Publications
51 results found
Schurz H, Naranbhai V, Yates TA, et al., 2024, Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture, eLife, Vol: 12, ISSN: 2050-084X
The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h2 = 26.3%, 95% CI 23.7–29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 × 10-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 × 10-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure.
Yates TA, Halliday N, 2024, Re: Association of CMV DNAemia with Long-Term Mortality in a Randomized Trial of Preemptive Therapy (PET) and Antiviral Prophylaxis (AP) for Prevention of CMV Disease in High-Risk Donor Seropositive, Recipient Seronegative (D+R-) Liver Transplant Recipients., Clin Infect Dis
Hamilton F, Schurz H, Yates TA, et al., 2023, Altered IL-6 signalling and risk of tuberculosis disease: a meta-analysis and Mendelian randomisation study., medRxiv
IL-6 responses are ubiquitous in Mycobacterium tuberculosis (Mtb) infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor (IL6R) gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome of Mtb infection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.
Yates TA, Karat AS, Bozzani F, et al., 2023, Time to change the way we think about tuberculosis infection prevention and control in health facilities: insights from recent research., Antimicrob Steward Healthc Epidemiol, Vol: 3
In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.
Dempsey PC, Rowlands A, Strain T, et al., 2022, Physical activity volume, intensity, and incident cardiovascular disease, EUROPEAN HEART JOURNAL, Vol: 43, Pages: 4789-4800, ISSN: 0195-668X
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- Citations: 12
Yates TA, Griffith GJ, Morris TT, 2022, Human Cytomegalovirus and Risk of Incident Cardiovascular Disease in UK Biobank, JOURNAL OF INFECTIOUS DISEASES, Vol: 225, Pages: 1301-1302, ISSN: 0022-1899
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- Citations: 1
McCreesh N, Karat AS, Govender I, et al., 2022, Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa, BMJ GLOBAL HEALTH, Vol: 7, ISSN: 2059-7908
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- Citations: 2
Karat AS, McCreesh N, Baisley K, et al., 2022, Estimating waiting times, patient flow, and waiting room occupancy density as part of tuberculosis infection prevention and control research in South African primary health care clinics., PLOS Glob Public Health, Vol: 2
Transmission of respiratory pathogens, such as Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. Reducing overcrowding of health facilities is a recognised infection prevention and control (IPC) strategy; reliable estimates of waiting times and 'patient flow' would help guide implementation. As part of the Umoya omuhle study, we aimed to estimate clinic visit duration, time spent indoors versus outdoors, and occupancy density of waiting rooms in clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa. We used unique barcodes to track attendees' movements in 11 clinics, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration. 2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36-3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001). Overall, attendees spent more of their time indoors (median 95.6% [IQR 46-100]) than outdoors (2.5% [IQR 0-35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1-75]) of their time outdoors. In two clinics in KZN (no appointment system), occupancy densities of ~2.0 persons/m2 were observed in smaller waiting rooms during busy periods. In one clinic in WC (appointment system, larger waiting areas), occupancy density did not exceed 1.0 persons/m2 despite higher overall attendance. In this study, longer waiting times were associated with early arrival, being female, and attending with a young child. Occupancy of waiting rooms varied substantially between rooms and over the clinic day. Light-to
McCreesh N, Karat AS, Govender I, et al., 2021, Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>There is a high risk of <jats:italic>Mycobacterium tuberculosis</jats:italic> (<jats:italic>Mtb</jats:italic>) transmission in healthcare facilities in high burden settings. Recent World Health Organization guidelines on tuberculosis infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare and institutional settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide tuberculosis incidence and mortality.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We developed an individual-based model of <jats:italic>Mtb</jats:italic> transmission between household members, in primary healthcare clinics (PHCs), and in other congregate settings; drug sensitive and multidrug resistant tuberculosis disease development and resolution; and HIV and antiretroviral therapy (ART) and their effects on tuberculosis. The model was parameterised using data from a high HIV prevalence, rural/peri-urban community in KwaZulu-Natal, South Africa, including data on social contact in clinics and other settings by sex, age group, and HIV/ART status; and data on the prevalence of tuberculosis in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics in 2019, and the impact of a range of IPC interventions in clinics on community-wide TB incidence and mortality.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We estimate that 7.6% (plausible range 3.9-13.9%) of drug sensitive and multidrug resistant tuberculosis in adult
McCreesh N, Karat AS, Baisley K, et al., 2021, Modelling the effect of infection prevention and control measures on rate of <i>Mycobacterium tuberculosis</i> transmission to clinic attendees in primary health clinics in South Africa
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Elevated rates of tuberculosis in health care workers demonstrate the high rate of <jats:italic>Mycobacterium tuberculosis (Mtb)</jats:italic> transmission in health facilities in high burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on <jats:italic>Mtb</jats:italic> transmission to patients and other clinic attendees.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>An individual-based model of patient movements through clinics, ventilation in waiting areas, and <jats:italic>Mtb</jats:italic> transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions – co-developed with health professionals and policy-makers - were simulated: 1. queue management systems with outdoor waiting areas, 2. ultraviolet germicidal irradiation systems (UVGI), 3. appointment systems, 4. opening windows and doors, 5. surgical mask wearing by clinic attendees, 6. simple clinic retrofits, and 7. increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the CCMDD service.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the model, 1. outdoor waiting areas reduced the transmission to clinic attendees by 83% (interquartile range [IQR] 76-88%), 2. UVGI by 77% (IQR 64-85%), 3. appointment systems by 62% (IQR 45-75%), 4. opening windows and doors by 55% (IQR 25-72%), 5. masks by 47% (IQR 42-50%), 6. clinic retrofits by 45% (IQR 16-64%), and 7. increasing the coverage of CCMDD by 22% (IQR 12-32%).</jats:p></jats:sec><
Karat AS, McCreesh N, Baisley K, et al., 2021, Waiting times, patient flow, and occupancy density in South African primary health care clinics: implications for infection prevention and control
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Transmission of respiratory pathogens, such as<jats:italic>Mycobacterium tuberculosis</jats:italic>and severe acute respiratory syndrome coronavirus 2, is more likely during close, prolonged contact and when sharing a poorly ventilated space. In clinics in KwaZulu-Natal (KZN) and Western Cape (WC), South Africa, we estimated clinic visit duration, time spent indoors and outdoors, and occupancy density of waiting rooms.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used unique barcodes to track attendees’ movements in 11 clinics in two provinces, multiple imputation to estimate missing arrival and departure times, and mixed-effects linear regression to examine associations with visit duration.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>2,903 attendees were included. Median visit duration was 2 hours 36 minutes (interquartile range [IQR] 01:36–3:43). Longer mean visit times were associated with being female (13.5 minutes longer than males; p<0.001) and attending with a baby (18.8 minutes longer than those without; p<0.01), and shorter mean times with later arrival (14.9 minutes shorter per hour after 0700; p<0.001) and attendance for tuberculosis or ante/postnatal care (24.8 and 32.6 minutes shorter, respectively, than HIV/acute care; p<0.01).</jats:p><jats:p>Overall, attendees spent more of their time indoors (median 95.6% [IQR 46–100]) than outdoors (2.5% [IQR 0–35]). Attendees at clinics with outdoor waiting areas spent a greater proportion (median 13.7% [IQR 1– 75]) of their time outdoors.</jats:p><jats:p>In two clinics in KZN (no appointment system), occupancy densities of ∼2.0 persons/m<jats:sup>2</jats:sup>were
Deol AK, Scarponi D, Beckwith P, et al., 2021, Estimating ventilation rates in rooms with varying occupancy levels: Relevance for reducing transmission risk of airborne pathogens, PLoS One, Vol: 16, ISSN: 1932-6203
BACKGROUND: In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed. METHODS: The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model. RESULTS: The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632-3181] and Q from approach 2 was 2743 l/s [95% CI: 2139-4429]. CONCLUSIONS: We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.
Reynolds CJ, Yates TA, Gill D, et al., 2021, MENDELIAN RANDOMIZATION STUDY OF CIGARETTE SMOKING IN IDIOPATHIC PULMONARY FIBROSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A47-A48, ISSN: 0040-6376
Surey J, Stagg HR, Yates TA, et al., 2021, An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study, BMC Infectious Diseases, Vol: 21, ISSN: 1471-2334
BackgroundEnding the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks.MethodsAn open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded.ResultsFifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7–91.4), compared with 19 of 25 (76.0%, CI 54.9–90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms.ConclusionIn this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferi
Kielmann K, Karat AS, Zwama G, et al., 2020, Tuberculosis infection prevention and control: why we need a whole systems approach, Infectious Diseases of Poverty, Vol: 9
<jats:title>Abstract</jats:title><jats:p>Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled <jats:italic>Umoya omuhle</jats:italic> (“good air”), conducted in two provinces of South Africa, that adopts an interdisciplinary, ‘whole systems’ approach to problem analysis and intervention development for reducing nosocomial transmission of <jats:italic>Mycobacterium tuberculosis</jats:italic> (<jats:italic>Mtb</jats:italic>) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial <jats:italic>Mtb</jats:italic> transmission occurs, as well as opportunities to address the problem holistically. A ‘whole systems’ approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial <jats:italic>Mtb</jats:italic> transmission.</jats:p>
Yates T, Cooke G, MacPherson P, 2020, Rational use of SARS-CoV-2 polymerase chain reaction tests within institutions caring for the vulnerable [version1; [peer revoew: 2 approved], F1000Research, Vol: 9, Pages: 1-13, ISSN: 2046-1402
Institutions such as hospitals and nursing or long-stay residential homes accommodate individuals at considerable risk of mortality should they acquire SARS-CoV-2 infection. In these settings, polymerase chain reaction tests play a central role in infection prevention and control. Here, we argue that both false negative and false positive tests are possible and that careful consideration of the prior probability of infection and of test characteristics are needed to prevent harm. We outline evidence suggesting that regular systematic testing of asymptomatic and pre-symptomatic individuals could play an important role in reducing transmission of SARS-CoV-2 within institutions. We discuss how such a programme might be organised, arguing that frequent testing and rapid reporting of results are particularly important. We highlight studies demonstrating that polymerase chain reaction testing of pooled samples can be undertaken with acceptable loss of sensitivity, and advocate such an approach where test capacity is limited. We provide an approach to calculating the most efficient pool size. Given the current limitations of tests for SARS-CoV-2 infection, physical distancing and meticulous infection prevention and control will remain essential in institutions caring for vulnerable people.
McCreesh N, Grant AD, Yates TA, et al., 2020, Tuberculosis from transmission in clinics in high HIV settings may be far higher than contact data suggest, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 24, Pages: 403-408, ISSN: 1027-3719
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- Citations: 6
Yates TA, Tomlinson LA, Douglas IJ, 2020, Proton pump inhibitors and tuberculosis risk, The International Journal of Tuberculosis and Lung Disease, Vol: 24, Pages: 353-354, ISSN: 1027-3719
Yates TA, Barr DA, 2020, Tuberculosis and Dysglycemia, CLINICAL INFECTIOUS DISEASES, Vol: 70, Pages: 545-545, ISSN: 1058-4838
Goldacre B, Reynolds C, Powell-Smith A, et al., 2019, Do doctors in dispensing practices with a financial conflict of interest prescribe more expensive drugs? A cross-sectional analysis of English primary care prescribing data, BMJ OPEN, Vol: 9, ISSN: 2044-6055
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- Citations: 12
Ahmed S, Moore DAJ, Nimmo C, et al., 2019, Linezolid for drug-susceptible tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: 357-357, ISSN: 1473-3099
Khan PY, Yates TA, Osman M, et al., 2019, Transmission of drug-resistant tuberculosis in HIV-endemic settings, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: E77-E88, ISSN: 1473-3099
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- Citations: 34
Yates TA, 2018, Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: E56-E56, ISSN: 2213-2600
Yates T, 2018, Household-Contact Investigation for Detection of Tuberculosis in Vietnam, New England Journal of Medicine, ISSN: 0028-4793
Yates TA, Ayles H, Leacy FP, et al., 2018, Socio-economic gradients in prevalent tuberculosis in Zambia and the Western Cape of South Africa, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 23, Pages: 375-390, ISSN: 1360-2276
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- Citations: 7
Yates TA, Tomlinson LA, Bhaskaran K, et al., 2017, Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort, PLOS MEDICINE, Vol: 14, ISSN: 1549-1277
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- Citations: 12
Barr DA, Yates TA, 2017, Whole-genome sequencing identifies nosocomial transmission of extra-pulmonary <i>Mycobacterium tuberculosis</i>, QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, Vol: 110, Pages: 611-612, ISSN: 1460-2725
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- Citations: 4
Yates TA, Atkinson SH, 2017, Ironing out sex differences in tuberculosis prevalence, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 21, Pages: 483-484, ISSN: 1027-3719
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- Citations: 11
Leacy FP, Floyd S, Yates TA, et al., 2017, Analyses of Sensitivity to the Missing-at-Random Assumption Using Multiple Imputation With Delta Adjustment: Application to a Tuberculosis/HIV Prevalence Survey With Incomplete HIV-Status Data, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 185, Pages: 304-315, ISSN: 0002-9262
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- Citations: 31
Yates TA, Nunn AJ, 2016, Efficacy and safety of regimens for drug-resistant tuberculosis, LANCET INFECTIOUS DISEASES, Vol: 16, Pages: 1218-1219, ISSN: 1473-3099
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- Citations: 1
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