18 results found
Vegvari C, Giardina F, Bajaj S, et al., 2021, Deworming women of reproductive age during adolescence and pregnancy: what is the impact on morbidity from soil-transmitted helminths infection?, PARASITES & VECTORS, Vol: 14, ISSN: 1756-3305
Celma CC, Beard S, Douglas A, et al., 2020, Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance, Eurosurveillance, Vol: 25, Pages: 1-8, ISSN: 1025-496X
BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.MethodsRotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.ResultsHospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.ConclusionsThis report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.
Anderson RM, Hollingsworth TD, Baggaley RF, et al., 2020, COVID-19 spread in the UK: the end of the beginning?, LANCET, Vol: 396, Pages: 587-590, ISSN: 0140-6736
Vegvari C, Giardina F, Bajaj S, et al., 2020, Deworming Women of Reproductive Age During Adolescence and Pregnancy: What is the Impact on Morbidity From Soil-transmitted Helminths Infection?
<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>Soil-transmitted helminths (STHs) are a major cause of poor health in low- and middle-income countries. In particular, hookworm is known to cause anaemia in children and women of reproductive age (WRA). One goal of the World Health Organization’s (WHO) 2030 roadmap for neglected tropical diseases is to reduce STH-related morbidity in WRA. As a minimal intervention the WHO recommends deworming adolescent girls annually during human papilloma virus vaccination programmes and women of reproductive age (WRA) during pregnancy and lactation. These routine interventions are low cost can be implemented even from the most basic health services in endemic countries. In this study we use a cohort model to investigate the potential impact on STH-related morbidity in WRA.<jats:bold>Results:</jats:bold> We find that annual deworming of adolescent girls reduces morbidity in a similar way treatment programmes for pre-school-age and school-age children (pSAC and SAC). Treatment of WRA during pregnancy and lactation on its own has a small but significant effect on morbidity although it does not achieve the morbidity target (<2% moderate-to-high intensity infections) in this age group. However, depending on the age-intensity profile of infection, which may vary geographically, and assumptions on the density-dependence of egg production by fertilised female worms, continued school-based treatment may be able to reduce the force of infection acting on WRA, both through an indirect effect on the overall population based force of infection and via reducing the burden of infection as children age and move into the WRA age classes. As a result, morbidity in WRA may be eliminated.<jats:bold>Conclusion:</jats:bold> While deworming during pregnancy and lactation does not achieve the morbidity target in WRA and its efficacy may vary by setting
Hardwick RJ, Vegvari C, Truscott JE, et al., 2020, The 'breakpoint' of soil-transmitted helminths with infected human migration, JOURNAL OF THEORETICAL BIOLOGY, Vol: 486, ISSN: 0022-5193
Coffeng L, Malizia V, Vegvari C, et al., 2019, Impact of different sampling schemes for decision making in soil-transmitted helminthiasis control programs, Journal of Infectious Diseases, Vol: 221, Pages: S531-S538, ISSN: 0022-1899
Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.
Vegvari C, Truscott JE, Kura K, et al., 2019, Human population movement can impede the elimination of soil-transmitted helminth transmission in regions with heterogeneity in mass drug administration coverage and transmission potential between villages: a metapopulation analysis, Parasites and Vectors, Vol: 12, Pages: 1-12, ISSN: 1756-3305
BackgroundSoil-transmitted helminth (STH) infections affect predominantly socio-economically disadvantaged populations in sub-Saharan Africa, East Asia and the Americas. Previous mathematical modelling studies have evaluated optimal intervention strategies to break STH transmission in clusters of villages. These studies assumed that villages are closed independent units with no movement of people in or out of communities. Here we examine how human population movement, for example, of seasonal migrant labourers, affect the outcome of mass drug administration (MDA) programmes.ResultsWe used a stochastic individual-based metapopulation model to analyse the impact of human population movement at varying rates on STH elimination efforts. Specifically, we looked at seasonal clumped movement events of infected individuals into a village. We showed that even if on average 75% of the entire resident population within a village are treated, an annual rate of 2–3% of the population arriving from an untreated source village can reduce the probability of STH elimination to less than 50% in high-prevalence settings. If a village is infection-free, an annual movement rate of 2–3% from an infected source village imposes a risk of re-introduction of STH of 75% or higher, unless the prevalence in the source village is less than 20%. Even a single arrival of 2–3% of the population can impose a risk of re-introducing STH of 50% or greater depending on the prevalence in the source village. The risk of re-introduction also depends on both the age group of moving individuals and STH species, since the pattern of cross-sectional age-prevalence and age-intensity profiles of infection in the human host are species-specific.ConclusionsPlanning for STH elimination programmes should account for human mobility patterns in defined regions. We recommend that individuals arriving from areas with ongoing STH transmission should receive preventive chemotherapy for STHs. This can mos
Vegvari C, Truscott J, Kura K, et al., 2019, IMPACT OF POPULATION MOVEMENT BETWEEN VILLAGES ON THE LIKELIHOOD OF BREAKING TRANSMISSION OF SOIL-TRANSMITTED HELMINTHS, Publisher: OXFORD UNIV PRESS, Pages: S53-S54, ISSN: 0035-9203
Giardina F, Coffeng LE, Farrell SH, et al., 2019, Sampling strategies for monitoring and evaluation of morbidity targets for soil-transmitted helminths, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
BackgroundThe current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020. In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear. Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target.Methodology/Principal findingsUsing two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. districts). As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district. The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence. Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points. If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points. Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV.Conclusions/SignificanceAlthough the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species. There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species. A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strat
Vegvari C, Hardwick R, Truscott J, et al., 2019, RELEVANT SPATIAL SCALE FOR EVALUATION UNITS FOR ELIMINATION PROGRAMS FOR SOIL-TRANSMITTED HELMINTHS GIVEN GEOGRAPHY OF SETTLEMENTS AND HUMAN MOVEMENT, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 618-618, ISSN: 0002-9637
Werkman M, Toor J, Vegvari C, et al., 2018, Defining stopping criteria for ending randomized clinical trials that investigate the interruption of transmission of soil-transmitted helminths employing mass drug administration, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
The current World Health Organization strategy to address soil-transmitted helminth (STH) infections in children is based on morbidity control through routine deworming of school and pre-school aged children. However, given that transmission continues to occur as a result of persistent reservoirs of infection in untreated individuals (including adults) and in the environment, in many settings such a strategy will need to be continued for very extended periods of time, or until social, economic and environmental conditions result in interruption of transmission. As a result, there is currently much discussion surrounding the possibility of accelerating the interruption of transmission using alternative strategies of mass drug administration (MDA). However, the feasibility of achieving transmission interruption using MDA remains uncertain due to challenges in sustaining high MDA coverage levels across entire communities. The DeWorm3 trial, designed to test the feasibility of interrupting STH transmission, is currently ongoing. In DeWorm3, three years of high treatment coverage—indicated by mathematical models as necessary for breaking transmission—will be followed by two years of surveillance. Given the fast reinfection (bounce-back) rates of STH, a two year no treatment period is regarded as adequate to assess whether bounce-back or transmission interruption have occurred in a given location. In this study, we investigate if criteria to determine whether transmission interruption is unlikely can be defined at earlier timepoints. A stochastic, individual-based simulation model is employed to simulate core aspects of the DeWorm3 community-based cluster-randomized trial. This trial compares a control arm (annual treatment of children alone with MDA) with an intervention arm (community-wide biannual treatment with MDA). Simulations were run for each scenario for both Ascaris lumbricoides and hookworm (Necator americanus). A range of threshold prevalences meas
Vegvari C, Kura K, Truscott J, et al., 2018, MIGRATION AND LOCAL MOVEMENT CAN IMPEDE ELIMINATION EFFORTS OF SOIL-TRANSMITTED HELMINTHS (STH) BY MASS DRUG ADMINISTRATION (MDA), 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 239-239, ISSN: 0002-9637
Lawrence E, Vegvari C, Ower A, et al., 2017, A Systematic Review of Longitudinal Studies Which Measure Alzheimer's Disease Biomarkers, JOURNAL OF ALZHEIMERS DISEASE, Vol: 59, Pages: 1359-1379, ISSN: 1387-2877
Alzheimer’s disease (AD) is a progressive and fatal neurodegenerative disease, with no effective treatment orcure. A gold standard therapy would be treatment to slow or halt disease progression; however, knowledge of causationin the early stages of AD is very limited. In order to determine effective endpoints for possible therapies, a number ofquantitative surrogate markers of disease progression have been suggested, including biochemical and imaging biomarkers.The dynamics of these various surrogate markers over time, particularly in relation to disease development, are, however,not well characterized. We reviewed the literature for studies that measured cerebrospinal fluid or plasma amyloid-andtau, or took magnetic resonance image or fluorodeoxyglucose/Pittsburgh compound B-positron electron tomography scans,in longitudinal cohort studies. We summarized the properties of the major cohort studies in various countries, commonlyused diagnosis methods and study designs. We have concluded that additional studies with repeat measures over time in arepresentative population cohort are needed to address the gap in knowledge of AD progression. Based on our analysis, wesuggest directions in which research could move in order to advance our understanding of this complex disease, includingrepeat biomarker measurements, standardization and increased sample sizes.
Vegvari C, Hadjichrysanthou C, Cauët E, et al., 2016, How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?, PLOS One, Vol: 11, ISSN: 1932-6203
Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.
Vegvari C, Cauët E, Hadjichrysanthou C, et al., 2016, Using Clinical Trial Simulators to Analyse the Sources of Variance in Clinical Trials of Novel Therapies for Acute Viral Infections., PLOS One, Vol: 11, ISSN: 1932-6203
BACKGROUND: About 90% of drugs fail in clinical development. The question is whether trials fail because of insufficient efficacy of the new treatment, or rather because of poor trial design that is unable to detect the true efficacy. The variance of the measured endpoints is a major, largely underestimated source of uncertainty in clinical trial design, particularly in acute viral infections. We use a clinical trial simulator to demonstrate how a thorough consideration of the variability inherent in clinical trials of novel therapies for acute viral infections can improve trial design. METHODS AND FINDINGS: We developed a clinical trial simulator to analyse the impact of three different types of variation on the outcome of a challenge study of influenza treatments for infected patients, including individual patient variability in the response to the drug, the variance of the measurement procedure, and the variance of the lower limit of quantification of endpoint measurements. In addition, we investigated the impact of protocol variation on clinical trial outcome. We found that the greatest source of variance was inter-individual variability in the natural course of infection. Running a larger phase II study can save up to $38 million, if an unlikely to succeed phase III trial is avoided. In addition, low-sensitivity viral load assays can lead to falsely negative trial outcomes. CONCLUSIONS: Due to high inter-individual variability in natural infection, the most important variable in clinical trial design for challenge studies of potential novel influenza treatments is the number of participants. 100 participants are preferable over 50. Using more sensitive viral load assays increases the probability of a positive trial outcome, but may in some circumstances lead to false positive outcomes. Clinical trial simulations are powerful tools to identify the most important sources of variance in clinical trials and thereby help improve trial design.
Hadjichrysanthou C, Cauët E, Lawrence E, et al., 2016, Understanding the within-host dynamics of influenza A virus: from theory to clinical implications, Journal of the Royal Society Interface, Vol: 13, ISSN: 1742-5689
Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell-limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection.
Vegvari C, Foley R, 2014, Competition and Culture Change in Prehistoric Socio-Environmental Systems, Computer Applications and Quantitative Methods in Archaeology 2013
Vegvari C, Foley RA, 2014, High Selection Pressure Promotes Increase in Cumulative Adaptive Culture, PLOS ONE, Vol: 9, ISSN: 1932-6203
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