Imperial College London

Dr Joanna Lewis

Faculty of MedicineSchool of Public Health

Visiting Researcher
 
 
 
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Contact

 

joanna.lewis

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

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29 results found

Lewis J, White PJ, Price MJ, 2021, Per-partnership transmission probabilities for Chlamydia trachomatis infection: Evidence synthesis of population-based survey data, International Journal of Epidemiology, Vol: 50, Pages: 510-517, ISSN: 0300-5771

BackgroundChlamydia is the most commonly diagnosed sexually transmitted infection worldwide. Mathematical models used to plan and assess control measures rely on accurate estimates of chlamydia’s natural history, including the probability of transmission within a partnership. Several methods for estimating transmission probability have been proposed, but all have limitations.MethodsWe have developed a new model for estimating per-partnership chlamydia transmission probabilities from infected to uninfected individuals, using data from population-based surveys. We used data on sexual behaviour and prevalent chlamydia infection from the second UK National Study of Sexual Attitudes and Lifestyles (Natsal-2) and the US National Health and Nutrition Examination Surveys 2009–2014 (NHANES) for Bayesian inference of average transmission probabilities, across all new heterosexual partnerships reported. Posterior distributions were estimated by Markov chain Monte Carlo sampling using the Stan software.ResultsPosterior median male-to-female transmission probabilities per partnership were 32.1% [95% credible interval (CrI) 18.4–55.9%] (Natsal-2) and 34.9% (95%CrI 22.6–54.9%) (NHANES). Female-to-male transmission probabilities were 21.4% (95%CrI 5.1–67.0%) (Natsal-2) and 4.6% (95%CrI 1.0–13.1%) (NHANES). Posterior predictive checks indicated a well-specified model, although there was some discrepancy between reported and predicted numbers of partners, especially in women.ConclusionsThe model provides statistically rigorous estimates of per-partnership transmission probability, with associated uncertainty, which is crucial for modelling and understanding chlamydia epidemiology and control. Our estimates incorporate data from several sources, including population-based surveys, and use information contained in the correlation between number of partners and the probability of chlamydia infection. The evidence synthesis approach means that it is ea

Journal article

Lewis J, Horner P, White P, 2020, Incidence of pelvic inflammatory disease associated with mycoplasma genitalium infection: Evidence synthesis of cohort study data, Clinical Infectious Diseases, Vol: 71, Pages: 2719-2722, ISSN: 1058-4838

We synthesized evidence from the POPI sexual-health cohort study, and estimated that 4.9% (95% credible interval 0.4-14.1%) of Mycoplasma genitalium infections in women progress to pelvic inflammatory disease, versus 14.4% (5.9-24.6%) of chlamydial infections. For validation, we predicted PID rates in four age groups that agree well with surveillance data.

Journal article

Winter JR, Jackson C, Lewis JEA, Taylor GS, Thomas OG, Stagg HRet al., 2020, Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature, Journal of Global Health, Vol: 10, Pages: 1-16, ISSN: 2047-2978

Background Epstein-Barr virus (EBV) is an important human pathogen; it infects >90% people globally and is linked to infectious mononucleosis and several types of cancer. Vaccines against EBV are in development. In this studywe present the first systematic review of the literature on risk factors for EBVinfection, and discuss how they differ between settings, in order to improveour understanding of EBV epidemiology and aid the design of effective vaccination strategies.Methods MEDLINE, Embase, and Web of Science were searched on 6th March2017 for observational studies of risk factors for EBV infection. Studies wereexcluded if they were published before 2008 to ensure relevance to the modernday, given the importance of influencing future vaccination policies. There wereno language restrictions. After title, abstract and full text screening, followed bychecking the reference lists of included studies to identify further studies, datawere extracted into standardised spreadsheets and quality assessed. A narrativesynthesis was undertaken.Results Seventy-seven papers met our inclusion criteria, including data from 31countries. There was consistent evidence that EBV seroprevalence was associated with age, increasing throughout childhood and adolescence and remainingconstant thereafter. EBV was generally acquired at younger ages in Asia thanEurope/North America. There was also compelling evidence for an associationbetween cytomegalovirus infection and EBV. Additional factors associated withEBV seroprevalence, albeit with less consistent evidence, included ethnicity, socioeconomic status, other chronic viral infections, and genetic variants of HLAand immune response genes.Conclusions Our study is the first systematic review to draw together the globalliterature on the risk factors for EBV infection and includes an evaluation of thequality of the published evidence. Across the literature, the factors examinedare diverse. In Asia, early vaccination of infants would be requi

Journal article

Bakkalci D, Jia Y, Winter JR, Lewis JEA, Taylor GS, Stagg HRet al., 2020, Risk factors for Epstein Barr virus-associated cancers: a systematic review, critical appraisal, and mapping of the epidemiological evidence, Journal of Global Health, Vol: 10, Pages: 1-4, ISSN: 2047-2978

Background Epstein Barr Virus (EBV) infects 90%-95% of all adults globally and causes~1% of all cancers. Differing proportions of Burkitt’s lymphoma (BL), gastric carcinoma (GC), Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC) are associated with EBV. We sought tosystematically review the global epidemiological evidence for risk factorsthat (in addition to EBV) contribute to the development of the EBV-associated forms of these cancers, assess the quality of the evidence, andcompare and contrast the cancers.Methods MEDLINE, Embase and Web of Science were searched for studies of risk factors for EBV-associated BL, GC, HL and NPC without language or temporal restrictions. Studies were excluded if there was nocancer-free comparator group or where analyses of risk factors were inadequately documented. After screening and reference list searching, datawere extracted into standardised spreadsheets and quality assessed. Dueto heterogeneity, a narrative synthesis was undertaken.Results 9916 hits were retrieved. 271 papers were retained: two BL, 24HL, one GC and 244 NPC. The majority of studies were from China,North America and Western Europe. Risk factors were categorised as dietary, environmental/non-dietary, human genetic, and infection and clinical. Anti-EBV antibody load was associated with EBV-associated GC andBL. Although the evidence could be inconsistent, HLA-A alleles, smoking, infectious mononucleosis and potentially other infections were riskfactors for EBV-associated HL. Rancid dairy products; anti-EBV antibodyand EBV DNA load; history of chronic ear, nose and/or throat conditions;herbal medicine use; family history; and human genetics were risk factorsfor NPC. Fresh fruit and vegetable and tea consumption may be protective against NPC.Conclusions Many epidemiological studies of risk factors in addition toEBV for the EBV-associated forms of BL, GC, HL and NPC have been undertaken, but there is a dearth of evidence for GC and BL. Available e

Journal article

Lewis J, White PJ, 2020, Understanding relationships between chlamydial infection, symptoms and testing behavior: an analysis of data from Natsal-3, Epidemiology, Vol: 31, Pages: 263-271, ISSN: 1044-3983

Background: Genital chlamydial infection is the most commonly-diagnosed sexually- transmitted infection worldwide, and can have serious long-term sequelae. Numerous countries invest substantially in testing but evidence for programs’ effectiveness is inconclusive. The effects of testing programs in different groups of people need to be understood. Methods: We analyzed data on sexual behavior and chlamydia testing from 16-24-year-olds in Britain’s third National Survey of Sexual Attitudes and Lifestyles, considering test setting, reason and result. We conducted descriptive analysis accounting for the survey design using design variables and nonresponse weightings, and Bayesian analysis using a mathematical model of chlamydial infection and testing. Results: Most men testing due to symptoms tested in sexual health settings (63.1%; 95% confidence interval 42.5-83.6%) but most women testing due to symptoms were tested by GPs (59.3%; 42.9-75.8%). Within behavioral groups, positivity of chlamydia screens (tests not prompted by symptoms or partner notification) was similar to population prevalence. Screening rates were higher in women and in those reporting more partners: median (95% credible interval) rates per year in those reporting 0, 1 and ≥2 new partners in the last year were 0.30(0.24-0.35), 0.45(0.37-0.53) and 0.59(0.48-0.71) (men) and 0.59(0.52-0.68), 0.88(0.74-1.03) 20 and 1.16(0.97-1.39) (women). Conclusions: The proportion of testing occurring in sexual health is not a proxy for the proportion prompted by symptoms. Test positivity depends on a combination of force of infection and screening rate and does not simply reflect prevalence or behavioral risk. The analysis highlights the value of recording testing reason and behavioral characteristics to inform cost-effective control.

Journal article

Winter JR, Taylor GS, Thomas OG, Jackson C, Lewis JEA, Stagg HRet al., 2019, Predictors of Epstein-Barr virus serostatus in young people in England, BMC INFECTIOUS DISEASES, Vol: 19

Journal article

White P, Lewis J, 2019, Response to Kounali et al.’s letter of response, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688

Journal article

Davis K, Lewis J, Liva-Pye K, Liebow A, Horner Pet al., 2019, P462 Re-testing for chlamydia in the national chlamydia screening programme in Bristol, England: an analysis of surveillance data, Abstracts for the STI & HIV World Congress (Joint Meeting of the 23rd ISSTDR and 20th IUSTI), July 14–17, 2019, Vancouver, Canada, Publisher: BMJ Publishing Group, Pages: A215-A216, ISSN: 1368-4973

Background England’s National Chlamydia Screening Programme (NCSP) recommends that sexually active people <25 years test for Chlamydia trachomatis annually and on change of sexual partner. Since 2013, NCSP has also recommended re-testing three months after testing positive. We used a detailed dataset to investigate characteristics associated with repeated chlamydia testing.Methods We used surveillance data of community-based chlamydia testing (excluding online testing and specialist sexual health services) among men and women aged 15–24 years in the Bristol area, January 2011-December 2017. Repeat-testing was defined as returning for further testing within the Bristol area, at least 42 days after initially testing. Initial tests <3 months from December 2017 were excluded. We used logistic regression to compare odds of repeat-testing by initial test result, testing service, residence, initial test result and sexual risk behaviour, adjusted for age and whether the 2013 guidance was operating.Results 14.11% (n=76,758) of women and 7.81% (n=28,038) of men repeat-tested within the study period. Of those with a positive result, 31.21% (n=5,104) of women and 14.88% (n=2,386) of men repeat-tested. Repeat-testing was associated with positive initial tests (Females: Adjusted Odds Ratio 1.90, 95% Confidence Interval 1.76–2.05; Males: 1.98, 1.71–2.27), having ≥2 sexual partners in the last year (1.17, 1.11–1.23; 1.15, 1.02–1.31), having a new sexual partner in the last 3 months (1.31, 1.24–1.38; 1.55, 1.36–1.77), living in the city of Bristol (1.68, 1.57–1.80; 1.43, 1.25–1.65) and testing through Contraception and Sexual Health clinics, which can treat uncomplicated infections, rather than other settings (1.34, 1.28–1.41; 1.37, 1.23–1.53).Conclusion It was encouraging that initial positive tests and riskier sexual behaviour, which mean individuals are more likely to be infected, were associated wit

Conference paper

Gosce L, Winter JR, Taylor GS, Lewis JEA, Stagg HRet al., 2019, Modelling the dynamics of EBV transmission to inform a vaccine target product profile and future vaccination strategy, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

Journal article

Payne H, Chain G, Adams S, Hunter P, Luckhurst N, Gilmour K, Lewis J, Babiker A, Cotton M, Violari A, Gibb D, Callard R, Klein Net al., 2019, Naive B Cell Output in HIV-Infected and HIV-Uninfected Children., AIDS Res Hum Retroviruses, Vol: 35, Pages: 33-39

In this study, we aimed to quantify KREC (kappa-deleting recombination excision circle) levels and naive B cell output in healthy HIV-uninfected children, compared with HIV-infected South African children, before and after starting ART (antiretroviral therapy). Samples were acquired from a Child Wellness Clinic (n = 288 HIV-uninfected South African children, 2 weeks-12 years) and the Children with HIV Early Antiretroviral Therapy (CHER) trial (n = 153 HIV-infected South African children, 7 weeks-8 years). Naive B cell output was estimated using a mathematical model combining KREC levels to reflect B cell emigration into the circulation, flow cytometry measures of naive unswitched B cells to quantify total body naive B cells, and their rates of proliferation using the intracellular marker Ki67. Naive B cell output increases from birth to 1 year, followed by a decline and plateau into late childhood. HIV-infected children on or off ART had higher naive B cell outputs than their uninfected counterparts (p = .01 and p = .04). This is the first study to present reference ranges for measurements of KRECs and naive B cell output in healthy and HIV-infected children. Comparison between HIV-uninfected healthy children and HIV-infected children suggests that HIV may increase naive B cell output. Further work is required to fully understand the mechanisms involved and clinical value of measuring naive B cell output in children.

Journal article

White PJ, Lewis J, 2018, Estimating chlamydia prevalence: more difficult than modelling suggests – Authors' reply, Lancet Public Health, Vol: 3, Pages: e417-e417, ISSN: 2468-2667

Journal article

Lewis JEA, White P, 2018, Changes in chlamydia prevalence and duration of infection inferred from testing and diagnosis rates in England: an evidence synthesis using surveillance data, 2000-2015, Lancet Public Health, Vol: 3, Pages: E271-E278, ISSN: 2468-2667

Background: Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence and reproductive sequelae remain unclear. In England, despite increases in testing with the roll-out of the National Chlamydia Screening Programme (2003-2008), prevalence estimated in population-based surveys was similar in 1999-2001 and 2010-12 – although the precision of the estimates was limited. Methods: We used newly-published annual figures for chlamydia test coverage and diagnoses in England before, during and after the scale-up of national screening, with recently-developed statistical methods which account for symptomatic chlamydia testing and asymptomatic screening, to infer changes in prevalence and average duration of infections in each year. Findings: The data provided numbers of tests and diagnoses in 15-19 and 20-24-year-old men and women in England each year from 2000 to 2015, allowing annual – rather than ten-yearly – estimates of prevalence change. We inferred reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, inferred prevalence reductions were 0.7(0.3,1.4) and 0.8(0.4-1.3) percentage points in 15-24-year-old men and women, respectively (posterior median; 95% credible interval), and average duration of infection fell by 74(17-247) days in men and 30(22-40) days in women. Progress has recently reversed with declining testing. Interpretation: Our analysis provides the first evidence for a reduction in chlamydia prevalence in England concurrent with large-scale population testing. It also shows a consistent decline in the average duration of infections: a measure of screening effectiveness that is unaffected by behavioural changes.

Journal article

Lewis J, White PJ, 2018, Changes in chlamydia prevalence and duration of infection estimated from testing and diagnosis rates in England: a model-based analysis using surveillance data, 2000–15, Lancet Public Health, ISSN: 2468-2667

Background:Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence, and reproductive sequelae remain unclear. In England, despite increases in testing with the rollout of the National Chlamydia Screening Programme (NCSP; 2003–08), prevalence estimated in 10-yearly population-based surveys was similar before (1999–2001) and after (2010–12) the programme. However, the precision of these previous estimates was limited by the low numbers of infections. We aimed to establish annual, rather than 10-yearly, estimates of chlamydia prevalence and infection duration.Methods:In this model-based analysis, we used previously published minimum and maximum estimates and Public Health England data for chlamydia test coverage and diagnoses in men and women aged 15–24 years in England, before, during, and after the scale-up of national chlamydia screening. We used a mechanistic model, which accounted for symptomatic chlamydia testing and asymptomatic screening, to estimate changes in prevalence and average duration of infections for each year. We describe estimates derived from the maximum and minimum numbers of tests and diagnoses as maximum and minimum estimates, regardless of their relative magnitude.FindingsThe data included numbers of tests and diagnoses in men and women aged 15–19 years and 20–24 years in England each year from 2000 to 2015. We estimated reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, estimated posterior median prevalence reductions in people aged 15–24 years were 0·68 percentage points (95% credible interval 0·26–1·40; minimum) and 0·66 percentage points (0·25–1·37; maximum) for men and 0·77 percentage points (0·45–1·27) for women (minimum and maximum estimates were the same for women). Ove

Journal article

Lewis JEA, Payne H, Walker AS, Otwombe K, Gibb DM, Babiker AG, Panchia R, Cotton MF, Violari A, Klein N, Callard REet al., 2017, Thymic output and CD4 T-cell reconstitution in HIV-infected children on early and interrupted antiretroviral treatment: evidence from the CHER trial., Frontiers in Immunology, Vol: 8, ISSN: 1664-3224

Objectives: Early treatment of HIV-infected children and adults is important for optimal immune reconstitution. Infants’ immune systems are more plastic and dynamic than older children’s or adults’, and deserve particular attention. This study aimed to understand the response of the HIV-infected infant immune system to early antiretroviral therapy (ART) and planned ART interruption and re-start.Design: We used linear and nonlinear regression and mixed-effects models to describe children’s CD4 trajectories and to identify predictors of CD4 count during early and interrupted ART.Methods: Data from HIV-infected children enrolled CHER trial, starting ART aged between 6 and 12 weeks, was used to explore the effect of ART on immune reconstitution. Results: Early treatment arrested the decline in CD4 count but did not fully restore it to the levels observed in HIV-uninfected children. Treatment interruption at 40 or 96 weeks resulted in a rapid decline in CD4 T-cells, which on retreatment returned to levels observed before interruption. Naïve CD4 T-cell count was an important determinant of overall CD4 levels. A strong correlation was observed between thymic output and the stable CD4 count both before and after treatment interruption.Conclusions: Early identification and treatment of HIV-infected infants is important to stabilize CD4 counts at the highest levels possible. Once stabilized, children’s CD4 counts appear resilient, with good potential for recovery following treatment interruption. The naïve T-cell pool and thymic production of naive cells are key determinants of children’s CD4 levels.

Journal article

Lewis J, White PJ, 2017, Estimating local chlamydia incidence and prevalence using surveillance data, Epidemiology, Vol: 28, Pages: 492-502, ISSN: 1531-5487

Background: Understanding patterns of chlamydia prevalence is important for addressing inequalities and planning cost-effective control programs. Population-based surveys are costly; the best data for England come from the Natsal national surveys which are only available once per decade, and are nationally representative but not powered to compare prevalence in different localities. Prevalence estimates at finer spatial and temporal scales are required.Methods: We present a method for estimating local prevalence by modeling the infection, testing and treatment processes. Prior probability distributions for parameters describing natural history and treatment-seeking behavior are informed by the literature or calibrated using national prevalence estimates. By combining them with surveillance data on numbers of chlamydia tests and diagnoses, we obtain estimates of local screening rates, incidence and prevalence. We illustrate the method by application to data from England.Results: Our estimates of national prevalence by age group agree with the Natsal-3 survey. They could be improved by additional information on the number of diagnosed cases that were asymptomatic. There is substantial local-level variation in prevalence, with more infection in deprived areas. Incidence in each sex is strongly correlated with prevalence in the other. Importantly, we find that positivity (the proportion of tests which were positive) does not provide a reliable proxy for prevalence.Conclusion: This approach provides local chlamydia prevalence estimates from surveillance data, which could inform analyses to identify and understand local prevalence patterns and assess local programs. Estimates could be more accurate if surveillance systems recorded additional information, including on symptoms.

Journal article

Lewis JEA, Price MJ, Horner PJ, White PJet al., 2017, Genital C. trachomatis infections clear more slowly in men than women, but are less likely to become established., Journal of Infectious Diseases, Vol: 216, Pages: 237-244, ISSN: 1537-6613

BackgroundRigorous estimates for clearance rates of untreated chlamydia infections are important for understanding chlamydia epidemiology and designing control interventions, but were previously only available for women.MethodsWe used data from published studies of chlamydia-infected men who were retested at a later date without having received treatment. Our analysis allowed new infections to take one of 1, 2, or 3 courses, each clearing at a different rate. We determined which of these 3 models had the most empirical support.ResultsThe best-fitting model had 2 courses of infection in men, as was previously found for women: “slow-clearing” and “fast-clearing.” Only 68% (57%–78%) (posterior median and 95% credible interval [CrI]) of incident infections in men were slow-clearing, vs 77% (69%–84%) in women. The slow clearance rate in men (based on 6 months’ follow-up) was 0.35 (.05–1.15) year-1 (posterior median and 95% CrI), corresponding to mean infection duration 2.84 (.87–18.79) years. This compares to 1.35 (1.13–1.63) years in women.ConclusionsOur estimated clearance rate is slower than previously assumed. Fewer infections become established in men than women but once established, they clear more slowly. This study provides an improved description of chlamydia’s natural history to inform public health decision making. We describe how further data collection could reduce uncertainty in estimates.

Journal article

Majekodunmi AO, Thorne C, Malyuta R, Volokha A, Callard RE, Klein NJ, Lewis Jet al., 2017, Modelling CD4 T Cell Recovery in Hepatitis C and HIV Co-infected Children Receiving Antiretroviral Therapy, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 36, Pages: E123-E129, ISSN: 0891-3668

Journal article

Lewis JEA, Breeze CE, Charlesworth J, Maclaren OJ, Cooper Jet al., 2016, Where next for the reproducibility agenda in computational biology?, BMC Systems Biology, Vol: 10, ISSN: 1752-0509

Background: The concept of reproducibility is a foundation of the scientific method. With the arrival of fast and powerful computers over the last few decades, there has been an explosion of results based on complex computational analyses and simulations. The reproducibility of these results has been addressed mainly in terms of exact replicability or numerical equivalence, ignoring the wider issue of the reproducibility of conclusions through equivalent, extended or alternative methods. Results: We use case studies from our own research experience to illustrate how concepts of reproducibility might be applied in computational biology. Several fields have developed ‘minimum information’ checklists to support the full reporting of computational simulations, analyses and results, and standardised data formats and model description languages can facilitate the use of multiple systems to address the same research question. We note the importance of defining the key features of a result to be reproduced, and the expected agreement between original and subsequent results. Dynamic, updatable tools for publishing methods and results are becoming increasingly common, but sometimes come at the cost of clear communication. In general, the reproducibility of computational research is improving but would benefit from additional resources and incentives.Conclusions: We conclude with a series of linked recommendations for improving reproducibility in computational biology through communication, policy, education and research practice. More reproducible research will lead to higher quality conclusions, deeper understanding and more valuable knowledge.

Journal article

Payne H, Mkhize N, Otwombe K, Lewis J, Panchia R, Callard R, Morris L, Babiker A, Violari A, Cotton MF, Klein NJ, Gibb DMet al., 2015, Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis, LANCET INFECTIOUS DISEASES, Vol: 15, Pages: 803-809, ISSN: 1473-3099

Journal article

Payne H, Mkhize N, Otwombe K, Lewis J, Panchia R, Callard R, Morris L, Babiker A, Violari A, Cotton MF, Klein NJ, Gibb DMet al., 2015, Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis, The Lancet Infectious Diseases, Vol: 15, Pages: 803-809, ISSN: 1473-3099

Journal article

Knapp B, Bardenet R, Bernabeu MO, Bordas R, Bruna M, Calderhead B, Cooper J, Fletcher AG, Groen D, Kuijper B, Lewis J, McInerny G, Minssen T, Osborne J, Paulitschke V, Pitt-Francis J, Todoric J, Yates CA, Gavaghan D, Deane CMet al., 2015, Ten Simple Rules for a Successful Cross-Disciplinary Collaboration, PLOS Computational Biology, Vol: 11, ISSN: 1553-734X

Journal article

Yin DE, Warshaw MG, Miller WC, Castro H, Fiscus SA, Harper LM, Harrison LJ, Klein NJ, Lewis J, Melvin AJ, Tudor-Williams G, McKinney REet al., 2014, Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation, PEDIATRICS, Vol: 134, Pages: E1104-E1116, ISSN: 0031-4005

Journal article

Barker CIS, Germovsek E, Hoare RL, Lestner JM, Lewis J, Standing JFet al., 2014, Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology, ADVANCED DRUG DELIVERY REVIEWS, Vol: 73, Pages: 127-139, ISSN: 0169-409X

Journal article

Sandgaard KS, Lewis J, Adams S, Klein N, Callard Ret al., 2014, Antiretroviral therapy increases thymic output in children with HIV, AIDS, Vol: 28, Pages: 209-214, ISSN: 0269-9370

Journal article

Hapuarachchi T, Lewis J, Callard RE, 2013, A mechanistic model for naive CD4 T cell homeostasis in healthy adults and children, Frontiers in Immunology, Vol: 4, ISSN: 1664-3224

The size and composition of the T lymphocyte compartment is subject to strict homeostatic regulation and is remarkably stable throughout life in spite of variable dynamics in cell production and death during T cell development and immune responses. Homeostasis is achieved by careful orchestration of lymphocyte survival and cell division. New T cells are generated from the thymus and the number of peripheral T cells is regulated by controlling survival and proliferation. How these processes combine is however very complex. Thymic output increases in the first year of life and then decreases but is crucial for establishing repertoire diversity. Proliferation of new naive T cells plays a crucial role for maintaining numbers but at a potential cost to TCR repertoire diversity. A mechanistic two-compartment model of T cell homeostasis is described here that includes specific terms for thymic output, cell proliferation, and cell death of both resting and dividing cells. The model successfully predicts the homeostatic set point for T cells in adults and identifies variables that determine the total number of T cells. It also accurately predicts T cell numbers in children in early life despite rapid changes in thymic output and growth over this period.

Journal article

Picat M-Q, Lewis J, Musiime V, Prendergast A, Nathoo K, Kekitiinwa A, Nahirya Ntege P, Gibb DM, Thiebaut R, Walker AS, Klein N, Callard Ret al., 2013, Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study, PLOS Medicine, Vol: 10, ISSN: 1549-1277

Journal article

Lewis J, Walker AS, Klein N, Callard Ret al., 2012, CD31(+) Cell Percentage Correlation With Speed of CD4(+) T-Cell Count Recovery in HIV-Infected Adults Is Reversed in Children: Higher Thymic Output May Be Responsible, CLINICAL INFECTIOUS DISEASES, Vol: 55, Pages: 304-307, ISSN: 1058-4838

Journal article

Lewis J, Walker AS, Castro H, De Rossi A, Gibb DM, Giaquinto C, Klein N, Callard Ret al., 2012, Age and CD4 Count at Initiation of Antiretroviral Therapy in HIV-Infected Children: Effects on Long-term T-Cell Reconstitution, JOURNAL OF INFECTIOUS DISEASES, Vol: 205, Pages: 548-556, ISSN: 0022-1899

Journal article

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