103 results on '"García HH"'
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2. Current Diagnostic Criteria for Neurocysticercosis
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Guzman C and Garcia HH
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cysticercosis ,neurocysticercosis ,taenia solium ,diagnosis ,epilepsy ,epidemiology ,Arctic medicine. Tropical medicine ,RC955-962 - Abstract
Carolina Guzman,1 Hector H Garcia1,2 for The Cysticercosis Working Group in Peru1Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Perú; 2Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Lima, PerúCorrespondence: Hector H Garcia Email hgarcia@jhsph.eduAbstract: Neurocysticercosis (NCC) causes significant neurological morbidity around the world, and is the most common preventable factor for epilepsy in adults. It is endemic in most developing countries, and also diagnosed with some frequency in industrialized countries because of travel and migration. The clinical manifestations of NCC are extremely variable and may include almost any neurological symptom, depending on the number of lesions, location, size and evolutive stage of the infecting parasitic larvae and the immune response of the host. Thus, the diagnosis of NCC relies mostly on neuroimaging and immunological tests. Despite being a disease with a known etiology, the lack of specificity of clinical manifestations and auxiliary examinations makes its diagnosis difficult. In an attempt for developing a standard diagnosis approach, a chart of diagnostic criteria for NCC was initially published in 1996, and revised in 2001 and 2017. This chart of diagnostic criteria systematized the diagnosis of NCC and became widely used worldwide. This manuscript describes the structure of the chart, the principles behind the changes for each revision, as well as the context of its use and potential for improvement.Keywords: cysticercosis, neurocysticercosis, Taenia solium, diagnosis, epilepsy, epidemiology
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- 2021
3. Neurocysticercosis: unraveling the nature of the single cysticercal granuloma.
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García HH, Gonzalez AE, Rodriguez S, Tsang VC, Pretell EJ, Gonzales I, Gilman RH, Cysticercosis Working Group in Peru, García, H H, Gonzalez, A E, Rodriguez, S, Tsang, V C W, Pretell, E J, Gonzales, I, and Gilman, R H
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- 2010
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4. Frequency of diarrhoea as a predictor of elevated blood pressure in children.
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Miranda JJ, Davies AR, Smith GD, Smeeth L, Cabrera L, Gilman RH, García HH, Ortega YR, Cama VA, Miranda, Juan Jaime, Davies, Alisha R, Smith, George Davey, Smeeth, Liam, Cabrera, Lilia, Gilman, Robert H, García, Héctor H, Ortega, Ynes R, and Cama, Vitaliano A
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- 2009
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5. Taenia solium cysticercosis.
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García HH, Gonzalez AE, Evans CAW, Gilman RH, Cysticercosis Working Group in Peru, García, Héctor H, Gonzalez, Armando E, Evans, Carlton A W, and Gilman, Robert H
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The larval stage of the pork tapeworm (Taenia solium) infects the human nervous system, causing neurocysticercosis. This disease is one of the main causes of epileptic seizures in many less developed countries and is also increasingly seen in more developed countries because of immigration from endemic areas. Little information is available on the natural evolution of taeniasis or cysticercosis. Available therapeutic measures include steroids, treatments for symptoms, surgery, and, more controversially, antiparasitic drugs to kill brain parasites. Efforts to control and eliminate this disease are underway through antiparasitic treatment of endemic populations, development of pig vaccines, and other measures. [ABSTRACT FROM AUTHOR]
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- 2003
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6. Transclival endoscopic approach for prepontine cistern neurocysticercosis causing trigeminal neuralgia: illustrative case.
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Lines-Aguilar WW, García HH, Saavedra LJ, Caucha Y, Heredia D, Romero F, Vargas-Urbina J, Daniel Cuya C, Lozano M, Rene Apaza-Tintaya A, and Mao Vásquez C
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Background: Neurocysticercosis (NCC) is a public health problem in most of the world. Approximately 50 million people worldwide experience this disease, and it remains one of the most important causes of neurological morbidity. Extraparenchymal NCC (basal cisterns) is associated with high rates of morbidity and mortality. Currently, minimally invasive approaches, including the endoscopic endonasal approach, are used with good functional results., Observations: A 25-year-old patient presented with headache and pain in the left hemiface. Magnetic resonance imaging (MRI) showed cystic lesions in the prepontine basal cisterns compressing and displacing the left trigeminal nerve. The cysticercal lesions were excised using a transclival endoscopic approach. There were no complications during surgery, and pathology confirmed the diagnosis of NCC. The pain subsided after surgery. No residual cysts were observed on control MRI., Lessons: Minimally invasive approaches can be used to treat tumor and infectious problems of the skull base, as in this case, with good functional results. https://thejns.org/doi/10.3171/CASE24223.
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- 2024
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7. Mass chemotherapy with niclosamide for the control of Taenia solium : population-based safety profile and treatment effectiveness.
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Wardle MT, Allen SE, Gamboa R, Vilchez P, O'Neal SE, Muro C, Lescano AG, Moyano LM, Gonzalvez GE, González AE, Gilman RH, and García HH
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Background: Mass drug administration (MDA) with niclosamide (NSM) can be used to control taeniasis, the cause of neurocysticercosis. NSM is 84.3% effective against taeniasis and is considered safe as it is not absorbed from the intestinal tract. However, information on its safety and effectiveness during MDA is limited. We evaluated the effectiveness of NSM and reported adverse events (AEs) during a cysticercosis elimination program in Tumbes, Peru., Methods: Three rounds of NSM at 4-month intervals were offered to 77,397 eligible residents. We revisited all participants in their homes 72 h after each round to collect information regarding AEs. We also collected post-treatment stool samples to diagnose taeniasis after the first round, followed by a second sample at 30 days from those infected to evaluate NSM's effectiveness., Findings: During implementation, 68,751 individuals were administered at least one dose of NSM (mean age 29 years, SD 20; 52% male), and 65,551 (95.3%) were visited post-treatment. 988 (1.5%) reported experiencing at least one AE. Almost all AEs (99.2%) were of mild intensity, with no severe AEs recorded. Of 211 participants diagnosed with taeniasis, 188 provided a follow-up stool sample 30-days after treatment and 141 were cured (treatment effectiveness 75.0%). Older age and higher coproantigen levels were significantly associated with treatment failure., Interpretation: MDA with NSM is safe in Taenia solium endemic settings. However, the effectiveness following one dose is lower than expected, which suggests additional treatment may be necessary to enhance the infection control efforts., Funding: The Bill and Melinda Gates Foundation., Competing Interests: RG, PV, CM, and LMM were partially supported by the US National Institutes of Health, the Fogarty International Center (TW001140), AGL was supported by Emerge, the Emerging Diseases Epidemiology Research Training of the US National Institutes of Health, the Fogarty International Center (D43 TW007393), and MTW was supported by the National Center for Advancing Translational Sciences of the US National Institutes of Health under award number (TL1TR00237). HG was supported by a Wellcome Trust International Senior Research Fellowship in Public Health and Tropical Medicine. All authors declare no conflicts of interests., (© 2024 The Author(s).)
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- 2024
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8. [Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic].
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Rivera D, Santos D, Carmant L, García HH, Pimentel R, Wiebe S, Aponte V, González L, Castillo JC, Matos B, Paliza JM, Fermín R, Stoeter P, and Pérez-Then E
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- Humans, Dominican Republic epidemiology, Antibodies, Educational Status, Neurocysticercosis complications, Neurocysticercosis diagnosis, Neurocysticercosis epidemiology, Epilepsy epidemiology, Epilepsy etiology
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Introduction: Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country's south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces., Patients and Methods: A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS. NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants' sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC., Conclusions: This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases.
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- 2024
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9. Multiantigen print immunoassay (MAPIA) for the diagnosis of neurocysticercosis: a single-center diagnostic optimization and accuracy study in Lima, Peru.
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Toribio L, Guzman C, Noazin S, Zimic-Sheen A, Zimic M, Gonzales I, Saavedra H, Pretell EJ, Bustos JA, Handali S, and García HH
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- Animals, Humans, Peru, Antigens, Helminth, Sensitivity and Specificity, Immunoassay, Enzyme-Linked Immunosorbent Assay, Antibodies, Helminth, Neurocysticercosis diagnosis, Neurocysticercosis parasitology, Taenia solium
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Neurocysticercosis (NCC) is the most common helminthic infection of the human central nervous system. The antibody detection assay of choice is the enzyme-linked immunoelectrotransfer blot assay using lentil-lectin purified parasite antigens (LLGP-EITB, Western blot), an immunoassay with exceptional performance in clinical samples. However, its use is mainly restricted to a few research laboratories because the assay is labor-intensive and requires sophisticated equipment, expertise, and large amounts of parasite material for preparation of reagents. We report a new immunoprint assay (MAPIA) that overcomes most of these barriers. We initially compared the performance of five different antigen combinations in a subset of defined samples in the MAPIA format. After selecting the best-performing assay format (a combination of rGP50 + rT24H + sTs14 antigens), 148 archived serum samples were tested, including 40 from individuals with parenchymal NCC, 40 with subarachnoid NCC, and 68 healthy controls with no evidence of neurologic disease. MAPIA using three antigens (rGP50 + rT24H + sTs14) was highly sensitive and specific for detecting antibodies in NCC. It detected 39 out of 40 (97.5%) parenchymal NCC cases and 40/40 (100%) subarachnoid cases and was negative in 67 out of 68 (98.53%) negative samples. MAPIA using three recombinant and synthetic antigens is a simple and economical tool with a performance equivalent to the LLGP-EITB assay for the detection of specific antibodies to NCC. The MAPIA overcomes existing barriers to adoption of the EITG LLGP and is a candidate for worldwide use., Competing Interests: The authors declare no conflict of interest.
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- 2023
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10. Assembly and phylogeographical analysis of novel Taenia solium mitochondrial genomes suggest stratification within the African-American genotype.
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Jiménez-Avalos G, Soto-Obando A, Solis M, Gilman RH, Cama V, Gonzalez AE, García HH, Sheen P, Requena D, and Zimic M
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- Animals, Humans, Bayes Theorem, Genotype, Cysticercosis epidemiology, Cysticercosis parasitology, Genome, Mitochondrial, Taenia solium genetics, Taeniasis epidemiology, Taeniasis parasitology
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Background: Taenia solium is a parasite of public health concern, causing human taeniasis and cysticercosis. Two main genotypes have been identified: Asian and African-American. Although characterizing T. solium genotypes is crucial to understanding the genetic epidemiology of its diseases, not much is known about the differences between T. solium mitochondrial genomes from different genotypes. Also, little is known about whether genotypes are further subdivided. Therefore, this study aimed to identify a set of point mutations distributed throughout the T. solium mitochondrial genome that differentiate the African-American from the Asian genotype. Another objective was to identify whether T. solium main genotypes are further stratified., Methods: One Mexican and two Peruvian T. solium mitochondrial genomes were assembled using reads available in the NCBI Sequence Read Archive and the reference genome from China as a template. Mutations with respect to the Chinese reference were identified by multiple genome alignment. Jensen-Shannon and Grantham scores were computed for mutations in protein-coding genes to evaluate whether they affected protein function. Phylogenies by Bayesian inference and haplotype networks were constructed using cytochrome c oxidase subunit 1 and cytochrome b from these genomes and other isolates to infer phylogeographical relationships., Results: A set of 31 novel non-synonymous point mutations present in all genomes of the African-American genotype were identified. These mutations were distributed across the mitochondrial genome, differentiating the African-American from the Asian genotype. All occurred in non-conserved protein positions. Furthermore, the analysis suggested a stratification of the African-American genotypes into an East African and a West African sublineage., Conclusions: A novel set of 31 non-synonymous mutations differentiating the main T. solium genotypes was identified. None of these seem to be causing differences in mitochondrial protein function between parasites of the two genotypes. Furthermore, two sublineages within the African-American genotype are proposed for the first time. The presence of the East African sublineage in the Americas suggests an underestimated connection between East African and Latin American countries that might have arisen in the major slave trade between Portuguese Mozambique and the Americas. The results obtained here help to complete the molecular epidemiology of the parasite., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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11. Trigeminal neuralgia secondary to vascular compression and neurocysticercosis: illustrative case.
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Vásquez M, Saavedra LJ, García HH, Vela E, Medina JE, Lozano M, Hoyos C, and Lines-Aguilar WW
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Background: Trigeminal neuralgia (TN) is a frequent neurosurgical problem negatively influencing the quality of life of patients. The standard surgical treatment is microvascular decompression for primary cases and decompression of the mass effect, mainly tumors, for secondary cases. Neurocysticercosis (NCC) in the cerebellopontine angle is a rare etiology of TN. The authors report a case in which NCC cysts around the trigeminal nerve coexisted with a vascular loop, which compressed the exit of the trigeminal nerve from the pons., Observations: A 78-year-old woman presented with a 3-year history of persistent severe pain in the left side of her face, refractory to medical treatment. On gadolinium-enhanced magnetic resonance imaging, cystic lesions were observed around the left trigeminal nerve and a vascular loop was also present and in contact with the nerve. A retrosigmoid approach for cyst excision plus microvascular decompression of the trigeminal nerve was successfully performed. There were no complications. The patient was discharged without facial pain., Lessons: Albeit rare, TN secondary to NCC cysts should be considered in the differential diagnosis in NCC-endemic regions. In this case, the cause of the neuralgia was probably both problems, because when both were treated, the patient improved.
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- 2023
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12. Transventricular endoscopic approach to the anterior interhemispheric fissure for neurocysticercosis: illustrative cases.
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Vásquez M, Saavedra LJ, García HH, Apaza A, Caucha Y, Medina JE, Heredia D, Romero F, and Lines-Aguilar WW
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Background: Neurocysticercosis (NCC) is a global public health problem. It is a complex disease to manage and a cause of great morbidity and mortality in affected patients. Conventional surgical approaches have been used for many years, but currently, minimally invasive approaches are being used with good results. The authors present a case of NCC in the anterior interhemispheric fissure that was treated with a transventricular endoscopic approach., Observations: A 32-year-old male patient was admitted for persistent moderate headache and dizziness. Gadolinium-enhanced magnetic resonance imaging (MRI) showed multiple parenchymal, ventricular, and subarachnoid cystic lesions, especially in the anterior interhemispheric space. A transventricular endoscopic approach was selected and applied. There were no complications during surgery. Pathological analysis confirmed the diagnosis of NCC. Control MRI demonstrated the absence of cysts in the anterior interhemispheric space., Lessons: Minimally invasive approaches are an excellent alternative for patients with NCC, especially if a patient requires more than one surgery.
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- 2022
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13. Experimental brain infection with cysticercosis in sheep.
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Sota KA, Bustos JA, Verastegui MR, Toribio L, Chile N, Angulo N, Cangalaya C, Calcina J, González AE, Gilman RH, and García HH
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- Animals, Sheep, Antibodies, Monoclonal, Brain, Cysts
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Objective.: To explore the feasibility of developing a sheep model of neurocysticercosis (NCC) by intracranial infection with T. solium oncospheres., Materials and Methods.: We carried out an experimental infection model of NCC in sheep. Approximately 10 T. solium oncospheres previously cultured for 30 days were inoculated intracranially into ten sheep. The oncospheres, in 0.1 mL of physiological saline, were injected into the parietal lobe through an 18-gauge needle., Results.: After three months, granulomas were found in two sheep. In a third sheep we identified a 5 mm diameter cyst in the right lateral ventricle and histological evaluation confirmed that the cyst corresponded to a T. solium larva. Immunohistochemistry with monoclonal antibodies directed against membrane components and excretory/secretory antigens of the T. solium cyst was also used to confirm the etiology of the found granulomas. One of them showed reactivity to the monoclonal antibodies used, thus confirming that it was a cysticercus., Conclusion.: This experiment is the proof of concept that it is possible to infect sheep with cysticercosis by intracranial inoculation.
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- 2022
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14. Endoscopic endonasal surgery for massive subarachnoid neurocysticercosis: illustrative case.
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Lines WW, Gómez-Amador JL, García HH, Medina JE, Lira E, Antonio LA, Calderon J, Félix J, Saavedra LJ, Caucha Y, and Vásquez CM
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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., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)
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- 2021
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15. Prevalence of stroke survival in rural communities living in northern Peru.
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Moyano LM, Montano SM, Vilchez Barreto P, Reto N, Larrauri L, Mori N, Cornejo-Olivas M, Guevara-Silva E, Urizar F, Najar E, Gamboa R, Azabache C, Herrer Ticse R, Bolivar-Herrada L, Doud A, Martinez P, Miranda JJ, Zunt JR, and García HH
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- Humans, Peru epidemiology, Female, Male, Prevalence, Adult, Middle Aged, Aged, Aged, 80 and over, Adolescent, Young Adult, Child, Child, Preschool, Risk Factors, Stroke epidemiology, Stroke mortality, Rural Population statistics & numerical data
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Background and Purpose: Stroke is the leading cause of neurological impairment in the South American Andean region. However, the epidemiology of stroke in the region has been poorly characterized., Methods: We conducted a staged three-phase population-based study applying a validated eight-question neurological survey in 80 rural villages in Tumbes, northern Peru, then confirmed presence or absence of stroke through a neurologist's examination to estimate the prevalence of stroke., Results: Our survey covered 90% of the population (22,278/24,854 individuals, mean age 30±21.28, 48.45% females), and prevalence of stroke was 7.05/1,000 inhabitants. After direct standardization to WHO's world standard population, adjusted prevalence of stroke was 6.94/1,000 inhabitants. Participants aged ≥85 years had higher stroke prevalence (>50/1000 inhabitants) compared to other stratified ages, and some unusual cases of stroke were found among individuals aged 25-34 years. The lowest age reported for a first stroke event was 16.8 years. High blood pressure (aPR 4.2 [2.7-6.4], p>0.001), and sedentary lifestyle (aPR 1.6 [1.0-2.6], p = 0.045) were more prevalent in people with stroke., Conclusions: The age-standardized prevalence of stroke in this rural coastal Peruvian population was slightly higher than previously reported in studies from surrounding rural South American settings, but lower than in rural African and Asian regions. The death rate from stroke was much higher than in industrialized and middle-income countries., Competing Interests: The authors have declared that no competing interests exist.
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- 2021
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16. Stereotactic surgery for neurocysticercosis of the 4th ventricle: illustrative cases.
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Saavedra LJ, Vásquez CM, García HH, Antonio LA, Caucha Y, Félix J, Medina JE, and Lines WW
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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., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2021 The authors.)
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- 2021
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17. SARS-CoV-2 in Rural Latin America. A Population-based Study in Coastal Ecuador.
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Del Brutto OH, Costa AF, Mera RM, Recalde BY, Bustos JA, and García HH
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- Adult, Ecuador epidemiology, Humans, Latin America, Rural Population, COVID-19, SARS-CoV-2
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Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were detected in 303/673 rural Ecuadorian adults (45%), 77% of whom had compatible clinical manifestations. Seropositivity was associated with the use of open latrines. Our findings support the fears of mass spread of SARS-CoV-2 in rural Latin America and cannot exclude a contributing role for fecal-oral transmission., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2021
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18. Evidence for Transmission of Taenia solium Taeniasis/Cysticercosis in a Rural Area of Northern Rwanda.
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Acosta Soto L, Parker LA, Irisarri-Gutiérrez MJ, Bustos JA, Castillo Y, Perez E, Muñoz-Antoli C, Esteban JG, García HH, and Bornay-Llinares FJ
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Cysticercosis is a parasitic infection caused by the metacestode larval stage (cysticercus) of Taenia solium . In humans, cysticercosis may infect the central nervous system and cause neurocysticercosis, which is responsible for over 50,000 deaths per year worldwide and is the major cause of preventable epilepsy cases, especially in low-income countries. Cysticercosis infection is endemic in many less developed countries where poor hygiene conditions and free-range pig management favor their transmission. A cross-sectional study was conducted in 680 children from a rural primary school in Gakenke district (Northern province of Rwanda). Stool samples were collected from participants and analyzed using the Kato-Katz method (KK), formol-ether concentration (FEC), and/or copro-antigen enzyme-linked immunosorbent assay (CoAg-ELISA) to detect taeniasis. Blood samples were collected and analyzed using enzyme-linked immunoelectrotransfer blot (EITB) and antigen enzyme-linked immunosorbent assay (Ag-ELISA) to detect human cysticercosis. The overall proportion of taeniasis positivity was 0.3% (2/680), and both cases were also confirmed by CoAg-ELISA. A total of 13.3% (76/572) of the children studied were positive to cysticercosis ( T. solium -specific serum antibodies detected by EITB), of whom 38.0% (27/71) had viable cysticercus ( T. solium antigens by Ag-ELISA). This study provides evidence of the highest cysticercosis prevalence reported in Rwanda in children to date. Systematic investigations into porcine and human cysticercosis as well as health education and hygiene measures for T. solium control are needed in Gakenke district., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Acosta Soto, Parker, Irisarri-Gutiérrez, Bustos, Castillo, Perez, Muñoz-Antoli, Esteban, García and Bornay-Llinares.)
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- 2021
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19. [Evaluation of the accuracy of different body composition prediction formulas, compared to dual energy X-ray absorptiometry, in soccer players of Colombian professional teams].
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Kammerer López M, Ceballos Feria NDC, Mayor Rengifo MC, Hoyos García HH, and Gómez Velásquez S
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- Adipose Tissue, Adiposity, Adult, Athletic Performance, Colombia, Cross-Sectional Studies, Data Accuracy, Humans, Male, Young Adult, Absorptiometry, Photon, Anthropometry methods, Body Composition physiology, Soccer physiology
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Introduction: Introduction: professional soccer both in the local setting and in other countries is highly competitive, and those who practice must have specific morphological, anthropometric, and body composition characteristics, in addition to constant monitoring of nutritional and training interventions. Currently, the gold-standard criterion for the evaluation of body composition is Dual Energy X-ray Absorciometry (DXA), which is a costly laboratory method with limited use for many professionals. Knowing which field methods obtain similar results to this would allow a better interdisciplinary approach, which could have a positive impact on sports performance. The objective of this study was to evaluate the accuracy of different formulas for predicting fat percentage and fat mass, as compared to DXA, in Colombian soccer team players. Methods: a cross-sectional, analytical study using convenience sampling. A total of 79 professional male soccer players, belonging to 4 Colombian first and second division clubs, were included. Thirty anthropometric variables were measured, wherewith a descriptive analysis was performed using the SPSS v.21 program, and a procedure with analytical scope was carried out to establish concordance indices between different measurements using the Bland and Altman method. This statistical process was performed using the library (BlandAltmanLeh) of the statistical program "R". Results: average age was 23 ± 4.4 years, and the percentage of body fat was estimated using six equations: Jackson and Pollock (7.20 ± 2.58 %), Yuhasz as modified by Carter (7.52 ± 8.50 %), Reilly (10.04 ± 1.43 %), Faulkner (11.23 ± 11.90 %), Pariskova and Buskova (11.08 ± 16.06 %), and Durnin and Womersley (12.41 ± 20,10 %), in addition to the calculation of fat percentage for fat mass using the five-component method (13.17 ± 2.86 %). The percentage of body fat that showed the lowest intermethod difference was fractionation by five components (0.54 ± 3.56), followed by Durnin and Womersley (0.66 ± 3.52). Conclusion: the calculations of fat percentage using the fractionation of 5 components method and the Durnin and Womersley equation were closest to the results obtained by the gold-standard method (DXA) in soccer players of Colombian professional teams.
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- 2021
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20. Procedure for infusion of autologous mitochondria through the carotid artery in porcine brain.
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Orrego MA, Levy S, Kelly C, Arroyo G, Toribio L, García HH, and Walker M
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- Animals, Brain, Carotid Arteries, Swine, Central Nervous System Diseases, Mitochondria
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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.
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- 2021
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21. SARS-CoV-2 RNA in Swabbed Samples from Latrines and Flushing Toilets: A Case-Control Study in a Rural Latin American Setting.
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Del Brutto OH, Costa AF, Mera RM, Andrade-Molina D, Recalde BY, García HH, and Fernández-Cadena JC
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- COVID-19 epidemiology, COVID-19 immunology, Case-Control Studies, Family Characteristics, Humans, Latin America epidemiology, SARS-CoV-2 immunology, SARS-CoV-2 isolation & purification, Serologic Tests, Toilet Facilities, Young Adult, Bathroom Equipment virology, COVID-19 virology, RNA, Viral analysis, RNA, Viral genetics, Rural Population statistics & numerical data, SARS-CoV-2 genetics
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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.
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- 2021
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22. Late incidence of SARS-CoV-2 infection in a highly-endemic remote rural village. A prospective population-based cohort study.
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Del Brutto OH, Costa AF, Mera RM, Recalde BY, Bustos JA, and García HH
- Subjects
- Adult, Aged, Antibodies, Viral blood, COVID-19 blood, COVID-19 virology, COVID-19 Serological Testing, Cross-Sectional Studies, Ecuador epidemiology, Female, Humans, Incidence, Male, Middle Aged, Prospective Studies, Rural Population statistics & numerical data, SARS-CoV-2 genetics, SARS-CoV-2 physiology, Seroconversion, COVID-19 diagnosis, COVID-19 epidemiology, SARS-CoV-2 isolation & purification
- Abstract
Data on SARS-CoV-2 transmission in rural communities is scarce or non-existent. A previous cross-sectional study in middle-aged and older adults enrolled in the Atahualpa Project Cohort demonstrated that 45% of participants had SARS-CoV-2 antibodies, 77% of whom were symptomatic. Here, we assessed the incidence of SARS-CoV-2 infection in the above-mentioned rural population. One month after baseline testing, 362 of 370 initially seronegative individuals were re-tested to assess incidence of seroconversion and associated risk factors. Twenty-eight of them (7.7%) became seropositive. The overall incidence rate ratio was 7.4 per 100 person months of potential virus exposure (95% C.I.: 4.7-10.2). Six seroconverted individuals (21.4%) developed SARS-CoV-2-related symptomatology. The only covariate significantly associated with seroconversion was the use of an open latrine. Predictive margins showed that these individuals were 2.5 times more likely to be infected (95% C.I.: 1.03-6.1) than those using a flushing toilet. Therefore, along one month, approximately 8% of seronegative individuals became infected, even after almost half of the population was already seropositive. Nevertheless, a smaller proportion of incident cases were symptomatic (21% versus 77% of the earlier cases), and no deaths were recorded. Whether this decreased clinical expression resulted from a lower viral load in new infections cannot be determined. Increased seroconversion in individuals using latrines is consistent with a contributory role of fecal-oral transmission, although we cannot rule out the possibility that latrines are acting as a proxy for poverty or other unknown interacting variables.
- Published
- 2020
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23. SARS-CoV-2-related mortality in a rural Latin American population.
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Del Brutto OH, Costa AF, Mera RM, Recalde BY, Bustos JA, and García HH
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- Adult, Aged, Aged, 80 and over, COVID-19, Coronavirus Infections mortality, Ecuador epidemiology, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral mortality, SARS-CoV-2, Betacoronavirus, Coronavirus Infections epidemiology, Pneumonia, Viral epidemiology, Rural Population, Seroepidemiologic Studies
- Abstract
A sudden increase in adult mortality associated with respiratory diseases was noticed in Atahualpa (a rural Ecuadorian village), coinciding with the introduction of SARS-CoV-2 in the region. From a total of 1,852 individuals aged ≥18 years, 40 deaths occurred between January and June, 2020. In addition, a seroprevalence survey showed that 45% of the adult population have SARS-CoV-2 antibodies. Verbal autopsies revealed SARS-CoV-2 as the most likely cause of death in 29 cases. The mean age of suspected or confirmed SARS-CoV-2 cases was 76.9±12.1 years, while that of those dying from unrelated causes was 60.3±20.4 years (p=0.003). The overall mortality rate was 21.6 per 1,000 population (95% C.I.: 15.9 - 29.2), almost three-quarters of it due to SARS-CoV-2 (15.7 per 1,000; 95% C.I.: 11 - 22.4). This configures a 266% of excess mortality when compared to 5.9 per 1,000 (95% C.I.: 3.3 - 10.6) deaths from other causes. When SARS-CoV-2 mortality rate was calculated in individuals aged ≥60 years, it raised up to 68.9 per 1,000 (95% C.I.: 47.8 - 98.4). After peaking in April and May, mortality significantly decreased. It is possible that the high proportion of infected individuals and the resulting herd immunity contributed to the observed reduction in mortality., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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24. Incident SARS-CoV-2 Infection and a Shared Latrine.
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Del Brutto OH, Costa AF, and García HH
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- COVID-19, Female, Humans, Male, Pandemics, SARS-CoV-2, Betacoronavirus, Coronavirus Infections transmission, Hygiene, Pneumonia, Viral transmission, Toilet Facilities
- Published
- 2020
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25. Household Clustering of SARS-CoV-2 in Community Settings: A Study from Rural Ecuador.
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Del Brutto OH, Costa AF, Mera RM, Recalde BY, Bustos JA, and García HH
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Viral blood, COVID-19, Case-Control Studies, Child, Cluster Analysis, Ecuador epidemiology, Family Characteristics, Female, Humans, Immunoglobulin G blood, Immunoglobulin M blood, Male, Middle Aged, Pandemics, SARS-CoV-2, Young Adult, Betacoronavirus, Coronavirus Infections epidemiology, Pneumonia, Viral epidemiology
- 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
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26. Fake news in neglected tropical diseases: The case of neurocysticercosis.
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García HH and Del Brutto OH
- Subjects
- Humans, Deception, Disease Transmission, Infectious, Health Education methods, Information Dissemination methods, Neglected Diseases, Neurocysticercosis transmission
- Abstract
Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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27. Lack of evidence for Toxocara infection in Italian myelitis patients.
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Nicoletti A, García HH, Cicero CE, Portaro G, Giuliano L, Patti F, Sofia V, Noh J, Handali S, and Zappia M
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- Adult, Aged, Animals, Autoantibodies cerebrospinal fluid, Female, Humans, Male, Middle Aged, Myelitis epidemiology, Retrospective Studies, Sicily epidemiology, Toxocariasis epidemiology, Myelitis cerebrospinal fluid, Myelitis diagnostic imaging, Toxocara canis, Toxocariasis cerebrospinal fluid, Toxocariasis diagnostic imaging
- Abstract
Acute myelitis is a common neurological manifestation due to different causes, but in about 15-30% of cases its etiology remains unknown (idiopathic myelitis). Myelitis represents the most common manifestation of neurotoxocariasis, the infection of the human nervous system by larvae of the nematode Toxocara spp.; however, despite the high seroprevalence worldwide, its contribution to the burden of disease has not been assessed. We evaluated the presence of antibodies against Toxocara spp. in cerebrospinal fluid (CSF) from a sample of 28 patients with a diagnosis of idiopathic myelitis (N = 20) or encephalomyelitis (N = 8) who attended the Neurological Unit of the University Hospital of Catania, Sicily. Antibodies against Toxocara spp. were measured using a multiplex bead-based assay and Toxocara immunoblot using Toxocara canis excretory secretory antigens. All samples tested negative for the presence of anti-T. canis IgG antibodies. In this series, we found no evidence of a contribution of neurotoxocariasis to the burden of myelitis.
- Published
- 2020
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28. Use of magnetic particles in the purification of IgM antibodies against Taenia solium.
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Perez LA, Castillo Y, Espinoza C, Toribio LM, Santos Y, Martel KS, Wilkins PP, Bustos JA, García HH, and Castro-Sesquen YE
- Subjects
- Animals, Antibodies, Monoclonal isolation & purification, Immunoglobulin M immunology, Magnetic Phenomena, Taenia solium immunology
- 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.
- Published
- 2020
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29. No Confirmed Cases of Taenia solium Taeniasis in a Group of Recently Arrived Sub-Saharan Migrants to Italy.
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Zammarchi L, Tilli M, Mantella A, Botta A, Nicoletti A, García HH, Castillo Y, Aquilini D, Boccalini S, and Bartoloni A
- Abstract
One-hundred and sixty-four migrants from Sub-Saharan Africa to Italy were screened with the Taenia solium specific enzyme-linked immunosorbent assay coproantigen (ELISA CoAg) and four (2.4%) were recorded as positive, but with optical density values near to the cut-off. No ELISA CoAg positive samples were confirmed by parasitological methods. Low positivity could be attributed to false positive result or cross-reaction with other Taenia species. Further studies are needed to assess the role of migration on sporadic autochthonous transmission of T. solium taeniasis/cysticercosis in Europe.
- Published
- 2019
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30. Axonal swellings and spheroids: a new insight into the pathology of neurocysticercosis.
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Mejia Maza A, Carmen-Orozco RP, Carter ES, Dávila-Villacorta DG, Castillo G, Morales JD, Mamani J, Gavídia CM, Alroy J, Sterling CR, Gonzalez AE, García HH, Woltjer RL, Verástegui MR, and Gilman RH
- Subjects
- Animals, Brain pathology, Epilepsy pathology, Humans, Rats, Rats, Sprague-Dawley, Swine, Taenia solium pathogenicity, Axons pathology, Neurocysticercosis pathology, Spheroids, Cellular pathology
- Abstract
Neurocysticercosis is a parasitic brain disease caused by the larval form (Cysticercus cellulosae) of Taenia solium and is the leading cause of preventable epilepsy worldwide. However, the pathophysiology and relation to the wide range of clinical features remains poorly understood. Axonal swelling is emerging as an important early pathological finding in multiple neurodegenerative diseases and as a cause of brain injury, but has not been well described in neurocysticercosis. Histological analysis was performed on human, rat and porcine NCC brain specimens to identify axonal pathology. Rat infection was successfully carried out via two routes of inoculation: direct intracranial injection and oral feeding. Extensive axonal swellings, in the form of spheroids, were observed in both humans and rats and to a lesser extent in pigs with NCC. Spheroids demonstrated increased immunoreactivity to amyloid precursor protein and neurofilament indicating probable impairment of axonal transport. These novel findings demonstrate that spheroids are present in NCC which is conserved across species. Not only is this an important contribution toward understanding the pathogenesis of NCC, but it also provides a model to analyze the association of spheroids with specific clinical features and to investigate the reversibility of spheroid formation with antihelminthic treatment., (© 2018 International Society of Neuropathology.)
- Published
- 2019
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31. Performance of a Sandwich Antigen-Detection ELISA for the Diagnosis of Porcine Taenia solium Cysticercosis.
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Bustos JA, Ninaquispe BE, Rodriguez S, Castillo Y, Yang SY, Gilman RH, Dorny P, Gabriël S, García HH, Gonzalez AE, and For The Cysticercosis Working Group In Peru
- Subjects
- Animals, Antigens, Helminth, Cysticercosis diagnosis, Cysticercosis parasitology, Enzyme-Linked Immunosorbent Assay methods, Sensitivity and Specificity, Swine, Swine Diseases diagnosis, Cysticercosis veterinary, Enzyme-Linked Immunosorbent Assay veterinary, Swine Diseases parasitology, Taenia solium
- Abstract
The pig is the natural intermediate host of Taenia solium , a parasite causing significant burden of disease in both humans and pigs. Porcine cysticercosis is traditionally detected via tongue palpation and slaughterhouse meat inspection, both with limited sensitivity. Serum antibody detection has a better performance; however, it does not discriminate past from present infection. Serum antigen detection can demonstrate viable infection and gives a good estimate of parasitic load. This study evaluated a sandwich antigen-detection ELISA using monoclonal antibodies (MoAbs) 158C11 and 60H8 for the diagnosis of viable cysticercosis in pigs. Serum samples were used from 35 naturally T. solium cysticerci-infected pigs, 31 cysticercosis-negative pigs, and 22 pigs with Taenia hydatigena infection (to assess cross-reactions). Positive cysticercosis samples were subcategorized at necropsy according to parasitic burden as mild (1-10 viable cysts, n = 10), moderate (11-100 cysts, n = 5), or severe infection (more than 100 cysts, n = 20). This Ag-ELISA showed a sensitivity of 82.9% and a specificity of 96.8% when not considering cross-reactions with T. hydatigena . Hundred percentage of severely infected, 80% of moderately infected, and 50% of mildly T. solium -infected pigs tested positive. Twenty of 22 pigs with only T. hydatigena infections were positive, with 13 reaching saturating levels in the ELISA. The Ag-ELISA revealed the presence of live cysts and is, thus, a fairly reliable test to monitor experimental infection, response to treatment, and follow-up in animal models of cysticercosis. It should, however, be carefully interpreted when used in regions where T. hydatigena is endemic in pigs.
- Published
- 2019
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32. Characterization of a novel cathepsin L-like protease from Taenia solium metacestodes for the immunodiagnosis of porcine cysticercosis.
- Author
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León-Janampa N, Liendo R, Gilman RH, Padilla C, García HH, Gonzales A, Sheen P, Pajuelo MJ, and Zimic M
- Subjects
- Animals, Antibodies, Helminth blood, Baculoviridae genetics, Cathepsin L isolation & purification, Cysticercosis diagnosis, Enzyme-Linked Immunosorbent Assay, Immunoglobulin G blood, Immunologic Tests, Phylogeny, Recombinant Proteins genetics, Sf9 Cells, Swine, Swine Diseases parasitology, Antigens, Helminth genetics, Cathepsin L genetics, Cysticercosis veterinary, Swine Diseases diagnosis, Taenia solium enzymology
- Abstract
Porcine cysticercosis is an endemic parasitic disease caused by infection with Taenia solium that is found predominantly in developing countries. In order to aid in the development of simple diagnostic approaches, identification and characterization of potential new antigens for immunodiagnostic purposes is desired. The cysteine protease family has previously been found to have important immunodiagnostic properties. These proteases are expressed as zymogens which contain a signal peptide, pro-peptide, and an active domain. Subsequent catalytic cleavage of the pro-peptide converts these zymogens into enzymes. With the use of bioinformatic tools we identified an active domain of a novel cathepsin L-like cysteine protease (TsolCL) in the T. solium genome. The TsolCL gene includes 705 nucleotides (nt) within a single intron and a 633 nt exonic sequence encoding an active protein of 211 amino acids. Sequence alignment and phylogenetic analysis suggest that the TsolCL gene is closely related to genes found in Echinoccocus granulosus and E. multiloculars. In addition, TsolCL was found to have a 61.9%-99.0% similarity to other cathepsin L proteins found in other helminths and mammals. We cloned, expressed, purified, and characterized the recombinant active TsolCL (27 kDa) using the baculovirus-insect cell expression system. TsolCL showed cysteine protease enzymatic activity with the capacity to hydrolyze the Z-Phe-Arg-AMC substrate as well as bovine serum albumin. However, TsolCL was not able to hydrolyze human immunoglobulin. In addition, TsolCL has cathepsin L conserved amino acid residues in the catalytic site (Gln8, Cys14, His159, Asn179 and Trp181) and the motif GCNGG. Using ELISA, TsolCL was able to distinguish circulating IgG antibodies between healthy animals and naturally infected pigs with cysticercosis, showing a moderate sensitivity of 83.33% (40/48; 95% CI: [69.8%-92.5 %]), and a specificity of 83.78% (31/37; 95% CI: [67.9%-93.8%]). In conclusion, a novel cathepsin L-like cysteine protease from a T. solium metacestode was expressed successfully in Baculovirus system and was evaluated as a candidate antigen to diagnose porcine cysticercosis using the ELISA immunoassay., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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33. Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis.
- Author
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Carmen-Orozco RP, Dávila-Villacorta DG, Cauna Y, Bernal-Teran EG, Bitterfeld L, Sutherland GL, Chile N, Céliz RH, Ferrufino-Schmidt MC, Gavídia CM, Sterling CR, García HH, Gilman RH, and Verástegui MR
- Subjects
- Animals, Blood Vessels parasitology, Blood Vessels pathology, Blood-Brain Barrier parasitology, Blood-Brain Barrier pathology, Brain parasitology, Endothelial Cells metabolism, Endothelial Cells parasitology, Endothelial Cells pathology, Human Umbilical Vein Endothelial Cells, Humans, Immunoglobulin G metabolism, Neovascularization, Pathologic parasitology, Neurocysticercosis parasitology, Rats, Rats, Sprague-Dawley, Taenia solium, Blood-Brain Barrier physiopathology, Fibroblast Growth Factors metabolism, Neovascularization, Pathologic metabolism, Neurocysticercosis physiopathology, Vascular Endothelial Growth Factor A metabolism
- 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
- 2019
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34. A novel enolase from Taenia solium metacestodes and its evaluation as an immunodiagnostic antigen for porcine cysticercosis.
- Author
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Ponce R, León-Janampa N, Gilman RH, Liendo R, Roncal E, Luis S, Quiñones-Garcia S, Silverstein Z, García HH, Gonzales A, Sheen P, Zimic M, and Pajuelo MJ
- Subjects
- Amino Acid Sequence, Animals, Antibodies, Helminth biosynthesis, Antigens, Helminth chemistry, Antigens, Helminth genetics, Antigens, Helminth metabolism, Computational Biology, Confidence Intervals, Cysticercosis diagnosis, DNA, Complementary genetics, Enzyme-Linked Immunosorbent Assay veterinary, Female, Genetic Vectors, Phosphopyruvate Hydratase chemistry, Phosphopyruvate Hydratase genetics, Phosphopyruvate Hydratase metabolism, Phylogeny, Protein Structure, Secondary, Protein Structure, Tertiary, RNA, Messenger genetics, RNA, Messenger isolation & purification, ROC Curve, Rabbits, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins immunology, Recombinant Proteins metabolism, Sensitivity and Specificity, Sequence Alignment, Sf9 Cells, Spectrophotometry veterinary, Swine, Swine Diseases parasitology, Taenia solium classification, Taenia solium genetics, Taenia solium immunology, Antigens, Helminth immunology, Cysticercosis veterinary, Phosphopyruvate Hydratase immunology, Swine Diseases diagnosis, Taenia solium enzymology
- Abstract
Cysticercosis is a worldwide parasitic disease of humans and pigs principally caused by infection with the larvae of the pork tapeworm Taenia solium. Through the use of the recently-made-available T. solium genome, we identified a gene within a novel 1448 bp ORF that theoretically encodes for a 433 amino acid-long protein and predicted to be an α-enolase closely related to enolases of other flatworms. Additional bioinformatic analyses revealed a putative plasminogen-binding region on this protein, suggesting a potential role for this protein in pathogenesis. On this basis, we isolated the mRNA encoding for this presumptive enolase from T. solium metacestodes and reverse-transcribed it into cDNA before subsequently cloning and expressing it in both E. coli (rEnoTs) and insect cells (rEnoTsBac), in a 6xHis tagged manner. The molecular weights of these two recombinant proteins were ∼48 and ∼50 kDa, respectively, with the differences likely attributable to differential glycosylation. We used spectrophotometric assays to confirm the enolase nature of rEnoTs as well as to measure its enzymatic activity. The resulting estimates of specific activity (60.000 U/mg) and K
m (0.091 mM) are quite similar to the catalytic characteristics of enolases of other flatworms. rEnoTs also exhibited high immunogenicity, eliciting a strong polyclonal antibody response in immunized rabbits. We subsequently employed rEnoTsBac for use in an ELISA aimed at discriminating between healthy pigs and those infected with T. solium. This diagnostic assay exhibited a sensitivity of 88.4% (95% CI, 74.92%-96.11%) and a specificity of 83.7% (95% CI: 69.29%-93.19%). In conclusión, this study reports on and enzymatically characterizes a novel enolase from T. solium metacestode, and shows a potential use as an immunodiagnostic for porcine cysticercosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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35. Spontaneously Arrested Transmission of Cysticercosis in a Highly Endemic Village with a Very Low Migration Rate.
- Author
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Del Brutto OH, O'Neal SE, Dorny P, and García HH
- Subjects
- Adult, Animal Husbandry, Animals, Antibodies, Helminth blood, Antigens, Helminth urine, Ecuador epidemiology, Feces parasitology, Female, Humans, Male, Neurocysticercosis diagnostic imaging, Neurocysticercosis epidemiology, Neuroimaging methods, Prevalence, Rural Population, Swine, Swine Diseases epidemiology, Swine Diseases parasitology, Taenia solium physiology, Endemic Diseases prevention & control, Neurocysticercosis prevention & control, Neurocysticercosis transmission, Swine Diseases prevention & control, Swine Diseases transmission
- Abstract
Taenia solium cysticercosis is difficult to eliminate without interventions or societal development. Atahualpa is a rural Ecuadorian village with documented low migration rate, where domestic pig raising is common and human cysticercosis is endemic. To assess neurocysticercosis (NCC) prevalence, 1,273 villagers aged ≥ 20 years underwent neuroimaging studies, which showed calcified lesions in 121 (9.5%) individuals, but no active disease. Likewise, positive reactions, apparently nonspecific, were found in only 3/200 subjects by the use of a monoclonal antibody-based enzyme-linked immunosorbent assay to detect T. solium antigens in urine. Only 2/418 pigs reacted to three antibody bands on serum western blot and none to more than three bands. This is the first time that spontaneously arrested T. solium transmission is documented in a known endemic village. Understanding why active transmission stopped could provide insights on potential targets for control interventions. Atahualpa could provide an optimal scenario for longitudinal studies on the consequences of calcified NCC.
- Published
- 2018
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36. Clinical and Magnetic Resonance Imaging Findings of Neurotoxocariasis.
- Author
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Sánchez SS, García HH, and Nicoletti A
- Abstract
Human toxocariasis is one of the most prevalent helminthiases worldwide. Toxocara canis larvae can cross the blood-brain barrier leading to the neurotoxocariasis. The clinical presentation consists of a wide spectrum of neurological manifestations, but asymptomatic infection is probably common. Neurotoxocariasis is not a frequent diagnosis probably due to the non-specific nature of its symptoms as well as the lack of confirmatory diagnostic tests. Diagnosis of neurotoxocariasis is based on the presence of a high titer of anti- Toxocara antibody in the cerebrospinal fluid or in the serum, presence of eosinophilia in the serum or cerebrospinal fluid, and clinical and radiological improvement after anthelmintic therapy; however, universally accepted diagnostic criteria are lacking. Magnetic resonance imaging (MRI) findings include single or multiple, subcortical, cortical or white matter hyperintense lesions, best visualized on FLAIR and T2-weighted imaging, and usually isointense or hypointense on T1. These imaging findings are suggestive but not specific to neurotoxocariasis. Definitive diagnosis is made by histological confirmation, but it is rarely followed. This review provides an overview of the clinical manifestations, management options, and MRI findings of neurotoxocariasis.
- Published
- 2018
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37. Notes and recommendations for the establishment of control programs for taeniasis and cysticercosis due to Taenia solium in PeruNotes and recommendations for the establishment of control programs for Taeniasis/cysticercosis in Peru.
- Author
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García HH, González AE, O'Neal SE, and Gilman RH
- Subjects
- Cysticercosis epidemiology, Humans, Peru epidemiology, Practice Guidelines as Topic, Taeniasis epidemiology, Cysticercosis prevention & control, Taeniasis prevention & control
- Abstract
Neurocysticercosis is a nervous system infection caused by the larvae (cysticercus) of the pork tapeworm (Taenia solium). Neurocysticercosis is the primary cause of acquired epilepsy worldwide and, therefore, a global public health problem. On the other hand, T. solium taeniasis/cysticercosis is one of very few infectious diseases considered to be potentially eradicable. Recently, a large-scale elimination program in Tumbes, Peru, demonstrated the feasibility of interrupting transmission. Based on these advances, a series of initial guidelines are proposed aimed at setting out the foundations for regional and national taeniasis/cysticercosis control programs, with simple and feasible local interventions as a starting point.
- Published
- 2018
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38. Reproducibility of Diagnostic Criteria for Ventricular Neurocysticercosis.
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Bustos JA, García HH, and Del Brutto OH
- Subjects
- Granuloma, Heart Ventricles, Humans, Reproducibility of Results, Neurocysticercosis
- Published
- 2017
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39. TNF-α blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis.
- Author
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Mahanty S, Orrego MA, Cangalaya C, Adrianzen MP, Arroyo G, Calcina J, Gonzalez AE, García HH, Guerra-Giraldez C, and Nash TE
- Subjects
- Animals, Anticestodal Agents therapeutic use, Antiparasitic Agents adverse effects, Antiparasitic Agents therapeutic use, Blood-Brain Barrier drug effects, Brain parasitology, Cytokines genetics, Cytokines immunology, Dexamethasone administration & dosage, Dexamethasone adverse effects, Etanercept adverse effects, Immunosuppressive Agents adverse effects, Interferon-gamma genetics, Interferon-gamma immunology, Neurocysticercosis complications, Neurocysticercosis drug therapy, Neurocysticercosis immunology, Praziquantel administration & dosage, Praziquantel adverse effects, Praziquantel therapeutic use, Swine, Swine Diseases immunology, Taenia solium drug effects, Tumor Necrosis Factor-alpha genetics, Etanercept administration & dosage, Immunosuppressive Agents administration & dosage, Inflammation prevention & control, Neurocysticercosis veterinary, Swine Diseases drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors
- Abstract
Background: Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ)., Methodology/principal Findings: We followed the methods from a previously developed treatment model of NCC in naturally infected swine. The four study groups of infected pigs included 3 groups treated with PZQ on day 0: PZQ-treated alone (100 mg/kg PO; n = 9), pretreated with dexamethasone (DEX, 0.2 mg/kg IM administered on days -1, +1 and +3; n = 6), and pretreated with etanercept (ETN, 25 mg IM per animal on days -7 and 0; n = 6). The fourth group remained untreated (n = 3). As measured by quantitative RT-PCR, ETN pretreatment depressed transcription of a wide range of proinflammatory, regulatory and matrix protease encoding genes at 120 hr post PZQ treatment in capsules of cysts that demonstrated extravasated Evans Blue (EB) (a measure of blood brain barrier dysfunction) compared to animals not receiving ETN. Transcription was significantly depressed for the proinflammatory genes tumor necrosis factor (TNF)-α, and interferon (IFN)-γ; the inflammation regulating genes cytotoxic T-lymphocyte-associated protein (CTLA)4, interleukin (IL)-13 and transforming growth factor (TGF)-β; the tissue remodeling genes matrix metalloprotease (MMP)1 and 9, tissue inhibitors of metalloproteases (TIMP)1 and 2, and the genes regulating endothelial function vascular endothelial growth factor (VEGF)1, angiopoietin (Ang)1, Ang 2, and platelet endothelial cell adhesion molecule (PECAM)-1. In contrast, transcription was only modestly decreased in the DEX pretreated pigs compared to PZQ alone, and only for TNF-α, IL-6, IFN-γ, TGF-β and Ang1. IL-10 was not affected by either ETN or DEX pretreatments. The degree of inflammation, assessed by semi-quantitative inflammatory scores, was modestly decreased in both ETN and DEX pretreated animals compared to PZQ treated pigs whereas cyst damage scores were moderately decreased only in cysts from DEX pretreated pigs. However, the proportion of cysts with EB extravasation was not significantly changed in ETN and DEX pretreated groups., Conclusions/significance: Overall, TNF-α blockade using ETN treatment modulated expression of a large variety of genes that play a role in induction and control of inflammation and structural changes. In contrast the number of inflammatory cells was only moderately decreased suggesting weaker effects on cell migration into the inflammatory capsules surrounding cysts than on release of modulatory molecules. Taken together, these data suggest that TNF-α blockade may provide a viable strategy to manage post-treatment pericystic inflammation that follows antiparasitic therapy for neurocysticercosis.
- Published
- 2017
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40. On the relationship between calcified neurocysticercosis and epilepsy in an endemic village: A large-scale, computed tomography-based population study in rural Ecuador.
- Author
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Del Brutto OH, Arroyo G, Del Brutto VJ, Zambrano M, and García HH
- Subjects
- Adult, Animals, Calcinosis epidemiology, Cross-Sectional Studies, Ecuador epidemiology, Epilepsy epidemiology, Female, Humans, Male, Middle Aged, Neurocysticercosis epidemiology, Random Allocation, Swine, Taenia solium isolation & purification, Taeniasis diagnostic imaging, Taeniasis epidemiology, Young Adult, Calcinosis diagnostic imaging, Epilepsy diagnostic imaging, Neurocysticercosis diagnostic imaging, Population Surveillance methods, Rural Population, Tomography, X-Ray Computed methods
- Abstract
Objective: Using a large-scale population-based study, we aimed to assess prevalence and patterns of presentation of neurocysticercosis (NCC) and its relationship with epilepsy in community-dwellers aged ≥20 years living in Atahualpa (rural Ecuador)., Methods: In a three-phase epidemiological study, individuals with suspected seizures were identified during a door-to-door survey and an interview (phase I). Then, neurologists evaluated suspected cases and randomly selected negative persons to estimate epilepsy prevalence (phase II). In phase III, all participants were offered noncontrast computed tomography (CT) for identifying NCC cases. The independent association between NCC (exposure) and epilepsy (outcome) was assessed by the use of multivariate logistic regression models adjusted for age, sex, level of education, and alcohol intake. CT findings were subsequently compared to archived brain magnetic resonance imaging in a sizable subgroup of participants., Results: Of 1,604 villagers aged ≥20 years, 1,462 (91%) were enrolled. Forty-one persons with epilepsy (PWE) were identified, for a crude prevalence of epilepsy of 28 per 1,000 population (95% confidence interval [CI] = 20.7-38.2). A head CT was performed in 1,228 (84%) of 1,462 participants, including 39 of 41 PWE. CT showed lesions consistent with calcified parenchymal brain cysticerci in 118 (9.6%) cases (95% CI = 8.1-11.4%). No patient had other forms of NCC. Nine of 39 PWE, as opposed to 109 of 1,189 participants without epilepsy, had NCC (23.1% vs. 9.2%, p = 0.004). This difference persisted in the adjusted logistic regression model (odds ratio = 3.04, 95% CI = 1.35-6.81, p = 0.007)., Significance: This large CT-based study demonstrates that PWE had three times the odds of having NCC than those without epilepsy, providing robust epidemiological evidence favoring the relationship between NCC and epilepsy., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)
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- 2017
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41. Reliability of Diagnostic Criteria for Neurocysticercosis for Patients with Ventricular Cystic Lesions or Granulomas: A systematic review.
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Bustos JA, García HH, and Del Brutto OH
- Subjects
- Cerebral Ventricles parasitology, Granuloma parasitology, Granuloma pathology, Humans, Neurocysticercosis parasitology, Neurocysticercosis pathology, Sensitivity and Specificity, Cerebral Ventricles pathology, Granuloma diagnosis, Neurocysticercosis diagnosis
- Abstract
Intraventricular neurocysticercosis (NCC) is a severe form of NCC requiring prompt diagnosis and treatment. We aimed to assess the reliability of the most recent version of diagnostic criteria for this form of NCC. Two systematic literature reviews were performed; one included case reports of patients with intraventricular cysticercosis and the other included case reports of patients with intraventricular cystic lesions or granulomas caused by infections other than NCC. All assessed cases were categorized according to the last revision of the long-standing Del Brutto's set of diagnostic criteria to determine its sensitivity, specificity, and predictive value for this form of NCC. The search disclosed 128 patients with intraventricular NCC and 41 with other infections. The set of diagnostic criteria classified as definitive NCC 93 cases with intraventricular NCC (sensitivity 72.7%, 95% CI, 63.9-79.9%), as well as four cases with other infections (specificity 90.2%, 95% CI, 75.9-96.8%). The positive and negative predictive values of the criteria were 0.96 (95% CI, 0.89-0.99) and 0.51 (95% CI, 0.39-0.63), respectively. The revised Del Brutto's set of diagnostic criteria for NCC is acceptably sensitive and highly specific for diagnosing patients with the ventricular form of the disease.
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- 2017
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42. Prevalence, Age Profile, and Associated Risk Factors for Hymenolepis nana Infection in a Large Population-Based Study in Northern Peru.
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Vilchez Barreto PM, Gamboa R, Santivañez S, O'Neal SE, Muro C, Lescano AG, Moyano LM, Gonzálvez G, and García HH
- Subjects
- Adolescent, Age Factors, Animals, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Male, Peru, Population Surveillance, Prevalence, Risk Factors, Sanitation, Toilet Facilities, Feces parasitology, Hymenolepiasis epidemiology, Hymenolepis nana isolation & purification, Intestinal Diseases, Parasitic epidemiology
- Abstract
Hymenolepis nana , the dwarf tapeworm, is a common intestinal infection of children worldwide. We evaluated infection and risk factor data that were previously collected from 14,761 children aged 2-15 years during a large-scale program in northern Peru. We found that 1,124 of 14,761 children (7.61%) had H. nana infection, a likely underestimate given that only a single stool sample was examined by microscopy for diagnosis. The strongest association with infection was lack of adequate water (adjusted prevalence ratio [aPR] 2.22, 95% confidence interval [CI] 1.82-2.48) and sanitation infrastructure in the house (aPR 1.94, 95% CI 1.64-2.29). One quarter of those tested did not have a bathroom or latrine at home, which doubled their likelihood of infection. Similarly, one quarter did not have piped public water to the house, which also increased the likelihood of infection. Continued efforts to improve access to basic water and sanitation services will likely reduce the burden of infection in children for this and other intestinal infections.
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- 2017
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43. Screening, diagnosis and management of human cysticercosis and Taenia solium taeniasis: technical recommendations by the COHEMI project study group.
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Zammarchi L, Bonati M, Strohmeyer M, Albonico M, Requena-Méndez A, Bisoffi Z, Nicoletti A, García HH, and Bartoloni A
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- Animals, Europe, Humans, Latin America, Transients and Migrants, Antiparasitic Agents therapeutic use, Cysticercosis diagnosis, Cysticercosis drug therapy, Taenia solium isolation & purification
- Abstract
Neurocysticercosis, the central nervous system's localised form of cysticercosis, is considered to be the leading cause of epilepsy in the developing world. In Europe, the disease is mainly imported and affects both immigrants and travellers. However, autochthonous cases of cysticercosis in low-endemic countries could also originate from Taenia solium carriers (migrants or travellers) who acquired taeniasis overseas. Management of cysticercosis is a challenge for European healthcare providers as they are often hardly aware of this infection and have little familiarity in managing this disease. This study provides a summary of recommendations concerning screening, diagnosis and management of cysticercosis and T. solium taeniasis in Europe drawn up by nine experts in migrant health and imported diseases with experience in cysticercosis and T. solium taeniasis., (© 2017 John Wiley & Sons Ltd.)
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- 2017
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44. Radiological evolution of porcine neurocysticercosis after combined antiparasitic treatment with praziquantel and albendazole.
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Cangalaya C, Bustos JA, Calcina J, Vargas-Calla A, Mamani J, Suarez D, Arroyo G, Gonzalez AE, Chacaltana J, Guerra-Giraldez C, Mahanty S, Nash TE, and García HH
- Subjects
- Animals, Brain parasitology, Brain pathology, Cysts diagnostic imaging, Cysts pathology, Disease Models, Animal, Drug Therapy, Combination, Female, Magnetic Resonance Imaging, Male, Neurocysticercosis diagnostic imaging, Neurocysticercosis drug therapy, Radiography, Random Allocation, Swine Diseases parasitology, Albendazole administration & dosage, Anthelmintics administration & dosage, Neurocysticercosis veterinary, Praziquantel administration & dosage, Swine parasitology, Swine Diseases diagnostic imaging, Swine Diseases drug therapy
- Abstract
Background: The onset of anthelmintic treatment of neurocysticercosis (NCC) provokes an acute immune response of the host, which in human cases is associated with exacerbation of neurological symptoms. This inflammation can occur at the first days of therapy. So, changes in the brain cysts appearance may be detected by medical imaging. We evaluated radiological changes in the appearance of brain cysts (enhancement and size) on days two and five after the onset of antiparasitic treatment using naturally infected pigs as a model for human NCC., Methods and Results: Contrast T1-weighted magnetic resonance imaging with gadolinium was performed before and after antiparasitic treatment. Eight NCC-infected pigs were treated with praziquantel plus albendazole and euthanized two (n = 4) and five (n = 4) days after treatment; another group of four infected pigs served as untreated controls. For each lesion, gadolinium enhancement intensity (GEI) and cyst volume were measured at baseline and after antiparasitic treatment. Volume and GEI quantification ratios (post/pre-treatment measures) were used to appraise the effect of treatment. Cysts from untreated pigs showed little variations between their basal and post treatment measures. At days 2 and 5 there were significant increases in GEI ratio compared with the untreated group (1.32 and 1.47 vs 1.01, p = 0.021 and p = 0.021). Cyst volume ratios were significantly lower at days 2 and 5 compared with the untreated group (0.60 and 0.22 vs 0.95, p = 0.04 and p = 0.02). Cysts with lower cyst volume ratios showed more marked post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling., Conclusion/significance: A significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging.
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- 2017
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45. The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age.
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Del Brutto OH, Issa NP, Salgado P, Del Brutto VJ, Zambrano M, Lama J, and García HH
- Subjects
- Adult, Aged, Atrophy pathology, Case-Control Studies, Female, Hippocampus pathology, Humans, Male, Middle Aged, Neurocysticercosis pathology, Odds Ratio, Risk Factors, Rural Population, Aging, Atrophy parasitology, Hippocampus parasitology, Neurocysticercosis parasitology
- Abstract
Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case-control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6-14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop., (© The American Society of Tropical Medicine and Hygiene.)
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- 2017
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46. Antiepileptic drug therapy and recommendations for withdrawal in patients with seizures and epilepsy due to neurocysticercosis.
- Author
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Bustos JA, García HH, and Del Brutto OH
- Subjects
- Epilepsy etiology, Humans, Neuroimaging, Recurrence, Seizures etiology, Withholding Treatment, Anticonvulsants therapeutic use, Epilepsy drug therapy, Neurocysticercosis complications, Seizures drug therapy
- Abstract
Introduction: Neurocysticercosis (NCC) is a leading causes of secondary epilepsy worldwide. There is increasing evidence on the epileptogenic role of NCC, and the presence of edema, calcified scars, gliosis and hippocampal sclerosis support this phenomenon., Areas Covered: We summarized principles of antiepileptic drug (AED) therapy as well as risk factors associated with seizure recurrence after AED withdrawal in patients with NCC. Expert commentary: First-line AED monotherapy is effective as a standard approach to control seizures in most NCC patients. Risks and benefits of AED withdrawal have not been systematically studied, and this decision must be individualized. However, a seizure-free period of at least two years seem prudent before attempting withdrawal. Risk factors for seizure recurrence after AED withdrawal include a history of status epilepticus, poor seizure control during treatment, neuroimaging evidence of perilesional gliosis, hippocampal sclerosis and calcified lesions, as well as persistence of paroxysmal activity in the EEG.
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- 2016
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47. Perilesional Inflammation in Neurocysticercosis - Relationship Between Contrast-Enhanced Magnetic Resonance Imaging, Evans Blue Staining and Histopathology in the Pig Model.
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Cangalaya C, Bustos JA, Calcina J, Vargas-Calla A, Suarez D, Gonzalez AE, Chacaltana J, Guerra-Giraldez C, Mahanty S, Nash TE, and García HH
- Subjects
- Animals, Brain pathology, Disease Models, Animal, Evans Blue chemistry, Histology, Humans, Neurocysticercosis diagnostic imaging, Neurocysticercosis pathology, Swine, Magnetic Resonance Imaging methods, Neurocysticercosis immunology, Staining and Labeling methods
- Abstract
Background: Disease manifestations in neurocysticercosis (NCC) are frequently due to inflammation of degenerating Taenia solium brain cysts. Exacerbated inflammation post anthelmintic treatment is associated with leakage of the blood brain barrier (BBB) using Evans blue (EB) staining. How well EB extravasation into the brain correlates with magnetic resonance imaging (MRI) using gadolinium (Gd) enhancement as a contrast agent and pericystic inflammation was analyzed in pigs harboring brain cysts of Taenia solium., Methodology/principal Findings: Three groups of 4 naturally infected pigs were assessed. The first and second groups were treated with both praziquantel plus albendazole and sacrificed two and five days post treatment, respectively. A third untreated group remained untreated. Pigs were injected with EB two hours prior to evaluation by Gd-enhanced T1-MRI, and euthanized. The EB staining for each cyst capsule was scored (EB grades were 0: 0%; 1: up to 50%; 2: over 50% but less than 100%; 3: 100%). Similarly, the Gd enhancement around each cyst was qualitatively and quantitatively scored from the MRI. The extent of pericystic inflammation on histology was scored in increasing severity as IS1, IS2, IS3 and IS4. Grade 3 EB staining and enhancement was only seen in treated capsules. Also, treated groups had higher Gd intensity than the untreated group. Grades of enhancement correlated significantly with Gd enhancement intensity. EB staining was correlated with Gd enhancement intensity and with IS4 in the treated groups. These correlations were stronger in internally located cysts compared to superficial cysts in treated groups., Significance: EB staining and Gd enhancement strongly correlate. The intensity of enhancement determined by MRI is a good indication of the degree of inflammation. Similarly, EB staining highly correlates with the degree of inflammation and may be applied to study inflammation in the pig model of NCC.
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- 2016
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48. Anti-Taenia solium monoclonal antibodies for the detection of parasite antigens in body fluids from patients with neurocysticercosis.
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Paredes A, Sáenz P, Marzal MW, Orrego MA, Castillo Y, Rivera A, Mahanty S, Guerra-Giraldez C, García HH, and Nash TE
- Subjects
- Animals, Antibodies, Helminth immunology, Antibodies, Monoclonal metabolism, Antibody Specificity, Antigens, Helminth blood, Antigens, Helminth urine, Bile immunology, Enzyme-Linked Immunosorbent Assay, Female, Fluorescent Antibody Technique, Hybridomas immunology, Mice, Mice, Inbred BALB C, Neurocysticercosis immunology, Rabbits, Species Specificity, Swine, Antibodies, Monoclonal immunology, Antigens, Helminth analysis, Neurocysticercosis diagnosis, Taenia solium immunology
- Abstract
Neurocysticercosis (NCC), an infection of the brain by Taenia solium (Ts) cysts, is the most common cause of adult-onset epilepsy in developing countries. Serological testing consists primarily of varying methods to detect antibodies in body fluids and more recently antigen (Ag) detection assays to identify individuals or animals with viable parasites. Antigen assays currently in use employ monoclonal antibodies (mAbs) raised against T. saginata, which have known cross reactivity to animal cestodes but are highly specific in human samples. We produced, characterized and tested 21 mAbs raised against T. solium whole cyst antigens, vesicular fluid or excretory secretory products. Reactivity of the TsmAbs against specific cyst structures was determined using immunofluorescence and immunohistochemistry on histological sections of Ts muscle cysts. Four TsmAbs reacted to vesicular space alone, 9 to the neck and cyst wall, one to the neck and vesicular space and 7 to the neck, cyst wall and vesicular space. An in-house ELISA assay to detect circulating Ts antigen, using the TsmAbs as capture antibodies and a rabbit polyclonal anti-Ts whole cyst antibody as a detector antibody demonstrated that eight of the 21 TsmAbs detected antigens in known NCC-positive human sera and three of these also in urine samples. Reactivity was expressed as normalized ratios of optical densities (OD positive control/OD negative control). Three TsmAbs had ratios >10 and five between 2 and 10. The TsmAbs have potential utility for the diagnosis and post-treatment monitoring of patients with viable NCC infections., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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49. Towards sustainable partnerships in global health: the case of the CRONICAS Centre of Excellence in Chronic Diseases in Peru.
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Miranda JJ, Bernabé-Ortiz A, Diez-Canseco F, Málaga G, Cárdenas MK, Carrillo-Larco RM, Lazo-Porras M, Moscoso-Porras M, Pesantes MA, Ponce V, Araya R, Beran D, Busse P, Boggio O, Checkley W, García PJ, Huicho L, León-Velarde F, Lescano AG, Mohr DC, Pan W, Peiris D, Perel P, Rabadán-Diehl C, Rivera-Chira M, Sacksteder K, Smeeth L, Trujillo AJ, Wells JC, Yan LL, García HH, and Gilman RH
- Subjects
- Biomedical Research organization & administration, Capacity Building organization & administration, Chronic Disease prevention & control, Humans, Organizational Case Studies, Peru, Global Health, International Cooperation
- Abstract
Human capital requires opportunities to develop and capacity to overcome challenges, together with an enabling environment that fosters critical and disruptive innovation. Exploring such features is necessary to establish the foundation of solid long-term partnerships. In this paper we describe the experience of the CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia in Lima, Peru, as a case study for fostering meaningful and sustainable partnerships for international collaborative research. The CRONICAS Centre of Excellence in Chronic Diseases was established in 2009 with the following Mission: "We support the development of young researchers and collaboration with national and international institutions. Our motivation is to improve population's health through high quality research." The Centre's identity is embedded in its core values - generosity, innovation, integrity, and quality- and its trajectory is a result of various interactions between multiple individuals, collaborators, teams, and institutions, which together with the challenges confronted, enables us to make an objective assessment of the partnership we would like to pursue, nurture and support. We do not intend to provide a single example of a successful partnership, but in contrast, to highlight what can be translated into opportunities to be faced by research groups based in low- and middle-income countries, and how these encounters can provide a strong platform for fruitful and sustainable partnerships. In defiant contexts, partnerships require to be nurtured and sustained. Acknowledging that all partnerships are not and should not be the same, we also need to learn from the evolution of such relationships, its key successes, hurdles and failures to contribute to the promotion of a culture of global solidarity where mutual goals, mutual gains, as well as mutual responsibilities are the norm. In so doing, we will all contribute to instil a new culture where expectations, roles and interactions among individuals and their teams are horizontal, the true nature of partnerships.
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- 2016
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50. Update on Cysticercosis Epileptogenesis: the Role of the Hippocampus.
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Del Brutto OH, Engel J Jr, Eliashiv DS, and García HH
- Subjects
- Animals, Epilepsy etiology, Humans, Neurocysticercosis complications, Sclerosis complications, Seizures physiopathology, Epilepsy physiopathology, Hippocampus
- Abstract
Neurocysticercosis (NCC) is the most common helminthic infection of the nervous system and a frequent cause of reactive seizures and epilepsy worldwide. In many cases, multiple episodes of focal seizures related to an identifiable parenchymal brain cyst (and likely attributable to local damage) continue for years after the cyst resolves. However, cases where seizure semiology, interictal EEG abnormalities, and parasites location do not correlate raise concerns about the causal relationship between NCC and either reactive seizures or epilepsy, as well as the epileptogenic potential of parasites. Neurosurgical series of patients with intractable epilepsy and cross-sectional population-based studies have shown a robust association between NCC and hippocampal sclerosis (HS), which might contribute to the above-referred inconsistencies. Current information does not allow to define whether in patients with NCC, HS could result from recurrent seizure activity from a local or distant focus or from chronic recurrent inflammation. In either case, HS may become the pathological substrate of subsequent mesial temporal lobe epilepsy (MTLE). Longitudinal clinical- and population-based cohort studies are needed to evaluate the causal relationship between NCC and HS and to characterize this association with the occurrence of MTLE. If a cause-and-effect relationship between NCC and HS is demonstrated, NCC patients could be assessed to examine neuronal mechanisms of hippocampal epileptogenesis in comparison with animal models, to identify biomarkers of hippocampal epileptogenesis, and to develop novel interventions to prevent epilepsy in NCC and perhaps in other forms of acquired epilepsy.
- Published
- 2016
- Full Text
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