RESUMEN
Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.
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Anticuerpos Antivirales/análisis , COVID-19/diagnóstico , Líquido del Surco Gingival/inmunología , Inmunoglobulina G/análisis , SARS-CoV-2/inmunología , Adolescente , Niño , Preescolar , Humanos , Técnicas para Inmunoenzimas , Lactante , Sensibilidad y Especificidad , Estudios SeroepidemiológicosRESUMEN
BackgroundMonitoring hepatitis C virus (HCV) incidence is important for assessing intervention impact. Longitudinal studies of people who inject drugs (PWID), using repeated biological tests, are costly; alternatively, incidence can be estimated using biological markers of recent infection in cross-sectional studies.AimWe aimed to compare incidence estimates obtained from two different biological markers of recent infection in a cross-sectional study to inform monitoring approaches for HCV elimination strategies.MethodSamples from an unlinked anonymous bio-behavioural survey of PWID were tested for two recent infection markers: HCV RNA with anti-HCV negative ('RNA') and low-avidity anti-HCV with HCV RNA present ('avidity'). These two markers were used separately and in combination to estimate HCV incidence.ResultsBetween 2011 and 2013, 2,816 anti-HIV-negative PWID (25% female) who had injected during the preceding year were either HCV-negative or had one of the two markers of recent infection: 57 (2.0%) had the RNA marker and 90 (3.2%) the avidity marker. The two markers had similar distributions of risk and demographic factors. Pooled estimated incidence was 12.3 per 100 person-years (pyrs) (95% credible interval: 8.8-17.0) and not significantly different to avidity-only (p = 0.865) and RNA-only (p = 0.691) estimates. However, the RNA marker is limited by its short duration before anti-HCV seroconversion and the avidity marker by uncertainty around its duration.ConclusionBoth markers have utility in monitoring HCV incidence among PWID. When HCV transmission is high, one marker may provide an accurate estimate of incidence; when it is low or decreasing, a combination may be required.
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Biomarcadores/sangre , Hepacivirus/inmunología , Hepatitis C/prevención & control , ARN Viral/sangre , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/virología , Adulto , Estudios Transversales , Inglaterra/epidemiología , Femenino , Hepatitis C/sangre , Hepatitis C/epidemiología , Hepatitis C/transmisión , Anticuerpos contra la Hepatitis C/sangre , Anticuerpos contra la Hepatitis C/inmunología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Irlanda del Norte/epidemiología , Prevalencia , Abuso de Sustancias por Vía Intravenosa/epidemiología , Gales/epidemiologíaRESUMEN
BACKGROUND: Initial serological testing for chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is conducted using either rapid diagnostic tests (RDT) or laboratory-based enzyme immunoassays (EIA)s for detection of hepatitis B surface antigen (HBsAg) or antibodies to HCV (anti-HCV), typically on serum or plasma specimens and, for certain RDTs, capillary whole blood. WHO recommends the use of standardized testing strategies - defined as a sequence of one or more assays to maximize testing accuracy while simplifying the testing process and ideally minimizing cost. Our objective was to examine the diagnostic outcomes of a one- versus two-assay serological testing strategy. These data were used to inform recommendations in the 2017 WHO Guidelines on hepatitis B and C testing. METHODS: Few published studies have compared diagnostic outcomes for one-assay versus two-assay serological testing strategies for HBsAg and anti-HCV. Therefore, the principles of Bayesian statistics were used to conduct a modelling exercise to examine the outcomes of a one-assay versus two-assay testing strategy when applied to a hypothetical population of 10,000 individuals. The resulting model examined the diagnostic outcomes (true and false positive diagnoses; true and false negative diagnoses; positive and negative predictive values as a function of prevalence; and total tests required) for both one-assay and two-assay testing strategies. The performance characteristics assumed for assays used within the testing strategies were informed by WHO prequalification assessment findings and systematic reviews for diagnostic accuracy studies. Each of the presumptive testing strategies (one-assay or two-assay) was modelled at varying prevalences of HBsAg (10%, 2% and 0.4%) and of anti-HCV (40%, 10%, 2% and 0.4%), aimed at representing the range of testing populations typically encountered in WHO Member States. When the two-assay testing strategy was considered, the model assumed the independence of the two assays. RESULTS: Modeling demonstrated that applying a single assay (HBsAg or anti-HCV), even with high specificity (99%), may result in considerable numbers of false positive diagnoses and low positive predictive values (PPV), particularly in lower prevalence settings. Even at very low prevalences shifting to a two-assay testing strategy would result in a PPV approaching 1.0. When test sensitivity is high (>99%) false negative reactions are rare at all but the highest prevalences; but a two-test strategy might yield more false negative diagnoses. The order in which the tests are used has no impact on the overall accuracy of a two-assay strategy though it may impact the total number of tests needed to complete the diagnostic strategy, incurring added cost and complexity. HBsAg assays may have a low sensitivity (<90%), and result in large numbers of false negative diagnoses, particularly in high prevalence settings, which would be exacerbated in the two-assay testing strategy. In contrast, most anti-HCV assays have high sensitivity and lead to fewer false negative results, both in the one-assay and two-assay testing strategies. At prevalences ≤2% the number of tests needed using a second assay was nearly always small, at <300 per 10,000 individuals tested, making sustainability of a second assay uncertain in such a setting. CONCLUSIONS: A key public health objective of an effective testing strategy is to identify all individuals who would benefit from treatment. Therefore, a strategy that prioritizes a high NPV (minimal false negatives) may be acceptable even if the PPV is suboptimal (some false positives) as the implementation of such a public health programme must also take account of other factors such as costs, feasibility, impact on testing uptake and linkage to care, and consequences of a false-positive test. This rationale informed the development of the WHO Viral Hepatitis Testing Guidelines, with a conditional recommendation for a one-assay serological testing strategy in most testing settings and populations (≥0.4% prevalence in population tested). A one-test strategy results in few failures to diagnose infection and, although it is associated under most assumptions with a sub-optimal PPV, benefits include greater simplicity, easier implementation, lower costs and better feasibility, uptake and linkage to care. Furthermore, prior to antiviral therapy all those diagnosed either HBsAg or anti-HCV positive will require confirmation of viræmia, preventing unnecessary treatment of those who may be false positive on serology. For HBsAg, in low-prevalence settings (≤0.4%), a second recommendation was made to consider a two-assay testing strategy, using a confirmatory neutralization step or a second different HBsAg assay.
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Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Pruebas Serológicas/métodos , Teorema de Bayes , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Humanos , Técnicas para Inmunoenzimas , Modelos Teóricos , Juego de Reactivos para Diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: While people who inject drugs (PWID) typically use peripheral veins, some inject into their central veins, including the femoral and jugular veins. Injection into the jugular vein can have serious adverse health consequences, including jugular vein thrombosis, deep neck infections, pneumothorax, endocarditis and sepsis. This study examined the prevalence of, and factors associated with, jugular vein injection among a large sample of PWID in the United Kingdom. METHOD: Unlinked anonymous surveys (2011-14) recruited PWID from agencies providing services to this population. Self-reported demographic and injection-related data were collected from consenting respondents using a brief questionnaire and dried blood spot samples were tested for exposure to HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). Univariate and multivariable logistic regression were used to examine factors associated with jugular vein injection. RESULTS: Among 5261 PWID, one third had injected into a central vein in the previous 28 days, including 6% (n=339) who had injected into their jugular vein and 1% (n=52) who had used this site exclusively for recent injections. Factors independently associated with recent jugular vein injection in multivariable analysis included female gender, a lifetime history of imprisonment, sharing needles and syringes, poly-drug injection and injection into multiple body sites. Jugular vein injection was also associated with experiencing injection-related injuries, although no associations were identified with respect to exposure to blood borne viral infections. CONCLUSION: A significant minority of PWID inject into the jugular vein in the United Kingdom. Public health responses should investigate ways to support and promote good injection site management in order to minimise vascular damage and reduce problems with peripheral venous access. Women who inject drugs, PWID with a history of imprisonment and those people who are experiencing early signs of injection-related skin and soft tissue injuries are priority sub-populations for interventions.
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Venas Yugulares , Compartición de Agujas/estadística & datos numéricos , Traumatismos de los Tejidos Blandos/etiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Prisioneros/estadística & datos numéricos , Factores de Riesgo , Factores Sexuales , Abuso de Sustancias por Vía Intravenosa/complicaciones , Encuestas y Cuestionarios , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Infection risks among people who inject drugs (PWID) are widely recognized, but few studies have focused on image and performance enhancing drugs (IPEDs). Globally, concern about IPED injection has increased and, in the United Kingdom, IPED injectors have become the largest group using Needle and Syringe Programmes. Blood-borne virus prevalence trends among IPED injectors are explored. METHOD: Data from 2 surveys of IPED injectors (2010-2011; 2012-2013) and the national bio-behavioral surveillance system for PWID (1992-1997; 1998-2003; 2004-2009) were merged. Psychoactive drug injectors and women were excluded. Logistic regression analyses explored temporal changes. RESULTS: Between 1992 and 2009, median age increased from 25 to 29 years (N = 1296), years injecting from 2 to 4. There were 53 men who had sex with men (MSM). Overall, 0.93% had HIV, 4.4% ever had hepatitis B (HBV), and 3.9% hepatitis C (HCV, from 1998, N = 1083). In multivariable analyses, HIV increased in 2004-2009 [adjusted odds ratio (AOR) = 10 (95% confidence interval (CI): 0.94 to 106) vs. 1992-2003], and remained elevated (AOR = 4.12, 95% CI: 0.31 to 54, 2012-2013); HBV also increased in 2004-2009 (AOR = 3.98, 95% CI: 1.59 to 9.97). HCV prevalence increase was only borderline significant (AOR = 2.47, 95% CI: 0.90 to 6.77, 2010-2011). HIV and HBV were associated with MSM and HCV with sharing needles/syringes. Uptake of diagnostic testing for HIV and HCV, and HBV vaccination increased (to 43%, 32% and 44% respectively). Condom use was consistently poor; needle/syringe sharing occurred. CONCLUSION: Blood-borne virus prevalences among IPED injectors have increased and for HIV, is now similar to that among psychoactive drug injectors. Targeted interventions to reduce risks are indicated.
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Infecciones por VIH/complicaciones , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Sustancias para Mejorar el Rendimiento/administración & dosificación , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Estudios Transversales , Recolección de Datos , Inglaterra/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/etiología , Hepatitis B/epidemiología , Hepatitis B/etiología , Hepatitis C/epidemiología , Hepatitis C/etiología , Homosexualidad Masculina , Humanos , Modelos Logísticos , Masculino , Prevalencia , Factores de Riesgo , Abuso de Sustancias por Vía Intravenosa/epidemiología , Encuestas y Cuestionarios , Factores de Tiempo , Gales/epidemiología , Adulto JovenRESUMEN
To determine uptake of home sampling kit (HSK) for STI/HIV compared to clinic-based testing, whether the availability of HSK would increase STI testing rates amongst HIV infected MSM, and those attending a community-based HIV testing clinic compared to historical control. Prospective observational study in three facilities providing STI/HIV testing services in Brighton, UK was conducted. Adult MSM attending/contacting a GUM clinic requesting an STI screen (group 1), HIV infected MSM attending routine outpatient clinic (group 2), and MSM attending a community-based rapid HIV testing service (group 3) were eligible. Participants were required to have no symptomatology consistent with STI and known to be immune to hepatitis A and B (group 1). Eligible men were offered a HSK to obtain self-collected specimens as an alternative to routine testing. HSK uptake compared to conventional clinic-based STI/HIV testing in group 1, increase in STI testing rates due to availability of HSK compared to historical controls in group 2 and 3, and HSK return rates in all settings were calculated. Among the 128 eligible men in group 1, HSK acceptance was higher (62.5% (95% CI: 53.5-70.9)) compared to GUM clinic-based testing (37.5% (95% CI: 29.1-46.5)), (p = 0.0004). Two thirds of eligible MSM offered an HSK in all three groups accepted it, but HSK return rates varied (highest in group 1, 77.5%, lowest in group 3, 16%). HSK for HIV testing was acceptable to 81% of men in group 1. Compared to historical controls, availability of HSK increased the proportion of MSM testing for STIs in group 2 but not in group 3. HSK for STI/HIV offers an alternative to conventional clinic-based testing for MSM seeking STI screening. It significantly increases STI testing uptake in HIV infected MSM. HSK could be considered as an adjunct to clinic-based services to further improve STI/HIV testing in MSM.
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Atención a la Salud/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Homosexualidad Masculina/psicología , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/prevención & control , Manejo de Especímenes/métodos , Adolescente , Adulto , Instituciones de Atención Ambulatoria , Autoevaluación Diagnóstica , Infecciones por VIH/psicología , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades de Transmisión Sexual/psicología , Adulto JovenAsunto(s)
Consumidores de Drogas/estadística & datos numéricos , Trabajo Sexual/estadística & datos numéricos , Trabajadores Sexuales/estadística & datos numéricos , Abuso de Sustancias por Vía Intravenosa/epidemiología , Sexo Inseguro/estadística & datos numéricos , Adulto , Consumidores de Drogas/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Prevalencia , Medición de Riesgo , Factores de Riesgo , Trabajo Sexual/psicología , Trabajadores Sexuales/psicología , Enfermedades de Transmisión Sexual/epidemiología , Abuso de Sustancias por Vía Intravenosa/diagnóstico , Abuso de Sustancias por Vía Intravenosa/fisiopatología , Encuestas y Cuestionarios , Reino Unido/epidemiología , Sexo Inseguro/psicologíaRESUMEN
BACKGROUND: Persistent infection with oncogenic Human Papillomavirus (HPV) is associated with the development of cervical cancer with each genotype differing in their relative contribution to the prevalence of cervical disease. HPV DNA testing offers improved sensitivity over cytology testing alone but is accompanied by a generally low specificity. Potential molecular markers of cervical disease include type-specific viral load (VL), integration of HPV DNA into the host genome and methylation of the HPV genome. The aim of this study was to evaluate the relationship between HPV type-specific viral load, integration and methylation status and cervical disease stage in samples harboring HPV16, HPV18, HPV31 or HPV45. METHODS: Samples singly infected with HPV16 (n=226), HPV18 (n=32), HPV31 (n=75) or HPV45 (n=29) were selected from a cohort of 4,719 women attending cervical screening in England. Viral load and integration status were determined by real-time PCR while 3'L1-URR methylation status was determined by pyrosequencing or sequencing of multiple clones derived from each sample. RESULTS: Viral load could differentiate between normal and abnormal cytology with a sensitivity of 75% and a specificity of 80% (odds ratio [OR] 12.4, 95% CI 6.2-26.1; p<0.001) with some variation between genotypes. Viral integration was poorly associated with cervical disease. Few samples had fully integrated genomes and these could be found throughout the course of disease. Overall, integration status could distinguish between normal and abnormal cytology with a sensitivity of 72% and a specificity of 50% (OR 2.6, 95% CI 1.0-6.8; p=0.054). Methylation levels were able to differentiate normal and low grade cytology from high grade cytology with a sensitivity of 64% and a specificity of 82% (OR 8.2, 95% CI 3.8-18.0; p<0.001). However, methylation varied widely between genotypes with HPV18 and HPV45 exhibiting a broader degree and higher magnitude of methylated CpG sites than HPV16 and HPV31. CONCLUSIONS: This study lends support for HPV viral load and CpG methylation status, but not integration status, to be considered as potential biomarkers of cervical disease.
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Metilación de ADN/genética , Neoplasias del Cuello Uterino/genética , Carga Viral/genética , Integración Viral/genética , Adulto , Islas de CpG/genética , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/patogenicidad , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virologíaRESUMEN
OBJECTIVE: Certain intra-type variants of HPV16 have been shown to be associated with an increased risk of developing high grade cervical disease, but their potential association is confounded by apparent geographic and phylogenetic lineage dependency. The objective of this study was to evaluate the relationship between HPV16 sequence variants and cervical disease stage in monospecific infection samples from a single lineage (European, EUR) in England. METHODS: One hundred and twelve women singly infected with HPV16 and displaying normal and abnormal cytology grades were selected. An 1187 bp fragment encompassing the entire LCR and a portion of the E6 open reading frame was sequenced to identify intra-type variants. Intra-type diversity was estimated using Shannon entropy. RESULTS: Almost all samples (110/112; 98%) were assigned to the EUR lineage, one sample was classified as European-Asian (EAS) and another African (Afr1a). The mean pairwise distance of the EUR sequences in this study was low (0.29%; 95%CI 0.13-0.45%) but there were nevertheless several sites in the LCR (n=5) and E6 (n=2) that exhibited a high degree of entropy. None of these sites, however, including the T350G non-synonymous (L83V) substitution in E6, alone or in combination, were found to be associated with cervical disease stage. CONCLUSIONS: Despite using single infection samples and samples from a single variant lineage, intra-type variants of HPV16 were not differentially associated with cervical disease. Monitoring intra-lineage, site-specific variants, such as T350G, is unlikely to be of diagnostic value.
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Variación Genética , Papillomavirus Humano 16/genética , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Proteínas Represoras/genética , Secuencias Repetidas Terminales , Enfermedades del Cuello del Útero/etiología , Enfermedades del Cuello del Útero/patología , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Genotipo , Papillomavirus Humano 16/clasificación , Humanos , Oportunidad Relativa , Filogenia , Análisis de Secuencia de ADNRESUMEN
OBJECTIVE: To describe drug use, sexual risks and the prevalence of blood-borne viral infections among men who inject image and performance enhancing drugs (IPEDs). DESIGN: A voluntary unlinked-anonymous cross-sectional biobehavioural survey. SETTING: 19 needle and syringe programmes across England and Wales. PARTICIPANTS: 395 men who had injected IPEDs. RESULTS: Of the participants (median age 28 years), 36% had used IPEDs for <5 years. Anabolic steroids (86%), growth hormone (32%) and human chorionic gonadotropin (16%) were most frequently injected, with 88% injecting intramuscularly and 39% subcutaneously. Two-thirds also used IPEDs orally. Recent psychoactive drug use was common (46% cocaine, 12% amphetamine), 5% had ever injected a psychoactive drug and 9% had shared injecting equipment. 'Viagra/Cialis' was used by 7%, with 89% reporting anal/vaginal sex in the preceding year (20% had 5+ female-partners, 3% male-partners) and 13% always using condoms. Overall, 1.5% had HIV, 9% had antibodies to the hepatitis B core antigen (anti-HBc) and 5% to hepatitis C (anti-HCV). In multivariate analysis, having HIV was associated with: seeking advice from a sexual health clinic; having had an injection site abscess/wound; and having male partners. After excluding those reporting male partners or injecting psychoactive drugs, 0.8% had HIV, 8% anti-HBc and 5% anti-HCV. Only 23% reported uptake of the hepatitis B vaccine, and diagnostic testing uptake was poor (31% for HIV, 22% for hepatitis C). CONCLUSIONS: Previous prevalence studies had not found HIV among IPED injectors. HIV prevalence in this, the largest study of blood-borne viruses among IPED injectors, was similar to that among injectors of psychoactive drugs. Findings indicate a need for targeted interventions.
RESUMEN
OBJECTIVES: In the UK, although transmission of HIV among injecting drug user (IDUs) has been limited since the 1980s, IDUs and men who have sex with men (MSM) have higher HIV and hepatitis C virus (HCV) prevalences than the general population. MSM who are also IDUs (MSM-IDUs) may therefore have a higher risk of infection than male IDUs who only have sex with women. METHODS: Analysis of data from a national survey of IDUs attending services (England, Wales and Northern Ireland) between 1998 and 2007, which collected demographic and behavioural data and oral fluid samples for HIV and HCV antibody testing. RESULTS: Of the 8671 men who reported injecting drugs and having sex during the preceding year, 96% (8354) were men who only had sex with women (MSW). MSM-IDUs and MSW-IDUs had similar age and number of years of injecting. MSM-IDUs had a higher prevalence of HIV (adjusted OR=4.08, 95% CI 1.9 to 8.5) and of HCV (adjusted OR =1.34, 95% CI 1.1 to 1.8) and were about four times (adjusted OR =3.78, 95% CI 2.9 to 4.9) more likely to have unprotected sex with multiple partners. Among those who injected in the 4 weeks prior to participation, the MSM-IDUs had a higher level of needle/syringe sharing (adjusted OR =1.72, 95% CI 1.3 to 2.2). DISCUSSION: MSM-IDUs have a fourfold higher risk of HIV; HCV prevalence in MSM-IDUs is a third higher than among MSW-IDUs, suggesting elevated risk from injecting and possibly sexual transmission. These findings emphasise the need for public health interventions specifically targeted at MSM-IDUs.
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Patógenos Transmitidos por la Sangre/aislamiento & purificación , Infecciones por VIH/epidemiología , Hepatitis C/epidemiología , Heterosexualidad , Homosexualidad Masculina , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adolescente , Adulto , Inglaterra/epidemiología , Femenino , Infecciones por VIH/diagnóstico , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Irlanda del Norte/epidemiología , Prevalencia , Medición de Riesgo , Gales/epidemiología , Adulto JovenRESUMEN
OBJECTIVE(S): To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays. METHODS: Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4 °C, 25 °C and 37 °C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay). RESULTS: Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4 °C or 25 °C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37 °C prior to testing. CONCLUSIONS: Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4 °C or 25 °C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays.
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Errores Diagnósticos/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Manejo de Especímenes/normas , Sesgo , Conservación de la Sangre/métodos , Conservación de la Sangre/normas , Estudios Transversales , Criopreservación/métodos , Criopreservación/normas , Infecciones por VIH/epidemiología , Humanos , Incidencia , Manejo de Especímenes/métodos , Temperatura , Factores de TiempoRESUMEN
The ability to detect type-specific high risk HPV (HR-HPV) infections in samples from females and males is important for monitoring the epidemiology of HPV and the impact of vaccination. Type-specific detection concordance between paired urine and genital samples from females (n = 264) undergoing routine colposcopy and males (n = 88) attending a genito-urinary medicine clinic was evaluated using an in-house genotyping assay. The overall inter-rater agreement (κ) was 0.781 for female pairs and 0.346 for male pairs. Female urine had sensitivity for detection of HPV16/18 and HR-HPV of 75% and 84%, respectively, while male urine had sensitivities of 13% and 28%, respectively. Genital samples had a higher HPV DNA copy number than urine although a small proportion (10%) of urine samples had a higher copy number than the corresponding genital sample. The proportion of females with normal cytology positive for HPV16/18 was 19%, increasing to 57% in moderate or severely dyskaryotic samples. The same trend was seen in the corresponding urine (19-43%) compounded by the reduced sensitivity of this sample type. The HPV16 viral load in female genital samples, but not in urine, was weakly associated with cervical disease stage. Despite reduced sensitivity, urine appears to be an appropriate surrogate sample for type-specific HPV detection in females for epidemiological objectives. The lower sensitivity and lack of association between viral load and disease stage in urine suggest that urine may not be useful for clinical management of HPV infection. The utility of urine for type-specific detection in males is less certain.
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Alphapapillomavirus/clasificación , Alphapapillomavirus/genética , Genitales Femeninos/virología , Genitales Masculinos/virología , Infecciones por Papillomavirus/diagnóstico , Orina/virología , ADN Viral/orina , Femenino , Genotipo , Humanos , Masculino , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Enfermedades del Cuello del Útero/diagnóstico , Enfermedades del Cuello del Útero/virología , Frotis Vaginal , Carga ViralRESUMEN
OBJECTIVES: To identify biological factors associated with HIV transmission in men who have sex with men (MSM). DESIGN: A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data. METHODS: Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling. RESULTS: Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54-0.86], P=0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15-2.25), P=0.005], recent infection [rate ratio 3.88 (95% CI 1.76-8.55), P=0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51-11.29), P=0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07-0.27, P=0.0001). CONCLUSION: Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission.
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Infecciones por VIH/transmisión , VIH-1/genética , Homosexualidad Masculina , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Inglaterra/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Filogenia , Enfermedades de Transmisión Sexual/epidemiología , Carga ViralRESUMEN
Changes in hepatitis C virus (HCV) prevalence from 1992 to 2006 were examined by using 24,311 records from unlinked anonymous surveillance of injecting drug users in England and Wales. Bayesian logistic regression was used to estimate annual prevalence, accounting for changing recruitment patterns (age, gender, injecting duration, geographic region, interactions) and the sensitivity and specificity of different oral fluid testing devices. After controlling for these differences, the authors found that the adjusted HCV prevalence decreased from 70% (95% credible interval: 62, 78) in 1992 to 47% (95% credible interval: 43, 51) in 1998 before rising again to 53% (95% credible interval: 48, 58) in 2006. Women injecting drug users had a higher HCV risk than did men (odds ratio = 1.50, 95% credible interval: 1.31, 1.73). Two regions (London and North West) had a markedly higher HCV prevalence than did the rest of England and Wales. Among individuals who had injected for less than 1 year, the adjusted HCV prevalence in 2006 was higher than that in 1992 (28% vs. 19%, respectively). HCV infection can be prevented. The public health challenge in England and Wales is to increase action in order to regain a downward trend in HCV risk and the benefit that has been lost since 1998.
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Consumidores de Drogas/estadística & datos numéricos , Hepacivirus , Hepatitis C/epidemiología , Hepatitis C/etiología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adolescente , Adulto , Teorema de Bayes , Inglaterra/epidemiología , Femenino , Encuestas Epidemiológicas , Hepacivirus/aislamiento & purificación , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Gales/epidemiologíaRESUMEN
BACKGROUND: Little is known about the prevalence of HIV or HCV in injecting drug users (IDUs) in Serbia and Montenegro. We measured prevalence of antibodies to HIV (anti-HIV) and hepatitis C virus (anti-HCV), and risk factors for anti-HCV, in community-recruited IDUs in Belgrade and Podgorica, and determined the performance of a parallel rapid HIV testing algorithm. METHODS: Respondent driven sampling and audio-computer assisted survey interviewing (ACASI) methods were employed. Dried blood spots were collected for unlinked anonymous antibody testing. Belgrade IDUs were offered voluntary confidential rapid HIV testing using a parallel testing algorithm, the performance of which was compared with standard laboratory tests. Predictors of anti-HCV positivity and the diagnostic accuracy of the rapid HIV test algorithm were calculated. RESULTS: Overall population prevalence of anti-HIV and anti-HCV in IDUs were 3% and 63% respectively in Belgrade (n = 433) and 0% and 22% in Podgorica (n = 328). Around a quarter of IDUs in each city had injected with used needles and syringes in the last four weeks. In both cities anti-HCV positivity was associated with increasing number of years injecting (eg Belgrade adjusted odds ratio (AOR) 5.6 (95% CI 3.2-9.7) and Podgorica AOR 2.5 (1.3-5.1) for >or= 10 years v 0-4 years), daily injecting (Belgrade AOR 1.6 (1.0-2.7), Podgorica AOR 2.1 (1.3-5.1)), and having ever shared used needles/syringes (Belgrade AOR 2.3 (1.0-5.4), Podgorica AOR 1.9 (1.4-2.6)). Half (47%) of Belgrade participants accepted rapid HIV testing, and there was complete concordance between rapid test results and subsequent confirmatory laboratory tests (sensitivity 100% (95%CI 59%-100%), specificity 100% (95%CI 98%-100%)). CONCLUSION: The combination of community recruitment, ACASI, rapid testing and a linked diagnostic accuracy study provide enhanced methods for conducting blood borne virus sero-prevalence studies in IDUs. The relatively high uptake of rapid testing suggests that introducing this method in community settings could increase the number of people tested in high risk populations. The high prevalence of HCV and relatively high prevalence of injecting risk behaviour indicate that further HIV transmission is likely in IDUs in both cities. Urgent scale up of HIV prevention interventions is needed.
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Consumidores de Drogas , Seroprevalencia de VIH , Encuestas Epidemiológicas , Abuso de Sustancias por Vía Intravenosa/epidemiología , Serodiagnóstico del SIDA , Adulto , Pruebas Anónimas , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Montenegro/epidemiología , Prevalencia , Factores de Riesgo , Serbia/epidemiologíaRESUMEN
OBJECTIVES: To investigate whether combining clinical data with the serological testing algorithm for recent HIV seroconversion (STARHS) reliably identifies otherwise unrecognized recent infections and observe their trends. DESIGN: Incorporation of STARHS into routine HIV diagnosis. METHODS: STARHS was applied to serum collected between 1996 and 2005 at HIV diagnosis and routine clinical/laboratory markers of recent infections were determined. The recent infections were identified by conventional means, by STARHS, and by both combined. RESULTS: Of 1526 infections diagnosed, 812 were new. Of these, 604 were in men who have sex with men (MSM); 208 in heterosexuals; 88% had serum available for STARHS, which identified 88 incident infections that would otherwise have been unrecognized (12% of all new infections, 34% of all recent infections). Of these, 88% reported recent high-risk sex; 47% reported seroconversion symptoms. STARHS confirmed recent infections in 71 of 74 (96%) known to be infected within 6 months by conventional methods. Combining both approaches, recent infections increased over time from 26% (1996) to 45% (2005) [P < 0.001]. STARHS results from 3% new diagnoses and 8% previous diagnoses were deemed false incident (associated with antiretroviral therapy, advanced disease or undetectable viral load). False incident results were only inexplicable in two individuals. CONCLUSION: Adjunctive use of STARHS with clinical data identified a high and increasing proportion of new HIV diagnoses as recent infections, confirming significant ongoing transmission. Since 2002, 50% of new diagnoses among MSM were recent infections. Identification of additional recent infections by STARHS enables effective intervention that may benefit the individual and reduce onward transmission.
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Serodiagnóstico del SIDA/métodos , Algoritmos , Seropositividad para VIH/epidemiología , VIH , Homosexualidad Masculina , Enfermedad Aguda , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Incidencia , Masculino , Reino Unido/epidemiología , Sexo InseguroRESUMEN
OBJECTIVE: To determine the specificity of the Abbott Murex HIV antigen/antibody combination enzyme immunoassay (EIA) for the diagnosis of HIV infection in Tanzania. METHODS: A cross-sectional survey of 7333 Tanzanian adolescents and young adults was carried out. Sera testing positive by the Murex assay were further evaluated using a battery of other EIA which detect either antibody to HIV-1 or p24 antigen, and by PCR using pol primers. RESULTS: Of the 674 sera testing positive by the Murex assay, only 53 (7.9%) were confirmed. The specificity of the Murex assay was 91.5%. CONCLUSIONS: Serological tests for HIV may perform differently in different populations. New diagnostic tests should not be introduced into populations in which they have not been evaluated.
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Serodiagnóstico del SIDA/métodos , Infecciones por VIH/diagnóstico , Técnicas para Inmunoenzimas/normas , Juego de Reactivos para Diagnóstico , Adolescente , Adulto , Reacciones Antígeno-Anticuerpo , Estudios Transversales , Anticuerpos Anti-VIH/inmunología , Humanos , Sensibilidad y Especificidad , TanzaníaRESUMEN
OBJECTIVES: To examine the geographical variations in HIV prevalence (diagnosed and undiagnosed), use of sexual health services, sexually transmitted infections and sexual behaviour in a community sample of men who have sex with men in three cities in England, specifically London, Brighton and Manchester. METHODS: Cross-sectional surveys of men visiting gay community venues in three large cities in England. Men self-completed a questionnaire and provided an anonymous oral fluid sample for HIV antibody testing. RESULTS: HIV prevalence ranged from 8.6% to 13.7% in the three cities. Over one-third of HIV infection remained undiagnosed in all sites despite 69% of HIV-positive men reporting attending a genitourinary medicine clinic in the last year. Similar and high levels of risk behaviour were reported in all three cities. 18% of HIV-negative men and 37% of HIV-positive men reported unprotected anal intercourse with more than one partner in the last year. 20% of negative men and 41% of positive men reported an STI in the last year. CONCLUSIONS: Across all cities, despite widespread availability of anti-retroviral treatment and national policy to promote HIV testing, many HIV infections remain undiagnosed. Data from this community sample demonstrate high levels of risk behaviour and STI incidence, especially among those who are HIV positive. Renewed efforts are needed to increase diagnosis and to reduce risk behaviour to stem the continuing transmission of HIV.
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Infecciones por VIH/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Sexo Inseguro/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Análisis de Varianza , Inglaterra , Infecciones por VIH/terapia , Humanos , Masculino , Aceptación de la Atención de Salud/estadística & datos numéricos , Prevalencia , Características de la Residencia , Parejas Sexuales , Factores Socioeconómicos , Revelación de la VerdadRESUMEN
The objective of this study was to assess the performance of 4 biologic tests designed to detect recent HIV-1 infections in estimating incidence in West Africa (BED, Vironostika, Avidity, and IDE-V3). These tests were assessed on a panel of 135 samples from 79 HIV-1-positive regular blood donors from Abidjan, Côte d'Ivoire, whose date of seroconversion was known (Agence Nationale de Recherches sur le SIDA et les Hépatites Virales 1220 cohort). The 135 samples included 26 from recently infected patients (< or =180 days), 94 from AIDS-free subjects with long-standing infection (>180 days), and 15 from patients with clinical AIDS. The performance of each assay in estimating HIV incidence was assessed through simulations. The modified commercial assays gave the best results for sensitivity (100% for both), and the IDE-V3 technique gave the best result for specificity (96.3%). In a context like Abidjan, with a 10% HIV-1 prevalence associated with a 1% annual incidence, the estimated test-specific annual incidence rates would be 1.2% (IDE-V3), 5.5% (Vironostika), 6.2% (BED), and 11.2% (Avidity). Most of the specimens falsely classified as incident cases were from patients infected for >180 days but <1 year. The authors conclude that none of the 4 methods could currently be used to estimate HIV-1 incidence routinely in Côte d'Ivoire but that further adaptations might enhance their accuracy.