A5027354335- Tuberculosis Research and Epidemiology
- HIV/AIDS Impact and Responses
- Pneumonia and Respiratory Infections
- Diagnosis and treatment of tuberculosis
- Mycobacterium research and diagnosis
- Pneumocystis jirovecii pneumonia detection and treatment
- Healthcare Systems and Reforms
- Child Nutrition and Water Access
- Global Maternal and Child Health
- Pleistocene-Era Hominins and Archaeology
- Vector-Borne Animal Diseases
- Gene Regulatory Network Analysis
- Health Systems, Economic Evaluations, Quality of Life
- Animal Disease Management and Epidemiology
- Global Health and Epidemiology
- Immune responses and vaccinations
- Microbial Metabolic Engineering and Bioproduction
- Agriculture and Farm Safety
- Archaeology and Rock Art Studies
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Probabilistic and Robust Engineering Design
- Archaeology and ancient environmental studies
- Diet, Metabolism, and Disease
- Protein Structure and Dynamics
University of London
2016-2024
London School of Hygiene & Tropical Medicine
2016-2024
World Health Organization
2018
The Pirbright Institute
2012-2017
Public Health England
2015
University of Cape Town
2013-2014
University College London
2009-2012
Institute of Structural and Molecular Biology
2012
University of the Witwatersrand
2011
BackgroundTargeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance a transcriptomic signature (RISK11) and efficacy signature-guided in parallel, using hybrid three-group study design.MethodsAdult volunteers aged 18–59 years were recruited five geographically distinct communities South Africa. Whole blood was sampled RISK11 quantitative RT-PCR assay from eligible without HIV, recent...
Significance To aid in prioritizing the development of tuberculosis (TB) vaccines most likely to reach 2050 TB elimination goal, we estimated impact and cost-effectiveness a range vaccine profiles low- middle-income countries. Using mathematical modeling, show that targeted at adolescents/adults could have much greater on burden over 2024–2050 time horizon than those infants. Such also be cost-effective, even with relatively high prices. Our results suggest achieve goals, future should focus...
BackgroundThe post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% mortality from by 2025. We aimed to assess whether these are feasible three high-burden countries with contrasting epidemiology previous programmatic achievements.Methods11 independently developed mathematical models transmission projected the epidemiological impact currently available interventions for prevention, diagnosis, treatment China, India, South Africa. Models were calibrated...
Global tuberculosis (TB) targets were set as part of the World Health Organization's End TB Strategy (2016-2035) and Sustainable Development Goals (2016-2030).
BackgroundThe post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality 75% 2025. We aimed to assess resource requirements cost-effectiveness strategies achieve these in China, India, South Africa.MethodsWe examined intervention scenarios developed consultation with country stakeholders, which scaled up existing interventions high but feasible coverage Nine independent modelling groups collaborated estimate policy outcomes, we estimated the cost...
One of the main challenges in development mathematical and computational models biological systems is precise estimation parameter values. Understanding effects uncertainties values on model behaviour crucial to successful use these models. Global sensitivity analysis (SA) can be used quantify variability predictions resulting from uncertainty multiple parameters shed light mechanisms driving system behaviour. We present a new methodology for global SA biology which computationally efficient...
BackgroundTuberculosis is the leading single-pathogen cause of death worldwide, and China has third largest number cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled potential impact vaccines in targeting adolescents (15–19 years) adults (60–64 with varying characteristics inform...
Tuberculosis vaccines should aim to protect infected populations against disease, but other vaccine types may be of use in high-transmission settings.
BackgroundA rapid, blood-based triage test that allows targeted investigation for tuberculosis at the point of care could shorten time to treatment and reduce mortality. We aimed performance a host blood transcriptomic signature (RISK11) in diagnosing predicting progression active pulmonary disease (prognosis) people with HIV community setting.MethodsIn this prospective diagnostic prognostic accuracy study, adults (aged 18–59 years) were recruited from five communities South Africa....
The economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims eliminate these potentially devastating effects. We assessed whether aggressive expansion of services might reduce catastrophic costs.We estimated the reduction in tuberculosis-related with an India South Africa from 2016 2035, line Strategy. Using modelled incidence mortality for patient-incurred cost estimates, we investigated three...
Significance Isoniazid preventive therapy (IPT) is a key tuberculosis prevention strategy in high-HIV-prevalent settings. While randomized controlled trials have shown IPT provides protection against disease HIV-positive patients during therapy, was quickly lost after cessation of therapy. It not known whether this loss due to reinfection and rapid progression disease, or lack cure. Using mathematical modeling, fitted trial data, we show does cure Mycobacterium infection the majority...
The role of host movement in the spread vector-borne diseases livestock has been little studied. Here we develop a mathematical framework that allows us to disentangle and quantify roles vector dispersal transmission between farms. We apply this outbreaks bluetongue virus (BTV) Schmallenberg (SBV) Great Britain, both which are by Culicoides biting midges have recently emerged northern Europe. For BTV estimate parameters fitting model outbreak data using approximate Bayesian computation,...
Tuberculosis remains a major public health problem in South Africa, with an estimated 300,000 cases and 55,000 deaths 2021. New tuberculosis vaccines could play important role reducing this burden. Phase IIb trials have suggested efficacy of the M72/AS01E vaccine candidate BCG-revaccination. The potential population impact these is unknown. We used age-stratified transmission model tuberculosis, calibrated to epidemiological data from estimate economic vaccination simulated scenarios over...
Tuberculosis (TB) remains a leading cause of infectious disease death. Modelling predicts new TB vaccines may reduce global burden but rely on assumptions about vaccine efficacy by stage and natural history, which be incorrect. We explored the sensitivity estimates impact to uncertainties in history. developed dynamic compartmental model for India, including early stages. Scenarios assumed 50% 10 years prevented progression a) only symptomatic disease, or b) any c) disease. estimated...
A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to data explored 1) factors contributing the lack impact, 2) best-achievable impact if all implementation characteristics were increased highest level achieved ("optimized...
The M72/AS01E tuberculosis vaccine showed 50% (95%CI: 2-74%) efficacy in a phase 2B trial preventing active pulmonary disease, but potential cost-effectiveness of adolescent immunisation is unknown. We estimated the impact and six scenarios routine M72/AS01E-like vaccination South Africa India. All suggested an would be highly (94-100%) cost-effective compared to threshold $2480/disability-adjusted life-year (DALY) averted. For India, prevention disease vaccine, effective irrespective...
Globally, men have a higher epidemiologic burden of tuberculosis (incidence, prevalence, mortality) than women do, possibly due to differences in disease incidence, treatment initiation, self-cure, and/or untreated-tuberculosis mortality rates. Using simple, sex-stratified compartmental model, we employed Bayesian approach explore which factors most likely explain men's burden. We applied the model smear-positive pulmonary Vietnam (2006–2007) and Malawi (2013–2014). Posterior estimates were...
<h3>Background</h3> Contact tracing is a key element in England9s 2015 collaborative TB strategy, although proposed indicators of successful contact remain undescribed. <h3>Methods</h3> We conducted descriptive and multivariable analyses cases London between 1 July 2012 31 December using cohort review data from London9s Register, identifying characteristics associated with improved yield. <h3>Results</h3> Of the pulmonary notified, 60% (2716/4561) had sufficient information for inclusion....
Isoniazid preventive therapy (IPT) is effective for preventing active tuberculosis (TB), although its mechanism of action poorly understood and the optimal disease burden IPT use has not been defined.To describe relationship between TB incidence effectiveness.We constructed a model transmission dynamics to investigate effectiveness under various epidemiological settings. The structure was intended be highly adaptable uncertainty in both input parameters IPT. To determine setting use, we...
National Tuberculosis Programmes (NTPs) require specialist input to support the development of policy and practice informed by evidence, typically against tight deadlines.To describe lessons learned from establishing a dedicated tuberculosis (TB) think tank advise South African NTP on TB policy.A national was established in evidence-informed policy. Support provided for activities, including meetings, modelling regular telephone calls, with wider network unpaid expert advisers under an...
A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on buffering glucose into glycogen, has been developed. The exemplifies an ‘engineering’ approach to modelling in systems biology, and was produced by linking together seven component models separate aspects physiology. use a variety paradigms degrees simplification. Model parameters were determined iterative hybrid fitting high-scale physiological data, determination from small-scale vitro...