Imperial College London

DrChristopherUzzell

Faculty of MedicineSchool of Public Health

Research Associate
 
 
 
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c.uzzell

 
 
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Building E - Sir Michael UrenWhite City Campus

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Summary

 

Publications

Publication Type
Year
to

10 results found

Barnes KG, Levy JI, Gauld J, Rigby J, Kanjerwa O, Uzzell CB, Chilupsya C, Anscombe C, Tomkins-Tinch C, Mbeti O, Cairns E, Thole H, McSweeney S, Chibwana MG, Ashton PM, Jere KC, Meschke JS, Diggle P, Cornick J, Chilima B, Jambo K, Andersen KG, Kawalazira G, Paterson S, Nyirenda TS, Feasey Net al., 2023, Utilizing river and wastewater as a SARS-CoV-2 surveillance tool in settings with limited formal sewage systems., Nat Commun, Vol: 14

The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance has been critical for pandemic control, however not all countries can currently sustain community pathogen surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but less is known about the utility of water surveillance of pathogens in low-income countries. Here we show how wastewater surveillance of SAR-CoV-2 can be used to identify temporal changes and help determine circulating variants quickly. In Malawi, a country with limited community-based COVID-19 testing capacity, we explore the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020-May 2022, we collect water from up to 112 river or defunct wastewater treatment plant sites, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predate peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights how wastewater can be used to detect emerging waves, identify variants of concern, and provide an early warning system in settings with no formal sewage systems.

Journal article

LeBoa C, Shrestha S, Shakya J, Naga SR, Shrestha S, Shakya M, Yu AT, Shrestha R, Vaidya K, Katuwal N, Aiemjoy K, Bogoch II, Uzzell CB, Garrett DO, Luby SP, Andrews JR, Tamrakar Det al., 2023, Environmental sampling for typhoidal Salmonellas in household and surface waters in Nepal identifies potential transmission pathways., PLoS Negl Trop Dis, Vol: 17

INTRODUCTION: Salmonella Typhi and Salmonella Paratyphi, fecal-oral transmitted bacterium, have temporally and geographically heterogeneous pathways of transmission. Previous work in Kathmandu, Nepal implicated stone waterspouts as a dominant transmission pathway after 77% of samples tested positive for Salmonella Typhi and 70% for Salmonella Paratyphi. Due to a falling water table, these spouts no longer provide drinking water, but typhoid fever persists, and the question of the disease's dominant pathway of transmission remains unanswered. METHODS: We used environmental surveillance to detect Salmonella Typhi and Salmonella Paratyphi A DNA from potential sources of transmission. We collected 370, 1L drinking water samples from a population-based random sample of households in the Kathmandu and Kavre Districts of Nepal between February and October 2019. Between November 2019 and July 2021, we collected 380, 50mL river water samples from 19 sentinel sites on a monthly interval along the rivers leading through the Kathmandu and Kavre Districts. We processed drinking water samples using a single qPCR and processed river water samples using differential centrifugation and qPCR at 0 and after 16 hours of liquid culture enrichment. A 3-cycle threshold (Ct) decrease of Salmonella Typhi or Salmonella Paratyphi, pre- and post-enrichment, was used as evidence of growth. We also performed structured observations of human-environment interactions to understand pathways of potential exposure. RESULTS: Among 370 drinking water samples, Salmonella Typhi was detected in 7 samples (1.8%) and Salmonella Paratyphi A was detected in 4 (1.0%) samples. Among 380 river water samples, Salmonella Typhi was detected in 171 (45%) and Salmonella Paratyphi A was detected in 152 (42%) samples. Samples located upstream of the Kathmandu city center were positive for Salmonella Typhi 12% of the time while samples from locations in and downstream were positive 58% and 67% of the time respectively.

Journal article

Uzzell CB, Abraham D, Rigby J, Troman CM, Nair S, Elviss N, Kathiresan L, Srinivasan R, Balaji V, Zhou NA, Meschke JS, John J, Kang G, Feasey N, Mohan VR, Grassly NCet al., 2023, Environmental surveillance for Salmonella Typhi and its association with typhoid fever incidence in India and Malawi, Journal of Infectious Diseases, ISSN: 0022-1899

BACKGROUND: Environmental surveillance (ES) for Salmonella Typhi potentially offers a low-cost tool to identify communities with a high burden of typhoid fever. METHODS: We developed standardised protocols for typhoid ES, including sampling site selection, validation, characterisation; grab or trap sample collection, concentration; and quantitative PCR targeting Salmonella genes (ttr, staG and tviB) and a marker of human faecal contamination (HF183). ES was implemented over 12-months in a historically high typhoid fever incidence setting (Vellore, India) and a lower incidence setting (Blantyre, Malawi) during 2021-2022. RESULTS: S. Typhi prevalence in ES samples was higher in Vellore compared with Blantyre; 39/520 (7.5%, 95% Confidence Interval 4.4-12.4%) vs. 11/533 (2.1%, 1.1-4.0%) in grab and 79/517 (15.3%, 9.8-23.0%) vs. 23/594 (3.9%, 1.9-7.9%) in trap samples. Detection was clustered by ES site and correlated with site catchment population in Vellore but not Blantyre. Incidence of culture-confirmed typhoid in local hospitals was low during the study and zero some months in Vellore despite S. Typhi detection in ES. CONCLUSIONS: ES describes the prevalence and distribution of S. Typhi even in the absence of typhoid cases and could inform vaccine introduction. Expanded implementation and comparison with clinical and serological surveillance will further establish its public health utility.

Journal article

Shaw AG, Troman C, Akello JO, O'Reilly KM, Gauld J, Grow S, Grassly N, Steele D, Blazes D, Kumar S, Environmental Surveillance Working Groupet al., 2023, Defining a research agenda for environmental wastewater surveillance of pathogens, Nature Medicine, Vol: 29, Pages: 2155-2157, ISSN: 1078-8956

Journal article

Shelton JMG, Rhodes J, Uzzell CB, Hemmings S, Brackin AP, Sewell TR, Alghamdi A, Dyer PS, Fraser M, Borman AM, Johnson EM, Piel FB, Singer AC, Fisher MCet al., 2023, Citizen science reveals landscape-scale exposures to multiazole-resistant Aspergillus fumigatus bioaerosols., Science Advances, Vol: 9, Pages: 1-9, ISSN: 2375-2548

Using a citizen science approach, we identify a country-wide exposure to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to the agricultural fungicide tebuconazole and first-line azole clinical antifungal drugs. Genomic analysis shows no distinction between resistant genotypes found in the environment and in patients, indicating that at least 40% of azole-resistant A. fumigatus infections are acquired from environmental exposures. Hotspots and coldspots of aerosolized azole-resistant spores were not stable between seasonal sampling periods. This suggests a high degree of atmospheric mixing resulting in an estimated per capita cumulative annual exposure of 21 days (±2.6). Because of the ubiquity of this measured exposure, it is imperative that we determine sources of azole-resistant A. fumigatus to reduce treatment failure in patients with aspergillosis.

Journal article

Barnes K, Levy J, Andersen K, Gauld J, Rigby J, Kanjerwa O, Uzzell C, Chilupsya C, Anscombe C, Tomkins-Tinch C, Mbeti O, Cairns E, Thole H, McSweeney S, Chibwana M, Ashton P, Jere K, Meschke J, Diggle P, Cornick J, Jambo K, Kawalazira G, Paterson S, Nyirenda T, Feasey N, Chilima Bet al., 2023, Utilizing river and wastewater as a SARS-CoV-2 surveillance tool to predict trends and identify variants of concern in settings with limited formal sewage systems., Res Sq

The COVID-19 pandemic continues to impact health systems globally and robust surveillance is critical for pandemic control, however not all countries can sustain community surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but little is known about how river and informal sewage in low-income countries can be used for environmental surveillance of SARS-CoV-2. In Malawi, a country with limited community-based COVID-19 testing capacity, we explored the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020 - January 2022, we collected water from up to 112 river or informal sewage sites/month, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predated peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights wastewater can be used for detecting emerging waves, identifying variants of concern and function as an early warning system in settings with no formal sewage systems.

Journal article

Uzzell CB, Troman CM, Rigby J, Raghava Mohan V, John J, Abraham D, Srinivasan R, Nair S, Meschke JS, Elviss N, Kang G, Feasey NA, Grassly NCet al., 2023, Environmental surveillance for Salmonella Typhi as a tool to estimate the incidence of typhoid fever in low-income populations., Publisher: F1000 Research Ltd

Background: The World Health Organisation recommends prioritised use of recently prequalified typhoid conjugate vaccines in countries with the highest incidence of typhoid fever. However, representative typhoid surveillance data are lacking in many low-income countries because of the costs and challenges of diagnostic clinical microbiology. Environmental surveillance (ES) of Salmonella Typhi in sewage and wastewater using molecular methods may offer a low-cost alternative, but its performance in comparison with clinical surveillance has not been assessed.Methods: We developed a harmonised protocol for typhoid ES and its implementation in communities in India and Malawi where it will be compared with findings from hospital-based surveillance for typhoid fever. The protocol includes methods for ES site selection based on geospatial analysis, grab and trap sample collection at sewage and wastewater sites, and laboratory methods for sample processing, concentration and quantitative polymerase chain reaction (PCR) to detect Salmonella Typhi. The optimal locations for ES sites based on digital elevation models and mapping of sewage and river networks are described for each community and their suitability confirmed through field investigation. We will compare the prevalence and abundance of Salmonella Typhi in ES samples collected each month over a 12-month period to the incidence of blood culture confirmed typhoid cases recorded at referral hospitals serving the study areas.Conclusions: If environmental detection of Salmonella Typhi correlates with the incidence of typhoid fever estimated through clinical surveillance, typhoid ES may be a powerful and low-cost tool to estimate the local burden of typhoid fever and support the introduction of typhoid conjugate vaccines. Typhoid ES could also allow the impact of vaccination to be assessed and rapidly identify circulation of drug resistant strains.

Working paper

Shelton J, Collins R, Uzzell CB, Alghamdi A, Dyer PS, Singer AC, Fisher Met al., 2022, Citizen-science surveillance of triazole-resistant Aspergillus fumigatus in UK residential garden soils, Applied and Environmental Microbiology, Vol: 88, Pages: 1-12, ISSN: 0099-2240

Compost is an ecological niche for Aspergillus fumigatus due to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels of A. fumigatus spores that are aerosolized from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages, and it is likely that they are being exposed to A. fumigatus spores when handling commercial compost or compost they have produced themselves. In the present study, 246 citizen scientists collected 509 soil samples from locations in their gardens in the UK, from which were cultured 5,174 A. fumigatus isolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treat A. fumigatus lung infections in humans. These isolates were found to contain the common resistance mechanisms in the A. fumigatus cyp51A gene TR34/L98H or TR46/Y121F/T289A, as well as the less common resistance mechanisms TR34, TR53, TR46/Y121F/T289A/S363P/I364V/G448S, and (TR46)2/Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow tebuconazole-susceptible and tebuconazole-resistant A. fumigatus strains than those that did not and that compost samples grew significantly higher numbers of A. fumigatus than other samples.IMPORTANCE The findings presented here highlight compost as a potential health hazard to individuals with predisposing factors to A. fumigatus lung infections and as a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. Furthermore, we found that 14% of A. fumigatus isolates in garden soils were resistant to an agricultural triazole, which confers cross-resistance to medical triazo

Journal article

Uzzell CB, Troman CM, Rigby J, Mohan VR, John J, Abraham D, Srinivasan R, Nair S, Meschke JS, Elviss N, Kang G, Feasey N, Grassly NCet al., 2021, Environmental surveillance for <i>Salmonella</i> Typhi as a tool to estimate the incidence of typhoid fever in low-income populations

<jats:p>Background: The World Health Organisation recommends prioritised use of recently prequalified typhoid conjugate vaccines in countries with the highest incidence of typhoid fever. However, representative typhoid surveillance data are lacking in many low-income countries because of the costs and challenges of diagnostic clinical microbiology. Environmental surveillance (ES) of <jats:italic>Salmonella</jats:italic> Typhi in sewage and wastewater using molecular methods may offer a low-cost alternative, but its performance in comparison with clinical surveillance has not been assessed. Methodology/Principal Findings: We developed a harmonised protocol for typhoid ES and its implementation in communities in India and Malawi where it will be compared with findings from hospital-based surveillance for typhoid fever. The protocol includes methods for ES site selection based on geospatial analysis, grab and trap sample collection at sewage and wastewater sites, and laboratory methods for sample processing, concentration and quantitative PCR to detect <jats:italic>Salmonella</jats:italic> Typhi. The optimal locations for ES sites based on digital elevation models and mapping of sewage and river networks are described for each community and their suitability confirmed through field investigation. We will compare the prevalence and abundance of <jats:italic>Salmonella</jats:italic> Typhi in ES samples collected each month over a 12-month period to the incidence of blood culture confirmed typhoid estimated from cases recorded at referral hospitals serving the study areas and community surveys of healthcare seeking for individuals with fever. Significance: If environmental detection of <jats:italic>Salmonella</jats:italic> Typhi correlates with the incidence of typhoid fever estimated through clinical surveillance, typhoid ES may be a powerful and low-cost tool to estimate the local burden of typhoid fever and support

Working paper

de Glanville WA, Davis A, Allan KJ, Buza J, Claxton JR, Crump JA, Halliday JEB, Johnson PCD, Kibona TJ, Mmbaga BT, Swai ES, Uzzell CB, Yoder J, Sharp J, Cleaveland Set al., 2020, Classification and characterisation of livestock production systems in northern Tanzania, PLOS ONE, Vol: 15, ISSN: 1932-6203

Journal article

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