Publications
296 results found
Tsui JL-H, McCrone JT, Lambert B, et al., 2023, Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1., Science, Vol: 381, Pages: 336-343
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) now arise in the context of heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron BA.1 genomes, we identified >6,000 introductions of the antigenically distinct VOC into England and analyzed their local transmission and dispersal history. We find that six of the eight largest English Omicron lineages were already transmitting when Omicron was first reported in southern Africa (22 November 2021). Multiple datasets show that importation of Omicron continued despite subsequent restrictions on travel from southern Africa as a result of export from well-connected secondary locations. Initiation and dispersal of Omicron transmission lineages in England was a two-stage process that can be explained by models of the country's human geography and hierarchical travel network. Our results enable a comparison of the processes that drive the invasion of Omicron and other VOCs across multiple spatial scales.
Zewdie K, Pickles M, Floyd S, et al., 2023, Uptake of medical male circumcision with household-based testing, and the association of traditional male circumcision and HIV infection, AIDS, Vol: 37, Pages: 795-802, ISSN: 0269-9370
OBJECTIVES: Voluntary medical male circumcision (VMMC) is an important component of combination HIV prevention. Inclusion of traditionally circumcised HIV negative men in VMMC uptake campaigns may be important if traditional male circumcision is less protective against HIV acquisition than VMMC. METHODS: We used data from the HIV Prevention Trials Network (HPTN) 071 (PopART) study. This cluster-randomized trial assessed the impact of a combination prevention package on population-level HIV incidence in 21 study communities in Zambia and South Africa. We evaluated uptake of VMMC, using a two-stage analysis approach and used discrete-time survival analysis to evaluate the association between the types of male circumcision and HIV incidence. RESULTS: A total of 10 803 HIV-negative men with self-reported circumcision status were included in this study. At baseline, 56% reported being uncircumcised, 26% traditionally circumcised and 18% were medically circumcised. During the PopART intervention, 11% of uncircumcised men reported uptake of medical male circumcision. We found no significant difference in the uptake of VMMC in communities receiving the PopART intervention package and standard of care {adj. rate ratio=1·10 [95% confidence interval (CI) 0.82, 1.50, P = 0.48]}. The rate of HIV acquisition for medically circumcised men was 70% lower than for those who were uncircumcised adjusted hazard ratio (adjHR) = 0.30 (95% CI 0.16-0.55; P < 0.0001). There was no difference in rate of HIV acquisition for traditionally circumcised men compared to those uncircumcised adjHR = 0.84 (95% CI 0.54, 1.31; P = 0.45). CONCLUSIONS: Household-based delivery of HIV testing followed by referral for medical male circumcision did not result in substantial VMMC uptake. Traditional circumcision is not associated with lower risk of HIV acquisition.
Balakrishna S, Loosli T, Zaheri M, et al., 2023, Frequency matters: comparison of drug resistance mutation detection by Sanger and next-generation sequencing in HIV-1, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 78, Pages: 656-664, ISSN: 0305-7453
Kendall M, Tsallis D, Wymant C, et al., 2023, Epidemiological impacts of the NHS COVID-19 app in England and Wales throughout its first year., Nat Commun, Vol: 14
The NHS COVID-19 app was launched in England and Wales in September 2020, with a Bluetooth-based contact tracing functionality designed to reduce transmission of SARS-CoV-2. We show that user engagement and the app's epidemiological impacts varied according to changing social and epidemic characteristics throughout the app's first year. We describe the interaction and complementarity of manual and digital contact tracing approaches. Results of our statistical analyses of anonymised, aggregated app data include that app users who were recently notified were more likely to test positive than app users who were not recently notified, by a factor that varied considerably over time. We estimate that the app's contact tracing function alone averted about 1 million cases (sensitivity analysis 450,000-1,400,000) during its first year, corresponding to 44,000 hospital cases (SA 20,000-60,000) and 9,600 deaths (SA 4600-13,000).
Groves-Kirkby N, Wakeman E, Patel S, et al., 2022, Large-scale calibration and simulation of COVID-19 epidemiologic scenarios to support healthcare planning, EPIDEMICS, Vol: 42, ISSN: 1755-4365
Fryer HR, Golubchik T, Hall M, et al., 2022, Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias
<jats:title>Abstract</jats:title><jats:p>In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated individuals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected individual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.</jats:p>
Zhao L, Hall M, de Cesare M, et al., 2022, The mutational spectrum of SARS-CoV-2 genomic and antigenomic RNA, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 289, ISSN: 0962-8452
Panovska-Griffiths J, Hinch R, Park J, et al., 2022, Slowly declining growth rates and dynamic reporting delays characterise the Monkeypox epidemic in the UK over May-August 2022
<jats:title>Abstract</jats:title> <jats:p>The monkeypox epidemic in the UK began in May 2022, and subsequently and rather quickly, rates of new cases have declined during August 2022. Identifying the causes of this decline requires accurate estimates of the time-varying epidemic growth rate r(t), which in turn depend upon the reporting delays (defined as the time from onset of symptoms to presenting to healthcare). Using a custom nowcasting method which allows for time-varying delays (EpiLine), we show that the reporting delay for Monkeypox in the UK decreased from an average of 22 days in early May 2022 to 10 days by early June and 7 days in August 2022. Accounting for these dynamic delays shows that the time-varying r(t) declined gradually in the UK over this period. Not accounting for varying time delays would have incorrectly characterised r(t) by a sharp increase followed by a rapid drop. We discuss the importance of this gradual decline, which helps identify the potential mechanisms responsible for the decline in the rate of spread of Monkeypox, which was gradual and started well before vaccines were widely used.</jats:p>
Lehtinen S, Croucher NJ, Blanquart F, et al., 2022, Epidemiological dynamics of bacteriocin competition and antibiotic resistance, PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 289, ISSN: 0962-8452
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- Citations: 1
Panovska-Griffiths J, Swallow B, Hinch R, et al., 2022, Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 380, ISSN: 1364-503X
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- Citations: 6
Hinch R, Panovska-Griffiths J, Probert WJM, et al., 2022, Estimating SARS-CoV-2 variant fitness and the impact of interventions in England using statistical and geo-spatial agent-based models, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Vol: 380, ISSN: 1364-503X
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- Citations: 3
Overton CE, Pellis L, Stage HB, et al., 2022, EpiBeds: Data informed modelling of the COVID-19 hospital burden in England, PLOS COMPUTATIONAL BIOLOGY, Vol: 18, ISSN: 1553-734X
Blenkinsop A, Monod M, van Sighem A, et al., 2022, Estimating the potential to prevent locally acquired HIV infections in a UNAIDS Fast-Track City, Amsterdam, Publisher: eLIFE SCIENCES PUBL LTD
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- Citations: 1
Fogel JM, Wilson EA, Piwowar-Manning E, et al., 2022, HIV drug resistance in a community-randomized trial of universal testing and treatment: HPTN 071 (PopART), JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 25
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- Citations: 1
Ragonnet-Cronin M, Golubchik T, Moyo S, et al., 2022, HIV genetic diversity informs stage of HIV-1 infection among patients receiving antiretroviral therapy in Botswana, The Journal of Infectious Diseases, Vol: 225, Pages: 1330-1338, ISSN: 0022-1899
BackgroundHIV-1 genetic diversity increases during infection and can help infer the time elapsed since infection. However the effect of antiretroviral treatment (ART) on the inference remains unknown.MethodsParticipants with estimated duration of HIV-1 infection based on repeated testing were sourced from cohorts in Botswana (n=1944). Full-length HIV genome sequencing was performed from proviral DNA. We optimized a machine learning model to classify infections as < or >1 year based on viral genetic diversity, demographic and clinical data.ResultsThe best predictive model included variables for genetic diversity of HIV-1 gag, pol and env, viral load, age, sex and ART status. Most participants were on ART. Balanced accuracy was 90.6% (95%CI:86.7%-94.1%). We tested the algorithm among newly diagnosed participants with or without documented negative HIV tests. Among those without records, those who self-reported a negative HIV test within <1 year were more frequently classified as recent than those who reported a test >1 year previously. There was no difference in classification between those self-reporting a negative HIV test <1 year, whether or not they had a record.ConclusionsThese results indicate that recency of HIV-1 infection can be inferred from viral sequence diversity even among patients on suppressive ART.
Zhao L, Wymant C, Blanquart F, et al., 2022, Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load, VIRUS EVOLUTION, Vol: 8
Magosi LE, Zhang Y, Golubchik T, et 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
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- Citations: 1
Wymant C, Bezemer D, Blanquart F, et al., 2022, A highly virulent variant of HIV-1 circulating in the Netherlands, SCIENCE, Vol: 375, Pages: 540-+, ISSN: 0036-8075
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- Citations: 13
Kraemer MUG, Pybus OG, Fraser C, et 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
Lythgoe K, Golubchik T, Hall M, et al., 2022, Lineage replacement and evolution captured by three years of the United Kingdom Covid Infection Survey
<jats:title>Abstract</jats:title><jats:p>The Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non- SGTF over time. Evolution was characterised by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, 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 in the current phase of the pandemic with routine RT-PCR testing now ended in the community.</jats:p>
Panovska-Griffiths J, Swallow B, Hinch R, et 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>
Willett BJ, Grove J, MacLean OA, et 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>
Twohig KA, Nyberg T, Zaidi A, et 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
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- Citations: 318
McCrone JT, Hill V, Bajaj S, et 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.
OToole Á, Hill V, Jackson B, et 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>
Limbada M, Macleod D, Situmbeko V, et 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
de Silva TI, Liu G, Lindsey BB, et 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.
Kraemer MUG, Pybus OG, Fraser C, et al., 2021, Monitoring key epidemiological parameters of SARS-CoV-2 transmission, NATURE MEDICINE, Vol: 27, Pages: 1854-1855, ISSN: 1078-8956
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- Citations: 8
Moher M, Erickson M, Black P, et 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
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Hall M, Golubchik T, Bonsall D, et al., 2021, Demographics of people who transmit HIV-1 in Zambia: a molecular epidemiology analysis in the HPTN-071 PopART study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>In the last decade, universally available antiretroviral therapy (ART) has led to greatly improved health and survival of people living with HIV in sub-Saharan Africa, and appears to have contributed to reduced rates of new infections. Individuals acting as sources of infection need to be characterised to design effective prevention strategies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used viral genomes to investigate the demographic characteristics of sources of HIV-1 infection. Between 2014 and 2018, the HPTN 071 PopART study was conducted to quantify the public health benefits of ART. Viral samples from 7,124 study participants in Zambia were deep-sequenced as part of HPTN 071-02 PopART Phylogenetics, an ancillary study. We identified 300 likely HIV-1 transmission pairs and investigated the source individuals in those pairs to better understand transmission in the general population.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>After demographic weighting, 59.4% of transmissions were male to female, with 43·2% (95% CI: 36·8%-49·7%) of transmissions being from males aged 25-40. Overall, men transmitted 2.09-fold (2·06-2·29) more infections per capita than women, a ratio peaking, when stratified by source age, at 5.88 (2·78-15·8) in the 35-39 age group. 17·4% of sources (12·5%-22·4%) carried viruses resistant to first-line ART. 12·9% (8·5%-17·3%) of transmissions linked individuals from different communities in the trial.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>HIV-1 transmission in the HPTN 071 study communities comes from a wide range of age and sex groups
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