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P Simmonds

Publications and source records attributed to P Simmonds.

At least 127 records · Page 7Linked to original sources
PubMed1996

Outbreak of acute hepatitis C following the use of anti-hepatitis C virus--screened intravenous immunoglobulin therapy.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been associated with intravenous (IV) immunoglobulin (Ig), and plasma donations used to prepare IV Ig are now screened to prevent transmission. Thirty-six patients from the United Kingdom received infusions from a batch of anti-HCV antibody-screened intravenous Ig (Gammagard; Baxter Healthcare Ltd., Thetford, Norfolk, England) that was associated with reports of acute hepatitis C outbreak in Europe. The aim of this study was to document the epidemiology of this outbreak. METHODS: Forty-six patients from the United Kingdom treated with Gammagard (34 exposed and 12 unexposed to the batch) returned epidemiological questionnaires. RESULTS: Eighty-two percent of the exposed patients (28 of 34) became positive for HCV RNA. Eighteen percent of the patients (6 of 34) who had infusions with this batch tested negative for HCV RNA, but 2 of the patients had abnormal liver function and subsequently seroconverted to anti-HCV antibody positive. Twenty-seven percent of the patients (9 of 34) developed jaundice, and 79% (27 of 34) had abnormal liver transferase levels. Virus isolates (n=21), including an isolate from the implicated batch, were genotype 1a and virtually identical by sequence analysis of the NS5 region, consistent with transmission from a single source. CONCLUSIONS: Hepatitis C infection can be transmitted by anti-HCV-screened IV Ig. Careful documentation of IV Ig batch numbers and regular biochemical monitoring is recommended for all IV Ig recipients.

Acute Disease↗
PubMed1996

Levels of hepatitis C virus in blood donors infected with different viral genotypes. International HCV Collaborative Study Group.

The level of hepatitis C virus (HCV) in the serum of 337 blood donors infected with different viral genotypes was investigated by branched DNA assay. Viral genotype was deduced by restriction analysis of the virus 5'-noncoding region. Samples included genotypes 1a, 1b, 2a, 2b, 3,4,5, and 6. Multivariate analysis revealed that the ranges of HCV levels were similar for all viral genotypes and subtypes (P=.18), with the possible exception of genotype 4. Virus levels were significantly lower in female than in male subjects (P<.001) but did not correlate with donor age (P=.06) or genotype or with donor age, sex, or country. These results indicate a similar replicative capacity in vivo for different HCV genotypes and clarify the influence of host and virus factors on disease severity and responsiveness to interferon treatment.

Blood Donors↗
PubMed1996

Influence of risk group and zidovudine therapy on the development of HIV encephalitis and cognitive impairment in AIDS patients.

OBJECTIVE: To determine the associations between HIV encephalitis and other central nervous system (CNS) pathology, viral burden, cognitive impairment, zidovudine therapy and risk group in AIDS patients. DESIGN: Planned autopsy study in AIDS patients evaluated prospectively for numerous clinical parameters. SETTING: Regional academic centre for clinical care and pathology examination of patients with HIV infection. PATIENTS: Edinburgh cohort of HIV-positive patients prospectively assessed for cognitive impairment, immunosuppression and clinical course. Unbiased series of consecutive autopsies in 27 homosexual men and 39 drug-using patients with AIDS. INTERVENTIONS: Zidovudine therapy monitored in all patients. MAIN OUTCOME MEASURES: Determination of CNS viral burden and pathology including immunocytochemically confirmed HIV encephalitis in injecting drug users (IDU) versus homosexual AIDS patients with known CD4 counts and cognitive function. RESULTS: HIV encephalitis was present in 59% of IDU and 15% of homosexuals: 88% of patients with encephalitis had displayed cognitive impairment. HIV encephalitis was strongly associated with a high viral load and HIV p24 immunopositivity. Opportunistic infections and lymphomas were more common in homosexuals (63%) than in IDU (31%) and were associated with the degree of immunosuppression before death. Within both groups, prolonged zidovudine treatment was associated with a lower incidence of HIV encephalitis. CONCLUSIONS: This study documents two separate CNS outcomes in AIDS patients in that HIV encephalitis occurs independently of opportunistic infections and lymphomas and shows different associations with risk group, immunosuppression and antiviral treatment before death.

AIDS Dementia Complex↗
PubMed1996

Evolutionary analysis of variants of hepatitis C virus found in South-East Asia: comparison with classifications based upon sequence similarity.

Variants of hepatitis C virus (HCV) have been classified by nucleotide sequence comparisons in different regions of the genome. Many investigators have defined the ranges of sequence similarity values or evolutionary distances corresponding to divisions of HCV into types, subtypes and isolates. Using these criteria, novel variants of HCV from Vietnam, Thailand and Indonesia have been classified as types 7, 8, 9, 10 and 11, many of which can be further subdivided into between two to four subtypes. In this study, this distance-based method of virus classification was compared with phylogenetic analysis and statistical measures to establish the confidence of the groupings. Using bootstrap resampling of phylogenetic trees in several subgenomic regions (core, E1, NS5) and with complete genomic sequences, we found that one set of novel HCV variants ('types 7, 8, 9 and 11') consistently grouped together into a single clade that also contained type 6a, while 'type 10a' grouped with type 3. In contrast, no robust higher-order groupings were observed between any of the other five previously described HCV genotypes (types 1-5). In each subgenomic region, the distribution of pairwise distances between members of the type 6 clade were consistently bi-modal and therefore provided no justification for classification of these variants into the three proposed categories (type, subtype, isolate). Based on these results, we propose that a more useful classification would regard all these variants as subtypes of type 6 or type 3, even though the level of sequence diversity within the clade was greater than observed for other genotypes. Classification by phylogenetic relatedness rules out simple sequence similarity measurements as a method for assigning HCV genotypes, but provides a more appropriate description of the evolutionary and epidemiological history of a virus.

Asia, Southeastern↗
PubMed1996

Response to interferon-alpha of Egyptian patients infected with hepatitis C virus genotype 4.

Hepatitis C virus (HCV) genotype 4 is the principal HCV genotype found in Egypt and the Middle East. Little is known concerning its propensity to cause disease and the frequency with which infected individuals respond to interferon-alpha (IFN-alpha). We have investigated the response to treatment in a cohort of 100 chronic hepatitis C patients infected with genotype 4. All patients had biopsy-proven chronic active liver disease. Each was treated with 3 million units (MU) IFN-alpha, thrice weekly. Response was monitored, in 92 patients who completed treatment, by alanine aminotransferase (ALT) measurements and by polymerase chain reaction (PCR) for HCV. ALT levels remained abnormal in 64 patients during treatment (69.6%). Of the 28 patients who showed a biochemical response during treatment (30.4%), 18 maintained this over the 6-month posttreatment period. Amongst the sustained biochemical responders, HCV RNA was cleared from serum in only four of the 18 (22.2%) in this period. Histological improvement was observed in 26/51 (50.9%) of the patients who had a second biopsy. Hence, patients infected with HCV genotype 4 show a poor response to IFN-alpha therapy compared with genotypes 2 and 3, but a similar response to IFN-alpha compared with those infected with type 1b HCV. These findings have major implications for treatment strategies in the Middle East, including Egypt, where HCV genotype 4 is widely distributed.

Adult↗
PubMed1996

Lack of association between type of hepatitis C virus, serum load and severity of liver disease.

Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription-polymerase chain reaction (RT-PCR) with a median level of 1003 x 10(3) genomic equivalents ml-1 according to the branched-DNA assay (b-DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype 1a + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non-progressive liver disease groups. Serum HCV-RNA levels were similar in the liver diseased groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.

Adult↗
PubMed1996

Comparative study of three methods for genotyping hepatitis C virus strains in samples from Spanish patients.

Hepatitis C virus (HCV) genotypes may be investigated by a variety of laboratory methods that target different parts of the HCV genome and have various degrees of technical difficulty. Since the choice of a particular method is difficult, we compared the performance of (i) a type-specific PCR with type-specific primers from the core region, (ii) molecular hybridization of the PCR-amplified 5' noncoding region to type-specific probes, and (iii) identification of type-specific antibodies against epitopes of nonstructural region 4 by enzyme-linked immunosorbent assay (ELISA). One hundred fifty-one patients with biopsy-proved chronic hepatitis and HCV RNA in serum were investigated. The HCV genotype was identified in 99%, 100%, and 85% of the cases by type-specific PCR, probe hybridization, and ELISA, respectively. The type-specific PCR disclosed infection with type 1a in 3%, type 1b in 74%, and type 3a in 4% of the cases and suggested infection with two or more HCV types, including 2a/2c and 2b, in the remaining 18%. Apparently mixed infections were more prevalent in patients with past intravenous drug use (P < 0.001), but cloning and sequencing of PCR products did not confirm a mixed infection in any of the four cases investigated. Concordant results were obtained by the three procedures with virtually all of the samples in which the type-specific PCR revealed a single HCV genotype. Type-specific hybridization and ELISA usually recognized the genotype producing the strongest DNA band in samples in which type-specific PCR suggested a mixed infection. In conclusion, the three procedures evaluated in this study are reliable for investigation of HCV genotype. Type-specific PCR provides information about HCV subtypes, but a mixed infection detected with this method should be interpreted with caution.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

Survey of type 6 group variants of hepatitis C virus in Southeast Asia by using a core-based genotyping assay.

Previous surveys of the prevalences of genotypes of hepatitis C virus (HCV) in different populations have often used genotyping assays based upon analysis of amplified sequences from the 5' noncoding region (5'NCR), such as restriction fragment length polymorphism (RFLP) or hybridization with type-specific probes (e.g., InnoLipa). Although highly conserved, this region contains several type-specific nucleotide polymorphisms that allow major genotypes 1 to 6 to be reliably identified. Recently, however, novel HCV variants found in Vietnam and Thailand that are distantly related to the type 6a genotype (type 6 group) by phylogenetic analysis of coding regions of the genome often have sequences in the 5'NCR that are similar or identical to those of type 1 and could therefore not be identified by an assay of sequences in this region. We developed a new genotyping assay based upon RFLP of sequences amplified from the more variable core region to investigate their distribution elsewhere in southeast (SE) Asia. Among 108 samples from blood donors in seven areas that were identified as type 1 by RFLP in the 5'NCR, type 6 group variants were found in Thailand (7 from 28 samples originally identified as type 1) and Burma (Myanmar) (1 of 3) but were not found in Hong Kong (n = 43), Macau (n = 8), Taiwan (n = 6), Singapore (n = 2), or Malaysia (n = 18). Although this small survey suggests a relatively limited distribution for type 6 group variants in SE Asia, larger studies will be required to explore their distribution in other geographical regions and the extent to which their presence would limit the practical usefulness of 5'NCR-based genotyping assays for clinical or epidemiological purposes.

Asia, Southeastern↗
PubMed1996

Hepatitis C virus: epidemiology and genotypes in the north east of England.

The epidemiology of hepatitis C virus (HCV) infection was studied in an English teaching hospital over an 18 month period. A total of 104 HCV antibody positive patients were referred for further investigation. They were divided into those diagnosed through screening (blood donors and intravenous drug abusers) and those diagnosed for other reasons, and their mean ages, known risk factors for HCV transmission, genotypes, and liver biopsy histology were analysed. Screened patients were significantly younger than the others. No significant difference in age was found between genotypes. Most patients genotyped (69%) were genotype 1. Intravenous drug abusers had a higher proportion of subtype 1a, and patients who acquired HCV through blood transfusion had a higher proportion of subtype 1b. Liver biopsy specimens were scored using a histological activity index for liver inflammation and fibrosis. Patients with subtype 1b had significantly more severe liver disease than other genotypes when the histological activity index scores for fibrosis were analysed (p < 0.05). Liver disease worsened significantly with age according to all three histological activity index scores (portal activity: p < 0.01, acinar activity: p < 0.001, fibrosis: p < 0.0001). Liver disease worsened with increased duration of infection (p < 0.002), and patients who also abused alcohol presented at a significantly younger age (cirrhosis, p < 0.05, hepatocellular carcinoma, p < 0.02).

Adult↗
PubMed1996

Prevalence of hepatitis C genotypes among patients with chronic hepatitis C in Norway. Construct Group.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

Adult↗
PubMed1995

Molecular epidemiology of an outbreak of infection with hepatitis C virus in recipients of anti-D immunoglobulin.

In a retrospective investigation of possible transmission of hepatitis C virus (HCV) by anti-rhesus D immunoglobulin (anti-D) in 1977, we compared variants infecting anti-D recipients in Ireland of one of the implicated batches with those of epidemiologically unrelated HCV-infected individuals. All 100 of the recipients of the batch investigated to date were infected with a single genotype (type 1), consistent with a single-source outbreak, whereas a wider range of genotypes (1, 2, and 3) were found in anti-HCV positive individuals from Ireland infected by different routes. Nucleotide sequences from a 222 base fragment from the NS-5 region of the genome amplified from stored aliquots of the implicated batch closely matched those detected in anti-D recipients 17 years after the transmission event. This study shows the value of molecular epidemiological techniques for identifying distant sources of infection, and for the epidemiological investigation of the current distribution and transmission of HCV in different populations.

Antibodies, Anti-Idiotypic↗
PubMed1995

Heterogeneity of hepatitis C virus genotypes in hemophilia: relationship with chronic liver disease.

In this study we have determined the hepatitis C virus (HCV) serotype and genotype in a cohort of 96 HCV-infected hemophiliacs and have examined the relationship between HCV genotype and severity of chronic liver disease as determined by liver biopsy. HCV serotype was determined by specific enzyme-linked immunosorbent assays (ELISAs) and genotype by restriction fragment length polymorphism (RFLP) and HCV viral sequencing. The pattern of genotype distribution was quite unlike that of HCV-infected United Kingdom (UK) blood donors in that five of the six known HCV genotypes were represented, 50% were type 1, 13% type 2, and 18% type 3. An unexpected observation was the presence of HCV genotype 4 in four patients and type 5 in two patients. An additional feature was the presence of mixed infection, detected in 14% and 7% by serotype and genotype analysis, respectively. Liver biopsies were available from 51 patients. Cirrhosis was present in five of 27 (19%) of individuals with type 1, in 2 of 9 (22%) with type 2, and 5 of 8 (63%) of those with type 3. The heterogeneous pattern of HCV genotype distribution in this cohort of patients and the observed relationship between the severity of the related liver disease and specific HCV genotype may have important implications with respect to the natural history and treatment of HCV-related chronic liver disease in infected hemophiliacs worldwide.

Alanine Transaminase↗
PubMed1995

Extrahepatic immunologic manifestations in chronic hepatitis C and hepatitis C virus serotypes.

OBJECTIVE: To determine, using a serotyping assay, whether the occurrence of extrahepatic immunologic disorders in patients with chronic hepatitis C is dependent on hepatitis C virus serotype. DESIGN: Prospective study. SETTING: Liver unit and virology laboratory of a university hospital. PATIENTS: 59 consecutive patients with chronic hepatitis C. MEASUREMENTS: Hepatitis C virus serotype was determined using a recently developed immunoenzymatic assay that detects antibodies directed to serotype-specific immunodominant epitopes. Cryoglobulin, rheumatoid factor, and numerous antitissue antibodies were sought. Biopsies of labial salivary glands were done in 49 of the 59 patients. RESULTS: Prevalence was 59% for serotype 1, 10% for serotype 2, 12% for serotype 3, and 3% for mixed infection. Fifteen percent of patients could not be serotyped. Cryoglobulinemia was found in 36% of patients and rheumatoid factor was found in the serum of 71%. At least one antitissue antibody was found in the serum of 41% of patients; salivary gland biopsy showed lymphocytic capillaritis in 49% of patients. These immunologic abnormalities were seen in patients infected with any of the three serotypes, and prevalences of the abnormalities did not differ significantly among patients infected with different serotypes. CONCLUSIONS: We confirm that the prevalence of extrahepatic immunologic abnormalities is high in patients with chronic hepatitis C. These abnormalities may occur in patients infected with any of the three major hepatitis C virus serotypes now present in developed countries.

Adolescent↗