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Biomedical subjects

C G Teo

Publications and source records attributed to C G Teo.

At least 19 recordsLinked to original sources

Conceptual emergence of human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) as an oral herpesvirus.

Recognition of the various clinico-epidemiologic forms of Kaposi's sarcoma, a disease putatively caused by an infectious agent, did not provide ready clues as to how that agent might be transmitted, although fecal and sexual routes were implicated. Application of serologic and genome-detection assays, and cell-culture studies following the identification of human herpesvirus 8 as the causative agent now implicate that virus as one that is orally shed. While oral transmission of the virus might account for the viral endemicity in Africa and Mediterranean countries, why it is particularly prevalent among male homosexuals in the West remains more difficult to explain. Such explanation may be sought from behavioral studies into the role saliva plays in sexual interactions.

AIDS-Related Opportunistic Infections↗

HCV infection: aspects of epidemiology and transmission relevant to oral health care workers.

Hepatitis C virus (HCV) infection is a common worldwide problem, giving rise to long-term viral carriage and risk of chronic hepatic disease, hepatic malignancy and a wide spectrum of immunologically mediated disorders. The present report describes relevant data suggesting that nosocomial transmission to oral health care workers is unlikely, but in view of medical and occupational consequences of such infection, and the absence of long-term effective treatment or vaccine, the oral surgery profession must continue to be vigilant and to maintain the highest standards of infection control procedures to minimize the possible acquisition of HCV during dental treatment.

Antiviral Agents↗

European multicenter evaluation of high-density DNA probe arrays for detection of hepatitis B virus resistance mutations and identification of genotypes.

Polymorphisms along the hepatitis B virus (HBV) genome have an impact on disease outcome, sensitivity to antiviral treatment, escape from vaccination, and laboratory diagnosis. We have designed a diagnostic tool based on duplex amplification of the whole HBV genome and a high-density DNA chip designed to detect 245 mutations, 20 deletions, and 2 insertions at 151 positions and to determine the genotype of the virus in serum. Assay performances were evaluated with 170 samples, characterized by determination of viral load and sequencing of the Pol, S, and precore genes and the basal core promoter. One hundred fifty-three samples (90%) could be amplified and analyzed by the chip. Only two samples with more than 10(3) genome copies/ml could not be analyzed. Genotype had no impact on analytical sensitivity. Reproducibility studies showed no difference between repeats for codon and genotype determination. Genotype determination by sequencing and the chip were concordant in 148 of 151 samples. Twelve thousand one hundred sixty-one codons were analyzed by both techniques. Only 89.4% could be determined by sequencing, and among the remaining 11,335 codons, 92.8% were identical by sequencing and the chip. Failures to identify an amino acid by the chip were mainly due to reduced hybridization efficiency attributed to unexpected polymorphisms. Optimization of the chip-based reagent for the analysis of the HBV genome is ongoing. This first evaluation showed that DNA chip technology can provide important information in relation to the clinical management of chronic hepatitis B.

DNA, Viral↗

Anesthetist to patient transmission of hepatitis C virus associated with non exposure-prone procedures.

A 44-year-old lady was diagnosed with acute hepatitis C virus (HCV) infection 8 weeks after hysterectomy at which the attending anesthetist was known to be hepatitis C seropositive. Comparative nucleotide sequence analysis and phylogenetic comparison proved that transmission had occurred from the anesthetist to the patient. The patient had received general anesthesia with endotracheal intubation and peripheral intravenous cannulation. No exposure-prone anesthetic procedures had been performed. This is the first case described in UK involving transmission from an anesthetist to a patient during anesthesia where no exposure prone procedures were carried out. It is the first example in which the anesthetist was known to be seropositive for hepatitis C prior to the operation.

Adult↗

Inter- and intra-person cytomegalovirus infection in Malawian families.

Sequence polymorphisms in the gN and gO genes of cytomegalovirus (CMV) amplified from mouth rinse and urine samples of 19 Malawian patients with Kaposi's sarcoma (KS) and 58 of their first-degree relatives were investigated. CMV-DNA was amplified from 41 people (53%) from either the gN or gO region in at least one sample, from 14 people (18%) in both domains in at least one sample, and from 13 (17%) in either domain in both samples. Twenty-one (51%) were seropositive for human immunodeficiency virus-1 (HIV). Identical gN sequences were recovered from eight families and non-identical sequences in six, while identical gO sequences were found in three families and non-identical sequences in five. Five people, four of whom were children, each carried multitypic gN sequences or gO sequences. The findings are consistent with CMV spread along intra- and extra-household routes, and with multiple intra-host CMV infection.

Adolescent↗

Molecular epidemiology of hepatitis B in England and Wales.

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.

Emigration and Immigration↗

Interactions between human immunodeficiency virus and herpes viruses within the oral mucosa.

There is evidence from clinical case reports and epidemiological studies that human immunodeficiency virus (HIV) can be transmitted through oral sex. Herpes viruses that appear in the oral mucosa might influence the oral replication of HIV. A review of data suggesting that interactions occur between HIV and herpes viruses indicates that such interactions might operate in the oral mucosa. Defining the mechanisms by which herpes viruses interact with HIV in the oral mucosa should permit intervention measures to be targeted more precisely.

CD4 Antigens↗

Multiple human herpesvirus-8 infection.

In Malawian patients with Kaposi sarcoma (KS) and their relatives, we investigated nucleotide-sequence variation in human herpesvirus-8 (HHV-8) subgenomic DNA, amplified from oral and blood samples by use of polymerase chain reaction. Twenty-four people had amplifiable HHV-8 DNA in >1 sample; 9 (38%) were seropositive for human immunodeficiency virus type 1, 21 (88%) were anti-HHV-8-seropositive, and 7 (29%) had KS. Sequence variation was sought in 3 loci of the HHV-8 genome: the internal repeat domain of open-reading frame (ORF) 73, the KS330 segment of ORF 26, and variable region 1 of ORF K1. Significant intraperson/intersample and intrasample sequence polymorphisms were observed in 14 people (60%). For 3 patients with KS, intraperson genotypic differences, arising from nucleotide sequence variations in ORFs 26 and K1, were found in blood and oral samples. For 2 other patients with KS and for 9 people without KS, intraperson genotypic and subgenotypic differences, originating predominantly from ORF K1, were found in oral samples; for the 2 patients with KS and for 4 individuals without KS, intrasample carriage of distinct ORF K1 sequences also were discernible. Our findings imply HHV-8 superinfection.

AIDS-Related Opportunistic Infections↗

A national survey of genitourinary medicine clinic attenders provides little evidence of sexual transmission of hepatitis C virus infection.

OBJECTIVE: To determine the prevalence and genetic diversity of hepatitis C virus in genitourinary medicine clinic attenders and to assess the extent of sexual transmission of the virus. METHODS: A cross sectional, unlinked, anonymous survey in 14 genitourinary medicine clinics situated in England, Wales, and Northern Ireland. Serum specimens from genitourinary medicine clinic attenders, retained as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP) serum archive, were tested in small pools, for the presence of antibody to hepatitis C virus (anti-HCV). The main outcome measures were prevalence of antibodies to hepatitis C virus and identification of hepatitis C virus genotypes. RESULTS: Testing of 17,586 specimens from 1995 showed an adjusted prevalence of anti-HCV in genitourinary medicine clinic attenders of 1.03% (95% CI: 0.89 to 1.16) overall and 0.65% (95% CI: 0.51 to 0.78) among those who did not report injecting drug use. Prevalence in injecting drug users attending genitourinary medicine clinics was 36.9% in both 1995 and 1996. Heterosexual injecting drug users had a higher prevalence of anti-HCV than homosexual/bisexual injectors. The most common hepatitis C genotypes were types 3a and 1a. There was a high degree of concordance between genotype and serotype. CONCLUSIONS: The low prevalence of anti-HCV in genitourinary medicine clinic attenders who deny injecting drugs suggests that the majority of hepatitis C infections have been acquired in adult life, mostly by injecting drug use, and that the hepatitis C virus is rarely transmitted sexually. The use of needle exchanges may explain the relatively low prevalence observed in the injecting drug users.

Adult↗

Tracking familial transmission of Kaposi's sarcoma-associated herpesvirus using restriction fragment length polymorphism analysis of latent nuclear antigen.

Intra-familial transmission of Kaposi's sarcoma associated herpesvirus (KSHV) is likely to occur in geographical regions where KSHV infection is highly endemic. Transmission has been studied previously indirectly using serological techniques, however direct documentation of specific transmission routes has yet to be reported. The internal repeat domain (IRD) of the KSHV opening reading frame (ORF) 73 was shown previously to exhibit restriction-fragment length polymorphism (RFLP). Analysis of such polymorphism was undertaken using nested ORF 73 IRD PCR products derived from the blood and mouth rinse samples of individuals in Malawian family groups. The resulting RFLP patterns were unique to an individual and could be compared between family members. In three of eight families studied, identical RFLP patterns were recovered from family members; in the remaining five families, dissimilar RFLP patterns were revealed. Results from RFLP analysis were compared to sequencing data recovered from family members for the first variable region of the hypervariable KSHV ORF K1. Patterns of intra- and extra-familial transmission inferred from ORF K1 sequencing data were corroborated mainly using ORF 73 IRD RFLP analysis.

Adolescent↗

Viral infections in the mouth.

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein-Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via nonglossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.

AIDS-Related Opportunistic Infections↗

Partial sequence analysis of indigenous hepatitis E virus isolated in the United Kingdom.

The first nucleotide sequences of hepatitis E virus (HEV) acquired in the United Kingdom are described. The sequences are novel and are related most closely to HEV isolated from Greece (Greece 2 strain), consistent with their having been derived from an indigenous European virus. HEV was assumed until recently to be rare in the United Kingdom and other industrialised countries and, consequently, hepatitis E may be under-diagnosed in industrialised countries.

Genotype↗

Diversity of hepatitis C virus quasispecies evaluated by denaturing gradient gel electrophoresis.

Denaturing gradient gel electrophoresis (DGGE) was used to study the diversity of hepatitis C virus (HCV) quasispecies. Optimized DGGE running conditions were applied to screen for variations in sequences cloned from amplicons originating from the nonstructural 5b (NS5b) gene of HCV in blood of hemophilia patients, intravenous drug users, and blood donors (five specimens from each study group, ca. 40 clones studied per specimen). Clones identified by DGGE as unique were sequenced. NS5b sequence entropy and mean genetic distance in hemophiliacs did not differ significantly from those in the other groups, pointing to a lack of correlation between HCV diversity and the multiplicity of past HCV exposures. DGGE was also applied to investigate variation in the HCV envelope 2/hypervariable region 1 (E2/HVR-1) in serum samples serially taken from two patients during the seroconversion phase of HCV infection. E2/HVR-1 sequence entropy changes were small and not correlated with rising anti-HCV antibody levels, reflecting mutational changes not mediated by antibody selection.

Base Sequence↗

Monitoring the emergence of hepatitis B virus polymerase gene variants during lamivudine therapy using the LightCycler.

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.

Antiviral Agents↗

Molecular epidemiology of a large outbreak of hepatitis B linked to autohaemotherapy.

BACKGROUND: Unregulated skin-piercing procedures potentially facilitate the transmission of bloodborne pathogens. In February, 1998, a patient who had recently received autohaemotherapy at an alternative medicine clinic in the UK was diagnosed with acute hepatitis B. The autohaemotherapy procedure involved the drawing of 1 mL of the patient's blood, mixing with saline, and reinjection of the autologous blood mixture. We investigated the extent of hepatitis B virus (HBV) infection in patients and staff of the clinic. METHODS: Patients who had attended the clinic between January, 1997, and February, 1998, were tested for serological markers of HBV, and for HBV DNA by PCR. HBV DNA was sequenced to assess the relatedness of the virus identified in the cases. We analysed the number and dates of visits with regard to HBV status. FINDINGS: Serum samples were received from 352 patients and four staff members. Serological evidence of exposure to HBV was found in 57 (16%). Of the 33 patients and staff who were positive for hepatitis B surface antigen, 30 (91%) showed complete nucleotide identity in the DNA segments derived from the surface and core genes. Five patients with linked infection had markers of chronic hepatitis B, and one of these was regarded as the likely source of the outbreak. The attack rate was associated with the number of visits (p<0.0001) and the week of visit (p=0.011). Contaminated saline in a repeatedly used bottle was the probable vehicle of transmission. INTERPRETATION: We have described a large community-based outbreak of hepatitis B due to transmission by a single HBV variant. Our findings emphasise the continuing risk of transmission of bloodborne viruses in all health-care settings where skin-piercing procedures are used.

Adult↗