐PePHD sequence (659–670) in patients with and without SVR were 4.53 ± 3.31 vs 2.83 ± 1.78 (P = 0.094), 2.45 ± 2.74 vs 1.03 ± 1.32 (P = 0.042) and 0.25 ± 0.70 vs 0.03 ± 0.17 (P = 0.109), respectively. Patients with a mutant‐type (≥ 4) NS5A–ISDR had a higher rate of SVR (six of nine, 67%) than those with wild‐type (five of 22, 23%) (P = 0.038). Stepwise multiple logistic regression analysis of the factors (age, gender, viral load, cirrhosis rate, IFN dosage and amino acid substitutions) revealed that the mutation in NS5A–ISDR (≥ 4 vs < 4) was the only independent variable of treatment outcome. Our study showed that NS5A–ISDR mutations were correlated with the SVR to combination therapy in chronic HCV‐1b patients in Taiwan.
Impact of deer in lowland Britain on agriculture, forestry and conservation habitats
Authors: Putman R. J. , Moore N. P.
Published: March 2003

Probably in response to recent changes in habitat structure, populations of a number of species of deer are increasing both in numbers and in geographical distribution in lowland Britain. In the wake of this expansion there is increasing awareness and concern over damage to agriculture/horticulture and forestry, as well as damage to sensitive vegetation in conservation areas.

Despite a perception that damage levels are rising, data that actually quantify the scale of impact by deer on lowland agriculture and forestry interests or conservation habitats are scarce. This review attempts to draw together such objective data as are available to assess more formally the actual impact of deer damage in these different contexts and the economic significance of damage caused. The review concludes with a brief consideration of implications for management.

The majority of agricultural damage reported in England and Wales was due to Fallow, Red and Roe Deer; Muntjac were only implicated in a little horticultural damage where they are numerous. Most reports were of damage to pasture or cereals, with oilseed rape, nursery and orchard crops also frequently damaged. Because of fundamental differences in ecology and distribution, different species of deer were implicated in different types of damage, depending on feeding habit and distribution in relation to geographical patterns of crop‐type. In a woodland context, Fallow, Red and Roe Deer were implicated in the majority of reported damage in lowland UK, which is most frequent in the north of England and lowest in Wales. Despite the apparent severity of damage caused to agriculture or forestry, the actual economic significance of such damage would appear in many cases to be negligible or small. Field crops frequently recover completely from such damage, and although woodland crops may be checked and quality of the timber may be reduced as a consequence of earlier browsing damage, losses may be far less than they first appear. This whole question of the true economic cost of deer damage needs further research.

Deer damage to conservation habitats in England and Wales appears largely restricted to woodland; impact on heathlands, grasslands and wetlands is generally welcomed as helping to arrest invasion of scrub. Within woodlands, while concern is expressed in a small number of cases over losses of sensitive ground flora or suppression of natural regeneration, the major problem is in damage to coppice regrowth on sites where coppice management has been recently reintroduced.
Impact of radio‐collars on Yellow‐necked Mice, Apodemus flavicollis (Mammalia, Rodentia)
Authors: De Mendonça Philippe Gil
Published: March 2003

The impact of wearing a radio‐collar was investigated for 124 Yellow‐necked Mice Apodemus flavicollis, in mixed deciduous woodlands. Collared mice neither lost more weight nor lost weight more frequently than control individuals. The cost of wearing a collar was not greater for small individuals than for larger ones. The impact of wearing a radio‐collar was mostly due to the shape and size of the radio‐collar and the external antenna rather than the package weight. This aspect was particularly acute in the presence of ticks. One solution to this problem may be to build and use radio‐transmitter packages as compact (but nevertheless resistant to gnawing) and symmetrical as possible and to use collars impregnated with tick repellent.
Status and conservation of the Asian Elephant Elephas maximus in north‐eastern India
Authors: Choudhury Anwaruddin
Published: March 2003

A status survey of Asian Elephants Elephas maximus was conducted in the 9 north‐eastern states of India. The habitat is contiguous with that in Bhutan, Myanmar and Bangladesh. Although the estimated population of 11 000 elephants is higher than in other regions of the Indian Sub‐continent, it is fragmented and a number of small inviable isolated populations have formed. About 35% of the population is partly protected, but protection is inadequate. More areas and migration routes need to be protected. Man–elephant conflict is serious in many areas. A comprehensive Action Plan with a more pragmatic protected‐area network has been proposed.
An analysis and review of models of the sociobiology of the Mustelidae
Authors: Johnson Dominic D. P. , MacDonald David W. , Dickman Amy J.
Published: March 2003

Classical models of social organization in mustelids suggest that female ranging patterns are determined by the dispersion of resources, whereas those of males are determined by the dispersion of females. However, mating systems and social spacing patterns vary widely both between and within species. For example, European Badgers exhibit a continuum from the classical mustelid model of intra‐sexual territoriality and inter‐sexual overlap to very large, mixed‐sex, promiscuous groups. We evaluated hypotheses and existing data to explain this variation, using comparative analyses and Principal Components Analysis of life history and ecological variables. In addition, we applied a null model of allometric scaling to test for associations between group mass and residual home range size. We found that: (1) the degree of social behaviour and breeding group size increased with life history variables indicative of K‐selected strategies of parental investment. (2) Absolute home range size and residual home range size (derived from allometric home range scaling) decreased, paradoxically, with breeding group size and group mass, respectively. These results provide support for ecological theories of social grouping in general and, in particular, for the importance of dispersed resource‐rich patches as developed in the Resource Dispersion Hypothesis.
The role of the Badger (Meles meles) in rabies epizootiology and the implications for Great Britain
Authors: Smith G. C.
Published: March 2003

The occurrence of a wildlife rabies epizootic in Britain remains a very unlikely event, but it is important to examine all the possible consequences of such an event. Here, I examine the possible role of the European Badger (Meles meles) in

such an epizootic. The population density of Badgers in Britain is much higher than

that in Europe, and appears to have increased substantially over the last decade

or so. The population parameters and epizootiology of rabies in the Badger are reviewed

in comparison with the Fox (Vulpes vulpes) and other species. Mustelids appear to be very susceptible to rabies, with the smaller mustelids becoming aggressive, although Badgers do not appear to show heightened aggression when infected. Badger populations on the continent become severely reduced when rabies arrives in the area, and circumstantial evidence strongly suggests that Badgers can easily transmit the virus. Preliminary models support the idea that the Badger could be a very significant secondary host, especially in the initial rabies outbreak. The population recovery rate of the Badger suggests that it is unlikely to become a primary host, although short‐term epizootics in the Badger population are likely. The potential for controlling rabies in the Badger is also examined.
The digestive tract and life history of small mammals
Authors: LANGER PETER
Published: March 2003

The type of food, differentiation of the large intestine and stomach, and methane production, as well as life history data, are considered in Insectivora, Rodentia and Lagomorpha. When food containing plant cell wall material is eaten, there is either a differentiation of the stomach or the large intestine. In animals with low body mass and little differentiation of the gastrointestinal tract, methane production is low, but structures essential for microbial digestion of plant cell wall material, such as haustration of the colon or formation of a caecum, can be found in many methane‐producers. Animals with a body mass < 500 g and a weaning time < 20 days are non‐producers of methane. Establishment of a balanced microbial population in the gastrointestinal tract requires some time. Many non‐producers of methane wean their young in < 10 days, but many producers need > 50 days for the weaning process. Caviomorpha, Thryonomyidae and Hystricidae seem to have ‘opened the door’ to the use of low quality food by microbial fermentation, but some of them have to ‘pay’ for this extension of the food range by an extended weaning period, which also means an extended dependency on the mother.
Use of odour‐baited sticky boards to trap tabanid flies and investigate repellents
Authors: HALL MARTIN J. R. , FARKAS RÓBERT , CHAINEY JOHN E.
Published: March 2003

Tabanid flies were captured in a sheep pasture in Hungary using black plastic boards (30 × 30 cm), coated with an adhesive sheet, which were either unbaited or baited with ethane‐ethiol or Swormlure‐4. Five species of tabanid were caught, of which Tabanus tergestinus was caught in the greatest number (87% of 192). The sex ratio of T. tergestinus on unbaited boards was not statistically significantly different to equality. However, on baited boards, males were significantly more numerous, probably due to a repellent effect of the odours on female tabanids. Because of the importance of repellents in tabanid control, this result encourages the exploration of a wider range of compounds as tabanid repellents than are used at present. Sticky boards offer a simple technique for trapping both sexes of tabanids, especially males, which are poorly represented in many tabanid traps.
Vector competence ofCulicoides bolitinosandC. imicolafor South African bluetongue virus serotypes 1, 3 and 4
Authors: Venter G. J. , Paweska J. T. , Van Dijk A. A. , Mellor P. S. , Tabachnick W. J.
Published: March 2003

Abstract.The susceptibility of field‐collected Culicoides bolitinos to infection by oral ingestion of bluetongue virus serotypes 1, 3 and 4 (BLU 1, 3 and 4) was compared with that of field‐collected C. imicola and laboratory reared C. variipennis sonorensis. The concentration of the virus per millilitre of bloodmeal was 105.0 and 106.0TCID50 for BLU 4 and 107.2TCID50 for BLU 1 and 3. Of 4927 C. bolitinos and 9585 C. imicola fed, 386 and 287 individual midges survived 10 days extrinsic incubation, respectively. Midges were assayed for the presence of virus using a microtitration assay on BHK‐21 cells and/or an antigen capture ELISA. Infection prevalences for the different serotypes as determined by virus isolation ranged from 22.7 to 82.0% in C. bolitinos and from 1.9 to 9.8% in C. imicola; infection prevalences were highest for BLU 1, and lowest for BLU 4 in both species. The mean log10 TCID50 titre of the three BLU viruses per single fly was higher in C. bolitinos than in C. imicola. The results suggested that C. bolitinos populations are capable vectors of the BLU viruses in South Africa. A high correlation was found between virus isolation and ELISA results for the detection of BLU 1, and less for BLU 4; the ELISA failed to detect the presence of BLU 3 in infected flies. The C. v. sonorensis colonies had a significantly lower susceptibility to infection with BLU 1, 3 and 4 than C. bolitinos and C. imicola. However, since infection prevalence of C. v. sonorensis was determined only by ELISA, this finding may merely reflect the insensitivity of this assay at low virus titres, compared to virus isolation.
Morphology and ultrastructure of spiracles in phlebotomine sandfly larvae
Authors: Fausto A. M. , Taddei A. R. , Mazzini M. , Maroli M.
Published: March 2003

The morphology and ultrastructure of the larval spiracle system of three phlebotomine sandfly species, Phlebotomus perniciosus, P. perfiliewi and P. papatasi, were examined by scanning (SEM) and transmission (TEM) electron microscopy and by confocal scanning laser microscopy (CSLM). During larval development, thoracic and abdominal spiracles show considerable modifications. In fourth instar larvae, the spiracles consist of a plate with a sclerotized central portion and a peripheral circle of papillae. The latter is distinctive in the larvae of P. papatasi, which are readily distinguished from the other species. Opening clefts across the papillae communicate with an internal chamber that encircles an electrondense plug. Many cylindrical projections cross the chamber, uniting the central plug with the larval body, forming an air filter. Spiracular development in successive larval instars has both a taxonomic and adaptive value.
Safety of pyrethroid‐treated mosquito nets
Authors: Zaim M. , Aitio A. , Nakashima N.
Published: March 2003

The use of insecticide treated nets (ITNs) for personal protection against malaria vector Anopheles mosquitoes (Diptera: Culicidae) has become popular during the past decade. With the precautions outlined in this paper, field use of pyrethroids – at concentrations recommended for treatment of mosquito nets – poses little or no hazard to people treating the nets or to users of the treated nets. With frequent exposure to low concentrations of pyrethroids, the risk of toxicity of any kind is remote. Pyrethroids entering the systemic circulation are rapidly metabolized to much less toxic metabolites. Toxicologically, pyrethroids have a useful characteristic – the production of skin paraesthesia – which gives an early indication of exposure. This reversible symptom of exposure is due to transient stimulation of peripheral sensory nerves and not a toxic effect. In the retail market, for home use, the provision of proper packaging and labelling, with clear instructions on safe and effective use of the product are most important. Because many domestic users of pyrethroid ‘home treatment kits’ for ITNs may not be fully literate, it is essential that ‘instructions for use’ should be portrayed via pictograms with supporting text in appropriate local language(s).
Anopheles arabiensis and An. funestus are equally important vectors of malaria in Matola coastal suburb of Maputo, southern Mozambique
Authors: Mendis C. , Jacobsen J. L. , Gamage‐Mendis A. , Bule E. , Dgedge M. , Thompson R. , Cuamba N. , Barreto J. , Begtrup K. , Sinden R. E. , Høgh B.
Published: March 2003

Transmission characteristics of malaria were studied in Matola, a coastal suburb of Maputo, the capital City, in southern Mozambique, from November 1994 to April 1996. The local climate alternates between cool dry season (May–October) and hot rainy season (November–April) with mean annual rainfall 650–850 mm. Saltmarsh and freshwater pools provide mosquito breeding sites in Matola. Malaria prevalence reached ∼60% among people living nearest to the main breeding sites of the vectors. Plasmodium falciparum caused 97% of malaria cases, others being P. malariae and P. ovale.

 Potential malaria vector mosquitoes (Diptera: Culicidae) collected at Matola during daytime indoor‐resting (n = 1021) and on human bait at night (n = 5893) comprised 12% Anopheles coustani Laveran (93% biting outdoors), 46% An. funestus Giles (68% biting indoors) and 42% An. gambiae Giles sensu lato (60% biting outdoors). All 215 specimens of An. gambiae s.l. identified genetically were An. arabiensis Patton. Anopheles funestus populations remained stable throughout the year, whereas densities of the An. gambiae complex fluctuated considerably, with An. arabiensis peaking during the rainy season. No concomitant rise in malaria incidence was observed. Human landing indices of An. funestus and An. arabiensis averaged 1.8 and 3.8 per man‐night, respectively. Overall Plasmodium sporozoite rates were 2.42 ± 1.24% in 2181 An. funestus and 1.11 ± 1.25% in 1689 An. arabiensis dissected and examined microscopically. Mean daily survival rates were 0.79 for both vector species. Estimated infective bites/person/year were 15 An. funestus and 12 An. arabiensis. Biting rates were greatest at 2100–24.00 hours for An. funestus (68% endophagic) and 21.00–03.00 hours for An. arabiensis (40% endophagic). The entomological inoculation rate (EIR) declined sharply over very short distances (50% per 90 m) away from breeding‐sites of the vectors. Consequently, P. falciparum prevalence among Matola residents was halved 350 m within the town. Implications for the protective effectiveness of a ‘cordon sanitaire' by residual house‐spraying and/or the use of insecticide‐treated bednets are discussed.
Field studies on efficacy of host odour baits for the biting midge Culicoides impunctatus in Scotland
Authors: Bhasin A. , (luntz) A. J. Mordue , Mordue W.
Published: March 2003

The efficacy of some putative attractants for the biting midge Culicoides impunctatus (Goetghebuer) (Diptera: Ceratopogonidae) was assessed using odour‐baited ‘delta traps’ and suction traps. 1‐octen‐3‐ol was confirmed as a potent olfactory attractant for C. impunctatus when released at 0.06 mg/h. Acetone (23 mg/h) and a mix of six phenolic compounds (phenol, 3‐ethylphenol, 4‐ethylphenol, 3‐methylphenol, 4‐methylphenol and 4‐propylphenol), at undetermined release rate, also significantly increased delta trap catches compared to unbaited controls. When tested in combination, there was evidence of synergism between CO2 (0.2 L/min) and acetone, 1‐octen‐3‐ol or cow urine, trap catches being, respectively, 4.7, 6.2 and 9.3‐fold greater than for CO2 alone. Highest catches were obtained with triple bait combinations comprising cow urine + acetone + CO2 or cow urine + 1‐octen‐3‐ol + CO2, which increased trap catches by × 22 and × 24, respectively, compared to CO2 alone. Culicoides impunctatus was found to be extremely sensitive to CO2 and responses, gauged over two field seasons, showed a significant dose‐dependent increase in catch across the entire range of release rates (0.2–2.5 L/min). Responses to these release rates, ranging from small to large mammal equivalents, emphasized the important role of CO2 in host location by C. impunctatus. Uses of olfactory attractants for monitoring and control of Culicoides are reviewed on the basis of these results.
Vector competence of South African Culicoides species for bluetongue virus serotype 1 (BTV‐1) with special reference to the effect of temperature on the rate of virus replication in C. imicola and C. bolitinos
Authors: Paweska J. T. , Venter G. J. , Mellor P. S.
Published: March 2003

Abstract. The oral susceptibility of 22 South African livestock associated Culicoides species to infection with bluetongue virus serotype 1 (BTV‐1) and its replication rate in C. imicola Kieffer and C. bolitinos Meiswinkel (Diptera: Ceratopogonidae) over a range of different incubation periods and temperatures are reported. Field‐collected Culicoides were fed on sheep blood containing 7.5 log10TCID50/mL of BTV‐1, and then held at constant different temperatures. Virus replication was measured over time by assaying individual flies in BHK‐21 cells using a microtitration procedure. Regardless of the incubation temperatures (10, 15, 18, 23.5 and 30°C) the mean virus titre/midge, infection rates (IR) and the proportion of infected females with transmission potential (TP = virus titre/midge ≥ 3 log10 TCID50) were found to be significantly higher in C. bolitinos than in C. imicola. Results from days 4–10 post‐infection (dpi), at 15–30°C, shows that the mean IR and TP values in C. bolitinos ranged from 36.7 to 87.8%, and from 8.4 to 87.7%, respectively; in C. imicola the respective values were 11.0–13.7% and 0–46.8%. In both species the highest IR was recorded at 25°C and the highest TP at 30°C. The time required for the development of TP in C. bolitinos ranged from 2 dpi at 25°C to 8 dpi at 15°C. In C. imicola it ranged from 4 dpi at 30°C to 10 dpi at 23.5°C; no individuals with TP were detected at 15°C. There was no evidence of virus replication in flies held at 10°C. When, at various points of incubation, individual flies were transferred from 10°C to 23.5°C and then assayed 4–10 days later, virus was recovered from both species. The mean virus titres/midge, and proportion of individuals with TP and IR, were again significantly higher in C. bolitinos than in C. imicola. Also the infection prevalence in C. magnus Colaço was higher than in C. imicola. Low infection prevalences were found in C. bedfordi Ingram & Macfie, C. leucostictus Kieffer, C. pycnostictus Ingram & Macfie, C. gulbenkiani Caeiro and C. milnei Austen. BTV‐1 was not detected in 14 other Culicoides species tested; however, some of these were tested in limited numbers. The present study indicates a multivector potential for BTV transmission in South Africa. In C. imicola and C. bolitinos the replication rates are distinct and are significantly influenced by temperature. These findings are discussed in relation to the epidemiology of bluetongue in South Africa.