Imperial College London

ProfessorChristopheFraser

Faculty of MedicineSchool of Public Health

Visiting Professor
 
 
 
//

Contact

 

c.fraser Website

 
 
//

Location

 

G28Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

279 results found

Magosi LE, Zhang Y, Golubchik T, DeGruttola V, Tchetgen Tchetgen E, Novitsky V, Moore J, Bachanas P, Segolodi T, Lebelonyane R, Pretorius Holme M, Moyo S, Makhema J, Lockman S, Fraser C, Essex MM, Lipsitch Met al., 2022, Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/Ya Tsie trial, ELIFE, Vol: 11, ISSN: 2050-084X

Journal article

Wymant C, Bezemer D, Blanquart F, Ferretti L, Gall A, Hall M, Golubchik T, Bakker M, Ong SH, Zhao L, Bonsall D, de Cesare M, MacIntyre-Cockett G, Abeler-Doerner L, Albert J, Bannert N, Fellay J, Grabowski MK, Gunsenheimer-Bartmeyer B, Gunthard HF, Kivela P, Kouyos RD, Laeyendecker O, Meyer L, Porter K, Ristola M, van Sighem A, Ben B, Kellam P, Cornelissen M, Reiss P, Fraser Cet al., 2022, A highly virulent variant of HIV-1 circulating in the Netherlands, SCIENCE, Vol: 375, Pages: 540-+, ISSN: 0036-8075

Journal article

Kraemer MUG, Pybus OG, Fraser C, Cauchemez S, Rambaut A, Cowling BJet al., 2022, Monitoring key epidemiological parameters of SARS-CoV-2 transmission (vol 27, pg 1854, 2021), NATURE MEDICINE, Vol: 28, Pages: 213-213, ISSN: 1078-8956

Journal article

Lythgoe KA, Golubchik T, Hall M, House T, MacIntyre-Cockett G, Fryer H, Thomson L, Nurtay A, Buck D, Green A, Trebes A, Piazza P, Lonie LJ, Studley R, Rourke E, Cook D, Smith D, Bashton M, Nelson A, Crown M, McCann C, Young GR, dos Santos RAN, Richards Z, Tariq A, Fraser C, Diamond I, Barrett J, Walker S, Bonsall Det al., 2022, Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey

<jats:title>Abstract</jats:title><jats:p>The Office for National Statistics COVID-19 Infection Survey is a large household-based surveillance study based in the United Kingdom. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing sequenced samples collected up until 13th November 2021. We observed four distinct sweeps or partial-sweeps, by lineages B.1.177, B.1.1.7/Alpha, B.1.617.2/Delta, and finally AY.4.2, a sublineage of B.1.617.2, with each sweeping lineage having a distinct growth advantage compared to their predecessors. Evolution was characterised by steady rates of evolution and increasing diversity within lineages, but with step increases in divergence associated with each sweeping major lineage, leading to a faster overall rate of evolution and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly as routine PCR testing is phased out or in settings where large-scale sequencing is not feasible.</jats:p>

Journal article

Panovska-Griffiths J, Swallow B, Hinch R, Cohen J, Rosenfeld K, Stuart RM, Ferretti L, Lauro FD, Wymant C, Izzo A, Waites W, Viner R, Bonell C, Fraser C, Klein D, Kerr CCet al., 2022, Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions

<jats:p>The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. We used these estimates in Covasim (calibrated between September 01, 2020 and June 20, 2021), in June 2021, to explore whether planned relaxation of restrictions should proceed or be delayed. We found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination.</jats:p>

Journal article

Willett BJ, Grove J, MacLean OA, Wilkie C, Logan N, Lorenzo GD, Furnon W, Scott S, Manali M, Szemiel A, Ashraf S, Vink E, Harvey WT, Davis C, Orton R, Hughes J, Holland P, Silva V, Pascall D, Puxty K, da Silva Filipe A, Yebra G, Shaaban S, Holden MTG, Pinto RM, Gunson R, Templeton K, Murcia PR, Patel AH, Haughney J, Robertson DL, Palmarini M, Ray S, Thomson ECet al., 2022, The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism

<jats:title>Abstract</jats:title><jats:p>Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicron <jats:italic>in vitro</jats:italic> using sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.</jats:p>

Journal article

Twohig KA, Nyberg T, Zaidi A, Thelwall S, Sinnathamby MA, Aliabadi S, Seaman SR, Harris RJ, Hope R, Lopez-Bernal J, Gallagher E, Charlett A, De Angelis D, Presanis AM, Dabrera Get al., 2021, Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study, LANCET INFECTIOUS DISEASES, Vol: 22, Pages: 35-42, ISSN: 1473-3099

Journal article

McCrone JT, Hill V, Bajaj S, Pena RE, Lambert BC, Inward R, Bhatt S, Volz E, Ruis C, Dellicour S, Baele G, Zarebski AE, Sadilek A, Wu N, Schneider A, Ji X, Raghwani J, Jackson B, Colquhoun R, O'Toole Á, Peacock TP, Twohig K, Thelwall S, Dabrera G, Myers R, COVID-19 genomics UK COG-UK consortium, Faria NR, Huber C, Bogoch II, Khan K, du Plessis L, Barrett JC, Aanensen DM, Barclay WS, Chand M, Connor T, Loman NJ, Suchard MA, Pybus OG, Rambaut A, Kraemer MUGet al., 2021, Context-specific emergence and growth of the SARS-CoV-2 Delta variant., medRxiv

The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases 1-3 . The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions 4,5 . Here we analyse 52,992 Delta genomes from England in combination with 93,649 global genomes to reconstruct the emergence of Delta, and quantify its introduction to and regional dissemination across England, in the context of changing travel and social restrictions. Through analysis of human movement, contact tracing, and virus genomic data, we find that the focus of geographic expansion of Delta shifted from India to a more global pattern in early May 2021. In England, Delta lineages were introduced >1,000 times and spread nationally as non-pharmaceutical interventions were relaxed. We find that hotel quarantine for travellers from India reduced onward transmission from importations; however the transmission chains that later dominated the Delta wave in England had been already seeded before restrictions were introduced. In England, increasing inter-regional travel drove Delta's nationwide dissemination, with some cities receiving >2,000 observable lineage introductions from other regions. Subsequently, increased levels of local population mixing, not the number of importations, was associated with faster relative growth of Delta. Among US states, we find that regions that previously experienced large waves also had faster Delta growth rates, and a model including interactions between immunity and human behaviour could accurately predict the rise of Delta there. Delta's invasion dynamics depended on fine scale spatial heterogeneity in immunity and contact patterns and our findings will inform optimal spatial interventions to reduce transmission of current and future VOCs such as Omicron.

Journal article

OToole Á, Hill V, Jackson B, Dewar R, Sahadeo N, Colquhoun R, Rooke S, McCrone JT, McHugh MP, Nicholls S, Poplawski R, Aanensen D, Holden M, Connor T, Loman N, Goodfellow I, Carrington CVF, Templeton K, Rambaut Aet al., 2021, Genomics-informed outbreak investigations of SARS-CoV-2 using civet

<jats:title>Abstract</jats:title><jats:p>The scale of data produced during the SARS-CoV-2 pandemic has been unprecedented, with more than 5 million sequences shared publicly at the time of writing. This wealth of sequence data provides important context for interpreting local outbreaks. However, placing sequences of interest into national and international context is difficult given the size of the global dataset. Often outbreak investigations and genomic surveillance efforts require running similar analyses again and again on the latest dataset and producing reports. We developed civet (cluster investigation and virus epidemiology tool) to aid these routine analyses and facilitate virus outbreak investigation and surveillance. Civet can place sequences of interest in the local context of background diversity, resolving the query into different ’catchments’ and presenting the phylogenetic results alongside metadata in an interactive, distributable report. Civet can be used on a fine scale for clinical outbreak investigation, for local surveillance and cluster discovery, and to routinely summarise the virus diversity circulating on a national level. Civet reports have helped researchers and public health bodies feedback genomic information in the appropriate context within a timeframe that is useful for public health.</jats:p>

Journal article

de Silva TI, Liu G, Lindsey BB, Dong D, Moore SC, Hsu NS, Shah D, Wellington D, Mentzer AJ, Angyal A, Brown R, Parker MD, Ying Z, Yao X, Turtle L, Dunachie S, COVID-19 Genomics UK COG-UK Consortium, Maini MK, Ogg G, Knight JC, ISARIC4C Investigators, Peng Y, Rowland-Jones SL, Dong Tet al., 2021, The impact of viral mutations on recognition by SARS-CoV-2 specific T cells., iScience, Vol: 24, Pages: 103353-103353, ISSN: 2589-0042

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Journal article

Kraemer MUG, Pybus OG, Fraser C, Cauchemez S, Rambaut A, Cowling BJet al., 2021, Monitoring key epidemiological parameters of SARS-CoV-2 transmission, NATURE MEDICINE, Vol: 27, Pages: 1854-1855, ISSN: 1078-8956

Journal article

Moher M, Erickson M, Black P, Price M, Fraser C, Norman WV, Guillemi S, Pick N, Elwood Martin Ret al., 2021, Improving Post-Release Care Engagement for People Living with HIV Involved in the Criminal Justice System: A Systematic Review, AIDS AND BEHAVIOR, Vol: 26, Pages: 1607-1617, ISSN: 1090-7165

Journal article

Hall M, Golubchik T, Bonsall D, Abeler-Dörner L, Limbada M, Kosloff B, Schaap A, de Cesare M, Mackintyre-Cockett G, Probert W, Ratmann O, Cruz AB, Piwowar-Manning E, Burns DN, Cohen MS, Donnell DJ, Eshleman SH, Simwinga M, Hayes R, Fidler S, Ayles H, Fraser Cet al., 2021, Demographic characteristics of sources of HIV-1 transmission in Zambia

<jats:title>Abstract</jats:title><jats:sec><jats:title>BACKGROUND</jats:title><jats:p>In the last decade, universally available antiretroviral therapy has led to reduced HIV incidence in sub-Saharan Africa. Sources of remaining transmission need to be characterised to design effective prevention strategies.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>We used phylogenetics to understand the population characteristics of people who are sources of infection. HIV samples from 6,864 individuals from Zambia were deep-sequenced as part of HPTN 071-02 (PopART) Phylogenetics between 2014 and 2018. We identified 300 likely directed transmission pairs and analysed their sources to better understand transmission in the general population.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>After demographic weighting of the recipient population to match the estimated total population infected during the trial period, 59.4% (95% CI: 53.1%-65.8%) of transmissions were male-to-female, with 43.1% (36.6%-49.5%) of transmissions from males aged 25-40. Since the adult HIV prevalence was 2.0 times higher in women than men, the per-capita transmission rate was 2.93 times higher per infected male than per infected female. 25.6% (19.9%-31.3%) of sources were estimated to have themselves been infected less than a year before the transmission event. 16.8% (12%-21.7%) of sources transmitted viruses resistant to first-line ART. 13% (8.6%-17.4%) of transmissions occurred between individuals from different study communities.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>Our findings suggest that HIV transmission in the study communities took place as part of common sexual mixing, and that there was no outsized contribution of importation, from drug resistance, or recent infection. Men

Journal article

Clemens SAC, Folegatti PM, Emary KRW, Weckx LY, Ratcliff J, Bibi S, Mendes AVDA, Milan EP, Pittella A, Schwarzbold A, Sprinz E, Aley PK, Bonsall D, Fraser C, Fuskova M, Gilbert SC, Jenkin D, Kelly S, Kerridge S, Lambe T, Marchevsky NG, Mujadidi YF, Plested E, Ramasamy MN, Simmonds P, Golubchik T, Voysey M, Pollard AJet al., 2021, Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil, NATURE COMMUNICATIONS, Vol: 12

Journal article

Bezemer D, Blenkinsop A, Hall M, Van Sighem A, Cornelissen M, Wessels E, van Kampen J, van de Laar T, Reiss P, Fraser C, Ratmann Oet al., 2021, Many but small HIV-1 non-B transmission chains in the Netherlands, AIDS, Vol: 36, Pages: 83-94, ISSN: 0269-9370

Objective To investigate introductions and spread of different HIV-1 subtypes in the Netherlands. Design We identified distinct HIV-1 transmission chains in the Netherlands within the global epidemic context through viral phylogenetic analysis of partial HIV-1 polymerase sequences from individuals enrolled in the ATHENA national HIV cohort of all persons in care since 1996, and publicly available international background sequences. Methods Viral lineages circulating in the Netherlands were identified through maximum parsimony phylogeographic analysis. The proportion of HIV-1 infections acquired in-country among heterosexuals and men having sex with men (MSM) was estimated from phylogenetically observed, national transmission chains using a branching process model that accounts for incomplete sampling. Results As of January 1st 2019, 2,589 (24%) of 10,971 (41%) HIV-1 sequenced individuals in ATHENA had non-B subtypes (A1, C, D, F, G) or circulating recombinant forms (CRF01AE, CRF02AG, CRF06-cpx). The 1,588 heterosexuals were in 1,224, and 536 MSM in 270 phylogenetically observed transmission chains. After adjustments for incomplete sampling, most heterosexual (75%) and MSM (76%) transmission chains were estimated to include only the individual introducing the virus (size=1). Onward transmission occurred mostly in chains size 2-5 amongst heterosexuals (62%) and in chains size ≥10 amongst MSM (64%). Considering some chains originated in-country from other risk-groups, 40% (95%CI: 36-44%) of non-B-infected heterosexuals and 62% (95%CI: 49%-73%) of MSM acquired infection in-country. Conclusions Whilst most HIV-1 non-B introductions showed no or very little onward transmission, a considerable proportion of non-B infections amongst both heterosexuals and MSM in the Netherlands have been acquired in-country.

Journal article

Kartsonaki C, 2021, Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world’s largest international, standardised cohort of hospitalised patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The size of our international database and the standardized da

Journal article

Pickles M, Cori A, Probert WJM, Sauter R, Hinch R, Fidler S, Ayles H, Bock P, Donnell D, Wilson E, Piwowar-Manning E, Floyd S, Hayes RJ, Fraser C, HPTN 071 PopART Study Teamet al., 2021, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial, PLoS Computational Biology, Vol: 17, ISSN: 1553-734X

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.

Journal article

Pickles M, Cori A, Probert WJM, Sauter R, Hinch R, Fidler S, Ayles H, Bock P, Donnell D, Wilson E, Piwowar-Manning E, Floyd S, Hayes RJ, Fraser Cet al., 2021, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial, PLOS COMPUTATIONAL BIOLOGY, Vol: 17, ISSN: 1553-734X

Journal article

Limbada M, Macleod D, Situmbeko V, Muhau E, Shibwela O, Chiti B, Floyd S, Schaap AJ, Hayes R, Fidler S, Ayles Het al., 2021, Rates of viral suppression in a cohort of people with stable HIV from two community models of ART delivery versus facility-based HIV care in Lusaka, Zambia: a cluster-randomised, non-inferiority trial nested in the HPTN 071 (PopART) trial, The Lancet HIV, Vol: 9, Pages: E13-E23, ISSN: 2405-4704

BackgroundNon-facility-based antiretroviral therapy (ART) delivery for people with stable HIV might increase sustainable ART coverage in low-income and middle-income countries. Within the HPTN 071 (PopART) trial, two interventions, home-based delivery (HBD) and adherence clubs (AC), which included groups of 15–30 participants who met at a communal venue, were compared with standard of care (SoC). In this trial we looked at the effectiveness and feasibility of these alternative models of care. Specifically, this trial aimed to assess whether these models of care had similar virological suppression to that of SoC 12 months after enrolment.MethodsThis was a three-arm, cluster-randomised, non-inferiority trial, done in two urban communities in Lusaka, Zambia included in the HPTN 071 trial. The two communities were split into zones, which were randomly assigned (1:1:1) to the three treatment strategies: 35 zones to the SoC group, 35 zones to the HBD group, and 34 zones to the AC group. ART and adherence support were delivered once every 3 months at home for the HBD group, in groups of 15–30 people in the AC group, or in the clinic for the SoC group. Adults with HIV who were receiving first-line ART for at least 6 months, virally suppressed using national HIV guidelines in the last 12 months, had no other health conditions requiring the clinicians attention, live in the study catchment area, and provided written informed consent, were eligible for inclusion. The primary endpoint was viral suppression at 12 months (with a 6 month final measurement window [ie, 9–15 months]), defined as less than 1000 HIV RNA copies per mL, with a non-inferiority margin of 5%.FindingsBetween May 5 and Dec 19, 2017, 9900 individuals were screened for inclusion, of whom 2489 (25·1%) participants were enrolled into the trial: 781 (31%) in the SoC group, 852 (34%) in the HBD group, and 856 (34%) in the AC group. A higher proportion of participants had viral load measurem

Journal article

Ferretti L, Wymant C, Nurtay A, Zhao L, Hinch R, Bonsall D, Kendall M, Masel J, Bell J, Hopkins S, Kilpatrick AM, Peto T, Abeler-Dörner L, Fraser Cet al., 2021, Modelling the effectiveness and social costs of daily lateral flow antigen tests versus quarantine in preventing onward transmission of COVID-19 from traced contacts

<jats:title>Abstract</jats:title><jats:p>Quarantining close contacts of individuals infected with SARS-CoV-2 for 10 to 14 days is a key strategy in reducing transmission. However, quarantine requirements are often unpopular, with low adherence, especially when a large fraction of the population has been vaccinated. Daily contact testing (DCT), in which contacts are required to isolate only if they test positive, is an alternative to quarantine for mitigating the risk of transmission from traced contacts. In this study, we developed an integrated model of COVID-19 transmission dynamics and compared the strategies of quarantine and DCT with regard to reduction in transmission and social/economic costs (days of quarantine/self-isolation). Specifically, we compared 10-day quarantine to 7 days of self-testing using rapid lateral flow antigen tests, starting 3 days after exposure to a case. We modelled both incomplete adherence to quarantine and incomplete adherence to DCT. We found that DCT reduces transmission from contacts with similar effectiveness, at much lower social/economic costs, especially for highly vaccinated populations. The findings were robust across a spectrum of scenarios with varying assumptions on the speed of contact tracing, sensitivity of lateral flow antigen tests, adherence to quarantine and uptake of testing. Daily tests would also allow rapid initiation of a new round of tracing from infected contacts.</jats:p>

Journal article

Hinch R, Probert WJM, Nurtay A, Kendall M, Wymant C, Hall M, Lythgoe K, Bulas Cruz A, Zhao L, Stewart A, Ferretti L, Montero D, Warren J, Mather N, Abueg M, Wu N, Legat O, Bentley K, Mead T, Van-Vuuren K, Feldner-Busztin D, Ristori T, Finkelstein A, Bonsall DG, Abeler-Dorner L, Fraser Cet al., 2021, OpenABM-Covid19-An agent-based model for non-pharmaceutical interventions against COVID-19 including contact tracing, PLOS COMPUTATIONAL BIOLOGY, Vol: 17, ISSN: 1553-734X

Journal article

Risher K, Cori A, Reniers G, Marston M, Calvert C, Crampin A, Dadirai T, Dube A, Gregson S, Herbst K, Lutalo T, Moorhouse L, Mtenga B, Nabukalu D, Newton R, Price AJ, Tlhajoane M, Todd J, Tomlin K, Urassa M, Vandormael A, Fraser C, Slaymaker E, Eaton Jet al., 2021, Age patterns of HIV incidence in eastern and southern Africa: a collaborative analysis of observational general population cohort studies, The Lancet HIV, Vol: 8, Pages: e429-e439, ISSN: 2405-4704

Background: As the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this has changed over the epidemic is needed to guide HIV prevention. We assessed trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in average age at infection, age distribution of new infections, and birth cohort cumulative incidence. Methods: We used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals’ HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe. The HIV incidence rate by age, time and sex was modelled using smooth splines functions. Incidence trends were estimated separately by sex and study. Estimated incidence and prevalence results for 2000-2017, standardised to study population distribution, were used to estimate average age at infection and proportion of new infections by age. Findings: Age-specific incidence declined at all ages, though the timing and pattern of decline varied by study. The average age at infection was higher in men (cohort means: 27·8-34·6 years) than women (cohort means: 24·8-29·6 years). Between 2000 and 2017, the average age at infection increased slightly: cohort means 0·5-2·8 years among men and -0·2-2·5 years among women. Across studies, between 38-63%(cohort means)of women’s infections were among 15-24-year-olds and between 30-63% of men’s infections were in 20-29-year-olds. Lifetime risk of HIV declined for successive birth cohorts. Interpretation: HIV incidence declined in all age groups and shifted slightly, but not dramatically, to older ages. Disproportionate new HIV infections occur among 15-24-year-old 4women and20-29-year-oldmen, supporting focused prevention in these groups. But 40-60% of infections were outside these

Journal article

Meng B, Kemp SA, Papa G, Datir R, Ferreira IATM, Marelli S, Harvey WT, Lytras S, Mohamed A, Gallo G, Thakur N, Collier DA, Mlcochova P, Duncan LM, Carabelli AM, Kenyon JC, Lever AM, De Marco A, Saliba C, Culap K, Cameroni E, Matheson NJ, Piccoli L, Corti D, James LC, Robertson DL, Bailey D, Gupta RKet al., 2021, Recurrent emergence of SARS-CoV-2 spike deletion H69/V70 and its role in the Alpha variant B.1.1.7, CELL REPORTS, Vol: 35, ISSN: 2211-1247

Journal article

ISARIC Clinical Characterisation Group, 2021, COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study, Infection: journal of infectious disease, Vol: 49, Pages: 899-905, ISSN: 0300-8126

BACKGROUND: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. METHODS: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. RESULTS: 'Typical' symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. INTERPRETATION: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Journal article

Magosi LE, Zhang Y, Golubchik T, De Gruttola V, Tchetgen ET, Novitsky V, Moore J, Bachanas P, Segolodi T, Lebelonyane R, Holme MP, Moyo S, Makhema J, Lockman S, Fraser C, Essex M, Lipsitch Met al., 2021, Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial

<jats:title>Abstract</jats:title><jats:p>Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV- intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3] versus 5% [0.9 – 22.9]) compatible with a benefit from treatment-as-prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.</jats:p>

Journal article

Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, Hinsley WR, Laydon DJ, Dabrera G, O'Toole Á, Amato R, Ragonnet-Cronin M, Harrison I, Jackson B, Ariani CV, Boyd O, Loman NJ, McCrone JT, Gonçalves S, Jorgensen D, Myers R, Hill V, Jackson DK, Gaythorpe K, Groves N, Sillitoe J, Kwiatkowski DP, COVID-19 Genomics UK COG-UK consortium, Flaxman S, Ratmann O, Bhatt S, Hopkins S, Gandy A, Rambaut A, Ferguson NMet al., 2021, Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England, Nature, Vol: 593, Pages: 266-269, ISSN: 0028-0836

The SARS-CoV-2 lineage B.1.1.7, designated a Variant of Concern 202012/01 (VOC) by Public Health England1, originated in the UK in late Summer to early Autumn 20202. Whole genome SARS-CoV-2 sequence data collected from community-based diagnostic testing shows an unprecedentedly rapid expansion of the B.1.1.7 lineage during Autumn 2020, suggesting a selective advantage. We find that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S-gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that the VOC has higher transmissibility than non-VOC lineages, even if the VOC has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with a larger share of under 20 year olds among reported VOC than non-VOC cases. Time-varying reproduction numbers for the VOC and cocirculating lineages were estimated using SGTF and genomic data. The best supported models did not indicate a substantial difference in VOC transmissibility among different age groups. There is a consensus among all analyses that the VOC has a substantial transmission advantage with a 50% to 100% higher reproduction number.

Journal article

Wymant C, Ferretti L, Tsallis D, Charalambides M, Abeler-Dorner L, Bonsall D, Hinch R, Kendall M, Milsom L, Ayres M, Holmes C, Briers M, Fraser Cet al., 2021, The epidemiological impact of the NHS COVID-19 app, NATURE, Vol: 594, Pages: 408-+, ISSN: 0028-0836

Journal article

Thomas R, Probert W, Sauter R, Mwenge L, Singh S, Kanema S, Vanqa N, Harper A, Burger R, Cori A, Pickles M, Bell-Mandla N, Yang B, Bwalya J, Phiri M, Shanaube K, Floyd S, Donnell D, Bock P, Ayles H, Fidler S, Hayes R, Fraser C, Hauck Ket al., 2021, Cost and cost-effectiveness of a universal HIV testing and treatment intervention in Zambia and South Africa: evidence and projections from the HPTN 071 (PopART) trial, The Lancet Global Health, Vol: 9, Pages: e668-e680, ISSN: 2214-109X

BackgroundThe HPTN 071 (PopART) trial showed that a combination HIV prevention package including universal HIV testing and treatment (UTT) reduced population-level incidence of HIV compared with standard care. However, evidence is scarce on the costs and cost-effectiveness of such an intervention.MethodsUsing an individual-based model, we simulated the PopART intervention and standard care with antiretroviral therapy (ART) provided according to national guidelines for the 21 trial communities in Zambia and South Africa (for all individuals aged >14 years), with model parameters and primary cost data collected during the PopART trial and from published sources. Two intervention scenarios were modelled: annual rounds of PopART from 2014 to 2030 (PopART 2014–30; as the UNAIDS Fast-Track target year) and three rounds of PopART throughout the trial intervention period (PopART 2014–17). For each country, we calculated incremental cost-effectiveness ratios (ICERs) as the cost per disability-adjusted life-year (DALY) and cost per HIV infection averted. Cost-effectiveness acceptability curves were used to indicate the probability of PopART being cost-effective compared with standard care at different thresholds of cost per DALY averted. We also assessed budget impact by projecting undiscounted costs of the intervention compared with standard care up to 2030.FindingsDuring 2014–17, the mean cost per person per year of delivering home-based HIV counselling and testing, linkage to care, promotion of ART adherence, and voluntary medical male circumcision via community HIV care providers for the simulated population was US$6·53 (SD 0·29) in Zambia and US$7·93 (0·16) in South Africa. In the PopART 2014–30 scenario, median ICERs for PopART delivered annually until 2030 were $2111 (95% credible interval [CrI] 1827–2462) per HIV infection averted in Zambia and $3248 (2472–3963) per HIV infection averted in South Afric

Journal article

Graham MS, Sudre CH, May A, Antonelli M, Murray B, Varsavsky T, Kläser K, Canas LS, Molteni E, Modat M, Drew DA, Nguyen LH, Polidori L, Selvachandran S, Hu C, Capdevila J, COVID-19 Genomics UK COG-UK Consortium, Hammers A, Chan AT, Wolf J, Spector TD, Steves CJ, Ourselin Set al., 2021, Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study, The Lancet Public Health, Vol: 6, Pages: e335-e345, ISSN: 2468-2667

BACKGROUND: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. METHODS: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. FINDINGS: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in repo

Journal article

Lythgoe KA, Hall M, Ferretti L, de Cesare M, MacIntyre-Cockett G, Trebes A, Andersson M, Otecko N, Wise EL, Moore N, Lynch J, Kidd S, Cortes N, Mori M, Williams R, Vernet G, Justice A, Green A, Nicholls SM, Ansari MA, Abeler-Dorner L, Moore CE, Peto TEA, Eyre DW, Shaw R, Simmonds P, Buck D, Todd JA, Connor TR, Ashraf S, Filipe ADS, Shepherd J, Thomson EC, Bonsall D, Fraser C, Golubchik Tet al., 2021, SARS-CoV-2 within-host diversity and transmission, SCIENCE, Vol: 372, Pages: 256-+, ISSN: 0036-8075

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00330412&limit=30&person=true