My research focuses on the development of mathematical and statistical models to inform policy decision-making for the control and elimination of infectious diseases, with a particular interest in Neglected Tropical Diseases (NTDs). My work has supported global policy, for example during the development of the 2021-2030 NTD roadmap, and I am also part of several informal WHO-led working groups and the United Against Rabies forum working group 1 (an FAO-OIE-WHO initiative). My research group at Surrey combines mathematical modelling with economic evaluation and stakeholder elicitation techniques to develop sustainable portfolios of interventions against NTDs (in particular zoonotic NTDs such as Echinococcosis and Rabies). I am part of the NTD Modelling Consortium (funded by the Bill & Melinda Gates Foundation) and participate in a number of projects from the One Health European Joint Programme (funded by the European Commission).
I also hold a visiting position at the University of Oxford.
University roles and responsibilities
- School of Veterinary Medicine Impact Champion
Background Human, animal, and environmental health are increasingly threatened by the emergence and spread of antibiotic resistance. Inappropriate use of antibiotic treatments commonly contributes to this threat, but it is also becoming apparent that multiple, interconnected environmental factors can play a significant role. Thus, a One Health approach is required for a comprehensive understanding of the environmental dimensions of antibiotic resistance and inform science-based decisions and actions. The broad and multidisciplinary nature of the problem poses several open questions drawing upon a wide heterogeneous range of studies. Objective This study seeks to collect and catalogue the evidence of the potential effects of environmental factors on the abundance or detection of antibiotic resistance determinants in the outdoor environment, i.e., antibiotic resistant bacteria and mobile genetic elements carrying antibiotic resistance genes, and the effect on those caused by local environmental conditions of either natural or anthropogenic origin. Methods Here, we describe the protocol for a systematic evidence map to address this, which will be performed in adherence to best practice guidelines. We will search the literature from 1990 to present, using the following electronic databases: MEDLINE, Embase, and the Web of Science Core Collection as well as the grey literature. We shall include full-text, scientific articles published in English. Reviewers will work in pairs to screen title, abstract and keywords first and then full-text documents. Data extraction will adhere to a code book purposely designed. Risk of bias assessment will not be conducted as part of this SEM. We will combine tables, graphs, and other suitable visualisation techniques to compile a database i) of studies investigating the factors associated with the prevalence of antibiotic resistance in the environment and ii) map the distribution, network, cross-disciplinarity, impact and trends in the literature.
Background Neglected tropical diseases (NTDs) disproportionately affect populations living in resource-limited settings. In the Amazon basin, substantial numbers of NTDs are zoonotic, transmitted by vertebrate (dogs, bats, snakes) and invertebrate species (sand flies and triatomine insects). However, no dedicated consortia exist to find commonalities in the risk factors for or mitigations against bite-associated NTDs such as rabies, snake envenoming, Chagas disease and leishmaniasis in the region. The rapid expansion of COVID-19 has further reduced resources for NTDs, exacerbated health inequality and reiterated the need to raise awareness of NTDs related to bites. Methods The nine countries that make up the Amazon basin have been considered (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Surinam and Venezuela) in the formation of a new network. Results The Amazonian Tropical Bites Research Initiative (ATBRI) has been created, with the aim of creating transdisciplinary solutions to the problem of animal bites leading to disease in Amazonian communities. The ATBRI seeks to unify the currently disjointed approach to the control of bite-related neglected zoonoses across Latin America. Conclusions The coordination of different sectors and inclusion of all stakeholders will advance this field and generate evidence for policy-making, promoting governance and linkage across a One Health arena.
Campylobacter jejuni and Campylobacter coli are important bacterial causes of human foodborne illness. Despite several years of reduced antibiotics usage in livestock production in the United Kingdom (UK) and United States (US), a high prevalence of antimicrobial resistance (AMR) persists in . Both countries have instigated genome sequencing-based surveillance programs for , and in this study, we have identified AMR genes in 32,256 C. jejuni and 8,776 C. coli publicly available genome sequences to compare the prevalence and trends of AMR in isolated in the UK and US between 2001 and 2018. AMR markers were detected in 68% of C. coli and 53% of C. jejuni isolates, with 15% of C. coli isolates being multidrug resistant (MDR), compared to only 2% of C. jejuni isolates. The prevalence of aminoglycoside, macrolide, quinolone, and tetracycline resistance remained fairly stable from 2001 to 2018 in both C. jejuni and C. coli, but statistically significant differences were observed between the UK and US. There was a statistically significant higher prevalence of aminoglycoside and tetracycline resistance for US C. coli and C. jejuni isolates and macrolide resistance for US C. coli isolates. In contrast, UK C. coli and C. jejuni isolates showed a significantly higher prevalence of quinolone resistance. Specific multilocus sequence type (MLST) clonal complexes (e.g., ST-353/464) showed >95% quinolone resistance. This large-scale comparison of AMR prevalence has shown that the prevalence of AMR remains stable for in the UK and the US. This suggests that antimicrobial stewardship and restricted antibiotic usage may help contain further expansion of AMR prevalence in but are unlikely to reduce it in the short term.
Schistosomiasis is a parasitic disease acquired through contact with contaminated freshwater. The definitive hosts are terrestrial mammals, including humans, with some Schistosoma species crossing the animal-human boundary through zoonotic transmission. An estimated 12 million people live at risk of zoonotic schistosomiasis caused by Schistosoma japonicum and Schistosoma mekongi, largely in the World Health Organization’s Western Pacific Region and in Indonesia. Mathematical models have played a vital role in our understanding of the biology, transmission, and impact of intervention strategies, however, these have mostly focused on non-zoonotic Schistosoma species. Whilst these non-zoonotic-based models capture some aspects of zoonotic schistosomiasis transmission dynamics, the commonly-used frameworks are yet to adequately capture the complex epi-ecology of multi-host zoonotic transmission. However, overcoming these knowledge gaps goes beyond transmission dynamics modelling. To improve model utility and enhance zoonotic schistosomiasis control programmes, we highlight three pillars that we believe are vital to sustainable interventions at the implementation (community) and policy-level, and discuss the pillars in the context of a One-Health approach, recognising the interconnection between humans, animals and their shared environment. These pillars are: (1) human and animal epi-ecological understanding; (2) economic considerations (such as treatment costs and animal losses); and (3) sociological understanding, including inter- and intra-human and animal interactions. These pillars must be built on a strong foundation of trust, support and commitment of stakeholders and involved institutions.
Toxocara canis and T. cati are zoonotic roundworm parasites of dogs, cats and foxes. These definitive hosts pass eggs in their faeces, which contaminate the environment and can subsequently be ingested via soil or contaminated vegetables. In humans, infection with Toxocara can have serious health implications. This proof-of-concept study aimed to investigate the presence of Toxocara spp. eggs on ‘ready-to-eat’ vegetables (lettuce, spinach, spring onion and celery) sampled from community gardens in southern England. The contamination of vegetables with Toxocara eggs has never been investigated in the UK before, and more widely, this is the first time vegetables grown in community gardens in Europe have been assessed for Toxocara egg contamination. Sixteen community gardens participated in the study, providing 82 vegetable samples fit for analysis. Study participants also completed an anonymous questionnaire on observed visits to the sites by definitive hosts of Toxocara. Comparison of egg recovery methods was performed using lettuce samples spiked with a series of Toxocara spp. egg concentrations, with sedimentation and centrifugal concentration retrieving the highest number of eggs. A sample (100 g) of each vegetable type obtained from participating community gardens was tested for the presence of Toxocara eggs using the optimised method. Two lettuce samples tested positive for Toxocara spp. eggs, giving a prevalence of 2.4% (95% CI =1.3–3.5%) for vegetable samples overall, and 6.5% (95% CI = 4.7–8.3%; n = 31) specifically for lettuce. Questionnaire data revealed that foxes, cats and dogs frequently visited the community gardens in the study, with 88% (68/77) of respondents reporting seeing a definitive host species or the faeces of a definitive host at their site. This proof-of-concept study showed for the first time the presence of Toxocara spp. eggs on vegetables grown in the UK, as well as within the soil where these vegetables originated, and highlights biosecurity and zoonotic risks in community gardens. This study establishes a method for assessment of Toxocara spp. eggs on vegetable produce and paves the way for larger-scale investigations of Toxocara spp. egg contamination on field-grown vegetables. •First report of Toxocara eggs on vegetables grown in community gardens in Europe.•Toxocara also detected in the soil where these vegetables originated.•Definitive hosts for Toxocara canis and T. cati frequently visit community gardens.•Sedimentation method recovered the most Toxocara eggs from spiked lettuce samples.
Abstract Background A large number of studies have assessed risk factors for infection with soil-transmitted helminths (STH), but few have investigated the interactions between the different parasites or compared these between host species across hosts. Here, we assessed the associations between Ascaris, Trichuris, hookworm, strongyle and Toxocara infections in the Philippines in human and animal hosts. Methods Faecal samples were collected from humans and animals (dogs, cats and pigs) in 252 households from four villages in southern Philippines and intestinal helminth infections were assessed by microscopy. Associations between worm species were assessed using multiple logistic regression. Results Ascaris infections showed a similar prevalence in humans (13.9%) and pigs (13.7%). Hookworm was the most prevalent infection in dogs (48%); the most prevalent infection in pigs was strongyles (42%). The prevalences of hookworm and Toxocara in cats were similar (41%). Statistically significant associations were observed between Ascaris and Trichuris and between Ascaris and hookworm infections in humans, and also between Ascaris and Trichuris infections in pigs. Dual and triple infections were observed, which were more common in dogs, cats and pigs than in humans. Conclusions Associations are likely to exist between STH species in humans and animals, possibly due to shared exposures and transmission routes. Individual factors and behaviours will play a key role in the occurrence of co-infections, which will have effects on disease severity. Moreover, the implications of co-infection for the emergence of zoonoses need to be explored further.
Human toxocariasis is a neglected tropical disease, which is actually global in distribution and has a significant impact on global public health. The infection can lead to several serious conditions in humans, including allergic, ophthalmic and neurological disorders such as epilepsy. It is caused by the common roundworm species Toxocara canis and Toxocara cati, with humans becoming accidentally infected via the ingestion of eggs or larvae. Toxocara eggs are deposited on the ground when infected dogs, cats and foxes defecate, with the eggs contaminating crops, grazing pastures, and subsequently food animals. However, transmission of Toxocara to humans via food consumption has received relatively little attention in the literature. To establish the risks that contaminated food poses to the public, a renewed research focus is required. This review discusses what is currently known about food-borne Toxocara transmission, highlighting the gaps in our understanding that require further attention, and outlining some potential preventative strategies which could be employed to safeguard consumer health.
The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.
Background Schistosomiasis is a major socio-economic and public health problem in many sub-Saharan African countries. After large mass drug administration (MDA) campaigns, prevalence of infection rapidly returns to pre-treatment levels. The traditional egg-based diagnostic for schistosome infections, Kato-Katz, is being substituted in many settings by circulating antigen recognition-based diagnostics, usually the point-of-care circulating cathodic antigen test (CCA). The relationship between these diagnostics is poorly understood, particularly after treatment in both drug-efficacy studies and routine monitoring. Results We created a model of schistosome infections to better understand and quantify the relationship between these two egg- and adult worm antigen-based diagnostics. We focused particularly on the interpretation of “trace” results after CCA testing. Our analyses suggest that CCA is generally a better predictor of prevalence, particularly after treatment, and that trace CCA results are typically associated with truly infected individuals. Conclusions Even though prevalence rises to pre-treatment levels only six months after MDAs, our model suggests that the average intensity of infection is much lower, and is probably in part due to a small burden of surviving juveniles from when the treatment occurred. This work helps to better understand CCA diagnostics and the interpretation of post-treatment prevalence estimations.
Defense against infection incurs costs as well as benefits that are expected to shape the evolution of optimal defense strategies. In particular, many theoretical studies have investigated contexts favoring constitutive versus inducible defenses. However, even when one immune strategy is theoretically optimal, it may be evolutionarily unachievable. This is because evolution proceeds via mutational changes to the protein interaction networks underlying immune responses, not by changes to an immune strategy directly. Here, we use a theoretical simulation model to examine how underlying network architectures constrain the evolution of immune strategies, and how these network architectures account for desirable immune properties such as inducibility and robustness. We focus on immune signaling because signaling molecules are common targets of parasitic interference but are rarely studied in this context. We find that in the presence of a coevolving parasite that disrupts immune signaling, hosts evolve constitutive defenses even when inducible defenses are theoretically optimal. This occurs for two reasons. First, there are relatively few network architectures that produce immunity that is both inducible and also robust against targeted disruption. Second, evolution toward these few robust inducible network architectures often requires intermediate steps that are vulnerable to targeted disruption. The few networks that are both robust and inducible consist of many parallel pathways of immune signaling with few connections among them. In the context of relevant empirical literature, we discuss whether this is indeed the most evolutionarily accessible robust inducible network architecture in nature, and when it can evolve.
Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever-rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify 'true' cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever-rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-Tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks. © Cambridge University Press 2018 This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Co-infection with multiple soil-transmitted helminth (STH) species is common in communities with a high STH prevalence. The life histories of STH species share important characteristics, particularly in the gut, and there is the potential for interaction, but evidence on whether interactions may be facilitating or antagonistic are limited. Methods: Data from a pretreatment cross-sectional survey of STH egg deposition in a tea plantation community in Sri Lanka were analysed to evaluate patterns of co-infection and changes in egg deposition. Results: There were positive associations between Trichuris trichiura (whipworm) and both Necator americanus (hookworm) and Ascaris lumbricoides (roundworm), but N. americanus and Ascaris were not associated. N. americanus and Ascaris infections had lower egg depositions when they were in single infections than when they were co-infecting. There was no clear evidence of a similar effect of co-infection in Trichuris egg deposition. Conclusions: Associations in prevalence and egg deposition in STH species may vary, possibly indicating that effects of co-infection are species dependent. We suggest that between-species interactions that differ by species could explain these results, but further research in different populations is needed to support this theory. © The Author(s) 2018. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.
Background. With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. Methods. We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Results. Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence
Mathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases. Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models.
Introduction All six WHO regions currently have goals for measles elimination by 2020. Measles vaccination is delivered via routine immunization programmes, which in most sub-Saharan African countries reach children around 9Â months of age, and supplementary immunization activities (SIAs), which target a wider age range at multi-annual intervals. In the absence of endemic measles circulation, the proportion of individuals susceptible to measles will gradually increase through accumulation of new unvaccinated individuals in each birth cohort, increasing the risk of an epidemic. The impact of SIAs and the financial investment they require, depend on coverage and target age range. Materials and methods We evaluated the impact of target population age range for periodic SIAs, evaluating outcomes for two different levels of coverage, using a demographic and epidemiological model adapted to reflect populations in 4 sub-Saharan African countries. Results We found that a single SIA can maintain elimination over short time-scales, even with low routine coverage. However, maintaining elimination for more than a few years is difficult, even with large (high coverage/wide age range) recurrent SIAs, due to the build-up of susceptible individuals. Across the demographic and vaccination contexts investigated, expanding SIAs to target individuals over 10Â years did not significantly reduce outbreak risk. Conclusions Elimination was not maintained in the contexts we evaluated without a second opportunity for vaccination. In the absence of an expanded routine program, SIAs provide a powerful option for providing this second dose. We show that a single high coverage SIA can deliver most key benefits in terms of maintaining elimination, with follow-up campaigns potentially requiring smaller investments. This makes post-campaign evaluation of coverage increasingly relevant to correctly assess future outbreak risk. Â© 2017 The Author(s)
Intestinal helminths are extremely widespread and highly prevalent infections of humans, particularly in rural and poor urban areas of low and middle-income countries. These parasites have chronic and often insidious effects on human health and child development including abdominal problems, anaemia, stunting and wasting. Certain animals play a fundamental role in the transmission of many intestinal helminths to humans. However, the contribution of zoonotic transmission to the overall burden of human intestinal helminth infection and the relative importance of different animal reservoirs remains incomplete. Moreover, control programmes and transmission models for intestinal helminths often do not consider the role of zoonotic reservoirs of infection. Such reservoirs will become increasingly important as control is scaled up and there is a move towards interruption and even elimination of parasite transmission. With a focus on southeast Asia, and the Philippines in particular, this review summarises the major zoonotic intestinal helminths, risk factors for infection and highlights knowledge gaps related to their epidemiology and transmission. Various methodologies are discussed, including parasite genomics, mathematical modelling and socio-economic analysis, that could be employed to improve understanding of intestinal helminth spread, reservoir attribution and the burden associated with infection, as well as assess effectiveness of interventions. For sustainable control and ultimately elimination of intestinal helminths, there is a need to move beyond scheduled mass deworming and to consider animal and environmental reservoirs. A One Health approach to control of intestinal helminths is proposed, integrating interventions targeting humans, animals and the environment, including improved access to water, hygiene and sanitation. This will require coordination and collaboration across different sectors to achieve best health outcomes for all.
There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings. © 2018 Davis et al.
Background: In this study, two traits related with resistance to gastrointestinal nematodes (GIN) were measured in 529 adult sheep: faecal egg count (FEC) and activity of immunoglobulin A in plasma (IgA). In dry years, FEC can be very low in semi-extensive systems, such as the one studied here, which makes identifying animals that are resistant or susceptible to infection a difficult task. A zero inflated negative binomial model (ZINB) model was used to calculate the extent of zero inflation for FEC; the model was extended to include information from the IgA responses. Results: In this dataset, 64 % of animals had zero FEC while the ZINB model suggested that 38 % of sheep had not been recently infected with GIN. Therefore 26 % of sheep were predicted to be infected animals with egg counts that were zero or below the detection limit and likely to be relatively resistant to nematode infection. IgA activities of all animals were then used to decide which of the sheep with zero egg counts had been exposed and which sheep had not been recently exposed. Animals with zero FEC and high IgA activity were considered resistant while animals with zero FEC and low IgA activity were considered as not recently infected. For the animals considered as exposed to the infection, the correlations among the studied traits were estimated, and the influence of these traits on the discrimination between unexposed and infected animals was assessed. Conclusions: The model presented here improved the detection of infected animals with zero FEC. The correlations calculated here will be useful in the development of a reliable index of GIN resistance that could be of assistance for the study of host resistance in studies based on natural infection, especially in adult sheep, and also the design of breeding programs aimed at increasing resistance to parasites. © 2016 The Author(s).