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      Validation of a spatial agent-based model for Taenia solium transmission (“CystiAgent”) against a large prospective trial of control strategies in northern Peru

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          Abstract

          Background

          The pork tapeworm ( Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy.

          Methods/Principal findings

          We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively.

          Conclusions/Significance

          The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment.

          Author summary

          Neurocysticercosis, caused by the ingestion of Taenia solium eggs, is a major cause of human epilepsy around the world. A wide spectrum of tools to fight T. solium is are now available and include antiparasitic treatment for pigs and humans, porcine vaccines, and sanitation improvements; however, the ideal combination of interventions applied to populations to maximize effectiveness and feasibility is not known. Transmission models are one tool that can be used to compare and evaluate different intervention strategies, but no currently available T. solium models have been tested for accuracy. In this research, we validated our model (“CystiAgent”) by comparing simulations of the model to the results of a large-scale trial testing a variety of T. solium control interventions. The model was calibrated using observed epidemiological data from these villages and evaluated for its ability to reproduce the effect of T. solium control interventions. The validation showed that the model was able to reproduce the baseline levels of disease, but generally overestimated the effect that each intervention would have on transmission. These results will allow us to identify limitations of the current model to improve future versions, and represent a step forward in the creation of a tool to design and evaluate future programs to control and eliminate T. solium.

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          Most cited references53

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          Taenia solium cysticercosis.

          The larval stage of the pork tapeworm (Taenia solium) infects the human nervous system, causing neurocysticercosis. This disease is one of the main causes of epileptic seizures in many less developed countries and is also increasingly seen in more developed countries because of immigration from endemic areas. Little information is available on the natural evolution of taeniasis or cysticercosis. Available therapeutic measures include steroids, treatments for symptoms, surgery, and, more controversially, antiparasitic drugs to kill brain parasites. Efforts to control and eliminate this disease are underway through antiparasitic treatment of endemic populations, development of pig vaccines, and other measures.
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            Infection prevalence and ecotypes of Anaplasma phagocytophilum in moose Alces alces , red deer Cervus elaphus , roe deer Capreolus capreolus and Ixodes ricinus ticks from Norway

            Background The geographical expansion of the tick Ixodes ricinus in northern Europe is a serious concern for animal and human health. The pathogen Anaplasma phagocytophilum is transmitted by ticks and causes emergences of tick-borne fever (anaplasmosis) in livestock. The transmission dynamics of the different ecotypes of A. phagocytophilum in the ecosystems is only partly determined. Red deer and roe deer contribute to circulation of different ecotypes of A. phagocytophilum in continental Europe, while the role of moose for circulation of different ecotypes is not fully established but an important issue in northern Europe. Methods We determined infection prevalence and ecotypes of A. phagocytophilum in moose (n = 111), red deer (n = 141), roe deer (n = 28) and questing ticks (n = 9241) in Norway. Results As previously described, red deer was exclusively linked to circulation of ecotype I, while roe deer was exclusively linked to circulation of ecotype II. Surprisingly, we found 58% ecotype I (n = 19) and 42% of ecotype II (n = 14) in moose. Both ecotypes were found in questing ticks in areas with multiple cervid species present, while only ecotype I was found in ticks in a region with only red deer present. Hence, the geographical distribution of ecotypes in ticks followed the distribution of cervid species present in a given region and their link to ecotype I and II. Conclusions Moose probably function as reservoirs for both ecotype I and II, indicating that the ecotypes of A. phagocytophilum are not entirely host-specific and have overlapping niches. The disease hazard depends also on both host abundance and the number of immature ticks fed by each host. Our study provides novel insights in the northern distribution and expansion of tick-borne fever.
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              Bovine ticks harbour a diverse array of microorganisms in Pakistan

              Background Ticks and tick-borne pathogens (TTBP) are a major constraint to livestock production in Pakistan; despite a high prevalence of TTBPs, knowledge on the capacity of Pakistani ticks to carry pathogens and endosymbionts is limited. Furthermore, mixed infections with multiple microorganisms further complicate and limit the detection potential of traditional diagnostic methods. The present study investigated the tick-borne microorganisms in bovine ticks in Pakistan, employing a high-throughput microfluidic real-time PCR based technique. Methods Ticks were collected from clinically healthy cattle (n = 116) and water buffaloes (n = 88) from 30 villages across six districts located in five agro-ecological zones (AEZs) of Pakistan from September to November 2017. The microfluidic real-time PCR was used to test the genomic DNA of individual ticks for the presence of 27 bacterial and eight parasitic microorganisms. Phylogenetic methods were used to assess the genetic relationship of DNA sequences determined herein. Results PCR detected DNA of at least one microorganism in each of 221 ticks tested (94.4%, 221/234). DNA-based detection inferred that single pathogens/endosymbionts were the most common (43.4%, 96/221) followed by double (38.9%, 86/221), triple (14.5%, 32/221), quadruple (2.3%, 5/221) and quintuple (0.9%, 2/221) mixed infections. Piroplasms (Babesia/Theileria spp.) were the most prevalent (31.6%, 74/234), followed by Ehrlichia spp. (20%, 47/234) and Anaplasma marginale (7.7%, 18/234). Anaplasma phagocytophilum, A. ovis, A. centrale, Babesia ovis, Borrelia spp., Rickettsia spp., R. massiliae, Bartonella spp. and Hepatozoon spp. were also detected. Endosymbionts such as Francisella-like (91.5%, 214/234) and Coxiella-like (1.3%, 3/234) organisms were also detected in ticks. The highest diversity of microorganisms was detected in Hyalomma anatolicum ticks (test-positive for 14/14 microorganisms), followed by Rhipicephalus microplus (4/14), Hy. hussaini (3/14) and Rh. annulatus (2/14). Ticks collected from cattle carried significantly more frequently piroplasms (41.2%, 54/131; P < 0.05) than those from buffaloes (19.4%, 20/103). However, the overall prevalence of microorganisms did not vary significantly among ticks from the two host species as well as across different AEZs. Conclusions To our knowledge, this is the first study to investigate a wide range of tick-borne microorganisms in bovine ticks using a high-throughput diagnostic method from different AEZs in Pakistan. These findings will aid in establishing the distribution patterns and the control of tick-borne pathogens of bovines in Pakistan.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                27 October 2021
                October 2021
                : 15
                : 10
                : e0009885
                Affiliations
                [1 ] School of Public Health, Oregon Health & Science University and Portland State University, Portland, Oregon, United States of America
                [2 ] Tropical and Highlands Veterinary Research Institute, School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, EL Mantaro, Peru
                [3 ] School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
                [4 ] Systems Science Program, Portland State University, Portland, Oregon, United States of America
                [5 ] Duke Global Health Institute & Nicholas School of Environment, Duke University, Durham, North Carolina, United States of America
                [6 ] School of Sciences, Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru
                [7 ] Center for Global Health Tumbes, Universidad Peruana Cayetano Heredia, Tumbes, Peru
                University of Zurich, SWITZERLAND
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-6935-5123
                https://orcid.org/0000-0002-5532-8770
                https://orcid.org/0000-0002-3539-5001
                https://orcid.org/0000-0001-7328-2983
                https://orcid.org/0000-0002-7407-7399
                https://orcid.org/0000-0003-1909-1873
                Article
                PNTD-D-20-02249
                10.1371/journal.pntd.0009885
                8575314
                34705827
                124bbc06-3702-4000-8b2c-a684a7ad80c9
                © 2021 Pray et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 January 2021
                : 8 October 2021
                Page count
                Figures: 4, Tables: 2, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;
                Award ID: R01AI141554
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;
                Award ID: R01NS080645
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000061, Fogarty International Center;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100010629, Fulbright Association;
                Award Recipient :
                This research was funded in part by the US National Institute of Allergy and Infectious Disease (R01AI141554), the National Institute of Neurologic Disorders and Stroke (R01NS080645), and the Fogarty International Center through the National Institutes of Health. Grants were awarded to SEO as principal investigator. SEO, FP, GB, EGG, WP, AEG and HHG receive salary through these grants. IWP was supported with travel and stipend for doctoral work by the Fulbright US Students Program and Fulbright Commission in Peru. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Swine
                Biology and Life Sciences
                Zoology
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                Vertebrates
                Amniotes
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                Custom metadata
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                2021-11-08
                All relevant data are within the manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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