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P Simmonds

Publications and source records attributed to P Simmonds.

At least 163 records · Page 9Linked to original sources
PubMed1995

Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification. The International HCV Collaborative Study Group.

Genotypes of hepatitis C virus (HCV) present within 104 samples from HCV-infected individuals from Africa, the Middle East, the Indian subcontinent and South-East Asia were identified by sequence comparisons in the core and NS-5 regions. Relatively short sequences (such as the 222 bp fragment of NS-5) provided effective discrimination of types, subtypes and isolates, and produced equivalent relationships between genotypes as were found upon comparison of longer sequences of NS-5, of the core region, and by comparison of the limited number of complete genomic sequences currently available. Measurement of evolutionary distances in the core and NS-5 regions allowed 79 of the 104 samples to be identified as examples of known genotypes, while 17 of the remainder could be provisionally classified as new subtypes of types 1 (Nigeria), 2 (Gambia), 3 (India, Pakistan and Bangladesh) and 4 (Middle East) on the basis of sequence comparison in core and NS-5 (n = 9) or provisionally using core alone (n = 8). The remaining sequences from Thailand made up two groups showing no close similarity to any of the six major genotypes classified to date, although one corresponded to an as yet unclassified variant of HCV also found in Thailand. However, phylogenetic analysis of the core and NS-5 regions indicated a distant relationship between these sequences with variants found in Vietnam and with type 6a, and collectively they formed a diverse single phylogenetic group. The existence of great diversity within a single genotype was also found amongst type 3 sequences in the Indian subcontinent, amongst type 4 variants in Central Africa and the Middle East, and amongst type variants in Nigeria. These findings may provide clues for understanding the origins and mechanisms of transmission of HCV.

Africa↗
PubMed1995

Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5' non-coding region.

A method is described for identifying different genotypes of hepatitis C virus (HCV) by restriction endonuclease cleavage of sequences amplified by PCR from the 5' non-coding region. Using the enzymes HaeIII-RsaI and HinfI-MvaI, followed by cleavage with BstU1 or ScrFI, it was possible to identify and distinguish HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5 and 6. The method was used to investigate the prevalence of these genotypes in 723 blood donors in 15 countries, the largest survey to date, and one which covered a wide range of geographical regions (Europe, America, Africa and Asia). These results, combined with a review of the existing literature, indicate the existence of several distinct regional patterns of HCV genotype distribution, and provide the framework for future detailed epidemiological investigations of HCV transmission.

Blood Donors↗
PubMed1995

Variation of the hepatitis C virus 5' non-coding region: implications for secondary structure, virus detection and typing. The International HCV Collaborative Study Group.

Variation in the 5' non-coding region (5'NCR) of hepatitis C virus (HCV) was investigated in detail by comparing 314 5'NCR sequences of viruses of genotypes 1 to 6. Evidence was obtained for the existence of associations between particular 5'NCR sequence motifs and virus types and subtypes. No recombination was observed between the 5'NCR and coding regions of different genotypes, implying that the sequence of subgenomic regions such as the 5'NCR can be used to deduce virus genotype. The distribution of polymorphic sites within the 5'NCR is used to propose improved oligonucleotide primers for virus detection and quantification that would be equally efficient in detecting RNA of different virus genotypes. The accuracy of two different genotyping methods (RFLP and the line probe assay) based on analysis of sequence polymorphisms in the 5'NCR is predicted from the sequences surveyed to be 97% and 83% respectively for types 1 to 6, with higher accuracies for distinguishing between subtypes 1a/1b, 2a/2b or 3a/3b. Several sites of genotype-specific polymorphism were covariant and maintained the base pairings required for a secondary structure model of the 5'NCR. Other sites of variation suggest minor modifications to this model and have implications for the probable functions of the 5'NCR.

Base Composition↗
PubMed1995

Absence of hepatitis A virus transmission by high-purity solvent detergent treated coagulation factor concentrates in Scottish haemophiliacs.

Recent reports of hepatitis A virus (HAV) infection in haemophiliacs receiving high-purity solvent detergent (HP.SD) treated factor VIII concentrates have brought into question the efficacy of this virucidal method for inactivating HAV. To assess whether HAV may have been transmitted by HP.SD concentrates, we compared seroprevalence in haemophiliacs with different disease severity, sought evidence of seroconversion to HAV since introduction of HP.SD products, and directly examined concentrates for HAV RNA by PCR. Our data suggest that Scottish haemophiliacs are not being infected with HAV by HP.SD concentrates produced initially by CRTS Lille and presently by PFC Edinburgh and supplied by the Scottish National Blood Transfusion Service (SNBTS).

Adolescent↗
PubMed1995

The distribution of hepatitis C virus genotypes in Turkish patients.

The distribution of hepatitis C virus (HCV) genotypes was investigated in 89 HCV-infected Turkish patients. Blood samples were collected from haemodialysis patients (n = 45), chronic liver disease (CLD) patients (n = 38), acute non-A, non-B (NANB) hepatitis patients (n = 2) and blood donors (n = 4). HCV RNA sequences were amplified in the 5' non-coding region and were typed by restriction fragment length polymorphism analysis. The predominant genotype was 1b (75.3%), followed by 1a (19.1%), 2 (3.4%) and 4 (2.2%). While there was no significant difference in the distribution of HCV genotypes with respect to age, sex, transfusion history, alanine aminotransferase levels or liver histology (in the CLD group), type 1a-infected patients were younger than type 1b-infected patients (P < 0.05) in the haemodialysis group. Serological reactivity to recombinant HCV proteins was assessed in 58 samples using the Chiron RIBA-2 assay. The reactivity of samples from patients infected with type 1b with 5-1-1 and c100 antigens was significantly lower (P < 0.05) than the reactivity of samples from those infected with type 1a. These results, together with the results of two previous studies, indicate that HCV genotypes 1, 2, 3 and 4 are prevalent in different frequencies in the Turkish population. Determination of the genotype distribution of HCV in a geographical area may provide important clues for studying the epidemiology, transmission and pathogenesis of HCV-related diseases and may also aid in improving serological assays to detect HCV infection.

Adult↗
PubMed1995

Acute hepatitis C infection after sexual exposure.

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.

Acute Disease↗
PubMed1995

Liver biopsy findings in patients with alcoholic liver disease complicated by chronic hepatitis C virus infection.

OBJECTIVE: To identify the features of concurrent hepatitis C virus (HCV) infection in liver biopsies from patients thought to have alcoholic liver disease. PATIENTS: Fifty-five patients with a history of excess alcohol consumption were studied. METHODS: All patients underwent liver biopsy. RESULTS: Eight of the 55 patients studied were found to be HCV-positive. CONCLUSION: The histological features found to be most useful for identifying concurrent HCV infection were the presence of lymphoid aggregates in portal tracts (predictive value 100%), the presence of lymphocytes in the lobules (predictive value 83%), and the pattern of fibrosis, particularly periportal spurring rather than perivenular fibrosis (predictive value 75%).

Adult↗
PubMed1995

Hepatitis C virus variants and the role of genotyping.

Hepatitis C virus demonstrates considerable divergence in nucleotide sequence. This variation may affect virus detection, disease outcome, and the effectiveness of interferon treatment. For example, infection with genotype 1 is associated with a lower response rate to interferon treatment. Hepatitis C virus can be classified into six distinct types, comprising at least 74 different subtypes. Both types and subtypes are subject to geographical differences in distribution, presumably reflecting the epidemiological history of the virus. However, because this history may be blurred by migration and by commerce in blood products between regions, screening and typing assays must recognize both the major indigenous and more exotic virus genotypes. Little information exists about the role of virus sequence variation in screening for hepatitis C virus antibodies, but there is some evidence that the reactivity of current serological screening assays for hepatitis C virus is genotype dependent. In the future, screening assays may need to include antigens specific for different virus types or may need to be designed with regard to the particular types found in a certain area. Antigenic variation may also mean that an effective vaccine needs to be multivalent to protect against all genotypes present in a given region. There are several polymerase chain reaction-based methods of distinguishing between hepatitis C virus variants. These methods must be continually updated, however, as new sequence variants are discovered. Alternative genotyping assays are based on the host's serological response to virus infection, but these cannot distinguish between virus subtypes and are unsuitable for immunocompromised patients. As more countries are sampled, it is likely that more genotypes will be identified and this may help elucidate the origins of hepatitis C virus. Detailed epidemiological studies may delineate past and current routes of transmission.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Redistribution of HIV outside the lymphoid system with onset of AIDS.

The basis for many of the symptoms and pathological changes found in patients with the acquired immunodeficiency syndrome (AIDS) remains poorly understood. We have used a quantitative polymerase chain reaction technique to investigate the extent to which direct infection with human immunodeficiency virus (HIV) produces the disease manifestations of AIDS. In five patients who died with AIDS-defining illnesses (Centers for Disease Control and Prevention class IV), we found variable, but in many cases extensive, infection by HIV at various sites, including brain, lung, colon, and liver. By contrast, in three HIV-positive subjects who died without HIV-related disease (CDC class II), we found no evidence of significant infection of any non-lymphoid organ. In both groups of patients there were high levels of infection in cells of the spleen, lymph nodes, and peripheral blood. Pathological examination of tissues from the AIDS patients revealed many abnormalities, of which some, such as giant-cell encephalitis in the brain, were specifically associated with the presence of high levels of HIV infection. These findings suggest that spread of HIV outside cells of the immune system is a late event in HIV infection and is extremely sensitive to the degree of immunosuppression in the patient.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Hepatitis C virus transmission by intravenous immunoglobulin.

The polymerase chain reaction was used to detect hepatitis C virus infection in patients who had previously been reported to have developed non-A, non-B hepatitis after intravenous immunoglobulin infusion. Of the 33 patients with intravenous immunoglobulin associated non-A, non-B hepatitis studied, HCV RNA could be detected in 15 out of 17 patients (88%) who were HCV RNA negative prior to the development of non-A, non-B hepatitis after implicated intravenous immunoglobulin batches. Similarly, eight out of nine patients (89%) in whom no sample was available for polymerase chain reaction testing prior to intravenous immunoglobulin therapy, had detectable HCV RNA after intravenous immunoglobulin therapy with intravenous immunoglobulin batches implicated in non-A, non-B hepatitis transmission. Two of the three intravenous immunoglobulin preparations implicated in non-A, non-B hepatitis transmissions that were available for polymerase chain reaction testing also had detectable HCV RNA, confirming that hepatitis C virus is the implicated virus in intravenous immunoglobulin-associated non-A, non-B hepatitis.

Hepacivirus↗
PubMed1994

Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs.

The frequency and dynamics of infection with different genotypes of hepatitis C virus were investigated in a cohort of hemophiliacs repeatedly exposed to non-virus-inactivated clotting factor. Among 63 infected hemophiliacs, genotype 1 (n = 38, subtypes 1a [27] and 1b [11]) was predominant; genotypes 2a (n = 1), 2b (n = 3), 3a (n = 20), and 5a (n = 1) accounted for the remainder. This distribution was similar to that found in Scottish blood donors from whom the infected blood products were manufactured. Hemophiliacs with severe disease were more likely to be polymerase chain reaction-positive than those with moderate or mild disease. Over 10 years, changes in the circulating major genotype and serotype were observed in 9 of 29 hemophiliacs and from one subtype to another in 3, although there was no clear trend toward replacement with any particular variant. Replacement occurred after the introduction of inactivated clotting factor in 4 subjects, implicating reactivation rather than reinfection. Those coinfected with human immunodeficiency virus were more likely to show a change in genotype.

Blood Donors↗
PubMed1994

Identification of genotypes of hepatitis C virus by sequence comparisons in the core, E1 and NS-5 regions.

Isolates of hepatitis C virus (HCV) show considerable nucleotide sequence variability throughout the genome. Comparisons of complete genome sequences have been used as the basis of classification of HCV into a number of genotypes that show 67 to 77% sequence similarity. In order to investigate whether sequence relationships between genotypes are equivalent in different regions of the genome, we have carried out formal sequence analysis of variants in the 5' non-coding region (5'NCR) and in the genes encoding the core protein, an envelope protein (E1) and a non-structural protein (NS-5). In the E1 region, variants grouped into a series of six major genotypes and a series of subtypes that could be matched to the phylogenetic groupings previously observed for the NS-5 region. Furthermore, core and E1 sequences showed three non-overlapping ranges of sequence similarity corresponding to those between different genotypes, subtypes and isolates previously described in NS-5. Each major genotype could also be reliably identified by sequence comparisons in the well conserved 5'NCR, although many subtypes, such as 1a/1b, 2a/2c and some of those of type 4, could not be reliably distinguished from each other in this region. These data indicate that subgenomic regions such as E1 and NS-5 contain sufficient phylogenetic information for the identification of each of the 11 or 12 known types and subtypes of HCV. No evidence was found for variants of HCV that had sequences of one genotype in the 5'NCR but of a different one in the E1 or NS-5 region. This suggests that recombination between different HCV types is rare or non-existent and does not currently pose a problem in the use of subgenomic regions in classification.

Base Sequence↗
PubMed1994

Sequence variability of hepatitis C virus and its clinical relevance.

Chronic type C hepatitis is a potentially serious disease that can lead to cirrhosis and hepatocellular carcinoma. This complex disease is caused by the hepatitis C virus (HCV), a positive sense, single-stranded RNA virus. HCV has been assigned to a separate genus within the Flaviviridae, and shares a close relationship to the pestiviruses. Nucleotide sequence variation has been observed in genomes amplified from serum of patients with HCV infection, and cloning of RNA amplified from patients infected with HCV has confirmed the heterogeneity of the agent responsible for post-transfusion and sporadic hepatitis C. The variability of HCV is structured in a way that immediately suggests a two tiered classification: this nomenclature comprises 'types' corresponding to the major branches in a phylogenetic tree of sequences from genomic or subgenomic regions of the genome, and 'subtypes', corresponding to the more closely related sequences within some of the major groups. This genotyping designation has provided an epidemiological tool for studying geographical differences in hepatitis C infection. Clearly discernible patterns of genotype distribution have been found in those countries that have been studied so far. In many European countries genotype distributions vary with the age of patients, reflecting rapid changes in genotype distribution with time within a single geographical area. Unfortunately we know very little about modes of transmission within different communities. There is considerable interest in the clinical significance of different HCV genotypes, and the intriguing question of whether these differences may affect the spectrum of the disease associated with hepatitis C. These data also have implications for diagnosis and treatment of acute and chronic hepatitis C. A uniform typing scheme and nomenclature will facilitate our understanding of the disease caused by this virus worldwide.

Genotype↗
PubMed1994

Prevalence and epidemiological characteristics of hepatitis C in Scottish blood donors.

All blood donors in Scotland who were found to be infected with hepatitis C virus (HCV) in the first 6 months of routine testing of all donations for anti-HCV were contacted. Those who attended were counselled, a history of exposure to risk was sought, and blood was taken for alanine aminotransferase (ALT) level as a measure of liver function. The epidemiological features were then correlated with the virological findings and ALT. In the period under study between September 1991 and February 1992, 180,658 blood donors attended. The prevalence of HCV infection was 0.088%. Of the 151 donors who attended for counselling, 101 (68%) were male. Intravenous drug use was the most common risk activity (39%), followed by previous blood transfusion (15.2%), other parenteral exposure (11.2%) and heterosexual contact with a parenterally infected partner (8.6%); 29.1% of donors gave no history of possible exposure. Elevated ALT levels were found in 59%. ALT levels were higher in donors with HCV types 1 and 3 than in HCV type 2 or non-viraemic donors. The prevalence of HCV in Scottish blood donors is thus relatively low. This may relate to the effectiveness of donor selection procedures, but donors with risk activities which should debar them continue to donate. The combination of ALT and PCR appears to be useful in counselling and assessing infected donors.

Alanine Transaminase↗