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Search Results: 1 - 10 of 28 matches for " Wondatir; Vyse "
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Pre-and post-vaccine measles antibody status in infants using serum and oral-fluid testing: an evaluation of routine immunization in Addis Ababa, Ethiopia
Wondatir Nigatu, DJ Nokes, BJ Cohen, DWG Brown, AJ Vyse
Ethiopian Journal of Health Development , 2003,
Abstract: Despite the use of measles vaccine, measles incidence in Ethiopia remains a serious public health concern. Progress towards the control of measles requires a national capacity to measure programme effectiveness. This includes evaluation of vaccine effectiveness in infants attending the routine immunization. Objective: To evaluate the effectiveness of the measles routine immunization activities in Addis Ababa. Methods: This study evaluated pre- and post-vaccine antibodies in children attending for routine measles immunization in Addis Ababa. Infants who presented to 3 health centres between September-November, 1998 for routine measles vaccination were enrolled in the study. In total 296 infants (median age 9 months) provided blood and oral-fluid samples, of which 230 (77%) returned to provide post vaccine samples (median interval of 15 days). Screening of sera was undertaken using commercial indirect ELISA kits, and of oral fluids using an in-house IgM-capture ELISA. Results: Pre-vaccination serology showed 1.4% IgM positive, 2.0% IgG positive, and 97.0% seronegative. Post-vaccination seroprevalence of IgM and IgG was 91.3% and 85.0%, respectively, and 92.9% overall. The seroconversion rate was 92.6% (95%CI 88.2-95.7). Based on oral fluid results, 87.3% (95% CI 82.0-91.4) of children showed specific IgM antibody conversion. Conclusion: These results are in support of the recommended age for measles vaccination in Addis Ababa, and show the merit of oral-fluid IgM screening as a non-invasive alternative to blood for assessing vaccine effectiveness. Ethiop.J.Health Dev. 2003; 17(3): 149-155
Has oral fluid the potential to replace serum for the evaluation of population immunity levels?: a study of measles, rubella and hepatitis B in rural Ethiopia
Nokes D. James,Enquselassie Fikre,Nigatu Wondatir,Vyse Andrew J.
Bulletin of the World Health Organization , 2001,
Abstract: OBJECTIVE: To assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. METHODS: Paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural Ethiopian community. Oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced IgG antibody capture (GAC) enzyme-linked immunosorbent assays (ELISAs), and for anti-HBc antibodies using a prototype GACELISA. IgG antibodies in serum to measles, rubella and HBc were determined using commercial ELISAs. FINDINGS: Relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-HBc. These assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages <20 years). CONCLUSION: Our results suggest that oral fluid could have the potential to replace serum in IgG antibody prevalence surveys. Further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays.
Has oral fluid the potential to replace serum for the evaluation of population immunity levels?: a study of measles, rubella and hepatitis B in rural Ethiopia
Nokes,D. James; Enquselassie,Fikre; Nigatu,Wondatir; Vyse,Andrew J.; Cohen,Bernard J.; Brown,David W.G.; Cutts,Felicity T.;
Bulletin of the World Health Organization , 2001, DOI: 10.1590/S0042-96862001000700003
Abstract: objective: to assess the suitability of using oral-fluid samples for determining the prevalence of immunity to vaccine-preventable infections. methods: paired blood and oral-fluid samples were obtained from 853 individuals of all ages from a rural ethiopian community. oral fluid around the gums was screened for measles- and rubella-specific antibodies using enhanced igg antibody capture (gac) enzyme-linked immunosorbent assays (elisas), and for anti-hbc antibodies using a prototype gacelisa. igg antibodies in serum to measles, rubella and hbc were determined using commercial elisas. findings: relative to serum, oral fluid assay sensitivity and specificity were as follows: 98% and 87% for measles, 79% and 90% for rubella, and 43% and 87% for anti-hbc. these assay characteristics yielded population prevalence estimates from oral fluid with a precision equal to that of serum for measles (all ages) and rubella (ages <20 years). conclusion: our results suggest that oral fluid could have the potential to replace serum in igg antibody prevalence surveys. further progress requires assessment of variation in assay performance between populations as well as the availability of standardized, easy to use assays.
Genetics of rheumatic disease
Alex Clarke, Timothy J Vyse
Arthritis Research & Therapy , 2009, DOI: 10.1186/ar2781
Abstract: The spectrum of rheumatic disease is wide and includes conditions with diverse pathology, although most have in common a heritable risk with a complex genetic basis. There has therefore been intense effort to understand the contribution of genotype to the expression of disease in terms of both basic pathogenesis and clinical characteristics. Recent technical advances in genotyping and statistical analysis and international collaborations assembling large cohorts of patients have led to a wealth of new data. In this review we describe insights gained into the pathogenesis of autoimmune rheumatic disease by the techniques of modern genetics, in particular evidence from genome-wide association (GWA) studies, which provide support for the existence of a common genetic risk basis to several diseases. To reflect the new data from GWA studies, our discussion will be confined to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS), which in some cases share a common autoimmune pathogenesis. Osteoarthritis and osteoporosis are also complex genetic traits but limitations of space are such that these two conditions will not be considered in this review.The concept of a systematic, GWA study became practical with the cataloguing of libraries of common polymorphisms. Currently, over 20 million single nucleotide polymorphisms (SNPs) have been identified [1] and platforms are available to type up to 1 million of these in a single reaction. Although not all SNPs are currently genotyped, as the human genome is arranged into haplotype blocks in linkage disequilibrium, it is only necessary to type so-called tag SNPs, which identify these areas of limited variability [2], to achieve good representation of the total amount of genetic variation. Most typed SNPs are relatively common (minor allele frequency of > 5%) and if associated with disease are likely, therefore, to have only modest pathogenic effects (odds ratios (ORs) usually between 1.2 a
The genetics of lupus: a functional perspective
Sandra G Guerra, Timothy J Vyse, Deborah S Cunninghame Graham
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3844
Abstract: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by hyperactive T and B cells, auto-antibody production, and immune complex(IC) deposition [1]. SLE has a prevalence of approximately 1 in 2,500 in European populations [2] and is more frequent in those of non-European ancestry. SLE affects predominantly women (the female-to-male ratio is 9:1) of child-bearing age and is characterized by variable clinical features, including malar rash, glomerulonephritis, arthritis, and neuropsychiatric disease [3]. Although the exact etiology of lupus is not fully understood, a strong genetic link has been identified through the use of association and family studies. The heritability of SLE is approximately 66%; the rates of concordance are 24% to 56% in monozygotic twins and 2% to 4% in dizygotic twins [4,5].To date, genome-wide association studies (GWASs) have identified more than 30 associated loci. In Table 1, we show the variants that have reached genome-wide significance (1.0 × 10?8) in one or more GWASs, a metaanalysis, or replication studies. We have also included the Fcγ locus, because it contains multiple associated variants, including a confirmed copy number variation (CNV) in SLE. However, these loci account for less than 10% of the genetic heritability [6].GWASs in SLE have been useful tools for expanding the genetic understanding of SLE by identifying new loci and replicating previously associated loci. In this review, we categorize these risk loci into a number of pathways on the basis of the current understanding of the potential role for the locus in SLE. We note that the clinical heterogeneity of SLE is mirrored by the diversity of the pathways reported to contain the associated loci from the genetic studies, apoptosis, innate immune response, ubiquitination, and phagocytosis (Table 1). Therefore, this review aims to highlight the known function(s) of the associated loci and to indicate where further functional studies are neede
The role of RT-PCR assay of oral fluid for diagnosis and surveillance of measles, mumps and rubella
Jin L.,Vyse A.,Brown D.W.G.
Bulletin of the World Health Organization , 2002,
Abstract:
A point-of-care test for measles diagnosis: detection of measles-specific IgM antibodies and viral nucleic acid
Warrener,Lenesha; Slibinskas,Rimantas; Chua,Kaw Bing; Nigatu,Wondatir; Brown,Kevin E; Sasnauskas,Kestutis; Samuel,Dhanraj; Brown,David;
Bulletin of the World Health Organization , 2011, DOI: 10.1590/S0042-96862011000900014
Abstract: objective: to evaluate the performance of a newly developed point-of-care test (poct) for the detection of measles-specific igm antibodies in serum and oral fluid specimens and to assess if measles virus nucleic acid could be recovered from used poct strips. methods: the poct was used to test 170 serum specimens collected through measles surveillance or vaccination programmes in ethiopia, malaysia and the russian federation: 69 were positive for measles immunoglobulin m (igm) antibodies, 74 were positive for rubella igm antibodies and 7 were positive for both. also tested were 282 oral fluid specimens from the measles, mumps and rubella (mmr) surveillance programme of the united kingdom of great britain and northern ireland. the microimmune measles igm capture enzyme immunoassay was the gold standard for comparison. a panel of 24 oral fluids was used to investigate if measles virus haemagglutinin (h) and nucleocapsid (n) genes could be amplified by polymerase chain reaction directly from used poct strips. findings: with serum poct showed a sensitivity and specificity of 90.8% (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and specificity were 90.0% (63/70) and 96.2% (200/208), respectively. both h and n genes were reliably detected in poct strips and the n genes could be sequenced for genotyping. measles virus genes could be recovered from poct strips after storage for 5 weeks at 20-25 oc. conclusion: the poct has the sensitivity and specificity required of a field-based test for measles diagnosis. however, its role in global measles control programmes requires further evaluation.
Genetic analysis of the pentraxin genes in SLE
AI Russell, CA Roberton, S Chadha, DS Cunninghame Graham, TJ Vyse
Arthritis Research & Therapy , 2001, DOI: 10.1186/ar156
Abstract: We are establishing a large collection of single case nuclear families with the aim of fine mapping the aetiologic polymorphisms. Using a candidate gene approach, we have examined several genes, which lie within the linked intervals. First, we identified genetic markers in the candidate genes. The inheritance of the markers in our nuclear families was then tested using the program TRANSMIT which compares the observed and expected rates of transmission of marker alleles (or haplotypes) from parents to offspring. A marked distortion away from random segregation indicates association with disease.We have hypothesised that genetic variation in the pentraxin genes, C-reactive protein (CRP) and serum amyloid component P (SAP) predisposes to SLE. These two genes are tightly linked on chromosome 1q21-23, a region linked to human SLE. Other evidence implicating these includes the defective CRP response in SLE and the presence of antinuclear autoimmunity in Sap knockout mice. We identified five novel single base pair polymorphisms (three in CRP and two in SAP) and tested these for evidence of association. Individuals from 354 families were studied.These data provide no evidence for a genetic contribution to human SLE from the pentraxin genes. When haplotypes across this locus were examined there was similarly no evidence of association. The defective CRP response in human SLE is unlikely to be related to variation at the CRP locus itself.
Determination of the Loss of Function Complement C4 Exon 29 CT Insertion Using a Novel Paralog-Specific Assay in Healthy UK and Spanish Populations
Lora Boteva, IMAGEN , Yee Ling Wu, Josefina Cortes-Hernández, Javier Martin, Timothy J. Vyse, Michelle M. A. Fernando
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022128
Abstract: Genetic variants resulting in non-expression of complement C4A and C4B genes are common in healthy European populations and have shown association with a number of diseases, most notably the autoimmune disease, systemic lupus erythematosus. The most frequent cause of a C4 “null” allele, following that of C4 gene copy number variation (CNV), is a non-sense mutation arising from a 2 bp CT insertion into codon 1232 of exon 29. Previous attempts to accurately genotype this polymorphism have not been amenable to high-throughput typing, and have been confounded by failure to account for CNV at this locus, as well as by inability to distinguish between paralogs. We have developed a novel, high-throughput, paralog-specific assay to detect the presence and copy number of this polymorphism. We have genotyped healthy cohorts from the United Kingdom (UK) and Spain. Overall, 30/719 (4.17%) individuals from the UK cohort and 8/449 (1.78%) individuals from the Spanish cohort harboured the CT insertion in a C4A gene. A single Spanish individual possessed a C4B CT insertion. There is weak correlation between the C4 CT insertion and flanking MHC polymorphism. Therefore it is important to note that, as with C4 gene CNV, disease-association due to this variant will be missed by current SNP-based genome-wide association strategies.
A Genetic Association Study of Serum Acute-Phase C-Reactive Protein Levels in Rheumatoid Arthritis: Implications for Clinical Interpretation
Benjamin Rhodes,Marilyn E. Merriman,Andrew Harrison,Michael J. Nissen,Malcolm Smith,Lisa Stamp,Sophia Steer,Tony R. Merriman,Timothy J. Vyse
PLOS Medicine , 2010, DOI: 10.1371/journal.pmed.1000341
Abstract: Background The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation. Methods and Findings We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, p<0.0005, p<0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR = 50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1–50.0) for haplotype 1 and 14.2 mg/l (9.5–23.2) for haplotype 4. Conclusions Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP–associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement. Please see later in the article for the Editors' Summary
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