Publications
486 results found
Elliott P, Whitaker M, Tang D, et al., 2023, Design and implementation of a national SARS-CoV-2 monitoring programme in England: REACT-1 Study, American Journal of Public Health, ISSN: 0090-0036
Data System. The REal-time Assessment of Community Transmission-1 (REACT-1) Study was funded by the Department of Health and Social Care in England to provide reliable and timely estimates of prevalence of SARS-CoV-2 infection by time, person and place.Data Collection/Processing. The data were obtained by writing to named individuals aged 5 years and above in random cross-sections of the population of England, using the National Health Service (NHS) list of patients registered with a general practitioner (>99% coverage) as sampling frame. Data were collected 2-3 weekly approximately every month across 19distinct rounds of data collection from May 1, 2020 to March 31, 2022.Data Analysis/Dissemination. The data and study materials are widely disseminated via the study website, preprints, publications in peer-reviewed journals and the media. Data tabulations suitably anonymised to protect participant confidentiality are available on request to the study’s Data Access Committee.Implications. The study provided inter alia real-time data on SARS-CoV-2 prevalence over time, by area, and by socio-demographic variables; estimates of vaccine effectiveness; symptom profiles and detected emergence of new variants based on viral genome sequencing.
Rowan A, Ponnusamy K, Ren H, et al., 2023, CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma, Frontiers in Immunology, Vol: 14, Pages: 1-11, ISSN: 1664-3224
Introduction: Most T cell receptor (TCR)Vβ chain-expressing T cell lymphomas (TCL) including those caused by Human T cell leukaemia virus type-1 (HTLV-1) have poor prognosis. We hypothesised that chimeric antigen receptor (CAR)-mediated targeting of the clonal, lymphoma-associated TCRβ chains would comprise an effective cell therapy for TCL that would minimally impact the physiological TCR repertoire.Methods: As proof of concept, we generated CAR constructs to target four TCRVβ subunits. Efficacy of the CAR constructs was tested using conventional T cells as effectors (CAR-T). Since invariant NKT (iNKT) cell do not incite acute graft-versus-host disease and are suitable for ‘off-the-shelf’ immunotherapy, we generated anti-TCRVβ CAR-iNKT cells.Results: We show that anti-TCRVβ CAR-T cells selectively kill their cognate tumour targets while leaving >90% of the physiological TCR repertoire intact. CAR-iNKT cells inhibited the growth of TCL in vivo, and were also selectively active against malignant cells from Adult T cell leukaemia/lymphoma patients without activating expression of HTLV-1.Discussion: Thus we provide proof-of-concept for effective and selective anti-TCRVβ CAR-T and -iNKT cell-based therapy of TCL with the latter providing the option for ‘off-the-shelf’ immunotherapy.
Bradshaw D, Khawar A, Patel P, et al., 2023, HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England., J Infect, Vol: 86, Pages: 245-247
OBJECTIVES: HTLV-1 is predominantly a sexually-transmitted infection but testing is not mentioned in HIV-PrEP guidelines. We ascertained HTLV-1/HTLV-2 seroprevalence amongst HIV-PrEP users in England. METHODS: An unlinked anonymous seroprevalence study. RESULTS: Amongst 2015 HIV-PrEP users, 95% were men, 76% of white ethnicity and 83% had been born in Europe. There were no HTLV-1/HTLV-2 seropositive cases (95% confidence interval 0% - 0.18%). CONCLUSIONS: There were no HTLV positive cases, likely reflecting the demographic of mostly white and European-born individuals. Similar studies are needed worldwide to inform public health recommendations for HIV-PrEP using populations, particularly in HTLV-endemic settings.
Takele Y, Mulaw T, Adem E, et al., 2023, Recurrent visceral leishmaniasis relapses in HIV co-infected patients are characterised by less efficient immune responses and higher parasite load, iScience, Vol: 26, Pages: 1-22, ISSN: 2589-0042
Visceral leishmaniasis (VL) and HIV co-infection (VL/HIV) has emerged as a significant public health problem in Ethiopia, with up to 30% of patients with VL co-infected with HIV. These patients suffer from recurrent VL relapses and increased mortality. Those with a previous history of VL relapses (recurrent VL/HIV) experience increased VL relapses as compared to patients with HIV presenting with their first episode of VL (primary VL/HIV). Our aim was to identify drivers that account for the higher rate of VL relapses in patients with recurrent VL/HIV (n = 28) as compared to primary VL/HIV (n = 21). Our results show that the relapse-free survival in patients with recurrent VL/HIV was shorter, that they had higher parasite load, lower weight gain, and lower recovery of all blood cell lineages. Their poorer prognosis was characterized by lower production of IFN-gamma, lower CD4+ T cell counts, and higher expression of programmed cell death protein 1 (PD1) on T cells.
Rosadas de Oliveira C, Senna K, Costa M, et al., 2023, Economic analysis of HTLV-1 antenatal screening in Brazil: An open access cost-utilitymodel, The Lancet Global Health, ISSN: 2214-109X
Rosadas C, Taylor GP, 2023, Pre-analytical long-term stability of neopterin and neurofilament light in stored cerebrospinal fluid samples, Clinical Chemistry and Laboratory Medicine, Pages: 1-5, ISSN: 1434-6621
ObjectivesThe aim of this study was to evaluate the impact of long-term sample storage on the concentrations of neopterin and neurofilament light (Nfl) in cerebrospinal fluid (CSF) samples. These are useful markers of neuroinflammation and neuronal damage and have been applied as biomarkers for several neurological diseases. However, different pre-analytical variables have potential to influence results.MethodsTwenty-one CSF samples donated by patients with HTLV-1-associated myelopathy (HAM) and stored for up to 11 years at −80 °C were retested after three-years for neopterin (n=10) and Nfl (n=11) by ELISA.ResultsThere was a strong correlation between the paired results (r>0.98, p<0.0001). Neopterin concentrations (nmol/L) ranged from 12.4 to 64 initially and from 11.5 to 64.4 when retested, with means (SD) of 30 (18.4) 1st test and 33 (19.1) 2nd test. Nfl concentrations (pg/mL) ranged from 79.9 to 3,733 initially and from 86.3 to 3,332, when retested with means (SD) of 1,138 (1,272) 1st test and 1,009 (1,114) at re-test.ConclusionsStoring CSF samples at −80 °C appears not to impact the quantification of neopterin and Nfl allowing confidence in the reporting of archived samples.
Dixon L, McNamara C, Dhasmana D, et al., 2023, The imaging spectrum of HTLV-1 related neurological disease: a pooled series and review, Neurology: Clinical Practice, ISSN: 2163-0402
Burnham KL, Maher AK, Jones EM, et al., 2022, Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19, Nature Communications, Vol: 13, Pages: 1-17, ISSN: 2041-1723
Although alterations in myeloid cells have been observed in COVID-19, the specific underlying mechanisms are not completely understood. Here, we examine the function of classical CD14+ monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals. Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes. Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis. COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2. Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation. These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.
Harding D, Rosadas C, Tsoti S, et al., 2022, Refining the risk of HTLV-1-associated myelopathy in people living with HTLV-1: Identification of a HAM-like phenotype in a proportion of asymptomatic carriers, Journal of NeuroVirology, Vol: 28, Pages: 473-482, ISSN: 1355-0284
Background: Up to 3.8% of human T-lymphotropic virus type-1 (HTLV-1)-infected asymptomatic carriers (AC) eventually develop HTLV-1-associated myelopathy (HAM). HAM occurs in patients with high (>1%) HTLV proviral load (PVL). However, this cut-off includes more than 50% of ACs and therefore the risk needs to be refined. As HAM is additionally characterised by an inflammatory response to HTLV-1, markers of T cell activation (TCA), β 2 -microglobulin (β 2 M) and neuronal damage were accessed for the identification of ACs at high risk of HAM. Methods: Retrospective analysis ofcross-sectional and longitudinal routine clinical data examining differences in TCA (CD4/CD25, CD4/HLA-DR, CD8/CD25 & CD8/HLA-DR), β 2 M and neurofilament light (NfL) in plasma in ACs with high or low PVL and patients with HAM. Results: Comparison between 74 low PVL ACs, 84 high PVL ACs and 58 patients with HAM revealed a significant, stepwise, increase in TCA and β 2 M. Construction of receiver operating characteristic (ROC) curves for each of these blood tests generated a profile that correctly identifies 88% of patients with HAM along with 6% of ACs. The 10 ACs with this ‘HAM-like’ profile had increased levels of NfL in plasma and two developed myelopathy during follow-up, compared to none of the 148 without this viral-immune-phenotype. Conclusions: A viral-immuno-phenotype resembling that seen in patients with HAM identifies asymptomatic carriers who are at increased risk of developing HAM and have markers of subclinical neuronal damage.
Rowan AG, Ponnusamy K, Ren H, et al., 2022, Anti-T Cell Receptor V ss Chain-Specific CAR-iNKT Cells As a Precise Strategy to Treat Mature T Cell Lymphomas, Publisher: AMER SOC HEMATOLOGY, Pages: 10257-10258, ISSN: 0006-4971
Wolf SN, Watber P, Haddow J, et al., 2022, HTLV-1 Carriers with Circulating Dominant Clones Harbor ATL-like Mutational and Transcriptomic Profiles Which Identify an Ultra-High Risk Group for Disease Transformation, Publisher: AMER SOC HEMATOLOGY, Pages: 9224-9225, ISSN: 0006-4971
Rosadas C, Taylor GP, 2022, Current interventions to prevent HTLV-1 mother-to-child transmission and their effectiveness: a systematic review and meta-analysis., Microorganisms, Vol: 10, Pages: 1-15, ISSN: 2076-2607
Human T lymphotropic virus 1 (HTLV-1) may be transmitted from mother to child and affects at least 5-10 million individuals worldwide, with severe consequences on health. Strategies to prevent transmission are important, as there is no treatment or vaccine. This systematic review aimed to identify interventions to prevent HTLV-1 mother-to-child transmission and to determine their effectiveness. Exclusive formula feeding, short-term breastfeeding, use of freeze-thaw milk, milk pasteurization, maternal and infant antiretroviral drugs, caesarean section, early clamping of umbilical cord, screening of milk donors and avoidance of cross-breastfeeding were identified as possible strategies. Avoidance of breastfeeding is an intervention that prevents 85% of transmissions. This strategy is recommended in Japan, Brazil, Colombia, Canada, Chile, Uruguay, the USA and some regions of French Guyana. Whilst breastfeeding for <3 months does not increase the risk of transmission compared to exclusive formula-feeding, concerns remain regarding the limited number of studies outside Japan, and the lack of information on women having higher risk of HTLV-1 transmission and on the ability of women to discontinue breastfeeding. Additional interventions are plausible, but data on their effectiveness are limited. The acceptance of interventions is high. These findings may guide healthcare professionals and support policymakers in implementing policies to avoid HTLV-1 mother-to-child transmission.
Hakki S, Zhou J, Jonnerby J, et al., 2022, Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study, The Lancet Respiratory Medicine, Vol: 10, Pages: 1061-1073, ISSN: 2213-2600
BACKGROUND: Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. METHODS: The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. FINDINGS: Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3-7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and
Mosscrop L, Watber P, Elliot P, et al., 2022, Evaluation of the impact of pre-analytical conditions on sample stability for the detection of SARS-CoV-2 RNA, Journal of Virological Methods, Vol: 309, Pages: 1-5, ISSN: 0166-0934
Demand for accurate SARS-CoV-2 diagnostics is high. Most samples in the UK are collected in the community and rely on the postal service for delivery to the laboratories. The current recommendation remains that swabs should be collected in Viral Transport Media (VTM) and transported with a cold chain to the laboratory for RNA extraction and RT-qPCR. This is not always possible. We aimed to test the stability of SARS-CoV-2 RNA subjected to different pre-analytical conditions. Swabs were dipped into PBS containing cultured SARS-CoV-2 and placed in either a dry tube or a tube containing either normal saline or VTM. The tubes were then stored at different temperatures (20–50 °C) for variable periods (8 h to 5 days). Samples were tested by RT-qPCR targeting SARS-CoV-2 E gene. VTM outperformed swabs in saline and dry swabs in all conditions. Samples in VTM were stable, independent of a cold chain, for 5 days, with a maximum increase in cycle threshold (Ct) of 1.34 when held at 40 °C. Using normal saline as the transport media resulted in a loss of sensitivity (increased Ct) over time and with increasing temperature (up to 7.8 cycles compared to VTM). SARS-CoV-2 was not detected in 3/9 samples in normal saline when tested after 120 h incubation. Transportation of samples in VTM provides a high level of confidence in the results despite the potential for considerable, uncontrolled variation in temperature and longer transportation periods. False negative results may be seen after 96 h in saline and viral loads will appear lower.
Cordery R, Reeves L, Zhou J, et al., 2022, Transmission of SARS-CoV-2 by children to contacts in schools and households: a prospective cohort and environmental sampling study in London, The Lancet Microbe, Vol: 3, Pages: e814-e823, ISSN: 2666-5247
Background: Assessing transmission of SARS-CoV-2 by children in schools is of critical importance to inform public health action. We assessed frequency of acquisition of SARS-CoV-2 by contacts of pupils with COVID-19 in schools and households, and quantified SARS-CoV-2 shed into air and onto fomites in both settings.Methods: Incidents involving exposure to at least one index pupil with COVID-19 in 8 schools were identified between October 2020-July 2021 (prevailing variants, original, alpha and delta). Weekly PCR testing for SARS-CoV-2 was undertaken on immediate classroom contacts (the “bubble”), non-bubble school contacts, and household contacts of index pupils, supported by genome sequencing, and on surface and air samples from school and home environments.Findings: Secondary transmission of SARS-CoV-2 was not detected in 28 bubble contacts, representing 10 bubble classes (participation rate 8.8%, IQR 4.6-15.3%). Across 8 non-bubble classes, 3/62 pupils tested positive but these were unrelated to the original index case (participation rate 22.5%, IQR 9.7-32.3%). All three were asymptomatic and tested positive in one setting on the same day. In contrast, secondary transmission to previously-negative household contacts from infected index pupils was 17.1% (6/35) rising to 27.7% (13/47) when considering all potentialinfections in household contacts. Environmental contamination with SARS-CoV-2 was rare in schools; fomite SARS-CoV-2 was identified in 4/189 (2.1%) samples in bubble classrooms, 2/127 (1.6%) samples in non-bubble classrooms, and 5/130 (3.8%) samples in washrooms. This contrasted with fomites in households, where SARS-CoV-2 was identified in 60/248 (24.2%) bedroom samples, 66/241 (27.4%) communal room samples, and 21/188 (11.2%) bathroom samples. Air sampling identified SARS-CoV-2 RNA in just 1/68 (1.5%) of school air samples, compared with 21/85 (24.7%) of air samples taken in homes.Interpretation: There was no evidence of large scale SARS-Co
Chadeau-Hyam M, Tang D, Eales O, et al., 2022, Omicron SARS-CoV-2 epidemic in England during February 2022: A series of cross-sectional community surveys, The Lancet Regional Health Europe, Vol: 21, Pages: 1-11, ISSN: 2666-7762
BackgroundThe Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.MethodsIn the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).FindingsWe estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London.InterpretationIn February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.FundingDepartment of Health and Social Care, England.
Taylor G, Cook L, 2022, A new paradigm for the management in ATL, British Journal of Haematology, Vol: 198, Pages: 941-942, ISSN: 0007-1048
Puccioni-Sohler M, Poton AR, Cabral-Castro MJ, et al., 2022, Human T Lymphotropic Virus 1-Associated Myelopathy: Overview of Human T Cell Lymphotropic Virus-1/2 Tests and Potential Biomarkers, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 38, Pages: 924-932, ISSN: 0889-2229
Schnell AP, Kohrt S, Aristodemou A, et al., 2022, HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients' T-cells, FRONTIERS IN IMMUNOLOGY, Vol: 13, ISSN: 1664-3224
Almeida Machado LF, Vallinoto ACR, Rosadas C, et al., 2022, Editorial: Prevention and control of human T lymphotropic viruses 1 and 2 (HTLV-1/2), FRONTIERS IN MEDICINE, Vol: 9
- Author Web Link
- Cite
- Citations: 1
Elliott P, Eales O, Bodinier B, et al., 2022, Dynamics of a national Omicron SARS-CoV-2 epidemic during January 2022 in England, Nature Communications, Vol: 13, ISSN: 2041-1723
Rapid transmission of the SARS-CoV-2 Omicron variant has led to record-breaking case incidence rates around the world. Since May 2020, the REal-time Assessment of Community Transmission-1 (REACT-1) study tracked the spread of SARS-CoV-2 infection in England through RT-PCR of self-administered throat and nose swabs from randomly-selected participants aged 5 years and over. In January 2022, we found an overall weighted prevalence of 4.41% (n=102,174), three-fold higher than in November to December 2021; we sequenced 2,374 (99.2%) Omicron infections (19 BA.2), and only 19 (0.79%) Delta, with a growth rate advantage for BA.2 compared to BA.1 or BA.1.1. Prevalence was decreasing overall (reproduction number R=0.95, 95% credible interval [CrI], 0.93, 0.97), but increasing in children aged 5 to 17 years (R=1.13, 95% CrI, 1.09, 1.18). In England during January 2022, we observed unprecedented levels of SARS-CoV-2 infection, especially among children, driven by almost complete replacement of Delta by Omicron.
Malaba TR, Nakatudde I, Kintu K, et al., 2022, 72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study., Lancet HIV, Vol: 9, Pages: e534-e543
BACKGROUND: Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. METHODS: DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. FINDINGS: Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) moth
Eales O, Martins LDO, Page AJ, et al., 2022, Dynamics of competing SARS-CoV-2 variants during the Omicron epidemic in England, Nature Communications, Vol: 13, ISSN: 2041-1723
The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant (first detected in November 2021) exhibited a high degree of immune evasion, leading to increased infection rates worldwide. However, estimates of the magnitude of this Omicron wave have often relied on routine testing data, which are prone to several biases. Using data from the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys assessing prevalence of SARS-CoV-2 infection in England, we estimated the dynamics of England’s Omicron wave (from 9 September 2021 to 1 March 2022). We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct variants, intermittent epidemics of similar magnitudes may become the ‘new normal’.
Eales O, Wang H, Bodinier B, et al., 2022, SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September - 27 September 2021) and 15 (19 October - 5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month.Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI, 8%-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England.Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.
Eales O, de Oliveira Martins L, Page A, et al., 2022, Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England, Nature Communications, ISSN: 2041-1723
Houston H, Hakki S, Pillay TD, et al., 2022, Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts, European Respiratory Journal, Vol: 60, Pages: 1-13, ISSN: 0903-1936
Background The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), i.e. fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.Methods Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test.Results Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion “≥1 of the CS, or ≥2 of the EP” identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than “≥1 of the CS”, with only modest reduction in specificity (5.7%).Conclusions Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.Tweetable abstract @ERSpublications
Barr R, Drysdale S, Boullier M, et al., 2022, A review of the prevention of mother-to-child transmission of human T-cell lymphotropic virus type 1 (HTLV-1) with a proposed management algorithm, Frontiers in Medicine, Vol: 9, Pages: 1-7, ISSN: 2296-858X
Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that is endemic in a number of regions across the world. There are an estimated 5-10 million people infected worldwide. Japan is currently the only country with a national antenatal screening programme in place. HTLV-1 is primarily transmitted sexually in adulthood, however it can be transmitted from mother-to-child perinatally. This can occur transplacentally, during the birth process or via breastmilk. If HTLV-1 is transmitted perinatally then the lifetime risk of adult T cell leukaemia/lymphoma rises from 5% to 20%, therefore prevention of mother-to-child transmission of HTLV-1 is a public health priority. There are reliable immunological and molecular tests available for HTLV-1 diagnosis during pregnancy and screening should be considered on a country by country basis. Further research on best management is needed particularly for pregnancies in women with high HTLV-1 viral load. A first step would be to establish an international registry of cases and to monitor outcomes for neonates and mothers. We have summarised key risk factors for mother-to-child transmission of HTLV-1 and subsequently propose a pragmatic guideline for management of mothers and infants in pregnancy and the perinatal period to reduce the risk of transmission. This is clinically relevant in order to reduce mother-to-child transmission of HTLV-1 and it’s complications.
Chadeau M, Tang D, Eales O, et al., 2022, Cross-sectional community surveys to monitor the Omicron SARS-CoV-2 epidemic in England during February 2022, The Lancet Regional Health Europe, ISSN: 2666-7762
Background: The Omicron wave of COVID-19 in England peaked in January 2022 resulting from the rapid transmission of the Omicron BA.1 variant. We investigate the spread and dynamics of the SARS-CoV-2 epidemic in the population of England during February 2022, by region, age and main SARS-CoV-2 sub-lineage.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study we obtained data from a random sample of 94,950 participants with valid throat and nose swab results by RT-PCR during round 18 (8 February to 1 March 2022).Findings: We estimated a weighted mean SARS-CoV-2 prevalence of 2.88% (95% credible interval [CrI] 2.76–3.00), with a within-round effective reproduction number (R) overall of 0.94 (0·91–0.96). While within-round weighted prevalence fell among children (aged 5 to 17 years) and adults aged 18 to 54 years, we observed a level or increasing weighted prevalence among those aged 55 years and older with an R of 1.04 (1.00–1.09). Among 1,616 positive samples with sublineages determined, one (0.1% [0.0–0.3]) corresponded to XE BA.1/BA.2 recombinant and the remainder were Omicron: N=1,047, 64.8% (62.4–67.2) were BA.1; N=568, 35.2% (32.8–37.6) were BA.2. We estimated an R additive advantage for BA.2 (vs BA.1) of 0.38 (0.34–0.41). The highest proportion of BA.2 among positives was found in London. Interpretation: In February 2022, infection prevalence in England remained high with level or increasing rates of infection in older people and an uptick in hospitalisations. Ongoing surveillance of both survey and hospitalisations data is required.Funding Department of Health and Social Care, England.
Chadeau M, Eales O, Bodinier B, et al., 2022, Breakthrough SARS-CoV-2 infections in double and triple vaccinated adults and single dose vaccine effectiveness among children in Autumn 2021 in England: REACT-1 study, EClinicalMedicine, Vol: 48, Pages: 1-14, ISSN: 2589-5370
Background: Prevalence of SARS-CoV-2 infection with Delta variant was increasing in England in late summer 2021 among children aged 5 to 17 years, and adults who had received two vaccine doses. In September 2021, a third (booster) dose was offered to vaccinated adults aged 50 years and over, vulnerable adults and healthcare/care-home workers, and a single vaccine dose already offered to 16 and 17 year-olds was extended to children aged 12 to 15 years. Methods: SARS-CoV-2 community prevalence in England was available from self-administered throat and nose swabs using reverse transcriptase polymerase chain reaction (RT-PCR) in round 13 (24 June to 12 July 2021, N= 98,233), round 14 (9 to 27 September 2021, N = 100,527) and round 15 (19 October to 5 November 2021, N = 100,112) from the REACT-1 study randomised community surveys. Linking to National Health Service (NHS) vaccination data for consenting participants, we estimated vaccine effectiveness in children aged 12 to 17 years and compared swab-positivity rates in adults who received a third dose with those who received two doses. Findings: Weighted SARS-CoV-2 prevalence was 1.57% (1.48%, 1.66%) in round 15 compared with 0.83% (0.76%, 0.89%) in round 14, and the previously observed link between infections and hospitalisations and deaths had weakened. Vaccine effectiveness against infection in children aged 12 to 17 years was estimated (round 15) at 64.0% (50.9%, 70.6%) and 67.7% (53.8%, 77.5%) for symptomatic infections. Adults who received a third vaccine dose were less likely to test positive compared to those who received two doses, with adjusted odds ratio of 0.36 (0.25, 0.53). Interpretation: Vaccination of children aged 12 to 17 years and third (booster) doses in adults were effective at reducing infection risk. High rates of vaccination, including booster doses, are a key part of the strategy to reduce infection rates in the community.
Rosadas C, Assone T, Sereno L, et al., 2022, "We need to translate research into meaningful HTLV health policies and programs": webinar HTLV World Day 2021., Frontiers in Public Health, Vol: 10, Pages: 1-5, ISSN: 2296-2565
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.