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Biomedical subjects

J V Parry

Publications and source records attributed to J V Parry.

At least 37 records · Page 2Linked to original sources

Prevalence of antibodies to hepatitis B, hepatitis C, and HIV and risk factors in Irish prisoners: results of a national cross sectional survey.

OBJECTIVES: To determine the prevalence of antibodies to hepatitis B core antigen, hepatitis C virus, and HIV in the prison population of the Republic of Ireland and to examine risk factors for infection. DESIGN: Cross sectional, anonymous, unlinked survey, with self completed risk factor questionnaire and provision of oral fluid specimen for antibody testing. SETTING: Nine of the 15 prisons in the Republic of Ireland. PARTICIPANTS: 1366 prisoners, of whom 1205 (57 women) participated. In the smaller prisons all prisoners were surveyed, while in the three largest prisons one half of the population was randomly sampled. Three small prisons believed not to have a problem with injecting drug use were excluded. MAIN OUTCOME MEASURES: Prevalence of antibodies to hepatitis B core antigen, antibodies to hepatitis C virus, and antibodies to HIV. Self reported risk factor status. RESULTS: Prevalence of antibodies to hepatitis B core antigen was 104/1193 (8.7%; 95% confidence interval 7.2% to 10.5%), to hepatitis C virus, 442/1193 (37%; 34.3% to 39.9%), and to HIV, 24/1193 (2%; 1.3% to 3%). The most important predictor of being positive for hepatitis B and hepatitis C was a history of injecting drug use. Thirty four women (60%) and 474 men (42%) reported ever injecting drugs. A fifth (104) of 501 injecting drug users reported first injecting in prison, and 347 (71%) users reported sharing needles in prison. CONCLUSIONS: Infection with hepatitis C secondary to use of injected drugs is endemic in Irish prisons. Better access to harm reduction strategies is needed in this environment.

AIDS-Related Opportunistic Infections↗

Problems in the interpretation of HIV-1 viral load assays using commercial reagents.

During routine monitoring of human immunodeficiency virus (HIV) viral load, two problems arose. First, a number of patients, the majority being African, were found to have low viral loads by the Chiron branched-chain DNA assay in conjunction with low CD4(+) cell numbers. In order to determine whether this was due to failure of the branched-chain DNA assay to detect non-B subtypes of HIV, selected samples were subtyped and HIV RNA quantified by branched-chain DNA, NASBA, and the Roche Monitor RT-PCR assay. Twenty-eight (97%) of 29 Africans were infected with a non-B subtype of HIV and 15 (93.7%) of 16 non-Africans with subtype B. Twenty-three samples had a low viral load by branched-chain DNA, which was confirmed by the NASBA and RT-PCR assays. All three assays detected B and non-B subtypes with similar efficiency; NASBA failed to detect HIV RNA in a small number of non-B samples. Discrepancies between viral load and CD4(+) cell numbers did not appear therefore to be related to subtype. Second, while quantification of HIV RNA was being conducted using version 2 of the branched-chain DNA assay (lower detection limit 500 HIV RNA copies/ml) the manufacturers had developed a more sensitive assay and a comparative evaluation was therefore conducted. In approximately 30% of samples the viral load was up to 10 times higher with the more sensitive assay. These experiences emphasise the importance of close collaboration between the clinic and the laboratory.

CD4 Lymphocyte Count↗

Accuracy of plasma HIV RNA quantification: a multicentre study of variability.

Inaccurate quantification of plasma HIV RNA concentration may be detrimental to patient care, yet little is known about how reproducible results are within and between laboratories. Each week between January and April 1998 a different laboratory represented at the Public Health Laboratory Service HIV Diagnosis Forum sent aliquots of the same anti-HIV positive plasma specimen by First Class Mail to the other 12 laboratories and to itself. Aliquots were frozen on receipt and examined in the next assay run. At the end of the 13 week period each laboratory reported their findings and provided further information about the specimen that they had dispatched. The correlation of results between laboratories and between the four different assay kits used was generally satisfactory. HIV RNA concentrations determined by the Roche Monitor and AcuGen kits were higher, and by the Chiron Quantiplex v 2.0 kit lower, than average. The Chiron Quantiplex gave the most reproducible concentrations. Nine 'below detection limit' results occurred, associated with three specimens. One specimen gave a below detection limit result in every one of six laboratories using the Organon Teknika Nuclisens HIV-1 QT kit, and was found to contain viral RNA of HIV-1 clade G. Another below detection limit result was probably due to technical error, and the remaining two to assay insensitivity. The findings suggested that an unsustained change in HIV RNA of <log(10)1.00 may not be a reliable basis for modifying treatment. This study confirms the need for performance assessment and for conservative interpretation of isolated changes in the estimate of HIV RNA concentration. Parallel testing of consecutive specimens from individual patients, though expensive, probably offers the best indication of significant change in the HIV RNA concentration.

Genotype↗

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

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 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) 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.

Adolescent↗

Post-transfusion HIV infection despite donor screening: a report of three cases.

In August 1996, a blood donation was collected which subsequently infected three patients post-transfusion with HIV 1. The donation itself was originally screened as negative for anti-HIV 1/2 using a sensitive EIA method, but subsequently was shown to contain p24 Ag and HIV RNA by an amplification technique. The proposed introduction of nucleic acid testing of all blood donations in the UK for hepatitis C, hepatitis B and HIV may further reduce the remote risk of further episodes of post-transfusion infection. The infection in the index recipient was detected on routine pre-transplant virological screening but proved difficult to confirm, at a time when she had recently received myeloablative treatment for a haematological malignancy which impaired the immune response. There is a need for continued vigilance in such patients to exclude post-transfusion infection, at a time when natural immunological responses have been impaired by their disease or treatment.

Aged↗

Prevalence of HIV, hepatitis B, and hepatitis C antibodies in prisoners in England and Wales: a national survey.

Prisoners in eight of the 135 prisons in England and Wales were surveyed in 1997 and 1998 to study the prevalence of and risk factors for transmission of bloodborne viruses in prison. Subjects voluntarily completed a risk factor questionnaire and provided oral fluid specimens for unlinked anonymous testing for the presence of antibodies to HIV, hepatitis C virus (HCV), and the core antigen of hepatitis B virus (HBc). Almost 8% (4778) of the total of 60,561 prisoners were eligible and four fifths (3942) of those eligible took part. Among all those tested (3930) 0.4% (14) were positive for anti-HIV, 8% (308) for anti-HBc, and 7% (293) for anti-HCV (the anti-HBc and anti-HCV prevalences were not adjusted for assay sensitivities of 82% and 80%, respectively). Twenty-four per cent (777/3176) of adult prisoners reported ever having injected drugs, 30% of whom (224/747) reported having injected in prison. Three quarters of those who injected in prison (167/224) shared needles or syringes. Among adult injecting drug users, 0.5% (4/775) had anti-HIV, 31% (240/775) anti-HCV, and 20% (158/775) anti-HBc. The presence of anti-HCV and anti-HBc was associated with injecting inside prison and number of previous times in prison. The results suggest that hepatitis viruses are probably being transmitted in prisons through sharing non-sterile injecting equipment and that a risk of HIV transmission exists. Harm minimisation measures for the 6% of prisoners who continue to inject while in prison should be strengthened.

Adult↗

Comparison between self-reported hepatitis B, hepatitis C, and HIV antibody status and oral fluid assay results in Irish prisoners.

Self-reported hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV infection status was compared with the results of oral fluid assays of antibodies to these viruses in prisoners from nine of the 15 prisons in the Republic of Ireland. A total of 1205 out of 1366 prisoners completed a confidential questionnaire and 1193 provided analysable oral fluid specimens for testing for antibodies to HBV core antigen (anti-HBc), HCV (anti-HCV), and HIV (anti-HIV). The self-reported prevalence of hepatitis infection (hepatitis B: 5%; hepatitis C: 19%) was lower than that derived from oral fluid assays (anti-HBc: 9%; anti-HCV: 37%). The self-reported prevalence of HIV infection was similar to that found by oral fluid assay (2%). Many discrepancies were found between self-reported results and the results of oral fluid assays. Of those who reported being positive for HBV, HCV, or HIV, 48%, 5%, and 58%, respectively, tested negative on the oral fluid assay. Of those who reported a previous negative test result for HBV, HCV, or HIV, 10%, 37%, and 2%, respectively, had positive oral fluid assays. Self-reports of hepatitis and HIV infection status are unreliable and should not be used as a basis for planning preventive and treatment services for prisoners. All prisoners should have the opportunity to be tested for HBV, HCV, and HIV infection.

Antibodies, Viral↗

HIV prevalence and risk behaviour among female injecting drug users in London, 1990 to 1996.

OBJECTIVE: To describe trends in HIV prevalence among female injecting drug users (IDU) in London between 1990 and 1996. DESIGN: HIV prevalence and risk behaviour were measured yearly between 1990 and 1993, and in 1996, in point prevalence HIV surveys of IDU recruited from both drug-treatment and community-based settings within Greater London. Sample sizes were 173 in 1990, 111 in 1991, 128 in 1992, 146 in 1993 and 200 in 1996. METHODS: Each survey used structured questionnaires and common sampling and interview strategies. Oral fluid specimens were collected for testing for antibodies to HIV (anti-HIV). Multiple logistic regression was used to assess the trend in HIV prevalence. RESULTS: The percentage of female IDU testing positive for antibodies to HIV showed a marked decline over the study period, from 15.0% in 1990 to 1.0% in 1996 (P < 0.001). This trend was independent of all other variables examined. Each year, higher HIV prevalences were found among IDU recruited from community settings compared with treatment agencies. CONCLUSIONS: These results concur with those of IDU recruited from treatment sites, although the yearly estimates in this study are higher. London benefits from low prevalence of HIV infection among IDU, coupled with behaviour change facilitated by early intervention. Continued surveillance of injectors recruited from both community and treatment settings is necessary in order properly to assess HIV prevalence among IDU.

Data Collection↗

Discrimination of subtype B and non-subtype B strains of human immunodeficiency virus type 1 by serotyping: correlation with genotyping.

The ability of a peptide-based serotyping assay to differentiate human immunodeficiency virus (HIV) type 1 (HIV-1) subtype B infections from non-subtype B infections was investigated with 166 anti-HIV-1- and HIV RNA-positive (by PCR) serum or plasma specimens. The specimens were divided genetically into those infected with subtype B and non-subtype B by application of a screening heteroduplex mobility assay (HMA) that used plasmids for subtypes A and B alone. Specimens that were not clearly infected with HIV-1 subtype B by HMA or for which the two methods had discordant results in distinguishing those infected with subtype B from those infected with non-subtype B were then investigated with a full HMA plasmid panel and, for selected specimens, env sequencing. For the 141 genotyped and serotypically reactive specimens, the correlation between genotyping and serotyping (all subtypes) was 69%. Of the 67 specimens that reacted monotypically as serotype B, 64 were shown to be infected with genotype B (positive predictive value, 96%). Of the 82 specimens that contained genotype B nucleic acid, 64 reacted monotypically as serotype B (sensitivity, 78%), and 4 specimens reacted with a single non-subtype B peptide; the viruses in 14 specimens could not be assigned a serotype. Initial screening results had indicated that 12 samples had results discordant between restricted HMA and serotyping. The V3 loop amino acids of the infecting HIV strains from the seven specimens with discordant serology results were analyzed. For five specimens discordance occurred when the amino acid sequence of the infecting virus closely resembled those of more than one consensus peptide antigen or when the observed V3 crown motif of the strain was atypical for the genetic subtype present. For the other two specimens no explanation for the discordance was identified. Five specimens gave unclear or discordant results in the initial HMA screen, but the results were resolved when the full plasmid panel was used. Serotyping, although of limited sensitivity, distinguishes between subtype B and non-subtype B infections with a high degree of specificity. However, it poorly differentiates the major non-subtype B subtypes, particularly subtypes A and C. When HIV-1 subtype B predominates, serological typing and/or subtype-restricted HMA screening usefully distinguishes between subtype B and non-subtype B infections.

Amino Acid Sequence↗

Simple/rapid test devices for anti-HIV screening: do they come up to the mark?

Thirteen simple/rapid test devices (S/RTDs) for the detection of antibodies to HIV 1 and HIV 2 were assessed. Ninety-two specimens in four categories were used and results with the thirteen S/RTDs were compared with those obtained with six currently available commercial laboratory-based anti-HIV 1/2 EIAs. Seven of the 13 S/RTDs scored all 26 blood donors' specimens as unreactive, and 11 correctly identified all the 25 "straightforward" anti-HIV positive specimens. False negative results arose when testing by Uni-Gold HIV and SeroCard HIV, which gave 72 and 68 correct positive observations, respectively, out of 75. No S/RTD detected seroconversion earlier than the most sensitive EIAs, but four S/RTDs performed similarly to most of the EIAs. On the low-titre panel specimens, six S/RTDs were less sensitive than the least sensitive EIA and, in contrast to four of the six EIAs, only one S/RTD was able correctly to identify all the positive specimens. A manufacturing problem was identified that allowed the HIV antigen-sensitised area on the membrane of two SeroCard HIV devices to be misaligned with the device's reading window so that the reaction was almost entirely obscured. As long as small numbers of specimens were involved, most S/RTDs required considerably less time and less equipment than EIAs, but overall they were slightly less sensitive. Their use in various health settings and for confirmatory procedures is discussed.

Developing Countries↗

Poor hepatitis B vaccine coverage in injecting drug users: England, 1995 and 1996.

Self-reported data on vaccination status collected in 1995 and 1996 from seven of the 39 drug agencies in England that took part in the unlinked anonymous HIV prevalence monitoring programme of injecting drug users were analysed to estimate hepatitis B vaccine coverage in this population. Twenty-seven per cent (374/1366) of injecting drug users (IDUs) reported vaccination against hepatitis B and 13% (172) reported having received three doses of vaccine. Eighteen per cent of the IDUs who reported vaccination (66/374) were found to have a marker in their saliva of past/current hepatitis B infection (antibody to hepatitis B core (anti-HBc)) compared with 23% (232/992) of those unvaccinated. Over half (760/1366) of all IDUs tested reported not having been vaccinated against hepatitis B were negative for anti-HBc, and therefore remained susceptible to infection. Targeted vaccination for IDUs against hepatitis B in England has had little success so far, suggesting that enhanced or alternative strategies need to be adopted.

Adolescent↗

The risk of infection with HIV and hepatitis B in individuals who inject steroids in England and Wales.

Data on injecting anabolic steroid users, within the national Unlinked Anonymous HIV Prevalence Monitoring Survey of injecting drug users (IDUs) were analysed to determine their risk of acquiring blood borne viruses. One hundred and forty-nine participants who had injected anabolic steroids in the previous month were identified from 1991-6, contributing 1.4% of all participation episodes in the survey. Rates of needle and syringe sharing by steroid users were low. Three of the 149 (2.0%) had anti-HBc and none had anti-HIV in their salivary specimens. The prevalence of anti-HBc in steroid injectors was significantly lower than in heroin injectors, 275/1509 (18%) (P < 0.001), or in amphetamine injectors, 28/239 (12%) (P < 0.001). The risk of blood borne virus transmission amongst these steroid injectors is low, probably due to hygienic use of injecting equipment and low levels of sharing. It is important to distinguish steroid injectors from other IDUs because they are a distinct group in terms of lifestyle and injecting practice.

Adolescent↗

False negativity by an anti-HIV assay kit (IMx 8B32) and evaluation of its replacement (IMx 8C98).

False negativity in a commercial anti-HIV kit (IMx HIV-1/HIV-2 3rd Generation Plus (code 8B32) was investigated, and the kit that superseded it (IMx HIV-1/HIV-2 III Plus, code 8C98) was evaluated. In a comparison on 574 freshly collected anti-HIV-1-positive specimens, 97.2% were more reactive in 8C98 than in 8B32; 35.5% were more than twice as reactive and 8.5% were more than four times as reactive. In 8B32, the signal from 55 specimens selected because of weak reactivity was enhanced 1.5 to 8.8 times by preliminary heating at 56 degrees C for 30 min. The reactivity of the 55 heated sera was then similar to that of the same specimens tested without heat treatment in the 8C98 assay. Reactivity in 8B32 was also increased in 66 of 76 (at least twofold in 20) randomly chosen anti-HIV-positive serum specimens by the addition of EDTA (10 mM final concentration). One of these specimens was false negative (signal:cutoff (S:CO) ratio 0.76) in 8B32, though its reactivity was restored by addition of EDTA (S:CO ratio 9.54). These findings indicate that the inhibitory effect that originally led to false negative findings in 8B32 was probably due to complement activity, and that the same activity was present in the freshly collected specimens used here to evaluate the replacement IMx anti-HIV assay (8C98). The specimen panel employed to evaluate 8C98 included 1,892 anti-HIV-positive and 779 anti-HIV-negative specimens. There were no false negative reactions. The lowest S:CO ratio observed was 6.2 and only 17 (0.2%) anti-HIV-positive specimens gave ratios less than 10. Nine unreproducible false positive reactions arose, all possibly attributable to specimen carryover by the IMx instrument. The performance of 8C98 was also compared with that of 10 other current anti-HIV kits using 21 sets of seroconversion specimens (127 specimens in total), and five performance assessment panels (92 specimens in total) comprised mostly of single bleeds from recent seroconverters. IMx 8C98 was the second most sensitive assay. We found no evidence that the 8C98 kit was prone to the effect that had given rise to false negative results in its predecessor (8B32).

AIDS Serodiagnosis↗

HIV antibody assay that gave false negative results: multicentre collaborative study.

OBJECTIVE: To identify false negative results arising from the use of a commercial kit to detect antibody to HIV-1 and HIV-2 between July 1995 and March 1996. DESIGN: The 56 laboratories in the United Kingdom that were using the assay were asked to retrieve and retest specimens with an alternative assay for HIV-1 and HIV-2. Details of false negative results were obtained and these serum samples further investigated. SUBJECTS: 24,181 patients tested with the assay who were reported as being negative for HIV antibody. An additional 497 patients were confirmed as HIV positive with the assay. RESULTS: Serum samples of 20,973 of the patients were retested, and four patients were found to have had false negative results with the kit; three further patients were found to have had false negative results in the course of other laboratory testing. The seven patients with false negative results with the kit were of diverse risk group and HIV-1 subtype. Four had evidence of recent HIV infection. CONCLUSION: The commercial kit had a sensitivity of 99.2% (497/501), or less if the additional three patients with false negative results were taken into account.

False Negative Reactions↗

Faulty washers and soiled micropipettors may generate false positive serological results.

BACKGROUND: Serological markers such as HBsAg and anti-HIV may be present in serum at very high concentrations and this may give rise to erroneous diagnoses due to cross-contamination. OBJECTIVES: To investigate poor equipment maintenance and use, including contamination with human serum, as a potential source of erroneous assay results. STUDY DESIGN: The potential of microtitre plate washers and micropipettors to transfer material between microplate wells and between specimens was examined. For the study of micropipettors we recruited 19 UK diagnostic laboratories. RESULTS: Four out of seven plate washers in use, until adjusted, had the potential to cause false positive HBsAg reactions. The centering of the probes that delivered the wash fluid, delivery pressure, wash volume and the use of a pre-programmed card to direct the washing procedure were important variables. We investigated soiling of tip cones of micropipettors. In every laboratory human IgG could be detected in at least a third of eluates from micropipettor tip cones; only 31 (14%) of 222 showed no evidence of contamination with human serum. Only one laboratory submitted eluates devoid of specific antibodies. Anti-HAV was the marker most commonly found (n = 68), followed by HBsAg (n = 27) and anti-HIV (n = 20). Seven micropipettor eluates from two laboratories were radioactively contaminated. CONCLUSIONS: Recommended precautions are regular checking, cleaning and servicing of equipment, care in interpreting weak reactions, reference back to serum left on the clot of the original specimen and testing of a follow up specimen. Poorly maintained immunoassay equipment can readily generate false positive results due to low-level cross-contamination, particularly with the current highly sensitive HBsAg and anti-HIV assays.

Equipment Contamination↗