Eosinophilic purpura, the syndrome of acquired platelet dysfunction with eosinophilia was first r... more Eosinophilic purpura, the syndrome of acquired platelet dysfunction with eosinophilia was first recognized in Singaporean children and later described in Thai children. It is a benign, transient thrombopathy associated with significant eosinophilia and characterized by the sudden onset of a superficial bleeding tendency. The first young adult with this haemostatic disturbance was documented in a National Servicemen 4 years ago. We report here our experience with 16 such patients (13 males, 3 females) and concur with the original observers on the benign nature of this syndrome. Stool helminths were present in 50% of the cases but the duration of symptoms and platelet dysfunction appeared unaffected by the rapidity with which the eosinophil count returned to normal following antihelminthic treatment. If platelet aggregation study is readily available it is desirable to document the presence of an abnormal platelet response to one or more aggregating agents but without it, it is still possible to diagnose this syndrome fairly confidently in the healthy, young patient in the first or second decade of life who develops recent onset bruising with or without mucosal bleeding, whose preliminary blood cell counts are normal apart from a moderate to marked absolute eosinophilia.
Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, th... more Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.
JC virus genomes have been localized in formalin‐fixed, paraffin‐embedded brain tissues of two ca... more JC virus genomes have been localized in formalin‐fixed, paraffin‐embedded brain tissues of two cases of known progressive multifocal leukoencephalopathy by in situ hybridization utilizing a biotinylated JC virus DNA probe. A three‐stage immunoperoxidase system with gold–silver amplification of the diaminobenzidine substrate was used to visualize biotinylated nucleic acid hybrids. Dot–blot quantification of this visualization system indicates that subpicogramme amounts of biotinylated DNA can be detected. Optimal detection of the virus genomes in the brain tissues required a microwave irradiation step prior to hybridization. JC virus genomes were observed in the nuclei of enlarged oligodendrocytes and of some bizarre astrocytes. No other cell types were found to harbour the genomes.
Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, th... more Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied. We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p<0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point
Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is associated with the app... more Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is associated with the appearance in the circulation of HBV variants with mutations in the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the polymerase gene. Fluorometric real-time PCR with the LightCycler assay was used for the detection of resistant variants. Differences in the hybridization melting curve kinetics of probes bound to the sequences encoding the wild-type or the mutant YMDD motifs (YIDD or YVDD in which the methionine residue is altered to an isoleucine or a valine, respectively) distinguished the single-base changes responsible for the resistance phenotype. The LightCycler probe hybridization assay was applied to 40 serum specimens from 19 patients, and the results were correlated with the nucleotide sequences determined for the corresponding PCR products. All three variants could be identified in the specimens. PCR clones obtained from four patients early in the course and prior to lamivudine therapy were investigated for the appearance of YIDD and YVDD variants with the LightCycler assay. In one patient, a transient appearance of the YIDD variant was observed 6 weeks into therapy. Subsequently, after 11 months of lamivudine therapy, the YVDD variant emerged in that patient.
A retrospective case-control study was conducted to determine why some infants born full-term wit... more A retrospective case-control study was conducted to determine why some infants born full-term without obstetric intervention to hepatitis B e antigen (HBeAg)-seropositive mothers become infected by hepatitis B virus (HBV) despite having received passive-active immunoprophylaxis. Cases and controls comprised 12 hepatitis B surface antigen (HBsAg)-seropositive infants and 22 HBsAgseronegative infants, respectively. Infants infected by putative vaccine-escape mutants were excluded. Risk factors, after adjustment for the level of maternal viremia, were the following allelic base changes in maternal HBV: C 158 , A 328 , G 365 , and A 479 (P Å .017, .005, .003, and .005, respectively). High-level maternal viremia (i.e., §10 8 genome equivalents/mL) was a significant factor only after adjustment for G 365 (P Å .027). HBV DNA sequences recovered from one of the cases, the case's mother, and three infected contacts all had the high-risk mutations. Specific allelic mutations in maternal HBV and level of maternal viremia are potential predictors of vertical breakthrough infection.
We aimed to determine factors associated with successful vaccination coverage and development of ... more We aimed to determine factors associated with successful vaccination coverage and development of infection in high-risk infants born to hepatitis B infected women. Immunisation of 860/932 (92%) of babies was started within 48 h of birth and three doses of vaccination completed for 794/921 (86%). Only 543 (58%) infants were tested and 26 (4.9%) were found to have evidence of current infection. Delayed start of immunisation was significantly associated with unbooked pregnancy, maternal hepatitis B e-markers and year. Current infection in the baby was strongly associated with maternal hepatitis B e-status, ethnicity and year of vaccination. The proportion of infants developing infection declined after 1998, coinciding with the publication of national recommendations and the wider use of the accelerated schedule.
A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute n... more A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute non-A-E hepatitis. The full-length genome sequence, referred to here as PM virus (PMV), was obtained and its relationship to other full or near full-length TTV sequences examined. Although it shares a common genomic arrangement and short conserved regions, the majority of the genome is extremely divergent, displaying an average genetic distance of 0n60 from all other TTV sequences. By comparing PMV with TTV genomes representing the most divergent types so far described, six major groups can be distinguished. The level of genetic diversity seen between these genomes is higher than would be expected within a single virus species. Indeed, PMV could be considered the prototype of an independent taxonomic group within the Circoviridae family. A genoprevalence study of sera from blood donors and patients with acute hepatitis suggests that PMV is rare.
Hepatitis C virus (HCV) genotypes were assigned to 567 individuals by restriction fragment length... more Hepatitis C virus (HCV) genotypes were assigned to 567 individuals by restriction fragment length polymorphism analysis of the 5&amp;#39; noncoding region of the HCV genome following reverse transcription-polymerase chain reaction. The groups of individuals in this study included hemophilia patients, injecting drug users (IDUs), blood donors, antenatal patients, those attending genitourinary medicine (GUM) clinics, and patients with chronic liver disease, all from England and Wales. The majority of HCV infections were types 1a (32%), 1b (15%), or 3a (37%). The genotype distribution in individual groups was similar to the overall genotype distribution except for hemophilia patients, in whom the frequencies were 1a (39%), 1b (23%), and 3a (21%). With the exception of hemophilia patients, subpopulations in England and Wales appear to share common modes of HCV transmission. There is a need for continued surveillance to monitor the spread of possibly more virulent or drug-resistant HCV genotypes.
Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thala... more Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thalassemia trait and 4 had probable alpha-thalassemia trait. Forty-six individuals with hemoglobinopathies were detected: 29 with probable alpha-thalassemia trait, 10 with beta-thalassemia trait and 7 with heterozygous HbE. Heterozygous alpha and beta-thalassemia occurred predominantly in Chinese while heterozygous HbE was found entirely in Malays. There were no cases of established iron deficiency anemia and only 1 had iron deficient erythropoiesis. Folate deficiency occurred only in 8 subjects with thalassemia traits, and no vitamin B12 deficiency was detected.
OBJECTIVE: To determine the frequency of detection of human herpesvirus‐8 (HHV‐8) in HIV‐related ... more OBJECTIVE: To determine the frequency of detection of human herpesvirus‐8 (HHV‐8) in HIV‐related oral ulcers. DESIGN: Analysis of archived biopsy material.METHODS: Nested polymerase chain reaction of DNA extracts.RESULTS: HHV‐8 DNA was detected in six of 10 oral ulcers of HIV‐positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non‐KS samples were derived from various oral sites.CONCLUSIONS: In HIV‐positive people, HHV‐8 can infect oral tissues that are not affected by KS.
The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinic... more The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0n43 % (95 % CI : 0n32-0n53) in London and 0n21 % (95 % CI : 0n14-0n28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.
This review focuses on general and molecular features of the epidemiology of incident and prevale... more This review focuses on general and molecular features of the epidemiology of incident and prevalent hepatitis B virus (HBV) infections in England and Wales. The situation in Scotland and Northern Ireland will not be reviewed.
: There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)‐relate... more : There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)‐related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co‐infection may be a feature of patients with HCV‐related OLP, which might explain these phenomena. HGV co‐infection was detected in 6 of 39 Italian patients with HCV‐related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co‐infection is unlikely to influence the clinical detection of HCV‐related OLP.
Eosinophilic purpura, the syndrome of acquired platelet dysfunction with eosinophilia was first r... more Eosinophilic purpura, the syndrome of acquired platelet dysfunction with eosinophilia was first recognized in Singaporean children and later described in Thai children. It is a benign, transient thrombopathy associated with significant eosinophilia and characterized by the sudden onset of a superficial bleeding tendency. The first young adult with this haemostatic disturbance was documented in a National Servicemen 4 years ago. We report here our experience with 16 such patients (13 males, 3 females) and concur with the original observers on the benign nature of this syndrome. Stool helminths were present in 50% of the cases but the duration of symptoms and platelet dysfunction appeared unaffected by the rapidity with which the eosinophil count returned to normal following antihelminthic treatment. If platelet aggregation study is readily available it is desirable to document the presence of an abnormal platelet response to one or more aggregating agents but without it, it is still possible to diagnose this syndrome fairly confidently in the healthy, young patient in the first or second decade of life who develops recent onset bruising with or without mucosal bleeding, whose preliminary blood cell counts are normal apart from a moderate to marked absolute eosinophilia.
Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, th... more Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.
JC virus genomes have been localized in formalin‐fixed, paraffin‐embedded brain tissues of two ca... more JC virus genomes have been localized in formalin‐fixed, paraffin‐embedded brain tissues of two cases of known progressive multifocal leukoencephalopathy by in situ hybridization utilizing a biotinylated JC virus DNA probe. A three‐stage immunoperoxidase system with gold–silver amplification of the diaminobenzidine substrate was used to visualize biotinylated nucleic acid hybrids. Dot–blot quantification of this visualization system indicates that subpicogramme amounts of biotinylated DNA can be detected. Optimal detection of the virus genomes in the brain tissues required a microwave irradiation step prior to hybridization. JC virus genomes were observed in the nuclei of enlarged oligodendrocytes and of some bizarre astrocytes. No other cell types were found to harbour the genomes.
Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, th... more Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied. We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease. Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured. Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p<0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158). Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point
Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is associated with the app... more Treatment of chronic hepatitis B virus (HBV) infection with lamivudine is associated with the appearance in the circulation of HBV variants with mutations in the YMDD (tyrosine, methionine, aspartate, aspartate) motif of the polymerase gene. Fluorometric real-time PCR with the LightCycler assay was used for the detection of resistant variants. Differences in the hybridization melting curve kinetics of probes bound to the sequences encoding the wild-type or the mutant YMDD motifs (YIDD or YVDD in which the methionine residue is altered to an isoleucine or a valine, respectively) distinguished the single-base changes responsible for the resistance phenotype. The LightCycler probe hybridization assay was applied to 40 serum specimens from 19 patients, and the results were correlated with the nucleotide sequences determined for the corresponding PCR products. All three variants could be identified in the specimens. PCR clones obtained from four patients early in the course and prior to lamivudine therapy were investigated for the appearance of YIDD and YVDD variants with the LightCycler assay. In one patient, a transient appearance of the YIDD variant was observed 6 weeks into therapy. Subsequently, after 11 months of lamivudine therapy, the YVDD variant emerged in that patient.
A retrospective case-control study was conducted to determine why some infants born full-term wit... more A retrospective case-control study was conducted to determine why some infants born full-term without obstetric intervention to hepatitis B e antigen (HBeAg)-seropositive mothers become infected by hepatitis B virus (HBV) despite having received passive-active immunoprophylaxis. Cases and controls comprised 12 hepatitis B surface antigen (HBsAg)-seropositive infants and 22 HBsAgseronegative infants, respectively. Infants infected by putative vaccine-escape mutants were excluded. Risk factors, after adjustment for the level of maternal viremia, were the following allelic base changes in maternal HBV: C 158 , A 328 , G 365 , and A 479 (P Å .017, .005, .003, and .005, respectively). High-level maternal viremia (i.e., §10 8 genome equivalents/mL) was a significant factor only after adjustment for G 365 (P Å .027). HBV DNA sequences recovered from one of the cases, the case's mother, and three infected contacts all had the high-risk mutations. Specific allelic mutations in maternal HBV and level of maternal viremia are potential predictors of vertical breakthrough infection.
We aimed to determine factors associated with successful vaccination coverage and development of ... more We aimed to determine factors associated with successful vaccination coverage and development of infection in high-risk infants born to hepatitis B infected women. Immunisation of 860/932 (92%) of babies was started within 48 h of birth and three doses of vaccination completed for 794/921 (86%). Only 543 (58%) infants were tested and 26 (4.9%) were found to have evidence of current infection. Delayed start of immunisation was significantly associated with unbooked pregnancy, maternal hepatitis B e-markers and year. Current infection in the baby was strongly associated with maternal hepatitis B e-status, ethnicity and year of vaccination. The proportion of infants developing infection declined after 1998, coinciding with the publication of national recommendations and the wider use of the accelerated schedule.
A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute n... more A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute non-A-E hepatitis. The full-length genome sequence, referred to here as PM virus (PMV), was obtained and its relationship to other full or near full-length TTV sequences examined. Although it shares a common genomic arrangement and short conserved regions, the majority of the genome is extremely divergent, displaying an average genetic distance of 0n60 from all other TTV sequences. By comparing PMV with TTV genomes representing the most divergent types so far described, six major groups can be distinguished. The level of genetic diversity seen between these genomes is higher than would be expected within a single virus species. Indeed, PMV could be considered the prototype of an independent taxonomic group within the Circoviridae family. A genoprevalence study of sera from blood donors and patients with acute hepatitis suggests that PMV is rare.
Hepatitis C virus (HCV) genotypes were assigned to 567 individuals by restriction fragment length... more Hepatitis C virus (HCV) genotypes were assigned to 567 individuals by restriction fragment length polymorphism analysis of the 5&amp;#39; noncoding region of the HCV genome following reverse transcription-polymerase chain reaction. The groups of individuals in this study included hemophilia patients, injecting drug users (IDUs), blood donors, antenatal patients, those attending genitourinary medicine (GUM) clinics, and patients with chronic liver disease, all from England and Wales. The majority of HCV infections were types 1a (32%), 1b (15%), or 3a (37%). The genotype distribution in individual groups was similar to the overall genotype distribution except for hemophilia patients, in whom the frequencies were 1a (39%), 1b (23%), and 3a (21%). With the exception of hemophilia patients, subpopulations in England and Wales appear to share common modes of HCV transmission. There is a need for continued surveillance to monitor the spread of possibly more virulent or drug-resistant HCV genotypes.
Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thala... more Among 990 young male adolescents studied, only 7 were anemic. Three of the anemics had beta-thalassemia trait and 4 had probable alpha-thalassemia trait. Forty-six individuals with hemoglobinopathies were detected: 29 with probable alpha-thalassemia trait, 10 with beta-thalassemia trait and 7 with heterozygous HbE. Heterozygous alpha and beta-thalassemia occurred predominantly in Chinese while heterozygous HbE was found entirely in Malays. There were no cases of established iron deficiency anemia and only 1 had iron deficient erythropoiesis. Folate deficiency occurred only in 8 subjects with thalassemia traits, and no vitamin B12 deficiency was detected.
OBJECTIVE: To determine the frequency of detection of human herpesvirus‐8 (HHV‐8) in HIV‐related ... more OBJECTIVE: To determine the frequency of detection of human herpesvirus‐8 (HHV‐8) in HIV‐related oral ulcers. DESIGN: Analysis of archived biopsy material.METHODS: Nested polymerase chain reaction of DNA extracts.RESULTS: HHV‐8 DNA was detected in six of 10 oral ulcers of HIV‐positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non‐KS samples were derived from various oral sites.CONCLUSIONS: In HIV‐positive people, HHV‐8 can infect oral tissues that are not affected by KS.
The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinic... more The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0n43 % (95 % CI : 0n32-0n53) in London and 0n21 % (95 % CI : 0n14-0n28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.
This review focuses on general and molecular features of the epidemiology of incident and prevale... more This review focuses on general and molecular features of the epidemiology of incident and prevalent hepatitis B virus (HBV) infections in England and Wales. The situation in Scotland and Northern Ireland will not be reviewed.
: There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)‐relate... more : There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)‐related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co‐infection may be a feature of patients with HCV‐related OLP, which might explain these phenomena. HGV co‐infection was detected in 6 of 39 Italian patients with HCV‐related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co‐infection is unlikely to influence the clinical detection of HCV‐related OLP.
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