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Journal articleMenkir TF, Citarella BW, Sigfrid L, et al., 2024,
Modeling the relative influence of socio-demographic variables on post-acute COVID-19 quality of life.
, medRxivBACKGROUND: Post-acute sequelae of SARS-CoV-2, referred to as "long COVID", are a globally pervasive threat. While their many clinical determinants are commonly considered, their plausible social correlates are often overlooked. METHODS: Here, we use data from a multinational prospective cohort study to compare social and clinical predictors of differences in quality of life with long COVID. We further measure the extent to which clinical intermediates may explain relationships between social variables and quality of life with long COVID. FINDINGS: Beyond age, neuropsychological and rheumatological comorbidities, educational attainment, employment status, and female sex were important predictors of long COVID-associated quality of life days (long COVID QALDs). Furthermore, most of their associations could not be attributed to key long COVID-predicting comorbidities. In Norway, 90% (95% CI: 77%, 100%) of the adjusted association between belonging to the top two quintiles of educational attainment and long COVID QALDs was not explained by these clinical intermediates. The same was true for 86% (73%, 100%) and 93% (80%,100%) of the adjusted association between full-time employment and long COVID QALDs in the United Kingdom (UK) and Russia. Additionally, 77% (46%,100%) and 73% (52%, 94%) of the adjusted associations between female sex and long COVID QALDs in Norway and the UK were unexplained by the clinical mediators. INTERPRETATION: Our findings highlight that socio-economic proxies and sex are key predictors of long COVID QALDs and that other (non-clinical) mechanisms drive their observed relationships. Importantly, we outline a multi-method, adaptable causal approach for evaluating the isolated contributions of social disparities to experiences with long COVID. FUNDING: UK Foreign, Commonwealth and Development Office; Wellcome Trust; Bill & Melinda Gates Foundation; Oxford COVID-19 Research Response Funding; UK National Institute for Health and Care Re
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Journal articleThompson R, Hart W, Keita M, et al., 2024,
Using real-time modelling to inform the 2017 Ebola outbreak response in DR Congo.
, Nat Commun, Vol: 15Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was R = 1.49 (95% credible interval ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT's measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.
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Journal articleShaw SY, Biegun JCS, Leung S, et al., 2024,
Describing the effect of COVID-19 on sexual and healthcare-seeking behaviours of men who have sex with men in three counties in Kenya: a cross-sectional study.
, Sex Transm InfectBACKGROUND: While the COVID-19 pandemic disrupted HIV preventative services in sub-Saharan Africa, little is known about the specific impacts the pandemic has had on men who have sex with men (MSM) in Kenya. METHODS: Data were from an HIV self-testing intervention implemented in Kisumu, Mombasa and Kiambu counties in Kenya. Baseline data collection took place from May to July 2019, and endline in August-October 2020, coinciding with the lifting of some COVID-19 mitigation measures. Using endline data, this study characterised the impact the pandemic had on participants' risk behaviours, experience of violence and behaviours related to HIV. Logistic regression was used to understand factors related to changes in risk behaviours and experiences of violence; adjusted AORs (AORs) and 95% CIs are reported. RESULTS: Median age was 24 years (IQR: 21-27). Most respondents (93.9%) reported no change or a decrease in the number of sexual partners (median number of male sexual partners: 2, IQR: 2-4). Some participants reported an increase in alcohol (10%) and drug (16%) consumption, while 40% and 28% reported decreases in alcohol and drug consumption, respectively. Approximately 3% and 10% reported an increase in violence from intimate partners and police/authorities, respectively. Compared with those with primary education, those with post-secondary education were 60% less likely to report an increase in the number of male sexual partners per week (AOR: 0.4, 95% CI: 0.2 to 0.9), while those who were HIV positive were at twofold the odds of reporting an increase or sustained levels of violence from intimate partners (AOR: 2.0, 95% CI: 1.1 to 4.0). CONCLUSION: The results of this study demonstrate heterogeneity in participants' access to preventative HIV and clinical care services in Kenya after the onset of the COVID-19 epidemic. These results indicate the importance of responding to specific needs of MSM and adapting programmes during times of crisis.
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Journal articleSilhol R, Maheu-Giroux M, Soni N, et al., 2024,
The impact of past HIV interventions and diagnosis gaps on new HIV acquisitions, transmissions, and HIV-related deaths in Côte d’Ivoire, Mali, and Senegal
, AIDS, ISSN: 0269-9370Objectives: To estimate the epidemiological impact of past HIV interventions and the magnitude and contribution of undiagnosed HIV among different risk groups on new HIV acquisitions in Côte d’Ivoire, Mali and Senegal.Design: HIV transmission dynamic models among the overall population and key populations [female sex workers (FSW), their clients, and MSM].Methods: Models were independently parameterized and calibrated for each set of country-specific demographic, behavioural, and epidemiological data. We estimated the fraction of new HIV infections over 2012–2021 averted by condom use and antiretroviral therapy (ART) uptake among key population and nonkey population, the direct and indirect contribution of specific groups to new infections [transmission population-attributable fraction (tPAF)] over 2012–2021 due to prevention gaps, and the distribution of undiagnosed PWH by risk group in January 2022 and their tPAF over 2022–2031.Results: Condom use and ART may have averted 81–88% of new HIV infections over 2012–2021 across countries, mostly because of condom use by key population. The tPAF of all key populations combined over 2012–2021 varied between 27% (Côte d’Ivoire) and 79% (Senegal). Male key population (clients of FSW and MSM) contributed most to new infections (>60% in Mali and Senegal) owing to their higher HIV prevalence and larger prevention gaps. In 2022, men represented 56% of all PWH with an undiagnosed infection in Côte d’Ivoire (male key population = 15%), 46% in Mali (male key population = 23%), and 69% in Senegal (male key population = 55%). If HIV testing and ART initiation rates remain at current levels, 20% of new HIV infections could be due to undiagnosed key population PWH in Côte d’Ivoire over 2022–2031, 53% in Mali, and 65% in Senegal.Conclusion: Substantial HIV diagnosis gaps remain in Western Africa, especially among male key population. Addressing
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Journal articleJorgensen D, Grassly NC, Pons Salort M, 2024,
Global age-stratified seroprevalence of Enterovirus D68: a systematic literature review
, The Lancet Microbe, ISSN: 2666-5247First isolated in 1962, enterovirus D68 (EV-D68) emerged in 2014, causing outbreaksof severe respiratory infections and acute flaccid myelitis. We conducted a systematicliterature review to compile all available EV-D68 age-stratified seroprevalenceestimates . Ten studies from six countries were retained, all using microneutralizationassays, although protocols and challenge viruses varied widely. Seroprevalence age profiles were similar across time and space, with seroprevalence increasing quicklywith age, reaching ~100% by 20 years old, and remaining high throughout adulthood.This suggests continuous or frequent exposure of the populations to the virus, orpossible cross-reactivity with other viruses. Studies with two or more cross-sectionalsurveys showed consistently higher seroprevalence at later time points, suggesting aglobal increase in transmission over time. Standardizing serological protocols,understanding the contribution of cross-reactivity with other pathogens to high reportedseroprevalence, and quantifying individual exposure to EV-D68 over time are mainresearch priorities.
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Journal articleGrassly N, Shaw AG, Owusu M, 2024,
Global wastewater surveillance for pathogens with pandemic potential: opportunities and challenges
, The Lancet Microbe, ISSN: 2666-5247Wastewater surveillance (WS) holds promise as a sensitive method to detect spillover of zoonotic infections and early pandemic emergence, thereby informing risk mitigation and public health response. Known pandemic-risk viruses are shed in human stool and/or urine and recent experience with SARS-CoV-2, mpox and Zika highlights the feasibility of community-based WS for pandemic viruses with different transmission routes. We review human shedding and WS data for prototype viruses representing viral families of concern to determine its likely sensitivity compared with clinical surveillance. We examine how data on WS detection together with virus genetic sequences and animal faecal biomarkers could be used to identify spillover infections or early human transmission and adaptation. The opportunities and challenges facing global WS for pandemic prevention are described, focusing on low- and middle-income countries where risk is highest. We propose a research and public agenda to ensure an equitable and sustainable solution to these challenges
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Journal articleBarnsley G, Olivera Mesa D, Hogan A, et al., 2024,
Impact of the 100 Days Mission for vaccines on COVID-19: a mathematical modelling study
, The Lancet Global Health, ISSN: 2214-109XBackgroundThe COVID-19 pandemic has underscored the beneficial impact of vaccines. It alsohighlighted the need for future investments to expedite an equitable vaccine distribution.The 100 Days Mission aims to develop and make available a new vaccine against a futurepathogen with pandemic potential within 100 days of that pathogen threat beingrecognised. We assessed the value of this mission by estimating the impact that it couldhave had on the COVID-19 pandemic.MethodsUsing a previously published model of SARS-CoV-2 transmission dynamics fit to excessmortality during the COVID-19 pandemic, we projected scenarios for three differentinvestment strategies: rapid development and manufacture of a vaccine, increasingmanufacturing capacity to eliminate supply constraints, and strengthening health systems toenable faster vaccine roll-outs and global equity. Each scenario was compared against theobserved COVID-19 pandemic to estimate the public health and health-economic impactsof each scenario.FindingsIf countries implemented non-pharmaceutical interventions (NPIs) as they did historically,the 100 Days Mission could have averted an estimated 8.33 million (95% credible interval7.70 – 8.68 million) deaths globally, mostly in low-middle income countries. Thiscorresponds to a monetary saving of $14.35 trillion (95% CrI $12.96 – $17.87) based on thevalue of statistical life years saved. Investment in manufacturing and health systems furtherincreases deaths averted to 11.01 million (95% CrI 10.60 – 11.49 million). Under analternative scenario whereby NPIs are lifted earlier based on vaccine coverage, the 100Days Mission alone could have reduced restrictions by 12,600 (95% CrI 12,300 – 13,100)days globally whilst still averting 5.76 million (95% CrI 4.91 – 6.81 million) deaths.InterpretationOur findings demonstrate the value of the 100 Days Mission and how these can beamplified through improvements in manufacturing and health systems equity. However,t
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Journal articleTurner HC, 2024,
Cost-effectiveness of a Wolbachia-based replacement strategy for dengue control in Brazil
, The Lancet Regional Health. Americas, Vol: 35, ISSN: 2667-193X -
Journal articleMesinovic M, Wong XC, Rajahram GS, et al., 2024,
At-admission prediction of mortality and pulmonary embolism in an international cohort of hospitalised patients with COVID-19 using statistical and machine learning methods
, Scientific Reports, Vol: 14, ISSN: 2045-2322By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Early recognition can help provide life-saving targeted anti-coagulation therapy right at admission. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Age, overall presence of symptoms, shortness of breath, and hypertension were found to be key predictors for PE using our extreme gradient boosted model. This analysis based on the, until now, largest global dataset for this set of problems can inform hospital prioritisation policy and guide long term clinical research and decision-making for COVID-19 patients globally. Our machine learning model developed from an international cohort can serve to bet
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Journal articleLu IJ, Silhol R, d'Elbée M, et al., 2024,
Cost-effectiveness analysis of community-led HIV self-testing among key populations in Côte d'Ivoire, Mali, and Senegal
, Journal of the International AIDS Society, Vol: 27, ISSN: 1758-2652INTRODUCTION: HIV self-testing (HIVST) is a promising strategy to improve diagnosis coverage among key populations (KP). The ATLAS (Auto Test VIH, Libre d'Accéder à la connaissance de son Statut) programme implemented HIVST in three West African countries, distributing over 380,000 kits up between 2019 and 2021, focussing on community-led distribution by KP to their peers and subsequent secondary distribution to their partners and clients. We aim to evaluate the cost-effectiveness of community-led HIVST in Côte d'Ivoire, Mali and Senegal. METHODS: An HIV transmission dynamics model was adapted and calibrated to country-specific epidemiological data and used to predict the impact of HIVST. We considered the distribution of HIVST among two KP-female sex workers (FSW), and men who have sex with men (MSM)-and their sexual partners and clients. We compared the cost-effectiveness of two scenarios against a counterfactual without HIVST over a 20-year horizon (2019-2039). The ATLAS-only scenario mimicked the 2-year implemented ATLAS programme, whereas the ATLAS-scale-up scenario achieved 95% coverage of HIVST distribution among FSW and MSM by 2025 onwards. The primary outcome is the number of disability-adjusted life-years (DALY) averted. Scenarios were compared using incremental cost-effectiveness ratios (ICERs). Costing was performed using a healthcare provider's perspective. Costs were discounted at 4%, converted to $USD 2022 and estimated using a cost-function to accommodate economies of scale. RESULTS: The ATLAS-only scenario was highly cost-effective over 20 years, even at low willingness-to-pay thresholds. The median ICERs were $126 ($88-$210) per DALY averted in Côte d'Ivoire, $92 ($88-$210) in Mali and 27$ ($88-$210) in Senegal. Scaling-up the ATLAS programme would also be cost-effective, and substantial epidemiological impacts would be achieved. The ICERs for the scale-up scenario were $199 ($122-$338) per DALY averted in Côte d'Ivo
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