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1.
J Infect Dis ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38547499

ABSTRACT

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.

2.
Pediatr Transplant ; 28(7): e14857, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39318279

ABSTRACT

BACKGROUND: Long-term renal function and survival after kidney transplantation rely on appropriate immunosuppressive treatment to prevent the risk of rejection. New biomarkers are needed to accurately assess the degree of immunosuppression in renal transplant recipients in order to avoid organ rejection and the development of opportunistic infections. Highly prevalent in humans, torque teno virus (TTV), which belongs to the family Anelloviridae, is a small, nonenveloped, single-stranded DNA virus which has not been linked with any specific human illness, but which constitutes a major component of the human virome. Host antiviral responses allow TTV levels to be controlled; however, viral persistence remains, explaining the high prevalence in human populations, including healthy individuals. Important confounders of TTV load include time since transplantation, age, gender, obesity, and smoking status. AIMS: TTV-based guidance of immunosuppressive drug dosing could help with risk stratification, reducing the risk of infection, graft rejection and oncologic disease on an individual level, enabling long-term patient and graft survival. METHODS: Original studies were accessed by a systematic search from electronic databases including PubMed, ScienceDirect and Wiley Online Library. RESULTS: The presented data mainly derive from adult transplant recipients showing an association between TTV plasma levels and the immune status of the host: High-TTV load and high immunosuppression are associated with a risk of infection, and low-TTV load and low immunosuppression indicate a risk of rejection. However, there is minimal information on pediatric transplant recipients with further research required in this cohort. To date, it has been demonstrated that longer posttransplant times are significantly associated with lower TTV levels in children with renal transplant. Meanwhile, an association between lower TTV loads and increased risk of graft reject during the first year of transplantation was also reported. More recently, Eibensteiner et al. revealed a robust, independent association between TTV plasma load and the onset of Cytomegalovirus and BK virus infections. CONCLUSION: Data from randomized controlled trials are still missing, even in adults, but a multicenter randomized controlled trial for TTV-guided immunosuppression in adult kidney recipients (TTVguideIT) began in 2022. There is, therefore, great promise for TTV levels to be used as a biomarker that could potentially improve both graft and patient survival in transplantation.


Subject(s)
Biomarkers , DNA Virus Infections , Graft Rejection , Immunosuppression Therapy , Immunosuppressive Agents , Kidney Transplantation , Torque teno virus , Viral Load , Humans , Child , DNA Virus Infections/immunology , Biomarkers/blood , Immunosuppressive Agents/therapeutic use , Immunosuppression Therapy/methods , Graft Rejection/immunology , Graft Rejection/prevention & control , Transplant Recipients
3.
Euro Surveill ; 29(16)2024 Apr.
Article in English | MEDLINE | ID: mdl-38639093

ABSTRACT

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.


Subject(s)
Monkeypox virus , Mpox (monkeypox) , Male , Humans , Adult , Female , Ireland/epidemiology , Monkeypox virus/genetics , Bayes Theorem , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Disease Outbreaks
4.
Emerg Infect Dis ; 29(4): 751-760, 2023 04.
Article in English | MEDLINE | ID: mdl-36957994

ABSTRACT

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.


Subject(s)
Adenovirus Infections, Human , Adenoviruses, Human , Hepatitis , Respiratory Tract Infections , Humans , Child , Wastewater , Ireland/epidemiology , Adenoviruses, Human/genetics , Hepatitis/epidemiology , Disease Outbreaks , Acute Disease , Adenovirus Infections, Human/epidemiology , Phylogeny , Respiratory Tract Infections/epidemiology
5.
Rev Med Virol ; 32(1): e2260, 2022 01.
Article in English | MEDLINE | ID: mdl-34043841

ABSTRACT

Despite over 140 million SARS-CoV-2 infections worldwide since the beginning of the pandemic, relatively few confirmed cases of SARS-CoV-2 reinfection have been reported. While immunity from SARS-CoV-2 infection is probable, at least in the short term, few studies have quantified the reinfection risk. To our knowledge, this is the first systematic review to synthesise the evidence on the risk of SARS-CoV-2 reinfection over time. A standardised protocol was employed, based on Cochrane methodology. Electronic databases and preprint servers were searched from 1 January 2020 to 19 February 2021. Eleven large cohort studies were identified that estimated the risk of SARS-CoV-2 reinfection over time, including three that enrolled healthcare workers and two that enrolled residents and staff of elderly care homes. Across studies, the total number of PCR-positive or antibody-positive participants at baseline was 615,777, and the maximum duration of follow-up was more than 10 months in three studies. Reinfection was an uncommon event (absolute rate 0%-1.1%), with no study reporting an increase in the risk of reinfection over time. Only one study estimated the population-level risk of reinfection based on whole genome sequencing in a subset of patients; the estimated risk was low (0.1% [95% CI: 0.08-0.11%]) with no evidence of waning immunity for up to 7 months following primary infection. These data suggest that naturally acquired SARS-CoV-2 immunity does not wane for at least 10 months post-infection. However, the applicability of these studies to new variants or to vaccine-induced immunity remains uncertain.


Subject(s)
COVID-19 , Reinfection , SARS-CoV-2 , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Vaccines , Humans , Pandemics
6.
Rev Med Virol ; 32(4): e2320, 2022 07.
Article in English | MEDLINE | ID: mdl-34957630

ABSTRACT

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n = 25; I2  = 81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n = 20; I2  = 52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n = 5; I2  = 37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Dried Blood Spot Testing , Hepacivirus/genetics , Hepatitis C/diagnosis , Hepatitis C Antigens/analysis , Humans , RNA , Sensitivity and Specificity
7.
Value Health ; 25(12): 1947-1957, 2022 12.
Article in English | MEDLINE | ID: mdl-35778325

ABSTRACT

OBJECTIVES: We aimed to evaluate the cost-effectiveness of offering once-off birth cohort testing for hepatitis C virus (HCV) to people in Ireland born between 1965 and 1985, the cohort with the highest reported prevalence of undiagnosed chronic HCV infection. METHODS: Systematic and opportunistic HCV birth cohort testing programs, implemented over a 4-year timeframe, were compared with the current practice of population risk-based testing only in a closed-cohort decision tree and Markov model hybrid over a lifetime time horizon. Outcomes were expressed in quality-adjusted life-years (QALYs). Costs were presented from the health system's perspective in 2020 euro (€). Uncertainty was assessed via deterministic, probabilistic, scenario, and threshold analyses. RESULTS: In the base case, systematic testing yielded the largest cost and health benefits, followed by opportunistic testing and risk-based testing. Compared with risk-based testing, the incremental cost-effectiveness ratio for opportunistic testing was €14 586 (95% confidence interval €4185-€33 527) per QALY gained. Compared with opportunistic testing, the incremental cost-effectiveness ratio for systematic testing was €16 827 (95% confidence interval €5106-€38 843) per QALY gained. These findings were robust across a range of sensitivity analyses. CONCLUSIONS: Both systematic and opportunistic birth cohort testing would be considered an efficient use of resources, but systematic testing was the optimal strategy at willingness-to-pay threshold values typically used in Ireland. Although cost-effective, any decision to introduce birth cohort testing for HCV (in Ireland or elsewhere) must be balanced with considerations regarding the feasibility and budget impact of implementing a national testing program given high initial costs and resource use.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Humans , Cost-Benefit Analysis , Hepacivirus , Birth Cohort , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Quality-Adjusted Life Years , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/epidemiology
8.
Rev Med Virol ; 31(3): e2184, 2021 05.
Article in English | MEDLINE | ID: mdl-33105071

ABSTRACT

A key consideration in the Covid-19 pandemic is the dominant modes of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The objective of this review was to synthesise the evidence for the potential airborne transmission of SARS-CoV-2 via aerosols. Systematic literature searches were conducted in PubMed, Embase, Europe PMC and National Health Service UK evidence up to 27 July 2020. A protocol was published and Cochrane guidance for rapid review methodology was adhered to throughout. Twenty-eight studies were identified. Seven out of eight epidemiological studies suggest aerosol transmission may occur, with enclosed environments and poor ventilation noted as possible contextual factors. Ten of the 16 air sampling studies detected SARS-CoV-2 ribonucleic acid; however, only three of these studies attempted to culture the virus with one being successful in a limited number of samples. Two of four virological studies using artificially generated aerosols indicated that SARS-CoV-2 is viable in aerosols. The results of this review indicate there is inconclusive evidence regarding the viability and infectivity of SARS-CoV-2 in aerosols. Epidemiological studies suggest possible transmission, with contextual factors noted. Viral particles have been detected in air sampling studies with some evidence of clinical infectivity, and virological studies indicate these particles may represent live virus, adding further plausibility. However, there is uncertainty as to the nature and impact of aerosol transmission of SARS-CoV-2, and its relative contribution to the Covid-19 pandemic compared with other modes of transmission.


Subject(s)
Aerosols/analysis , COVID-19/transmission , RNA, Viral/isolation & purification , SARS-CoV-2/physiology , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Humans , Retrospective Studies , SARS-CoV-2/pathogenicity , Uncertainty
9.
Rev Med Virol ; 31(2): e2162, 2021 03.
Article in English | MEDLINE | ID: mdl-32964627

ABSTRACT

In this review, we systematically searched and summarized the evidence on the immune response and reinfection rate following SARS-CoV-2 infection. We also retrieved studies on SARS-CoV and MERS-CoV to assess the long-term duration of antibody responses. A protocol based on Cochrane rapid review methodology was adhered to and databases were searched from 1/1/2000 until 26/5/2020. Of 4744 citations retrieved, 102 studies met our inclusion criteria. Seventy-four studies were retrieved on SARS-CoV-2. While the rate and timing of IgM and IgG seroconversion were inconsistent across studies, most seroconverted for IgG within 2 weeks and 100% (N = 62) within 4 weeks. IgG was still detected at the end of follow-up (49-65 days) in all patients (N = 24). Neutralizing antibodies were detected in 92%-100% of patients (up to 53 days). It is not clear if reinfection with SARS-CoV-2 is possible, with studies more suggestive of intermittent detection of residual RNA. Twenty-five studies were retrieved on SARS-CoV. In general, SARS-CoV-specific IgG was maintained for 1-2 years post-infection and declined thereafter, although one study detected IgG up to 12 years post-infection. Neutralizing antibodies were detected up to 17 years in another study. Three studies on MERS-CoV reported that IgG may be detected up to 2 years. In conclusion, limited early data suggest that most patients seroconvert for SARS-CoV-2-specific IgG within 2 weeks. While the long-term duration of antibody responses is unknown, evidence from SARS-CoV studies suggest SARS-CoV-specific IgG is sustained for 1-2 years and declines thereafter.


Subject(s)
COVID-19/immunology , Coronavirus Infections/immunology , Coronavirus/immunology , Immunity/immunology , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology
10.
Rev Med Virol ; 31(4): e2185, 2021 07.
Article in English | MEDLINE | ID: mdl-33091200

ABSTRACT

The collection of nasopharyngeal swabs to test for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an invasive technique with implications for patients and clinicians. Alternative clinical specimens from the upper respiratory tract may offer benefits in terms of collection, comfort and infection risk. The objective of this review was to synthesise the evidence for detection of SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) tested saliva or nasal specimens compared with RT-PCR tested nasopharyngeal specimens. Searches were conducted in PubMed, Embase, Europe PMC and NHS evidence from December 2019 to 20 July 2020. Eighteen studies were identified; 12 for saliva, four for nasal and two included both specimen types. For saliva-based studies, the proportion of saliva samples testing positive relative to all positive samples in each study ranged from 82.9% to 100%; detection in nasopharyngeal specimens ranged from 76.7% to 100%; positive agreement between specimens for overall detection ranged from 65.4% to 100%. For nasal-based studies, the proportion of nasal swabs testing positive relative to all positive samples in each study ranged from 81.9% to 100%; detection in nasopharyngeal specimens ranged from 70% to 100%; positive agreement between specimens for overall detection ranged from 62.3% to 100%. The results indicate an inconsistency in the detection of SARS-CoV-2 RNA in the specimen types included, often with neither the index nor the reference of interest detecting all known cases. Depending on the test environment, these clinical specimens may offer a viable alternative to standard. However, at present the evidence is limited, of variable quality, and relatively inconsistent.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Nasal Mucosa/virology , Nasopharynx/virology , Reverse Transcriptase Polymerase Chain Reaction/methods , Saliva/virology , Specimen Handling/methods , Humans , Reproducibility of Results
11.
Emerg Infect Dis ; 27(6): 1616-1626, 2021 06.
Article in English | MEDLINE | ID: mdl-34013874

ABSTRACT

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.


Subject(s)
Echovirus Infections , Enterovirus Infections , Enterovirus B, Human/genetics , Europe , Genotype , Humans , Molecular Epidemiology , Phylogeny , Sequence Analysis, DNA
12.
Pediatr Dev Pathol ; 24(5): 460-466, 2021.
Article in English | MEDLINE | ID: mdl-33754905

ABSTRACT

The Neuropathology of Human Parechovirus (HPeV) is not widely described due to the relatively recent discovery of the virus combined with a limited number of autopsy case reports. We report the case of an infant boy born at 38 weeks who, six days after birth, presented with fever and severe neurological dysfunction. Human Parechovirus Type 3 (HPeV3) RNA was detected in his cerebrospinal fluid (CSF) and blood. He died five days after his initial presentation. Neuropathologic examination demonstrated multicystic encephalomalacia (ME). This case report confirms that white matter pathology is dominant in HPeV3 infection. A unique feature, of HPeV encephalomalacia is absence of CSF pleocytosis and minimal inflammation in the meninges. The findings permit comment on the pathogenesis of brain injury by this virus.


Subject(s)
Encephalomalacia/pathology , Encephalomalacia/virology , Parechovirus , Picornaviridae Infections/pathology , Encephalomalacia/diagnosis , Fatal Outcome , Humans , Infant, Newborn , Male , Parechovirus/isolation & purification , Picornaviridae Infections/diagnosis
13.
Euro Surveill ; 26(48)2021 12.
Article in English | MEDLINE | ID: mdl-34857067

ABSTRACT

BackgroundRobust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.AimTo conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.MethodsUsing a cross-sectional study design, we selected population samples from individuals aged 12-69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age-sex distribution, and by simple random sampling within age-sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.ResultsParticipation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05-4.53) and 0.58% (95% CI: 0.18-1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13-2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772-85,176) people aged 12-69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0-4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.ConclusionThe majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June-July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.


Subject(s)
COVID-19 , Antibodies, Viral , Cross-Sectional Studies , Humans , Ireland/epidemiology , SARS-CoV-2 , Seroepidemiologic Studies
14.
Euro Surveill ; 26(45)2021 Nov.
Article in English | MEDLINE | ID: mdl-34763750

ABSTRACT

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.


Subject(s)
COVID-19 , Enterovirus D, Human , Enterovirus Infections , Enterovirus , Myelitis , Respiratory Tract Infections , Communicable Disease Control , Disease Outbreaks , Enterovirus D, Human/genetics , Enterovirus Infections/diagnosis , Enterovirus Infections/epidemiology , Europe/epidemiology , Humans , Myelitis/epidemiology , SARS-CoV-2
15.
Med Microbiol Immunol ; 208(5): 693-702, 2019 Oct.
Article in English | MEDLINE | ID: mdl-30859301

ABSTRACT

The suitability of routine diagnostic HIV assays to accurately discriminate between recent and non-recent HIV infections has not been fully investigated. The aim of this study was to compare an established HIV recency assay, the Sedia limiting antigen HIV avidity assay (LAg), with the diagnostic assays; Abbott ARCHITECT HIV Ag/Ab Combo and INNO-LIA HIV line assays. Samples from all new HIV diagnoses in Ireland from January to December 2016 (n = 455) were tested. An extended logistic regression model, the Spiegelhalter-Knill-Jones method, was utilised to establish a scoring system to predict recency of HIV infection. As proof of concept, 50 well-characterised samples were obtained from the CEPHIA repository whose stage of infection was blinded to the authors, which were tested and analysed. The proportion of samples that were determined as recent was 18.1% for LAg, 6.4% with the ARCHITECT, and 14.5% in the INNO-LIA assay. There was a significant correlation between the ARCHITECT S/CO values and the LAg results, r = 0.717, p < 0.001. ROC analysis revealed that an ARCHITECT S/CO < 250 had a sensitivity and specificity of 90.32% and 89.83%, respectively. Combining the Abbott ARCHITECT HIV Ag/Ab Combo assay and INNO-LIA HIV assays resulted in an observed risk of being recent of 100%. Analysis of the CEPHIA samples revealed a strong agreement between the LAg assay and the combination of routine assays (κ = 0.908, p < 0.001). Our findings provide evidence that assays routinely employed to diagnose and confirm HIV infection may be utilised to determine the recency of HIV infection.


Subject(s)
Antibody Affinity , HIV Antibodies/blood , HIV Infections/diagnosis , Serologic Tests/methods , Ireland , ROC Curve , Sensitivity and Specificity
16.
BMC Infect Dis ; 19(1): 815, 2019 Sep 18.
Article in English | MEDLINE | ID: mdl-31533639

ABSTRACT

BACKGROUND: Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers. CASE PRESENTATION: In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, HIV specific antibody levels and CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells. CONCLUSION: This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.


Subject(s)
HIV Infections/drug therapy , HIV-1/isolation & purification , Adult , Anti-Retroviral Agents/therapeutic use , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Female , HIV Antibodies/blood , HIV Infections/immunology , HIV Infections/pathology , HIV-1/genetics , Humans , RNA, Viral/blood , Viral Load
19.
J Med Virol ; 89(9): 1550-1558, 2017 09.
Article in English | MEDLINE | ID: mdl-28071799

ABSTRACT

Enteroviruses (EVs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (AM), encephalitis, hand, foot and mouth disease, acute flaccid paralysis, and acute flaccid myelitis. Epidemics occur sporadically and are associated with increased cases of AM in children. The present study describes the seroepidemiological analysis of circulating EVs in Ireland from 2005 to 2014 and phylogenetic characterization of echovirus 30 (E-30), enterovirus A71 (EV-A71), and enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010 to 2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EV-A71 positive CSF samples were identified in patients presenting with AM. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations.


Subject(s)
Central Nervous System Viral Diseases/epidemiology , Central Nervous System Viral Diseases/virology , Enterovirus A, Human/classification , Enterovirus B, Human/classification , Enterovirus D, Human/classification , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Adult , Child , Child, Preschool , Enterovirus A, Human/genetics , Enterovirus B, Human/genetics , Enterovirus B, Human/isolation & purification , Enterovirus D, Human/genetics , Female , Genotype , Humans , Infant , Infant, Newborn , Ireland/epidemiology , Male , Middle Aged , Phylogeny , Serotyping , Virus Cultivation , Young Adult
20.
Euro Surveill ; 22(30)2017 Jul 27.
Article in English | MEDLINE | ID: mdl-28797323

ABSTRACT

Robust data on hepatitis C virus (HCV) population prevalence are essential to inform national HCV services. In 2016, we undertook a survey to estimate HCV prevalence among the adult population in Ireland. We used anonymised residual sera available at the National Virus Reference Laboratory. We selected a random sample comprising persons ≥ 18 years with probability proportional to the general population age-sex distribution. Anti-HCV and HCV Ag were determined using the Architect anti-HCV and HCV Ag assays. Fifty-three of 3,795 specimens were seropositive (age-sex-area weighted seroprevalence 0.98% (95% confidence interval (CI): 0.73-1.3%)). Thirty-three specimens were HCV-antigen and antibody-positive (age-sex-area weighted prevalence of chronic infection 0.57% (95% CI: 0.40-0.81%)). The prevalence of chronic infection was higher in men (0.91%; 95% CI: 0.61-1.4%), in specimens from the east of the country (1.4%; 95%CI: 0.99-2.0%), and among persons aged 30-39 years and 40-49 years (1.1% (95% CI: 0.59-2.0%) and 1.1% (95% CI: 0.64-1.9%) respectively). Ireland ranks at the lower end of the spectrum of prevalence of chronic HCV infection internationally. Men born between 1965 and 1984 from the east of the country have the highest rate of chronic HCV infection.


Subject(s)
Hepacivirus/immunology , Hepatitis C Antibodies/analysis , Hepatitis C/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Hepatitis C/blood , Humans , Ireland/epidemiology , Male , Middle Aged , Population Surveillance , Prevalence , Risk Factors , Seroepidemiologic Studies , Sex Distribution
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