387 results on '"Hector H. Garcia"'
Search Results
2. Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment
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Miguel A. Orrego, Michal W. Szczesniak, Carlos M. Vasquez, Manuela R. Verastegui, Javier A. Bustos, Hector H. Garcia, Theodore E. Nash, and Cysticercosis Working Group in Peru
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Medicine ,Science - Abstract
Abstract Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapeworm Taenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.
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- 2024
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3. Concordance between two monoclonal antibody-based antigen detection enzyme-linked immunosorbent assays for measuring cysticercal antigen levels in sera from pigs experimentally infected with Taenia solium and Taenia hydatigena
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Gianfranco Arroyo, Luz Toribio, Sara Garrido, Nancy Chile, Teresa Lopez-Urbina, Luis A. Gomez-Puerta, Miguel Muro, Robert H. Gilman, Yesenia Castillo, Pierre Dorny, Seth E. O’Neal, Armando E. Gonzalez, Hector H. Garcia, and for The Cysticercosis Working Group in Peru (CWGP)
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Ag-ELISA ,Monoclonal antibodies ,TsW8/TsW5 ,Taenia solium ,Taenia hydatigena ,Concordance ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA. Methods We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland–Altman (BA) analysis and Lin’s concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA. Results The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin’s CCC: 0.69, 0.92, and 0.96, respectively, all P
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- 2024
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4. From laboratory to clinical practice: an update of the immunological and molecular tools for neurocysticercosis diagnosis
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Luz M. Toribio, Javier A. Bustos, and Hector H. Garcia
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neurocysticercosis ,immunodiagnosis ,molecular diagnosis ,Taenia solium ,Peru ,Infectious and parasitic diseases ,RC109-216 - Abstract
Neurocysticercosis (NCC) is caused by the invasion of Taenia solium larvae in the central nervous system (CNS) and stands as the predominant cause of epilepsy and other neurological disorders in many developing nations. NCC diagnosis is challenging because it relies on brain imaging exams (CT or MRI), which are poorly available in endemic rural or resource-limited areas. Moreover, some NCC cases cannot be easily detected by imaging, leading to inconclusive results. Multiple laboratory assays, principally immunological, have been developed to support the diagnosis and/or monitor the treatment efficacy, but its production can be costly, laborious, and non-globally accessible because they depend on parasite material. Therefore, recent advances have been focused on the implementation of recombinant or synthetic antigens as well as monoclonal antibodies for NCC immunodiagnosis purposes. Similarly, molecular diagnosis has been explored, obtaining promising results. Here we described the recent progress in the development of immunological and molecular diagnostic tools for NCC diagnosis over the past 13 years, discussing their potential application to address important challenges and how to focus future directions to improve NCC diagnosis with emphasis on enhance accessibility and the importance of test validation to provide an adequate support for clinical decisions.
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- 2024
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5. Spatial transferability of an agent-based model to simulate Taenia solium control interventions
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Francesco Pizzitutti, Gabrielle Bonnet, Eloy Gonzales-Gustavson, Sarah Gabriël, William K. Pan, Armando E. Gonzalez, Hector H. Garcia, Seth E. O’Neal, and for the Cysticercosis Working Group in Peru
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Taenia solium ,Agent-based modeling ,Model calibration ,Model transferability ,Human taeniasis ,Pig cysticercosis ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Models can be used to study and predict the impact of interventions aimed at controlling the spread of infectious agents, such as Taenia solium, a zoonotic parasite whose larval stage causes epilepsy and economic loss in many rural areas of the developing nations. To enhance the credibility of model estimates, calibration against observed data is necessary. However, this process may lead to a paradoxical dependence of model parameters on location-specific data, thus limiting the model’s geographic transferability. Methods In this study, we adopted a non-local model calibration approach to assess whether it can improve the spatial transferability of CystiAgent, our agent-based model of local-scale T. solium transmission. The calibration dataset for CystiAgent consisted of cross-sectional data on human taeniasis, pig cysticercosis and pig serology collected in eight villages in Northwest Peru. After calibration, the model was transferred to a second group of 21 destination villages in the same area without recalibrating its parameters. Model outputs were compared to pig serology data collected over a period of 2 years in the destination villages during a trial of T. solium control interventions, based on mass and spatially targeted human and pig treatments. Results Considering the uncertainties associated with empirical data, the model produced simulated pre-intervention pig seroprevalences that were successfully validated against data collected in 81% of destination villages. Furthermore, the model outputs were able to reproduce validated pig seroincidence values in 76% of destination villages when compared to the data obtained after the interventions. The results demonstrate that the CystiAgent model, when calibrated using a non-local approach, can be successfully transferred without requiring additional calibration. Conclusions This feature allows the model to simulate both baseline pre-intervention transmission conditions and the outcomes of control interventions across villages that form geographically homogeneous regions, providing a basis for developing large-scale models representing T. solium transmission at a regional level. Graphical Abstract
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- 2023
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6. Concomitant Parenchymal, Subarachnoid, and Ventricular Neurocysticercosis in Rome, Italy: A Case Report with a 4-Year Follow-Up
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Maria Letizia Giancola, Shalom Haggiag, Angela Corpolongo, Alessandro Stasolla, Andrea Mariano, Agazio Menniti, Paolo Campioni, Barbara Bartolini, Pierluigi Galizia, Antonella Vulcano, Carla Fontana, Claudio Gasperini, Elise O’Connell, Hector H. Garcia, Theodore E. Nash, and Emanuele Nicastri
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Taenia solium ,parenchymal neurocysticercosis ,subarachnoid neurocysticercosis ,ventricular neurocysticercosis ,brain infection ,quantitative polymerase chain reaction ,Medicine - Abstract
Neurocysticercosis (NCC) is caused by the larval stage of Taenia solium. This parasitic disease is endemic in many areas of the world and is emerging in Europe. NCC can affect different brain regions, but simultaneous involvement of the parenchymal, subarachnoid, and ventricular regions is rare. We report the case of a 39-year-old woman from Honduras, resident in Rome for 10 years, who presented to the Emergency Department complaining of headaches, transient hemianopsia, and bilateral papilledema. MRI showed a concomitant parenchymal, subarachnoid, and ventricular involvement in the brain. T. solium IgG antibodies were detected in the blood. The etiological diagnosis of NCC was obtained by identifying T. solium in cerebrospinal fluid using Next Generation Sequencing. Endoscopic neurosurgery with the placement of a ventricular shunt and medical long-term anti-parasitic treatment with a cumulative number of 463 days of albendazole and 80 days of praziquantel were performed. A successful 4-year follow-up is reported. NCC is one of the most common parasitic infections of the human CNS, but it is still a neglected tropical disease and is considered to be an emerging disease in Europe. Its diagnosis and clinical management remain a challenge, especially for European clinicians.
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- 2024
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7. Antibody Banding Patterns on the Enzyme-Linked Immunoelectrotransfer Blot (EITB) Assay Clearly Discriminate Viable Cysticercosis in Naturally Infected Pigs
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Gianfranco Arroyo, Andres G. Lescano, Cesar M. Gavidia, Teresa Lopez-Urbina, Miguel Ara-Gomez, Luis A. Gomez-Puerta, Javier A. Bustos, Cesar M. Jayashi, Seth E. O’Neal, Armando E. Gonzalez, Hector H. Garcia, and on behalf of the Cysticercosis Working Group in Peru (CWGP)
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EITB ,antibody banding patterns ,porcine cysticercosis ,Taenia solium ,Peru ,Medicine - Abstract
Enzyme-linked immunoelectrotransfer blot (EITB) detects antibodies against seven Taenia solium larvae antigens in three protein families (GP50, T24/42, and 8-kDa) with different structures and functions. EITB banding patterns against these antigens in pigs provide information about the course of infection and may discriminate viable cysticercosis. We analyzed the banding patterns and infection outcomes (presence of viable cysts, degenerated cysts, and any cysts) of 512 rural pigs. Banding patterns were grouped into homogenous classes using latent class analysis, and relationships with infection outcomes were assessed. Four classes were identified: 1 (n = 308, EITB-negative or positive for the GP50 family), 2 (n = 127, positive for GP50 (GP50 family), GP42-39 and GP24 (T24/42 family), but negative for 8-kDa antigens), 3 (n = 22, positive for GP50 and T24/42 antigens (GP42-39 and GP24), as well as to 8-kDa bands GP13, GP14, and GP18, but negative for GP21), and 4 (n = 55, positive for GP50 and T24/42 antigens, as well as to 8-kDa antigens GP21 and GP18 in combination). Pigs in classes 3 and 4 were more likely to have viable cysts (72.6% and 96.4%, respectively) than pigs in classes 1 and 2 (0.7% and 27.6%, respectively; p < 0.001). The number of infections with any cysts was higher in classes 3 and 4 (77.3% and 98.2%, respectively) and lower in classes 2 and 1 (34.7% and 4.9%, respectively; p < 0.001). Pigs with viable cysts represented >90% of pigs with any cysts in classes 3 and 4 (94.1% and 98.2%, respectively), while degenerated cysts were frequent among pigs with any cysts in classes 1, 3, and 2 (86.7%, 47.1%, and 43.2%, respectively; p < 0.001). EITB banding patterns strongly correlate with cysticercosis infection status in rural pigs, with classes 3 and 4 being more predictive of viable infections.
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- 2023
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8. Calcified Neurocysticercosis: Demographic, Clinical, and Radiological Characteristics of a Large Hospital-Based Patient Cohort
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Javier A. Bustos, Gianfranco Arroyo, Oscar H. Del Brutto, Isidro Gonzales, Herbert Saavedra, Carolina Guzman, Sofia S. Sanchez-Boluarte, Kiran T. Thakur, Christina Coyle, Seth E. O’Neal, and Hector H. Garcia
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Neurocysticercosis ,Taenia solium ,calcification ,epilepsy ,Peru ,Medicine - Abstract
Neurocysticercosis (NCC), the infection of the central nervous system caused by Taenia solium larvae (cysticerci), is a major cause of acquired epilepsy worldwide. Calcification in NCC is the most common neuroimaging finding among individuals with epilepsy in T. solium-endemic areas. We describe the demographic, clinical, and radiological profiles of a large hospital cohort of patients with calcified NCC in Peru (during the period 2012–2022) and compared profiles between patients with and without a previous known diagnosis of viable infection. A total of 524 patients were enrolled (mean age at enrollment: 40.2 ± 15.2 years, mean age at symptom onset: 29.1 ± 16.1 years, 56.3% women). Of those, 415 patients (79.2%) had previous seizures (median time with seizures: 5 years, interquartile range (IQR): 2–13 years; median number of seizures: 7 (IQR: 3–32)), of which 333 (80.2%) had predominantly focal to bilateral tonic-clonic seizures; and 358 (68.3%) used antiseizure medication). Patients had a median number of three calcifications (IQR: 1–7), mostly located in the frontal lobes (79%). In 282 patients (53.8%) there was a previous diagnosis of viable infection, while 242 only had evidence of calcified NCC since their initial neuroimaging. Most patients previously diagnosed with viable infection were male, had previous seizures, had seizures for a longer time, had more calcifications, and had a history of taeniasis more frequently than patients without previously diagnosed viable infection (all p < 0.05). Patients with calcified NCC were heterogeneous regarding burden of infection and clinical manifestations, and individuals who were diagnosed after parasites calcified presented with milder disease manifestations.
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- 2023
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9. Clinical Characteristics of Neurocysticercosis in a Peruvian Population-Based Epilepsy Cohort: A Descriptive Cross-Sectional Study of Baseline Clinical Intake
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Samantha E. Allen, Luz M. Moyano, Melissa T. Wardle, Carolina Guzman, Sofia S. Sanchez-Boluarte, Gabrielle Bonnet, Javier A. Bustos, Seth O’Neal, and Hector H. Garcia
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epidemiology ,epilepsy ,neurocysticercosis ,Medicine - Abstract
(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical cohort from 2007 to 2020 in Tumbes, Peru. All participants provided demographic and clinical history and received clinical evaluations. Diagnostics, including neuroimaging, cysticercosis serologies, and EEG, were obtained where possible. The data presented are from the cross-sectional baseline assessment of cohort participants. (3) Results: Approximately 38% of participants met the criteria for NCC. Those with NCC were more likely to have adult-onset epilepsy, as well as a longer duration of epilepsy, as compared to their counterparts without NCC. Overall, the data indicate a large treatment gap, with only approximately a quarter of the baseline population with prescriptions for anti-seizure medications. (4) Conclusions: These data reveal a high proportion of NCC among people living with epilepsy in these communities, with limited health care resources. At baseline, 74% of the population were not receiving anti-seizure treatments. Further analyses of these data will clarify the natural history of the disease for this population.
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- 2023
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10. New animal models of neurocysticercosis can help understand epileptogenesis in neuroinfection
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Hector H. Garcia, Manuela R. Verastegui, Gianfranco Arroyo, Javier A. Bustos, Robert H. Gilman, and for The Cysticercosis Working Group in Peru
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Taenia solium ,larval cestodes ,cysticercosis ,neurocysticercosis ,epilepsy ,Peru ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2022
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11. Cellular and molecular basis associated with metacestode proliferation in subarachnoid neurocysticercosis
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Miguel A. Orrego, Manuela R. Verastegui, and Hector H. Garcia
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Taenia solium ,neurocysticercosis ,subarachnoid cyst ,proliferation ,germinative cells ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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12. Geographically Targeted Interventions versus Mass Drug Administration to Control Taenia solium Cysticercosis, Peru
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Seth E. O’Neal, Ian W. Pray, Percy Vilchez, Ricardo Gamboa, Claudio Muro, Luz Maria Moyano, Viterbo Ayvar, Cesar M. Gavidia, Robert H. Gilman, Armando E. Gonzalez, and Hector H. Garcia
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Neglected tropical diseases ,pork tapeworm ,zoonoses ,One Health ,taeniasis ,neurocysticercosis ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p
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- 2021
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13. Consistent Measurement of Parasite-Specific Antigen Levels in Sera of Patients with Neurocysticercosis Using Two Different Monoclonal Antibody (mAb)-Based Enzyme-Linked Immunosorbent Assays
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Yesenia Castillo, Luz M. Toribio, Carolina Guzman, Gianfranco Arroyo, Cindy Espinoza, Herbert Saavedra, Javier A. Bustos, Pierre Dorny, Seth E. O’Neal, and Hector H. Garcia
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neurocysticercosis ,Taenia solium ,Ag-ELISA ,monoclonal antibodies ,agreement ,Medicine - Abstract
Monoclonal antibody (mAb)-based enzyme-linked immunosorbent assay (ELISA) is a complementary diagnosis technique for neurocysticercosis (NCC), which detects circulating parasite antigen (Ag) indicative of viable infection and Ag levels that correlate well with the parasite burden. In this study, we compared the performance of two Ag-ELISA techniques for the detection of NCC. We assessed the agreement between our in-house TsW8/TsW5 Ag-ELISA and the widely used B158/B60 Ag-ELISA for measuring T. solium antigen levels in the sera from 113 patients with calcified, parenchymal, and subarachnoid NCC. Concordance was demonstrated evaluating the limits of agreement (LoAs) stratified by the type of NCC. Both ELISA’s detected 47/48 (97.8%) subarachnoid NCC cases. In parenchymal and calcified NCC, the B158/B60 Ag-ELISA detected 19/24 (79.2%) and 18/41 (43.9%) cases, while the TsW8/TsW5 Ag-ELISA detected 21/24 (87.5%) and 13/41 (31.7%), respectively. Parenchymal and calcified NCC obtained a perfect agreement (100%), indicating that all sample results were within the predicted LoA, while for subarachnoid NCC, the agreement was 89.6%. The high concordance between the assays was confirmed by Lin’s concordance coefficient (LCC = 0.97). Patients with viable parenchymal NCC (LCC = 0.95) obtained the highest concordance between assays, followed by subarachnoid NCC (LCC = 0.93) and calcified NCC (LCC = 0.92). The TsW8/TsW5 Ag-ELISA and B158/B60 Ag-ELISA showed high Ag measurement correlations across diverse types of NCC.
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- 2023
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14. Evaluating the Role of Corrals and Insects in the Transmission of Porcine Cysticercosis: A Cohort Study
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Eloy Gonzales-Gustavson, Ian W. Pray, Ricardo Gamboa, Claudio Muro, Percy Vilchez, Luis Gomez-Puerta, Ana Vargas-Calla, Gabrielle Bonnet, Francesco Pizzitutti, Hector H. Garcia, Armando E. Gonzalez, and Seth E. O’Neal
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porcine cysticercosis ,cohort ,free roaming ,corrals ,insects ,seroincidence ,Medicine - Abstract
The widespread dispersion of pigs infected with cysticercosis across endemic villages, low cyst burden among infected pigs, and low prevalence of taeniasis all suggest that pig ingestion of human feces is not the only mode of transmission for Taenia solium. Our objective was to evaluate the risk of porcine cysticercosis associated with exposure to human feces, dung beetles, and flies in an endemic community setting. We used a cluster-randomized cohort design to compare the risk of developing antibodies and infection among 120 piglets raised in either free-roaming (FR), standard corral (SC), or netted corral environments (NC). We collected monthly blood samples to detect serum antibodies and necropsied all pigs after 10 months to identify cysts. A total of 66 piglets developed antibodies with the relative risk of seropositivity in FR vs. all corralled pigs increasing significantly after 18 weeks. Of 108 necropsied pigs, 15 had T. solium cysts, all belonging to the FR group. Corrals were protective against infection but less so against seropositivity. NC, which did not completely exclude insects, did not provide added protection against seropositivity as compared to SC. The results of this study suggest that dung beetles and flies do not play an important role in infection.
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- 2023
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15. Porcine model of neurocysticercosis by intracarotid injection of Taenia solium oncospheres: Dose assessment, infection outcomes and serological responses
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Gianfranco Arroyo, Luz Toribio, Ana Vargas-Calla, Juan F. Calcina, Edson Bernal, Nancy Chile, Miguel Zambrano, Luis A. Gomez-Puerta, Juan Chacaltana, Miguel Marzal, Javier A. Bustos, Manuela R. Verastegui, Robert H. Gilman, Seth E. O’Neal, Armando E. Gonzalez, Hector H. Garcia, and for The Cysticercosis Working Group in Peru
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Background Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. Methods/Principal findings Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. Conclusion/Significance Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment. Author summary Neurocysticercosis (NCC) is the infection of the central nervous system (CNS) with Taenia solium larvae and is considered a neglected disease that causes significant neurological morbidity in humans. Animal models are essential to better understand the pathophysiological processes that occur during NCC infection, disease progression and to evaluate the effects of antiparasitic treatment. Here, we demonstrated that by injecting 5000 or more activated T. solium oncospheres into the carotid artery of pigs we consistently reproduced NCC in a number that closely resemble human infection. All cysticerci found in the CNS were apparently viable, whereas in the musculature viable and degenerated cysticerci were found. Serum antigens in experimentally infected pigs were detected as early as 14 days post–infection and remained high in NCC pigs until necropsy. Histological analysis of brain cysticerci showed different degrees of inflammatory cell infiltration adjacent to the cyst wall, mostly composed of eosinophils, lymphocytes, and macrophages, whereas most of the cysticerci were apparently intact with cyst wall and neck without damage. Our findings demonstrated that the intracarotid pig model is suitable for studies on the pathogenesis and antiparasitic treatment in NCC.
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- 2022
16. Development of a dose-response model for porcine cysticercosis
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Daniel A. Andrade-Mogrovejo, Eloy Gonzales-Gustavson, Ana C. Ho-Palma, Joaquín M. Prada, Gabrielle Bonnet, Francesco Pizzitutti, Luis A. Gomez-Puerta, Gianfranco Arroyo, Seth E. O’Neal, Hector H. Garcia, Javier Guitian, Armando Gonzalez, and Cysticercosis Working Group in Peru
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Medicine ,Science - Abstract
Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods (“Proglottids”, “Eggs”, “Beetles” and “Carotid”). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the “Eggs” pathway and a merged “Oral” pathway combining the “Proglottids”, “Eggs” and “Beetles” pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.
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- 2022
17. Non-local validated parametrization of an agent-based model of local-scale Taenia solium transmission in North-West Peru
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Francesco Pizzitutti, Gabrielle Bonnet, Eloy Gonzales-Gustavson, Sarah Gabriël, William K. Pan, Ian W. Pray, Armando E. Gonzalez, Hector H. Garcia, and Seth E. O’Neal
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Medicine ,Science - Abstract
The pork tapeworm, Taenia solium, is the cause of a preventable zoonotic disease, cysticercosis, affecting both pigs and humans. Continued endemic transmission of T. solium is a major contributor of epilepsy and other neurologic morbidity, and the source of important economic losses, in many rural areas of developing countries. Simulation modelling can play an important role in aiding the design and evaluation of strategies to control or even eliminate transmission of the parasite. In this paper, we present a new agent based model of local-scale T. solium transmission and a new, non-local, approach to the model calibration to fit model outputs to observed human taeniasis and pig cysticercosis prevalence simultaneously for several endemic villages. The model fully describes all relevant aspects of T. solium transmission, including the processes of pig and human infection, the spatial distribution of human and pig populations, the production of pork for human consumption, and the movement of humans and pigs in and out in several endemic villages of the northwest of Peru. Despite the high level of uncertainty associated with the empirical measurements of epidemiological data associated with T. solium, the non-local calibrated model parametrization reproduces the observed prevalences with an acceptable precision. It does so not only for the villages used to calibrate the model, but also for villages not included in the calibration process. This important finding demonstrates that the model, including its calibrated parametrization, can be successfully transferred within an endemic region. This will enable future studies to inform the design and optimization of T. solium control interventions in villages where the calibration may be prevented by the limited amount of empirical data, expanding the possible applications to a wider range of settings compared to previous models.
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- 2022
18. Understanding transmission and control of the pork tapeworm with CystiAgent: a spatially explicit agent-based model
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Ian W. Pray, Wayne Wakeland, William Pan, William E. Lambert, Hector H. Garcia, Armando E. Gonzalez, Seth E. O’Neal, and for the Cysticercosis Working Group in Peru
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Taenia solium ,Cysticercosis ,Agent-based models ,Infectious disease modeling ,Peru ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The pork tapeworm, Taenia solium, is a serious public health problem in rural low-resource areas of Latin America, Africa and Asia, where the associated conditions of nuerocysticercosis (NCC) and porcine cysticercosis cause substantial health and economic harms. An accurate and validated transmission model for T. solium would serve as an important new tool for control and elimination, as it would allow for comparison of available intervention strategies, and prioritization of the most effective strategies for control and elimination efforts. Methods We developed a spatially-explicit agent-based model (ABM) for T. solium (“CystiAgent”) that differs from prior T. solium models by including a spatial framework and behavioral parameters such as pig roaming, open human defecation, and human travel. In this article, we introduce the structure and function of the model, describe the data sources used to parameterize the model, and apply sensitivity analyses (Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC)) to evaluate model parameters. Results LHS-PRCC analysis of CystiAgent found that the parameters with the greatest impact on model uncertainty were the roaming range of pigs, the infectious duration of human taeniasis, use of latrines, and the set of “tuning” parameters defining the probabilities of infection in humans and pigs given exposure to T. solium. Conclusions CystiAgent is a novel ABM that has the ability to model spatial and behavioral features of T. solium transmission not available in other models. There is a small set of impactful model parameters that contribute uncertainty to the model and may impact the accuracy of model projections. Field and laboratory studies to better understand these key components of transmission may help reduce uncertainty, while current applications of CystiAgent may consider calibration of these parameters to improve model performance. These results will ultimately allow for improved interpretation of model validation results, and usage of the model to compare available control and elimination strategies for T. solium.
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- 2020
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19. Use of magnetic particles in the purification of IgM antibodies against Taenia solium
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L. Agueda Perez, Yesenia Castillo, Cindy Espinoza, Luz M. Toribio, Yesica Santos, Kevin S. Martel, Patricia P. Wilkins, Javier A. Bustos, Hector H. Garcia, Yagahira E. Castro-Sesquen, and Grupo de Trabajo en Cisticercosis en Perú
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purificación ,concentración ,taenia solium ,cisticercosis ,anticuerpos monoclonales ,perú ,Medicine ,Medicine (General) ,R5-920 - Abstract
The use of L protein coupled magnetic particles for the concentration and purification of immunoglobulin M (mIgM) monoclonal antibodies against Taenia solium was evaluated. Three concentration methods and different elution times were evaluated and the ratio of particles to the ratio of mIgM was optimized. It is demonstrated that: 1) with the use of magnetic particles, a previous concentration of mIgM is not required, which reduces the manipulation of the antibodies and improves the recovery, 2) the use of a binding buffer can be omitted, since the pH of most cell culture supernatants are neutral, and 3) longer elution times (~ 45 minutes) are needed to increase recovery to a level greater than 80%. The study demonstrates that the use of L protein-coupled magnetic particles is a simple and efficient tool for mIgM concentration and purification.
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- 2020
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20. The many facets of disseminated parenchymal brain cysticercosis: A differential diagnosis with important therapeutic implications
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Oscar H. Del Brutto and Hector H. Garcia
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Neurocysticercosis (NCC), the infection of the nervous system by the cystic larvae of Taenia solium, is a highly pleomorphic disease because of differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response. Most patients with parenchymal brain NCC present with few lesions and a relatively benign clinical course, but massive forms of parenchymal NCC can carry a poor prognosis if not well recognized and inappropriately managed. We present the main presentations of massive parenchymal NCC and their differential characteristics.
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- 2021
21. 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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Ian W. Pray, Francesco Pizzitutti, Gabrielle Bonnet, Eloy Gonzales-Gustavson, Wayne Wakeland, William K. Pan, William E. Lambert, Armando E. Gonzalez, Hector H. Garcia, Seth E. O’Neal, and for the Cysticercosis Working Group in Peru.
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - 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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- 2021
22. Seasonal patterns in risk factors for Taenia solium transmission: a GPS tracking study of pigs and open human defecation in northern Peru
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Ian W. Pray, Claudio Muro, Ricardo Gamboa, Percy Vilchez, Wayne Wakeland, William Pan, William E. Lambert, Hector H. Garcia, Seth E. O’Neal, and for the Cysticercosis Working Group in Peru
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Taenia solium ,Cysticercosis ,Cestodes ,Pigs ,GPS ,Open defecation ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Taenia solium (cysticercosis) is a parasitic cestode that is endemic in rural populations where open defecation is common and free-roaming pigs have access to human feces. The purpose of this study was to examine the roaming patterns of free-range pigs, and identify areas where T. solium transmission could occur via contact with human feces. We did this by using GPS trackers to log the movement of 108 pigs in three villages of northern Peru. Pigs were tracked for approximately six days each and tracking was repeated in the rainy and dry seasons. Maps of pig ranges were analyzed for size, distance from home, land type and contact with human defecation sites, which were assessed in a community-wide defecation survey. Results Consistent with prior GPS studies and spatial analyses, we found that the majority of pigs remained close to home during the tracking period and had contact with human feces in their home areas: pigs spent a median of 79% (IQR: 61–90%) of their active roaming time within 50 m of their homes and a median of 60% of their contact with open defecation within 100 m of home. Extended away-from-home roaming was predominately observed during the rainy season; overall, home range areas were 61% larger during the rainy season compared to the dry season (95% CI: 41–73%). Both home range size and contact with open defecation sites showed substantial variation between villages, and contact with open defecation sites was more frequent among pigs with larger home ranges and pigs living in higher density areas of their village. Conclusions Our study builds upon prior work showing that pigs predominately roam and have contact with human feces within 50–100 m of the home, and that T. solium transmission is most likely to occur in these concentrated areas of contact. This finding, therefore, supports control strategies that target treatment resources to these areas of increased transmission. Our finding of a seasonal trend in roaming ranges may be useful for control programs relying on pig interventions, and in the field of transmission modeling, which require precise estimates of pig behavior and risk.
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- 2019
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23. Evaluation of cross-reactivity to Taenia hydatigena and Echinococcus granulosus in the enzyme-linked immunoelectrotransfer blot assay for the diagnosis of porcine cysticercosis
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Lucho Gomez-Puerta, Ana Vargas-Calla, Yesenia Castillo, Maria Teresa Lopez-Urbina, Pierre Dorny, Hector H. Garcia, Armando E. Gonzalez, Seth E. O’Neal, and the Cysticercosis Working Group in Peru
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Taenia solium ,Taenia hydatigena ,Echinococcus granulosus ,Cysticercosis ,Enzyme-linked immunoelectrotransfer blot ,Porcine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Taenia solium is an important zoonotic parasite that infects humans as definitive host (taeniasis) and pigs as intermediate host (cysticercosis). Serological diagnosis of porcine cysticercosis is limited to antigen detection using ELISA, which is known to cross-react with other Taenia species, and antibody detection using the lentil-lectin glycoprotein enzyme-linked immunoelectrotransfer blot (LLGP EITB), which has not been adequately evaluated for cross-reactivity to other parasites. Field studies suggest that the GP50 diagnostic band of the LLGP EITB may cross-react to Taenia hydatigena, a common non-zoonotic parasitic infection of pigs. The objective of this study was to evaluate the specificity of the LLGP EITB assay in pigs infected experimentally with T. hydatigena and Echinococcus granulosus. Results Twelve three-month-old seronegative were divided into two groups; six were each given an oral challenge with a single gravid proglottid of T. hydatigena and the other six were each given an oral challenge with 50 gravid proglottids of E. granulosus. Serum samples were collected biweekly until 14 weeks when all pigs underwent a detailed necropsy. Taenia hydatigena cysticerci were found in two of six pigs from the first group. Four T. hydatigena-exposed pigs were seropositive at the GP50-band only on EITB LLGP; two of these had cysts at necropsy while no seronegative pigs had cysts. One E. granulosus-exposed pig was positive to EITB LLGP, again with reactivity only to GP50; all six pigs had hepatic echinococcosis on necropsy. Conclusion These results provide definitive evidence that the GP50 diagnostic band in pigs cross-reacts with T. hydatigena. Evidence of cross-reaction with E. granulosus was not conclusive.
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- 2019
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24. A case for adoption of continuous albendazole treatment regimen for human echinococcal infections
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Francesca Tamarozzi, John Horton, Marin Muhtarov, Michael Ramharter, Mar Siles-Lucas, Beate Gruener, Dominique A. Vuitton, Solange Bresson-Hadni, Tommaso Manciulli, Enrico Brunetti, and Hector H. Garcia
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted “cyclic” treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically “off-label”, and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent “out-of-stock” situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.
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- 2020
25. Seroprevalence of Antibodies against Taenia solium Cysticerci among Refugees Resettled in United States
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Seth E. O’Neal, John M. Townes, Patricia P. Wilkins, John C. Noh, Deborah Lee, Silvia Rodriguez, Hector H. Garcia, and William M. Stauffer
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cysticercosis ,neurocysticercosis ,Taenia solium ,tapeworm ,refugees ,Bhutan ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Neurocysticercosis (NCC) is a disease caused by central nervous system infection by the larval stage of the pork tapeworm, Taenia solium. In developing countries, NCC is a leading cause of adult-onset epilepsy. Case reports of NCC are increasing among refugees resettled to the United States and other nations, but the underlying prevalence among refugee groups is unknown. We tested stored serum samples from the Centers for Disease Control and Prevention Migrant Serum Bank for antibodies against T. solium cysts by using the enzyme-linked immunoelectrotransfer blot. Seroprevalence was high among all 4 populations tested: refugees from Burma (23.2%), Lao People’s Democratic Republic (18.3%), Bhutan (22.8%), and Burundi (25.8%). Clinicians caring for refugee populations should suspect NCC in patients with seizure, chronic headache, or unexplained neurologic manifestations. Improved understanding of the prevalence of epilepsy and other associated diseases among refugees could guide recommendations for their evaluation and treatment before, during, and after resettlement.
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- 2012
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26. Epidemiología y control de la cisticercosis en el Perú Epidemiology and control of cysticercosis in Peru
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Hector H. Garcia, Armando E. Gonzalez, Silvia Rodriguez, Guillermo Gonzalvez, Fernando Llanos-Zavalaga, Víctor C.W. Tsang, and Robert H. Gilman
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Cisticercosis ,Taenia solium ,Epidemiología ,Control de enfermedades transmisibles ,Perú ,Cysticercosis ,Epidemiology ,Communicable disease control ,Peru ,Medicine ,Medicine (General) ,R5-920 - Abstract
La neurocisticercosis, infección del sistema nervioso humano por el estadio larvario de la Taenia solium, es una causa importante de epilepsia y otras manifestaciones neurológicas en el Perú y en la mayoría de países en desarrollo. Desde 1987, el Grupo de Trabajo en Cisticercosis en Perú ha desarrollado una serie de estudios epidemiológicos que han llevado a estimar el impacto y entender la transmisión de la Taenia solium, y que posteriormente se aplicaron al diseño y ejecución de un programa de control en Tumbes, en la costa norte del país. En este artículo se revisan los principales hallazgos epidemiológicos, así como las líneas generales del programa de eliminación y las herramientas utilizadas. Los avances en el control de la teniasis/cisticercosis en nuestro país abren el camino hacia su eliminación y eventual erradicación.Neurocysticercosis, the infection of the human central nervous system by the larval stage of the cestode Taenia solium, is an important cause of epilepsy and other neurological manifestations in Peru and most developing countries. Since 1987, the Cysticercosis Working Group in Peru has performed a series of epidemiological studies which led to estimate the impact and to better understand the transmission of Taenia solium. This information was later applied to the design and execution of a control program in Tumbes, in the Northern Coast of Peru. This paper reviews the main epidemiological findings, as well as the conceptual framework of the elimination program and the tools used. Advances in the control of taeniasis/cysticercosis in our country open the road towards its elimination and potential eradication.
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- 2010
27. Diagnóstico y manejo de la neurocisticercosis en el Perú Neurocysticercosis diagnosis and management in Peru
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Herbert Saavedra, Isidro Gonzales, Manuel A. Alvarado, Miguel A. Porras, Victor Vargas, Román A. Cjuno, Hector H. Garcia, and S. Manuel Martinez
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Neurocisticercosis ,Albendazol ,Praziquantel ,Taenia solium ,Perú ,Neurocysticercosis ,Albendazole ,Peru ,Medicine ,Medicine (General) ,R5-920 - Abstract
La neurocisticercosis (NCC) es la parasitosis humana más frecuente del sistema nervioso central y es causada por las larvas del céstodo Taenia solium. La NCC es endémica en prácticamente todos los paises en vías de desarrollo. En general se presenta como formas intraparenquimales asociadas con convulsiones o formas extraparenquimales asociadas con hipertensión endocraneana. La sospecha clínica y epidemiológica es importante pero el diagnóstico se realiza primariamente por imágenes y se confirma con serología. La tomografía axial computarizada y la resonancia magnética son las pruebas imagenológicas usadas. Como prueba confirmatoria se usa el diagnóstico inmunológico a través de western blot, que actualmente se pude realizar en el Instituto Nacional de Ciencias Neurológicas tanto en suero como en líquido cefalorraquídeo. El tratamiento involucra medidas sintomáticas (control de convulsiones o hipertensión endocraneana según sea el caso) y tratamiento antiparasitario (albendazol o praziquantel). El tratamiento antiparasitario debe hacerse bajo condiciones de hospitalización y en hospitales de tercer nivel.Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system and is caused by larvae of the tapeworn Taenia solium. NCC is endemic in almost all developing countries. It presents as intraparenchymal forms associated with seizures or as extraparenchymal forms associated with intracranial hypertension. The clinical and epidemiological suspicion are important but the diagnosis is made primarily by images and confirmed by serology. Computed tomography (CT) and magnetic resonance imaging tests are used. Inmunodiagnosis by Western Blot, which is currently perform in the Instituto Nacional de Ciencias Neurológicas in serum and cerebrospinal fluid serves as confirmatory test. Treatment involves symptomatic measures (control of seizures or intracranial hypertension) and anticysticercal medications (albendazole and praziquantel). Anticysticercal treatment should be used under hospital conditions because of secondary effects.
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- 2010
28. Factores domiciliarios asociados con la presencia de hidatidosis humana en tres comunidades rurales de Junín, Perú Household factors associated with the presence of human hydatid disease in three rural communities of Junin, Peru
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Saul J. Santivañez, Cesar Naquira, Cesar M. Gavidia, Luis Tello, Eddy Hernandez, Enrico Brunetti, Malika Kachani, Armando E. Gonzalez, and Hector H. Garcia
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Equinococosis ,Asentamientos rurales ,Domicilio ,Perú ,Echinococcosis ,Rural settlements ,Home ,Peru ,Medicine ,Medicine (General) ,R5-920 - Abstract
Introducción. La hidatidosis, zoonosis producida por el estadio larvario de la taenia Echinococcus granulosus, es un problema de salud pública a nivel nacional, en especial en aquellas regiones dedicadas a la crianza de ganado. A la fecha, se han descrito factores, a nivel individual, asociados con la infección por E. granulosus; sin embargo, no se encontró reporte previo que explore la asociación entre características de la vivienda y la presencia de esta enfermedad en alguno de sus miembros. Objetivos. Explorar la asociación entre las características de la vivienda y la presencia de hidatidosis entre las personas que la habitan. Materiales y métodos. Se realizó un estudio transversal en viviendas de tres comunidades rurales de Junín. Se evaluó el grado de asociación entre las características de la vivienda y la presencia de hidatidosis en el hogar mediante un análisis de regresión logística múltiple (RLM). Resultados. De un total de 417 viviendas evaluadas, 56 (13%) de ellas tenían al menos un caso positivo entre sus miembros; luego del análisis de RLM se observó que aquellas viviendas con más de tres miembros, localizadas en la comunidad con quintil de pobreza más bajo, que refirieron crianza de animales, y con una cobertura de evaluación mayor al 25% presentaron una mayor probabilidad de tener al menos un caso de positivo entre sus miembros. Conclusión. Las características observadas deben ser tomadas en cuenta para la determinación preliminar de subgrupos de alto riesgo, optimizando así el uso de los recursos y mejorando la eficacia de los programas de despistaje.Introduction. Hydatid disease, a zoonosis caused by the larval stage of the parasite Echinococcus granulosus, is a public health problem at national level, especially in those regions dedicated to raising livestock. By now, there are many factors, at individual level, that have been associated to the infection by E. granulosus; nevertheless there is not any previous report that explore the association between household characteristics and the presence of the disease among household members. Objective. To explore the association between household characteristics and the presence of hydatid disease among household members. Material and methods. We performed a cross-sectional study in the households of 3 rural communities located in Junín, we evaluated the association between household characteristics and the presence of hydatid disease by multiple logistic regression (MLR). Results. From 417 evaluated households, 56 (13%) of them had at least one positive case among its members. Multivariate analysis showed that households with three or more members, located in the community with the lowest quintile of poverty, that reported raising livestock, and with evaluation coverage greater than 25% were more likely to have at least one positive case among its members. Conclusion. The observed characteristics be taken into account in the preliminary definition of high-risk subgroups, optimizing the use of resources and improving the effectiveness of screening programs.
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- 2010
29. Diagnosis of Cystic Echinococcosis, Central Peruvian Highlands
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Cesar M. Gavidia, Armando E. Gonzalez, Wenbao Zhang, Donald P. McManus, Luis Lopera, Berenice Ninaquispe, Hector H. Garcia, Silvia Rodríguez, Manuela Verastegui, Carmen Calderon, William K.Y. Pan, and Robert H. Gilman
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Cystic echinococcosis ,diagnostic-test prevalence ,IBCF ,rEpC1-GST ,ultrasound ,X-ray ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We evaluated prevalence of cystic echinococcosis (CE) in a central Peruvian Highland district by using 4 diagnostic methods: ultrasonography for 949 persons, radiography for 829, and 2 serologic tests for 929 (2 immunoblot formats using bovine hydatid cyst fluid [IBCF] and recombinant EpC1 glutathione S-transferase [rEpC1-GST] antigens). For the IBCF and rEpC1-GST testing, prevalence of liver and pulmonary CE was 4.7% and 1.1% and seropositivity was 8.9% and 19.7%, respectively. Frequency of seropositive results for IBCF and rEpC1-GST testing was 35.7% and 16.7% (all hepatic cysts), 47.1% and 29.4% (hepatic calcifications excluded), and 22.2% and 33.3% (lung cysts), respectively. Weak immune response against lung cysts, calcified cysts, small cysts, and cysts in sites other than lung and liver might explain the poor performance of the serodiagnostic tests. We confirm that CE is highly endemic to Peru and emphasize the limited performance of available serologic assays in the field.
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- 2008
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30. Controversies in the Management of Cysticercosis
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Carlton Evans, Hector H. Garcia, Robert H. Gilman, and Jon S. Friedland
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Peru ,United Kingdom ,United States ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 1997
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31. Imaging of infectious and inflammatory cystic lesions of the brain, a narrative review
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Anna Cervantes-Arslanian, Hector H Garcia, and Otto Rapalino
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General Neuroscience ,Pharmacology (medical) ,Neurology (clinical) - Published
- 2023
32. Eficacia de dos formulaciones de oxfendazol producidas localmente para el tratamiento de la cisticercosis en cerdos infectados naturalmente
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Linda Gallegos, Luis A. Gomez-Puerta, Ana Vargas-Calla, Grupo de Trabajo en Cisticercosis en Perú, Armando E. Gonzalez, Gianfranco Arroyo, Hector H. Garcia, Juan Calcina, Teresa López, Javier A. Bustos, and Robert H. Gilman
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medicine.medical_specialty ,Oxfendazole ,Porcine ,Quistes ,Gastroenterology ,Cisticercosis ,Single oral dose ,Dosage ,Tongue ,Internal medicine ,Taenia solium ,Peru ,medicine ,Cysticercosis ,Cysts ,business.industry ,Public Health, Environmental and Occupational Health ,General Medicine ,medicine.disease ,Porcinos ,Porcine cysticercosis ,medicine.drug_formulation_ingredient ,medicine.anatomical_structure ,Dosificación ,business - Abstract
The efficacy of two locally produced oxfendazole (OFZ) formulations against cysticercosis at 22,5% and 10%, versus a commercial formulation (Synanthic 9,06%) was evaluated in twenty-two naturally infected pigs that received a single oral dose of 30 mg/kg. Pigs were sacrificed at eight weeks post-treatment to evaluate the cysts found in their carcasses, and to determine the cysticidal efficacy, which was defined as the proportion of degenerated cysts over total cysts. Only degenerated cysts were found in muscle, heart, and tongue of pigs treated with OFZ in all groups, which shows an efficacy of 100%. Viable and degenerated cysts were found in brains, being the efficacy lower in all groups (65% [commercial OFZ], 47% [local OFZ 22.5%] and 31% [local OFZ 10%], p = 0.355). Locally produced OFZ formulations were similarly effective to the commercial formulation and may provide a practical alternative for the treatment of porcine cysticercosis. Se evaluó la eficacia de dos formulaciones de oxfendazol (OFZ) contra cisticercosis producidas localmente, al 22,5% y 10% en comparación con una formulación comercial (Synanthic 9,06%) en 22 cerdos naturalmente infectados, que recibieron una dosis oral de 30 mg/kg. Los cerdos fueron sacrificados a las ocho semanas postratamiento para evaluar quistes en en sus carcasas, y se determinó la eficacia cisticida a través de la proporción de quistes degenerados sobre el total. Solo se encontraron quistes degenerados en la musculatura, corazón y lengua de los cerdos tratados con OFZ en todos los grupos, lo cual muestra una eficacia del 100%. En los cerebros se encontraron quistes viables y degenerados, con una eficacia menor en todos los grupos (65% [OFZ comercial], 47% [OFZ local 22,5%] y 31% [OFZ local 10%], p = 0,355. Las formulaciones de OFZ producidas localmente fueron igual de efectivas que la formulación comercial y pueden proporcionar una alternativa para el tratamiento de la cisticercosis porcina
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- 2021
33. Procedimiento para la infusión de mitocondrias autólogas por la arteria carótida en el cerebro porcino
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Cory M. Kelly, Melanie Walker, Luz Toribio, S Levy, Hector H. Garcia, Miguel A. Orrego, and Gianfranco Arroyo
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Carótida ,Cerebro ,Porcine ,Cell ,Central nervous system ,Infusión ,Mitochondrion ,Pharmacology ,In vivo ,Organelle ,medicine ,Infusion ,Mitocondria ,Cell damage ,Carotid ,Cerdo ,business.industry ,Therapeutic effect ,Public Health, Environmental and Occupational Health ,Brain ,General Medicine ,Microcatheter ,medicine.disease ,Transplantation ,medicine.anatomical_structure ,business ,Microcatéter - Abstract
Mitochondria are complex organelles that play a critical role within the cell; mitochondrial dysfunction can result in significant cell damage or death. Previous studies have demonstrated the promising therapeutic effects of autologous mitochondria transplantation into ischemic cardiac tissue; however, few studies have examined the in vivo effects of mitochondria infusion into the brain. The aim of this study is to report a procedure for carotid infusion of autologous mitochondria into porcine brains. By using this infusion technique, we propose that a selective and minimally invasive administration is feasible and may provide benefits in the treatment of various central nervous system disorders Las mitocondrias son organelas complejas que desempeñan un papel fundamental en la célula, la disfunción mitocondrial puede ocasionar daños celulares significativos o la muerte. Estudios previos han demostrado los prometedores efectos terapéuticos del trasplante de mitocondrias autólogas a un tejido cardiaco isquémico, sin embargo, pocos estudios han evaluado los efectos in vivo de la infusión de mitocondrias en el cerebro. El presente trabajo tiene como objetivo dar a conocer el procedimiento para la infusión vía carótida de mitocondrias autólogas en cerebros porcinos. Mediante esta técnica de infusión, proponemos que una administración selectiva y mínimamente invasiva es factible y puede proporcionar beneficios en el tratamiento de diversas patologías del sistema nervioso central
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- 2021
34. Improved Diagnosis of Viable Parenchymal Neurocysticercosis by Combining Antibody Banding Patterns on Enzyme-Linked Immunoelectrotransfer Blot (EITB) with Antigen Enzyme-Linked Immunosorbent Assay (ELISA)
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Pierre Dorny, John Noh, Gianfranco Arroyo, Robert H. Gilman, Sukwan Handali, Hector H. Garcia, E. Javier Pretell, Erika Perez, Armando E. Gonzalez, Yesenia Castillo, Seth E. O’Neal, Javier A. Bustos, Isidro Gonzales, Herbert Saavedra, and Andres G. Lescano
- Subjects
Microbiology (medical) ,chemistry.chemical_classification ,urogenital system ,Neurocysticercosis ,Antibodies, Helminth ,Enzyme-Linked Immunosorbent Assay ,Biology ,Sensitivity and Specificity ,Serology ,Blot ,Exact test ,Enzyme ,Antigen ,chemistry ,Antigens, Helminth ,Taenia solium ,Immunology ,Parenchyma ,biology.protein ,Animals ,Humans ,Parasitology ,Antibody - Abstract
The diagnosis of neurocysticercosis (NCC) depends on neuroimaging and serological confirmation. While antibody detection by enzyme-linked immunoelectrotransfer blot (EITB) fails to predict viable NCC, EITB banding patterns provide information about the host’s infection course. Adding antigen enzyme-linked immunosorbent assay (Ag-ELISA) results to EITB banding patterns may improve their ability to predict or rule out of viable NCC. We assessed whether combining EITB banding patterns with Ag-ELISA improves discrimination of viable infection in imaging-confirmed parenchymal NCC. EITB banding patterns were grouped into classes using latent class analysis. True-positive and false-negative Ag-ELISA results in each class were compared using Fisher’s exact test. Four classes were identified: 1, EITB negative or positive to GP50 alone (GP50 antigen family); 2, positive to GP42-39 and GP24 (T24/42 family), with or without GP50; and 3 and 4, positive to GP50, GP42-39, and GP24 and reacting to bands in the 8-kDa family. Most cases in classes 3 and 4 had viable NCC (82% and 88%, respectively) compared to classes 2 and 1 (53% and 5%, respectively). Adding positive Ag-ELISA results to class 2 predicted all viable NCC cases (22/22 [100%]), whereas 11/40 patients (27.5%) Ag-ELISA negative had viable NCC (P < 0.001). Only 1/4 patients (25%) Ag-ELISA positive in class 1 had viable NCC, whereas 1/36 patients (2.8%) Ag-ELISA negative had viable NCC (P = 0.192). In classes 3 and 4, adding Ag-ELISA was not contributory. Combining Ag-ELISA with EITB banding patterns improves discrimination of viable from nonviable NCC, particularly for class 2 responses. Together, these complement neuroimaging more appropriately for the diagnosis of viable NCC.
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- 2022
35. Urine 1H-NMR Metabolomics to Discriminate Neurocysticercosis Patients from Healthy Controls: An Exploratory Study
- Author
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Juan M. Lopez, Vanessa E. Leyva, Javier A. Bustos, Erika Perez, Sofía S. Sanchez, Herbert Saavedra, Isidro Gonzales, Helena Maruenda, and Hector H. Garcia
- Subjects
Infectious Diseases ,Virology ,Urine 1H-NMR ,Short Report ,Metabolomics ,Exploratory Study ,Parasitology ,Neurocysticercosis - Abstract
The diagnosis of neurocysticercosis (NCC) is principally based on neuroimaging (magnetic resonance imaging or computed tomography), instrumentation that is scarcely available in the rural regions where Taenia solium transmission, primarily occurs due to poor sanitation conditions. Immunological assays for antigen or antibody detection complement the neuroimaging approach. However, no field-applicable assays to diagnose viable NCC or to guide the referral of cases for neuroimaging or for appropriate management are available. We performed an exploratory study on urine and serum samples using 1H-nuclear magnetic resonance (NMR)-based metabolomics to discriminate NCC patients (n = 14) from healthy control subjects (n = 22). Metabolic profiles demonstrated a discrimination between the urines of NCC patients and noninfected control subjects with a moderate predictive accuracy (R2 = 0.999, Q2 = 0.434). NMR metabolomics analysis has been proven useful in depicting biomarkers linked to other infectious diseases, various types of cancer, and other disorders. Our results, albeit preliminary, open a door to the development of better methods for detecting NCC through the identification of biomarkers participating in disturbed metabolic pathways.
- Published
- 2022
36. A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis
- Author
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Madelynn Corda, Joshua Sciurba, Jiana Blaha, Siddhartha Mahanty, Adriana Paredes, Hector H. Garcia, Theodore E. Nash, Thomas B. Nutman, and Elise M. O’Connell
- Subjects
Hybridomas ,Public Health, Environmental and Occupational Health ,Antibodies, Helminth ,Enzyme-Linked Immunosorbent Assay ,Urine ,Blood plasma ,Neurocysticercosis ,Antigen isotypes ,Sensitivity and Specificity ,Recombinant Proteins ,Mice ,Infectious Diseases ,Cerebrospinal fluid ,Immunoglobulin M ,Antigens, Helminth ,Immunoglobulin G ,Comparators ,Taenia solium ,Animals ,Humans ,Enzyme-linked immunoassays - Abstract
Background Antigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits. Methods/Principal findings Three previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC. Conclusions/Significance A newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic. Clinical Trial Registration ClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645.
- Published
- 2022
37. Household Clustering of SARS-CoV-2 in Community Settings: A Study from Rural Ecuador
- Author
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Bettsy Y. Recalde, Oscar H. Del Brutto, Aldo F. Costa, Javier A. Bustos, Robertino M. Mera, and Hector H. Garcia
- Subjects
Adult ,Male ,Adolescent ,Isolation (health care) ,Pneumonia, Viral ,030231 tropical medicine ,Population ,Developing country ,Antibodies, Viral ,Betacoronavirus ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Pandemic ,Cluster Analysis ,Humans ,Rural ,Young adult ,Child ,education ,Cluster analysis ,Pandemics ,Aged ,Aged, 80 and over ,Family Characteristics ,education.field_of_study ,Community Settings ,SARS-CoV-2 ,Case-control study ,COVID-19 ,Articles ,Odds ratio ,Middle Aged ,Infectious Diseases ,Geography ,Immunoglobulin M ,Case-Control Studies ,Immunoglobulin G ,Female ,Parasitology ,Ecuador ,Coronavirus Infections ,purl.org/pe-repo/ocde/ford#3.03.06 [https] ,Demography - Abstract
The SARS-CoV-2 pandemic is now expanding into the developing world with devastating consequences. Departing from a population-based study in rural Ecuador where all adult individuals (aged 40 years or older) were tested for SARS-CoV-2 IgG and IgM antibodies, we expanded it to include a house-based case–control component assessing in-house clustering and other variables potentially associated with infection. We selected houses where exactly two study participants lived and were both seropositive (case-houses), and matched 1:1 to control-houses where both were seronegative. Younger household members had an antibody test performed. Infected household members were found in 33 (92%) case-houses and in only six (17%) control-houses. In 28/29 discordant house pairs, the case-house had seropositive household members and the control-house did not (odds ratio: 28; 95% CI: 4.6–1,144). Our data demonstrate strong in-house clustering of infection in community settings, stressing the importance of early case ascertainment and isolation for SARS-CoV-2 control.
- Published
- 2020
38. Frequency and Determinant Factors for Calcification in Neurocysticercosis
- Author
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Theodore E. Nash, Armando E. Gonzalez, Herbert Saavedra, Gianfranco Arroyo, Isidro Gonzales, Seth E. O’Neal, Percy Soto-Becerra, Oscar H. Del Brutto, Robert H. Gilman, Javier A. Bustos, Hector H. Garcia, and E. Javier Pretell
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,030231 tropical medicine ,Neurocysticercosis ,purl.org/pe-repo/ocde/ford#3.03.08 [https] ,Gastroenterology ,Albendazole ,calcification ,Perú ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Taenia solium ,medicine ,risk factors ,Cyst ,Dexamethasone ,Cysticercosis ,business.industry ,medicine.disease ,medicine.drug_formulation_ingredient ,Infectious Diseases ,Concomitant ,business ,030217 neurology & neurosurgery ,medicine.drug ,Calcification - Abstract
Background Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. Methods Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. Results The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02–1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05–1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08–1.46), mild antibody response (RR, 1.14; 95% CI, 1.002–1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14–1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02–1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08–1.93), or complete cure (RR, 1.48; 95% CI, 1.29–1.71) were associated with a increased risk of calcification. Conclusions Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.
- Published
- 2020
39. The many facets of disseminated parenchymal brain cysticercosis: A differential diagnosis with important therapeutic implications
- Author
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Hector H. Garcia and Oscar H. Del Brutto
- Subjects
Nervous system ,Pathology ,Physiology ,Neurocysticercosis ,RC955-962 ,Disease ,Steroid Therapy ,Diagnostic Radiology ,Medical Conditions ,Arctic medicine. Tropical medicine ,Taenia solium ,Medicine and Health Sciences ,Edema ,Tomography ,Pharmaceutics ,Radiology and Imaging ,Brain ,Cysticercosis ,Magnetic Resonance Imaging ,Viewpoints ,medicine.drug_formulation_ingredient ,Infectious Diseases ,medicine.anatomical_structure ,Helminth Infections ,Computed axial tomography ,embryonic structures ,Public aspects of medicine ,RA1-1270 ,Neglected Tropical Diseases ,medicine.medical_specialty ,Imaging Techniques ,Corticosteroid Therapy ,Neuroimaging ,Research and Analysis Methods ,Calcification ,Diagnosis, Differential ,Immune system ,Magnetic resonance imaging ,Signs and Symptoms ,Drug Therapy ,Diagnostic Medicine ,Parenchyma ,parasitic diseases ,medicine ,Parasitic Diseases ,Animals ,Humans ,Inflammation ,business.industry ,urogenital system ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,medicine.disease ,Tropical Diseases ,Computed Axial Tomography ,Lesions ,Differential diagnosis ,Clinical Medicine ,business ,Physiological Processes ,Neuroscience - Abstract
Neurocysticercosis (NCC), the infection of the nervous system by the cystic larvae of Taenia solium, is a highly pleomorphic disease because of differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response. Most patients with parenchymal brain NCC present with few lesions and a relatively benign clinical course, but massive forms of parenchymal NCC can carry a poor prognosis if not well recognized and inappropriately managed. We present the main presentations of massive parenchymal NCC and their differential characteristics.
- Published
- 2021
40. Parasitic Infections of the Nervous System
- Author
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Hector H Garcia
- Subjects
Nervous system ,Central Nervous System ,education.field_of_study ,Epilepsy ,business.industry ,Neurocysticercosis ,Population ,Malaria, Cerebral ,Brain ,Schistosomiasis ,medicine.disease ,Toxoplasmosis ,Article ,medicine.anatomical_structure ,Cerebral Malaria ,Immunology ,medicine ,Humans ,Neurology (clinical) ,education ,business ,Genetics (clinical) ,Malaria ,Encephalitis - Abstract
Purpose of review This article reviews how parasites affect the human nervous system, with a focus on four parasitic infections of major public health importance worldwide, two caused by protozoa (malaria and toxoplasmosis) and two by helminths (neurocysticercosis and schistosomiasis). Recent findings Parasitic infections in humans are common, and many can affect the central nervous system where they may survive unnoticed or may cause significant pathology that can even lead to the death of the host. Neuroparasitoses should be considered in the differential diagnosis of neurologic lesions, particularly in individuals from endemic regions or those with a history of travel to endemic regions. Summary Cerebral malaria is a significant cause of mortality, particularly in African children, in whom infected red blood cells affect the cerebral vessels, causing severe encephalopathy. Neurocysticercosis is the most common cause of acquired epilepsy worldwide and has varied clinical presentations, depending on the number, size, and location of the parasites in the nervous system as well as on the host's inflammatory response. Toxoplasmosis is distributed worldwide, affecting a significant proportion of the population, and may reactivate in patients who are immunosuppressed, causing encephalitis and focal abscesses. Schistosomiasis causes granulomatous lesions in the brain or the spinal cord.
- Published
- 2021
41. SARS-CoV-2 RNA in Swabbed Samples from Latrines and Flushing Toilets: A Case–Control Study in a Rural Latin American Setting
- Author
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Juan Carlos Fernandez-Cadena, Bettsy Y. Recalde, Oscar H. Del Brutto, Aldo F. Costa, Hector H. Garcia, Robertino M. Mera, and Derly Andrade-Molina
- Subjects
Rural Population ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Viral transmission ,Young Adult ,McNemar's test ,Virology ,Environmental health ,medicine ,Humans ,Rural ,Serologic Tests ,Toilet Facilities ,Latrines ,Family Characteristics ,business.industry ,SARS-CoV-2 ,Case-control study ,COVID-19 ,Case–Control Study ,Flushing Toilets ,Articles ,SARS-CoV-2 RNA ,Fecal coliform ,Infectious Diseases ,Latin America ,Case-Control Studies ,Bathroom Equipment ,Latrine ,Flushing ,RNA, Viral ,Parasitology ,Conditional logistic regression ,Latin American ,medicine.symptom ,business ,purl.org/pe-repo/ocde/ford#3.03.06 [https] - Abstract
Information about factors potentially favoring the spread of SARS-CoV-2 in rural settings is limited. Following a case–control study design in a rural Ecuadorian village that was severely struck by the pandemic, SARS-CoV-2 RNA were detected by real-time PCR in swabs obtained from inner and upper walls in 24/48 randomly selected latrines from case-houses and in 12/48 flushing toilets from paired control-houses (P = 0.014; McNemar’s test). This association persisted in a conditional logistic regression model adjusted for relevant covariates (OR: 4.82; 95% CI: 1.38–16.8; P = 0.014). In addition, SARS-CoV-2–seropositive subjects were more often identified among those living in houses with a latrine (P = 0.002). Latrines have almost five times the odds of containing SARS-CoV-2 RNA than their paired flushing toilets. Latrines are reservoirs of SARS-CoV-2 RNA, and it cannot be ruled out that latrines could contribute to viral transmission in rural settings. Frequent disinfection of latrines should be recommended to reduce the likelihood of fecal contamination.
- Published
- 2021
42. Endoscopic endonasal surgery for massive subarachnoid neurocysticercosis: illustrative case
- Author
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Luis J. Saavedra, Jesús Félix, Jose Calderon, Yelimer Caucha, Jorge E. Medina, Luis A. Antonio, Juan Luis Gómez-Amador, Carlos M. Vásquez, William W. Lines, Elías Lira, and Hector H. Garcia
- Subjects
medicine.medical_specialty ,Endoscopic endonasal surgery ,urogenital system ,business.industry ,embryonic structures ,parasitic diseases ,Neurocysticercosis ,Medicine ,General Medicine ,business ,Surgery - Abstract
BACKGROUND Subarachnoid neurocysticercosis (NCC) is associated with high morbidity and mortality rates. Conventional transcranial approaches and transventricular endoscopy have been previously reported for extraparenchymal NCC and ventricular NCC, respectively. By October 2019, endonasal endoscopic approaches had not been used for the treatment of NCC. OBSERVATIONS A 54-year-old-woman with NCC was admitted with acute neurological deterioration due to severe intracranial hypertension caused by massive subarachnoid NCC cysts, as evidenced on magnetic resonance imaging (MRI) with great brainstem compression. The case was discussed, and an endoscopic endonasal resection of the NCC cysts was scheduled. The diagnosis was confirmed by pathological anatomy. There were no complications in the surgery, with marked neurological improvement. Control MRIs demonstrated a significant reduction of NCC cysts. LESSONS Minimally invasive approaches are an excellent alternative for skull-base tumoral and infectious pathology. Prior knowledge of the pathophysiology and the authors’ experience in the management of patients with NCC allowed them to propose this approach, with optimal results.
- Published
- 2021
43. Development of a dose-response model for porcine cysticercosis
- Author
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Daniel A, Andrade-Mogrovejo, Eloy, Gonzales-Gustavson, Ana C, Ho-Palma, Joaquín M, Prada, Gabrielle, Bonnet, Francesco, Pizzitutti, Luis A, Gomez-Puerta, Gianfranco, Arroyo, Seth E, O'Neal, Hector H, Garcia, Javier, Guitian, and Armando, Gonzalez
- Subjects
Coleoptera ,Swine Diseases ,Multidisciplinary ,Cysticercosis ,Cysts ,Swine ,parasitic diseases ,Taenia solium ,Animals - Abstract
Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods (“Proglottids”, “Eggs”, “Beetles” and “Carotid”). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the “Eggs” pathway and a merged “Oral” pathway combining the “Proglottids”, “Eggs” and “Beetles” pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.
- Published
- 2021
44. Stereotactic surgery for neurocysticercosis of the 4th ventricle: illustrative cases
- Author
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William W. Lines, Yelimer Caucha, Luis A. Antonio, Hector H. Garcia, Carlos M. Vásquez, Jorge E. Medina, Luis J. Saavedra, and Jesús Félix
- Subjects
medicine.medical_specialty ,Stereotactic surgery ,medicine.anatomical_structure ,Ventricle ,business.industry ,Neurocysticercosis ,medicine ,General Medicine ,Radiology ,business - Abstract
BACKGROUND Neurocysticercosis, caused by the larval stage of Taenia solium, affects the cerebral ventricles in 20–30% of cases and may lead to hydrocephalus and other neurological morbidity. Conventional treatment for cysts in the 4th ventricle includes open surgery (suboccipital approach) and neuroendoscopy, with the latter being the option of choice. Stereotactic surgery, minimally invasive, offers a good alternative for this type of deep lesion. OBSERVATIONS The authors report the cases of two women, 30 and 45 years old, who presented with headache, dizziness, and ataxia and were diagnosed with 4th ventricle cysticercosis. Magnetic resonance imaging (MRI) revealed dilated 4th ventricles (approximately 2.5 cm in both cases, with cystic images inside the ventricular cavity). Both patients were treated with stereotactic surgery via a suboccipital transcerebellar approach. Cyst material was extracted, and the diagnosis was confirmed by pathological examination. The surgeries had no complications and resulted in clinical improvement. Control MRI scans showed reduction of the volume of the ventricle without residual cysts. LESSONS Minimally invasive stereotactic surgery provided a safe alternative for 4th ventricle neurocysticercosis cysts, with more benefits than risks in comparison with conventional techniques.
- Published
- 2021
45. Neurocysticercosis and HIV/AIDS co-infection: A scoping review
- Author
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Javier A. Bustos, Martin Walker, Matthew A. Dixon, Veronika Schmidt, Paul D Jewell, Bernard Ngowi, Hector H. Garcia, María-Gloria Basáñez, Kevin G Buell, Annette Abraham, Andrea Sylvia Winkler, and Medical Research Council (MRC)
- Subjects
medicine.medical_specialty ,Pediatrics ,LIVER ,Neurocysticercosis ,CYSTICERCOSIS ,PROGRESSION ,HIV Infections ,DIAGNOSIS ,Global Health ,DISEASE ,1117 Public Health and Health Services ,co-infection ,MALARIA ,Acquired immunodeficiency syndrome (AIDS) ,Tropical Medicine ,Taenia solium ,INFECTION ,Epidemiology ,medicine ,Humans ,Disease burden ,Public, Environmental & Occupational Health ,Science & Technology ,business.industry ,Coinfection ,Public Health, Environmental and Occupational Health ,HIV ,medicine.disease ,ddc ,AIDS ,medicine.drug_formulation_ingredient ,Infectious Diseases ,Systematic review ,taeniosis ,Parasitology ,Observational study ,Headaches ,medicine.symptom ,business ,Life Sciences & Biomedicine - Abstract
Objectives Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have high disease burden and are prevalent in overlapping low- and middle-income areas. Yet, treatment guidance for people living with HIV/AIDS (PLWH/A) co-infected with NCC is currently lacking. This study aims to scope the available literature on HIV/AIDS and NCC co-infection, focusing on epidemiology, clinical characteristics, diagnostics, and treatment outcomes. Methods The scoping literature review methodological framework, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of 16,969 records identified through database searching and 45 additional records from other sources were reduced to 52 included studies after a standardised selection process. Results Two experimental studies, ten observational studies, 23 case series/case reports and 17 reviews or letters were identified. Observational studies demonstrated similar NCC seroprevalence in PLWH/A and their HIV-negative counterparts. Of 29 PLWH/A and NCC co-infection, 17 (59%) suffered from epileptic seizures, 15 (52%) from headaches, and 15 (52%) had focal neurological deficits. Eighteen (62%) had viable vesicular cysts and six (21%) had calcified cysts. Fifteen (52%) were treated with albendazole, of which 11 (73%) responded well to treatment. Five individuals potentially demonstrated an immune-reconstitution inflammatory syndrome after commencing anti-retroviral therapy, although this was in the absence of immunological and neuroimaging confirmation. Conclusions There is a paucity of evidence to guide treatment of PLWH/A and NCC co-infection. There is a pressing need for high-quality studies in this patient group to appropriately inform diagnostic and management guidelines for HIV-positive patients with NCC.
- Published
- 2021
46. Neurocysticercosis. A frequent cause of seizures, epilepsy, and other neurological morbidity in most of the world
- Author
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I. Gonzales, Sukwan Handali, H. Saavedra, Javier A. Bustos, and Hector H. Garcia
- Subjects
medicine.medical_specialty ,Pediatrics ,Neurology ,Neurological morbidity ,Neurocysticercosis ,Disease ,Article ,03 medical and health sciences ,Epilepsy ,Therapeutic approach ,0302 clinical medicine ,Seizures ,Taenia solium ,medicine ,Animals ,Humans ,030212 general & internal medicine ,business.industry ,Cysticercosis ,medicine.disease ,medicine.drug_formulation_ingredient ,Neurology (clinical) ,Morbidity ,business ,human activities ,030217 neurology & neurosurgery - Abstract
Neurocysticercosis is endemic in most of the world and in endemic areas it accounts for approximately 30% of cases of epilepsy. Appropriate diagnosis and management of neurocysticercosis requires understanding the diverse presentations of the disease since these will vary in regards to clinical manifestation, sensitivity of diagnostic tests, and most importantly, therapeutic approach. This review attempts to familiarize tropical neurology practitioners with the diverse types of neurocysticercosis and the more appropriate management approaches for each.
- Published
- 2021
47. Seasonal patterns in risk factors for Taenia solium transmission: a GPS tracking study of pigs and open human defecation in northern Peru
- Author
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William Pan, Ian W Pray, Ricardo Gamboa, Claudio Muro, Seth E. O’Neal, William E. Lambert, Wayne W. Wakeland, Hector H. Garcia, and Percy Vilchez
- Subjects
Male ,pig ,Rural Population ,0301 basic medicine ,Veterinary medicine ,parasitology ,Swine ,GPS ,purl.org/pe-repo/ocde/ford#3.03.07 [https] ,animal behavior ,law.invention ,Feces ,0302 clinical medicine ,Risk Factors ,law ,Peru ,Dry season ,Taenia solium ,animal ,geographic information system ,Defecation ,Swine Diseases ,2. Zero hunger ,Human feces ,seasonal variation ,Behavior, Animal ,adult ,parasite transmission ,pilot study ,Feces/parasitology ,movement (physiology) ,Swine Diseases/epidemiology/parasitology/transmission ,infection control ,agricultural land ,medicine.drug_formulation_ingredient ,female ,Infectious Diseases ,Transmission (mechanics) ,risk factor ,contact examination ,Female ,Pigs ,Seasons ,Open defecation ,Wet season ,Swine/parasitology ,spatial analysis ,Movement ,Home range ,030231 tropical medicine ,Cysticercosis/epidemiology/transmission/veterinary ,Biology ,Article ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,vegetation ,global positioning system ,medicine ,Animals ,feces analysis ,Humans ,lcsh:RC109-216 ,human ,infection risk ,population density ,swine disease ,Spatial Analysis ,nonhuman ,isolation and purification ,Cysticercosis ,Research ,Cestodes ,land use ,home environment ,veterinary medicine ,030104 developmental biology ,Taenia solium/isolation & purification ,Geographic Information Systems ,Parasitology ,trend study ,Peru/epidemiology ,season - Abstract
Background Taenia solium (cysticercosis) is a parasitic cestode that is endemic in rural populations where open defecation is common and free-roaming pigs have access to human feces. The purpose of this study was to examine the roaming patterns of free-range pigs, and identify areas where T. solium transmission could occur via contact with human feces. We did this by using GPS trackers to log the movement of 108 pigs in three villages of northern Peru. Pigs were tracked for approximately six days each and tracking was repeated in the rainy and dry seasons. Maps of pig ranges were analyzed for size, distance from home, land type and contact with human defecation sites, which were assessed in a community-wide defecation survey. Results Consistent with prior GPS studies and spatial analyses, we found that the majority of pigs remained close to home during the tracking period and had contact with human feces in their home areas: pigs spent a median of 79% (IQR: 61–90%) of their active roaming time within 50 m of their homes and a median of 60% of their contact with open defecation within 100 m of home. Extended away-from-home roaming was predominately observed during the rainy season; overall, home range areas were 61% larger during the rainy season compared to the dry season (95% CI: 41–73%). Both home range size and contact with open defecation sites showed substantial variation between villages, and contact with open defecation sites was more frequent among pigs with larger home ranges and pigs living in higher density areas of their village. Conclusions Our study builds upon prior work showing that pigs predominately roam and have contact with human feces within 50–100 m of the home, and that T. solium transmission is most likely to occur in these concentrated areas of contact. This finding, therefore, supports control strategies that target treatment resources to these areas of increased transmission. Our finding of a seasonal trend in roaming ranges may be useful for control programs relying on pig interventions, and in the field of transmission modeling, which require precise estimates of pig behavior and risk. Electronic supplementary material The online version of this article (10.1186/s13071-019-3614-5) contains supplementary material, which is available to authorized users.
- Published
- 2019
48. To Really Know the Disease: Creating a Participatory Community Education Workshop about Taenia solium Focused on Physical, Economic, and Epidemiologic Evidence
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Lauralee Fernandez, Angela G. Spencer, Percy Vilchez, Claudio Muro, Ricardo Gamboa, Ian W Pray, Roberto Camizan, Brian Garvey, Michelle Beam, Seth E. O’Neal, Ruth Atto, and Hector H. Garcia
- Subjects
Medical education ,Community education ,education ,030231 tropical medicine ,Attendance ,Cysticercosis ,Disease ,medicine.disease ,Experiential learning ,03 medical and health sciences ,medicine.drug_formulation_ingredient ,0302 clinical medicine ,Infectious Diseases ,Virology ,parasitic diseases ,Taenia solium ,medicine ,Parasitology ,Health education ,Rural area ,Psychology - Abstract
Cysticercosis, caused by Taenia solium, is a neglected disease that causes preventable epilepsy. We conducted an experiential learning workshop in northern Peru to educate community members on T. solium transmission and motivate participation in community-led prevention and control. The workshop included presentation of local economic and epidemiologic data, followed by hands-on participation in pig dissection, group discussion of the T. solium life cycle, and viewing of eggs and nascent tapeworms with light microscopes. Among heads of household, we used community survey data to compare knowledge of the three-stage parasite life cycle at baseline and 2 months postworkshop. Knowledge of the life cycle increased significantly after the workshop, with greater gains for workshop attendees than non-attendees. Prior knowledge and workshop attendance were significant predictors of postworkshop knowledge. The use of local evidence and experiential learning positively affected knowledge of T. solium transmission, laying the foundation for subsequent community-engaged control efforts.
- Published
- 2019
49. CystiHuman: A model of human neurocysticercosis
- Author
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Gabrielle, Bonnet, Francesco, Pizzitutti, Eloy A, Gonzales-Gustavson, Sarah, Gabriël, William K, Pan, Hector H, Garcia, Javier A, Bustos, Percy, Vilchez, and Seth E, O'Neal
- Subjects
Epilepsy ,Ecology ,Cysts ,Swine ,Cysticercosis ,Eggs ,Neurocysticercosis ,Medical risk factors ,Cellular and Molecular Neuroscience ,Computational Theory and Mathematics ,Modeling and Simulation ,Lesions ,Genetics ,Animals ,Humans ,Intracranial Hypertension ,Surgical and invasive medical procedures ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Hydrocephalus ,Taeniasis - Abstract
Introduction The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. Methods This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. Results and discussion Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence.
- Published
- 2022
50. Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis
- Author
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Rogger P Carmen-Orozco, Charles R. Sterling, Nancy Chile, Manuela Verastegui, Hector H. Garcia, Danitza G Dávila-Villacorta, Graham L. Sutherland, Yudith Cauna, Robert H. Gilman, Rensson H. Céliz, Maria C. Ferrufino-Schmidt, Leandra Bitterfeld, Edson G. Bernal-Teran, and Cesar M. Gavidia
- Subjects
Vascular Endothelial Growth Factor A ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Biology ,Neurocysticercosis ,Fibroblast growth factor ,VEGF-A ,Article ,Umbilical vein ,Rats, Sprague-Dawley ,angiogenesis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Taenia solium ,parasitic diseases ,Human Umbilical Vein Endothelial Cells ,medicine ,Animals ,Humans ,BBB disruption ,Tube formation ,Neovascularization, Pathologic ,neurocysticercosis ,Brain ,Endothelial Cells ,purl.org/pe-repo/ocde/ford#3.01.04 [https] ,Rats ,Fibroblast Growth Factors ,Vascular endothelial growth factor ,Endothelial stem cell ,medicine.drug_formulation_ingredient ,030104 developmental biology ,chemistry ,Blood-Brain Barrier ,Immunoglobulin G ,Blood Vessels ,Immunohistochemistry ,purl.org/pe-repo/ocde/ford#3.04.02 [http] ,030217 neurology & neurosurgery ,T. solium - Abstract
Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood–brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2). Also, two markers for BBB disruption, the endothelial barrier antigen and immunoglobulin G, were evaluated using immunohistochemical and immunofluorescence techniques. Brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. Both VEGF-A and FGF2 were overexpressed in the tissue surrounding the cysticerci, and VEGF-A was overexpressed in astrocytes. Vessels showed decreased immunoreactivity to endothelial barrier antigen marker and an extensive staining for IgG was found in the tissues surrounding the cysts. Additionally, an endothelial cell tube formation assay using human umbilical vein endothelial cells showed that excretory and secretory antigens of T. solium cysticerci induce the formation of these tubes. This in vitro model supports the hypothesis that angiogenesis in NCC might be caused by the parasite itself, as opposed to the host inflammatory responses alone. In conclusion, brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. This study also demonstrates that cysticerci excretory-secretory processes alone can stimulate angiogenesis. © 2018 Wiley Periodicals, Inc.
- Published
- 2018
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