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Dolo H, Coulibaly YI, Sow M, et al., 2020, Serological evaluation of onchocerciasis and lymphatic filariasis elimination in the Bakoye and Faleme foci, Mali, Publisher: ELSEVIER SCI LTD, Pages: 427-428, ISSN: 1201-9712
Milne G, Webster JP, Walker M, 2020, <i>Toxoplasma gondii</i>: An Underestimated Threat?, TRENDS IN PARASITOLOGY, Vol: 36, Pages: 959-969, ISSN: 1471-4922
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Milne G, Webster JP, Walker M, 2020, Towards improving interventions against toxoplasmosis by identifying routes of transmission using sporozoite-specific serological tools., Clinical Infectious Diseases, Vol: 71, Pages: e686-e693, ISSN: 1058-4838
BACKGROUND: Horizontal transmission of Toxoplasma gondii occurs primarily via ingestion of environmental oocysts or consumption of undercooked/raw meat containing cyst-stage bradyzoites. The relative importance of these two transmission routes remains unclear. Oocyst infection can be distinguished from bradyzoite infection by identification of IgG antibodies against T. gondii-embryogenesis-related protein (TgERP). These antibodies are, however, thought to persist for only 6-8 months in human sera, limiting the use of TgERP serology to only those patients recently exposed to T. gondii. Yet recent serological survey data indicate a more sustained persistence of anti-TgERP antibodies. Elucidating the duration of anti-TgERP IgG will help to determine whether TgERP serology has epidemiological utility for quantifying the relative importance of different routes of T. gondii transmission. METHODS: We developed a sero-catalytic mathematical model to capture the change in seroprevalence of non-stage-specific IgG and anti-TgERP IgG antibodies with human age. The model was fitted to published datasets collected in an endemic region of Brazil to estimate the duration of anti-TgERP IgG antibodies, accounting for variable age-force of infection profiles and uncertainty in the diagnostic performance of TgERP serology. RESULTS: We found that anti-TgERP IgG persists for substantially longer than previously recognised, with estimates ranging from 8.3 to 41.1 years. The Brazilian datasets were consistent with oocysts being the predominant transmission route in these settings. CONCLUSIONS: The longer than previously recognised duration of anti-TgERP antibodies indicates that anti-TgERP serology could be a useful tool for delineating T. gondii transmission routes in human populations. TgERP serology may therefore be an important epidemiological tool for informing the design of tailored, setting-specific public health information campaigns and interventions.
Dixon MA, Winskill P, Harrison W, et al., 2020, Force-of-Infection of Taenia solium porcine cysticercosis: a modelling analysis to assess global incidence and prevalence trends, Scientific Reports, Vol: 10, ISSN: 2045-2322
The World Health Organization (WHO) called, in 2012, for a validated strategy towards Taenia solium taeniasis/cysticercosis control and elimination. Estimating pig force-of-infection (FoI, the average rate at which susceptible pigs become infected) across geographical settings will help understand local epidemiology and inform effective intervention design. Porcine cysticercosis (PCC) age-prevalence data (from 15 studies in Latin America, Africa and Asia) were identified through systematic review. Catalytic models were fitted to the data using Bayesian methods, incorporating uncertainty in diagnostic performance, to estimate rates of antibody seroconversion, viable metacestode acquisition, and seroreversion/infection loss. There was evidence of antibody seroreversion across 5 studies, and of infection loss in 6 studies measured by antigen or necropsy, indicating transient serological responses and natural resolution of infection. Concerted efforts should be made to collect robust data using improved diagnostics to better understand geographical heterogeneities in T. solium transmission to support post-2020 WHO targets.
Milne G, Fujimoto C, Bean T, et al., 2020, Infectious causation of abnormal host behavior: toxoplasma gondiiand Its potential association with dopey fox syndrome, Frontiers in Psychiatry, Vol: 11, Pages: 1-16, ISSN: 1664-0640
The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, can infect all warm-blooded animals. T. gondii can subtly alter host behaviors—either through manipulation to enhance transmission to the feline definitive host or as a side-effect, or “constraint,” of infection. In humans, T. gondii infection, either alone or in association with other co-infecting neurotropic agents, has been reliably associated with both subtle behavioral changes and, in some cases, severe neuropsychiatric disorders, including schizophrenia. Research on the potential impact of T. gondii on the behavior of other long-lived naturally infected hosts is lacking. Recent studies reported a large number of wild red foxes exhibiting a range of aberrant behavioral traits, subsequently classified as Dopey Fox Syndrome (DFS). Here we assessed the potential association between T. gondii and/or other neurotropic agents with DFS. Live, captive foxes within welfare centers were serologically tested for T. gondii and, if they died naturally, PCR-tested for vulpine circovirus (FoxCV). Post-mortem pseudo-control wild foxes, obtained from pest management companies, were PCR-tested for T. gondii, FoxCV, canine distemper virus (CDV), canine adenovirus type (CAV)-1 and CAV-2. We also assessed, using non-invasive assays, whether T. gondii–infected foxes showed subtle behavioral alterations as observed among infected rodent (and other) hosts, including altered activity, risk, and stress levels. All foxes tested negative for CAV, CDV, CHV, and DogCV. DFS was found to be associated with singular T. gondii infection (captives vs. pseudo-controls, 33.3% (3/9) vs. 6.8% (5/74)) and singular FoxCV infection (66.7% (6/9) vs. 11.1% (1/9)) and with T. gondii/FoxCV co-infection (33.3% (3/9) vs. 11.1% (1/9)). Overall, a higher proportion of captive foxes had signs of neuroinflammation compared to pseudo-controls (66.7% (4/6) vs. 11.1% (1/9)). Consistent with behavioral changes
Basanez M-G, Milton P, Hamley J, et al., 2020, Moxidectin: an oral treatment for human onchocerciasis, Expert Review of Anti-infective Therapy, Vol: 18, Pages: 1067-1081, ISSN: 1478-7210
Introduction: Moxidectin is a milbemycin endectocide recently approved for the treatment of humanonchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemicin Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether thepredominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient toachieve elimination in all endemic foci have refocussed attention upon alternative treatments.Moxidectin’s stronger and longer microfilarial suppression compared to ivermectin in both phase IIand III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination.Areas covered: This work summarizes the chemistry and pharmacology of moxidectin, reviews thephase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin’s current regulatory status.Expert opinion: Moxidectin’s superior clinical performance has the potential to substantially reducetimes to elimination compared to ivermectin. If donated, moxidectin could mitigate the additionalprogrammatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use theexisting community-directed treatment infrastructure. A pediatric indication (for children <12 years) anddetermination of its usefulness in onchocerciasis–loiasis co-endemic areas will greatly help fulfill thepotential of moxidectin for the treatment and elimination of onchocerciasis.
Webster JP, Neves MI, Webster BL, et al., 2020, Parasite population genetic contributions to the schistosomiasis consortium for operational research and evaluation within Sub-Saharan Africa, American Journal of Tropical Medicine and Hygiene, Vol: 103, Pages: 80-91, ISSN: 0002-9637
Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general.
Hamley J, Walker M, Coffeng LE, et al., 2020, Structural uncertainty in onchocerciasis transmission models influences the estimation of elimination thresholds and selection of age groups for seromonitoring, Journal of Infectious Diseases, Vol: 221, Pages: S510-S518, ISSN: 0022-1899
Background. The World Health Organization recommends monitoring Ov16 serologyin children aged <10 years for stopping mass ivermectin administration. Transmission models can help to identify the most informative age groups for serological monitoring and investigate the discriminatory power of serology-based elimination thresholds.Model predictions will depend on assumed age-exposure patterns and transmission efficiency at low infection levels. Methods. The individual-based transmission model, EPIONCHO-IBM, was used toassess: i) the most informative age groups for serological monitoring using receiveroperator characteristic curves for different elimination thresholds under various age-dependent exposure assumptions, including those of ONCHOSIM (another widely-used model), and ii) the influence of within-human density-dependent parasite establishment (included in EPIONCHO-IBM but not in ONCHOSIM) on positive predictive values for different serological thresholds.Results. When assuming EPIONCHO-IBM exposure patterns, under-10s are themost informative age group for seromonitoring; when assuming ONCHOSIM’s exposure patterns, 5–15-year olds are the most informative (as published elsewhere).Omitting density-dependent parasite establishment results in more lenientseroprevalence thresholds, even for higher baseline infection prevalence and shorter treatment durations.Conclusions. Selecting appropriate seromonitoring age groups depends critically onage-dependent exposure patterns. The role of density dependence on elimination thresholds largely explains differing EPIONCHO-IBM and ONCHOSIM elimination predictions.
Walker M, Hamley JID, Milton P, et al., 2020, Designing antifilarial drug trials using clinical trial simulators, Nature Communications, Vol: 11, Pages: 1-11, ISSN: 2041-1723
Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles.
Behrend M, Basanez M-G, Hamley JID, et al., 2020, Modelling for policy: the five principles of the Neglected Tropical Diseases Modelling Consortium, PLoS Neglected Tropical Diseases, ISSN: 1935-2727
Nana Djeunga H, Domche A, Niamsi-Emalio Y, et al., 2020, Situation analysis of onchocerciasis in Cameroon: a protocol for systematic review of epidemiological studies and impact of disease control interventions, Systematic Reviews, ISSN: 2046-4053
Dixon M, Braae UC, Winskill P, et al., 2020, Modelling for Taenia solium control strategies beyond 2020, Bulletin of the World Health Organization, Vol: 98, Pages: 198-205, ISSN: 0042-9686
The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. soliumtransmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.
Lam CT, Rosanowski SM, Walker M, et al., 2020, Sea lice exposure to non-lethal levels of emamectin benzoate after treatments: a potential risk factor for drug resistance, Scientific Reports, Vol: 10, Pages: 1-8, ISSN: 2045-2322
The avermectin derivative emamectin benzoate (EMB) has been widely used by salmon industries around the world to control sea lice infestations. Resistance to this anti-parasitic drug is also commonly reported in these industries. The objective of this study was to quantify the number of sea lice potentially exposed to sub-lethal concentrations of EMB while fish clear the drug after treatments. We assessed juvenile sea lice abundance after 38 EMB treatments on six Atlantic salmon farms, in a small archipelago in British Colombia, Canada, between 2007 and 2018. We fitted a standard EMB pharmacokinetic curve to determine the time when fish treated with this product would have EMB tissue concentrations below the recommended target therapeutic level. During the study, we estimated that for each sea lice treatment there was, on average, an abundance of 0.12 juvenile sea lice per fish during the time period when the concentrations of EMB would have been lower than 60ppb, the recommended therapeutic treatment level for sea lice. The findings from this study on metaphylactic anti-parasitic treatments identify a potential driver for drug resistance in sea lice that should be further explored.
Deol AK, Fleming FM, Calvo-Urbano B, et al., 2019, Schistosomiasis — assessing progress toward the 2020 and 2025 global goals, New England Journal of Medicine, Vol: 381, Pages: 2519-2528, ISSN: 0028-4793
BackgroundWith the vision of “a world free of schistosomiasis,” the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically.MethodsWe collated and analyzed multiyear cross-sectional data from nine national schistosomiasis control programs (in eight countries in sub-Saharan Africa and in Yemen). Data were analyzed according to schistosome species (Schistosoma mansoni or S. haematobium), number of treatment rounds, overall prevalence, and prevalence of heavy-intensity infection. Disease control was defined as a prevalence of heavy-intensity infection of less than 5% aggregated across sentinel sites, and the elimination target was defined as a prevalence of heavy-intensity infection of less than 1% in all sentinel sites. Heavy-intensity infection was defined as at least 400 eggs per gram of feces for S. mansoni infection or as more than 50 eggs per 10 ml of urine for S. haematobium infection.ResultsAll but one country program (Niger) reached the disease-control target by two treatment rounds or less, which is earlier than projected by current WHO guidelines (5 to 10 years). Programs in areas with low endemicity levels at baseline were more likely to reach both the control and elimination targets than were programs in areas with moderate and high endemicity levels at baseline, although the elimination target was reached only for S. mansoni infection (in Burkina Faso, Burundi, and Rwanda within three treatment rounds). Intracountry variation was evident in the relationships between overall prevalence and heavy-intensity infection (stratified according to treatment rounds), a finding that highlights the challenges of using one metric to define control or elimination across all epidemiologic settings.Conclusio
Hamley JID, Milton P, Walker M, et al., 2019, Modelling exposure heterogeneity and density dependence in onchocerciasis using a novel individual-based transmission model, EPIONCHO-IBM: Implications for elimination and data needs, PLoS Neglected Tropical Diseases, Vol: 13, Pages: e0007557-e0007557, ISSN: 1935-2727
BackgroundDensity dependence in helminth establishment and heterogeneity in exposure to infection are known to drive resilience to interventions based on mass drug administration (MDA). However, the interaction between these processes is poorly understood. We developed a novel individual-based model for onchocerciasis transmission, EPIONCHO-IBM, which accounts for both processes. We fit the model to pre-intervention epidemiological data and explore parasite dynamics during MDA with ivermectin.Methodology/Principal findingsDensity dependence and heterogeneity in exposure to blackfly (vector) bites were estimated by fitting the model to matched pre-intervention microfilarial prevalence, microfilarial intensity and vector biting rate data from savannah areas of Cameroon and Côte d’Ivoire/Burkina Faso using Latin hypercube sampling. Transmission dynamics during 25 years of annual and biannual ivermectin MDA were investigated. Density dependence in parasite establishment within humans was estimated for different levels of (fixed) exposure heterogeneity to understand how parametric uncertainty may influence treatment dynamics. Stronger overdispersion in exposure to blackfly bites results in the estimation of stronger density-dependent parasite establishment within humans, consequently increasing resilience to MDA. For all levels of exposure heterogeneity tested, the model predicts a departure from the functional forms for density dependence assumed in the deterministic version of the model.Conclusions/SignificanceThis is the first, stochastic model of onchocerciasis, that accounts for and estimates density-dependent parasite establishment in humans alongside exposure heterogeneity. Capturing the interaction between these processes is fundamental to our understanding of resilience to MDA interventions. Given that uncertainty in these processes results in very different treatment dynamics, collecting data on exposure heterogeneity would be essential for improvin
Buell KG, Whittaker C, Chesnais CB, et al., 2019, Atypical clinical manifestations of Loiasis and their relevance for endemic populations, Open Forum Infectious Diseases, Vol: 6, ISSN: 2328-8957
Background: Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis. Methods: We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations. Results: Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations. Conclusions: Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.
NTD Modelling Consortium Onchocerciasis Group, 2019, The World Health Organization 2030 goals for onchocerciasis: Insights and perspectives from mathematical modelling, Gates Open Research, Vol: 3, Pages: 1545-1545, ISSN: 2572-4754
The World Health Organization (WHO) has embarked on a consultation process to refine the 2030 goals for priority neglected tropical diseases (NTDs), onchocerciasis among them. Current goals include elimination of transmission (EOT) by 2020 in Latin America, Yemen and selected African countries. The new goals propose that, by 2030, EOT be verified in 10 countries; mass drug administration (MDA) with ivermectin be stopped in at least one focus in 34 countries; and that the proportion of the population no longer in need of MDA be equal or greater than 25%, 50%, 75% and 100% in at least 16, 14, 12, and 10 countries, respectively. The NTD Modelling Consortium onchocerciasis teams have used EPIONCHO and ONCHOSIM to provide modelling insights into these goals. EOT appears feasible in low-moderate endemic areas with long-term MDA at high coverage (≥75%), but uncertain in areas of higher endemicity, poor coverage and adherence, and where MDA has not yet, or only recently, started. Countries will have different proportions of their endemic areas classified according to these categories, and this distribution of pre-intervention prevalence and MDA duration and programmatic success will determine the feasibility of achieving the proposed MDA cessation goals. Highly endemic areas would benefit from switching to biannual or quarterly MDA and implementing vector control where possible (determining optimal frequency and duration of anti-vectorial interventions requires more research). Areas without loiasis that have not yet initiated MDA should implement biannual (preferably with moxidectin) or quarterly MDA from the start. Areas with loiasis not previously treated would benefit from implementing test-and(not)-treat-based interventions, vector control, and anti-Wolbachia therapies, but their success will depend on the levels of screening and coverage achieved and sustained. The diagnostic performance of IgG4 Ov16 serology for assessing EOT is currently uncertain. Verification of
CystiTeam Group for Epidemiology and Modelling of Taenia solium TaeniasisCysticercosis, 2019, The World Health Organization 2030 goals for Taenia solium: Insights and perspectives from transmission dynamics modelling, Gates Open Research, Vol: 3, Pages: 1546-1546, ISSN: 2572-4754
Taenia solium (TS), responsible for porcine cysticercosis, human taeniasis and (neuro)cysticercosis, was included in the World Health Organization neglected tropical disease (NTD) roadmap published in 2012. Targets set in this roadmap have not been met, but T. solium has been included in the consultation process for the new 2030 goals proposed for priority NTDs. Taenia solium transmission dynamics models can contribute to this process. A recent review has compared existing T. solium transmission models, identifying their similarities and differences in structure, parameterization and modelled intervention approaches. While a formal model comparison to investigate the impact of interventions is yet to be conducted, the models agree on the importance of coverage for intervention effectiveness and on the fact that human- and pig-focused interventions can be optimally combined. One of these models, cystiSim, an individual-based, stochastic model has been used to assess field-applicable interventions, some currently under evaluation in on-going trials in Zambia. The EPICYST, population-based, deterministic model has highlighted, based on simulating a generic sub-Saharan Africa setting, the higher efficacy (measured as the percentage of human cysticercosis cases prevented) of biomedical interventions (human and pig treatment and pig vaccination) compared to improved husbandry, sanitation, and meat inspection. Important questions remain regarding which strategies and combinations thereof provide sustainable solutions for severely resource-constrained endemic settings. Defining realistic timeframes to achieve feasible targets, and establishing suitable measures of effectiveness for these targets that can be quantified with current monitoring and evaluation tools, are current major barriers to identifying validated strategies. Taenia solium transmission models can support setting achievable 2030 goals; however, the refinement of these models is first required. Incorporating
Turner HC, Walker M, Pion SDS, et al., 2019, Economic evaluations of onchocerciasis interventions: a systematic review and research needs, Tropical Medicine and International Health, Vol: 24, Pages: 788-816, ISSN: 1360-2276
ObjectiveTo provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps.MethodA systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches.ResultsWe identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable).ConclusionsThe cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.
Dixon MA, Braae UC, Winskill P, et al., 2019, Strategies for tackling Taenia solium taeniosis/cysticercosis: A systematic review and comparison of transmission models, including an assessment of the wider Taeniidae family transmission models, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
BackgroundThe cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO).Methodology/Principal findingsA systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved.Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations.Conclusions/SignificanceGaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.
Neves M, Malkawi I, Walker M, et al., 2019, The transmission dynamics of Campylobacter jejuni among broilers in semi-commercial farms in Jordan, Epidemiology and Infection, Vol: 147, Pages: 1-7, ISSN: 0950-2688
Campylobacter is the leading cause of foodborne bacterial gastroenteritis in humans worldwide, often associated with the consumption of undercooked poultry. In Jordan, the majority of broiler chicken production occurs in semi-commercial farms, where poor housing conditions and low bio-security are likely to promote campylobacter colonisation. While several studies provided estimates of the key parameters describing the within-flock transmission dynamics of campylobacter in typical high-income countries settings, these data are not available for Jordan and Middle-East in general. A Bayesian model framework was applied to a longitudinal dataset on Campylobacter jejuni infection in a Jordan flock to quantify the transmission rate of C. jejuni in broilers within the farm, the day when the flock first became infected, and the within-flock prevalence (WFP) at clearance. Infection with C. jejuni is most likely to have occurred during the first 8 days of the production cycle, followed by a transmission rate value of 0.13 new infections caused by one infected bird/day (95% CI 0.11–0.17), and a WFP at clearance of 34% (95% CI 0.24–0.47). Our results differ from published studies conducted in intensive poultry production systems in high-income countries but are well aligned with the expectations obtained by means of structured questionnaires submitted to academics with expertise on campylobacter in Jordan. This study provides for the first time the most likely estimates and credible intervals of key epidemiological parameters driving the dynamics of C. jejuni infection in broiler production systems commonly found in Jordan and the Middle-East and could be used to inform Quantitative Microbial Risk Assessment models aimed to assess the risk of human exposure/infection to campylobacter through consumption of poultry meat.
Whittaker C, Kamgno J, Klion A, et al., 2019, THE EFFECT OF ALBENDAZOLE TREATMENT ON <i>LOA LOA</i>: A SYSTEMATIC REVIEW, META-ANALYSIS AND MODELLING STUDY, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 559-560, ISSN: 0002-9637
Dunn JC, Walker M, Bettis AA, et al., 2019, PREDISPOSITION AND HOUSEHOLD CLUSTERING OF SOIL-TRANSMITTED HELMINTH INFECTION EVIDENT IN MYANMAR COMMUNITIES THAT HAVE RECEIVED EXTENSIVE MASS DRUG ADMINISTRATION, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 616-617, ISSN: 0002-9637
Verver S, Walker M, Kim YE, et al., 2018, How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control, Clinical Infectious Diseases, Vol: 66, Pages: S267-S274, ISSN: 1058-4838
Background:Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated.Methods:We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination.Results:Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control.Conclusions:Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.
Routledge I, Walker M, Cheke R, et al., 2018, Modelling the impact of larviciding on the population dynamics and biting rates of Simulium damnosum s.l.: implications for vector control as a complementary strategy for onchocerciasis elimination in Africa, Parasites & Vectors, Vol: 11, Pages: 1-16, ISSN: 1756-3305
Background:In 2012, the World Health Organization set goals for the elimination of onchocerciasis transmission by 2020 in selected African countries. Epidemiological data and mathematical modelling have indicated that elimination may not be achieved with annual ivermectin distribution in all endemic foci. Complementary and alternative treatment strategies (ATS), including vector control, will be necessary. Implementation of vector control will require that the ecology and population dynamics of Simuliumdamnosum sensu latobe carefully considered.Methods:We adapted our previous SIMuliid POPulation dynamics (SIMPOP) model to explore the impact of larvicidal insecticides on S.damnosums.l.biting rates in different ecological contexts and to identify how frequently and for how long vector control should be continued to sustain substantive reductions in vector biting. SIMPOP was fitted to data from large-scale aerial larviciding trials in savannah sites (Ghana) and small-scale ground larviciding trials in forest areas (Cameroon). The model was validated against independent data from Burkina Faso/Côte d’Ivoire (savannah) and Bioko (forest). Scenario analysis explored the effects of ecological and programmatic factors such as pre-control daily biting rate (DBR) and larviciding scheme design on reductions and resurgences in biting rates.Results: The estimated efficacy of large-scale aerial larviciding in the savannah was greater than that of ground-based larviciding in the forest. Small changes in larvicidal efficacy can have large impacts on intervention success. At 93% larvicidal efficacy (a realistic value based on field trials), 10 consecutive weekly larvicidal treatments would reduce DBRs by 96% (e.g. from 400 to 16bites/person/day). At 70% efficacy, and for 10 weekly applications, the DBRwould decrease by 67% (e.g. from 400 to 132bites/person/day). Larviciding is more likely to succeed in areas with lower water temperatures and where blackfly species have lo
Whittaker C, Walker M, Pion SDS, et al., 2018, The population biology and transmission dynamics of Loa loa, Trends in Parasitology, Vol: 34, Pages: 335-350, ISSN: 1471-5007
Endemic to Central Africa, loiasis – or African eye worm (caused by the filarial nematode Loa loa) – affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.
Whittaker C, Walker M, Pion SDS, et al., 2018, Loa loa: more than meets the eye?, Trends in Parasitology, Vol: 34, Pages: 261-262, ISSN: 0169-4758
Whittaker C, Walker M, Pion S, et al., 2018, EVALUATING THE IMPACT OF ANTHELMINTIC-BASED INTERVENTION STRATEGIES FOR CONTROLLING <it>LOA LOA</it>: A MATHEMATICAL MODELLING STUDY USING EPILOA, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 16-16, ISSN: 0002-9637
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- Citations: 1
Laskaratos FM, Diamantopoulos L, Walker M, et al., 2018, Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia, NEUROENDOCRINOLOGY, Vol: 106, Pages: 366-380, ISSN: 0028-3835
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- Citations: 19
Laskaratos F-M, Walker M, Wilkins D, et al., 2018, Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours, NEUROENDOCRINOLOGY, Vol: 107, Pages: 292-304, ISSN: 0028-3835
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- Citations: 32
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