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PURPOSE OF REVIEW: Neurocysticercosis (NCC) is still a significant contributor to neurological disease in vast regions of the world, and increasingly diagnosed in nonendemic countries because of travel and immigration from endemic settings. There is a need for clinicians in endemic and nonendemic regions to understand the complexities of its diagnosis and management. RECENT FINDINGS: Recent information on the performance and use of available imaging and immunodiagnostic tools as well as antiparasitic and anti-inflammatory therapeutic regimes were assessed. SUMMARY: Imaging and serology data should be assessed in the context of the specific type of NCC to improve diagnostic precision. In terms of therapeutic approaches, more controlled data is required on the efficacy and safety of combined antiparasitic therapy, and antiseizure and anti-inflammatory regimes should be optimized to minimize perilesional damage and reduce the risk of epilepsy.
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Coproantigen detection by enzyme-linked immunosorbent assay (coAg ELISA) is a vital tool for detecting and treating cases of Taenia solium taeniasis. However, the assay's procedures require costly materials and sophisticated equipment, which are typically inaccessible in rural settings where the disease is endemic. To overcome these barriers, we developed and evaluated a field-applicable coAg ELISA. The field coAg ELISA was developed and evaluated across four phases using known positive and negative stool samples collected from northern Peru. Phase I focused on field assay development, phase II on a small-scale performance evaluation, phase III on a large-scale evaluation, and phase IV on the use and reliability of a colorimetric scale card. All samples were processed using the field and standard assay procedures and compared using signal-to-noise ratios, correlation tests, performance characteristics, and agreement statistics where appropriate. The field coAg ELISA using reagents stored at -20°C and commercially available water and milk powder, and relying on spontaneous separation of the supernatant, had performance comparable to the standard assay. The field coAg ELISA was strongly correlated with the standard in both the small- and large-scale laboratory evaluation (r = 0.99 and r = 0.98, respectively). Finally, the field assay had an almost perfect agreement between independent readers (kappa = 0.975) and between each reader and the spectrophotometer. The field coAg ELISA demonstrated performance comparable to the standard, providing a low-cost alternative to the standard assay for identifying cases of intestinal taeniasis in a low-resource setting.
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Cisticercosis , Taenia solium , Teniasis , Humanos , Animales , Perú , Reproducibilidad de los Resultados , Antígenos Helmínticos , Teniasis/diagnóstico , Teniasis/epidemiología , Ensayo de Inmunoadsorción Enzimática/métodos , Heces/química , Cisticercosis/diagnóstico , Cisticercosis/epidemiologíaRESUMEN
INTRODUCTION: The Taenia solium tapeworm is responsible for cysticercosis, a neglected tropical disease presenting as larvae in the body of a host following taenia egg ingestion. Neurocysticercosis (NCC), the name of the disease when it affects the human central nervous system, is a major cause of epilepsy in developing countries, and can also cause intracranial hypertension, hydrocephalus and death. Simulation models can help identify the most cost-effective interventions before their implementation. Modelling NCC should enable the comparison of a broad range of interventions, from treatment of human taeniasis (presence of an adult taenia worm in the human intestine) to NCC mitigation. It also allows a focus on the actual impact of the disease, rather than using proxies as is the case for other models. METHODS: This agent-based model is the first model that simulates human NCC and associated pathologies. It uses the output of another model, CystiAgent, which simulates the evolution of pig cysticercosis and human taeniasis, adding human and cyst agents, including a model of cyst location and stage, human symptoms, and treatment. CystiHuman also accounts for delays in the appearance of NCC-related symptoms. It comprises three modules detailing cyst development, seizure probability and timing, and intracranial hypertension/hydrocephalus, respectively. It has been implemented in Java MASON and calibrated in three endemic villages in Peru, then applied to another village (Rica Playa) to compare simulation results with field data in that village. RESULTS AND DISCUSSION: Despite limitations in available field data, parameter values found through calibration are plausible and simulated outcomes in Rica Playa are close to actual values for NCC prevalence and the way it increases with age and cases with single lesions. Initial simulations further suggest that short-term interventions followed by a rapid increase in taeniasis prevalence back to original levels may have limited impacts on NCC prevalence.
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Cisticercosis , Quistes , Hidrocefalia , Hipertensión Intracraneal , Neurocisticercosis , Teniasis , Animales , Cisticercosis/diagnóstico , Cisticercosis/epidemiología , Humanos , Neurocisticercosis/diagnóstico , Neurocisticercosis/epidemiología , Porcinos , Teniasis/diagnóstico , Teniasis/epidemiologíaRESUMEN
The diagnosis of neurocysticercosis (NCC) depends on neuroimaging and serological confirmation. While antibody detection by enzyme-linked immunoelectrotransfer blot (EITB) fails to predict viable NCC, EITB banding patterns provide information about the host's infection course. Adding antigen enzyme-linked immunosorbent assay (Ag-ELISA) results to EITB banding patterns may improve their ability to predict or rule out of viable NCC. We assessed whether combining EITB banding patterns with Ag-ELISA improves discrimination of viable infection in imaging-confirmed parenchymal NCC. EITB banding patterns were grouped into classes using latent class analysis. True-positive and false-negative Ag-ELISA results in each class were compared using Fisher's exact test. Four classes were identified: 1, EITB negative or positive to GP50 alone (GP50 antigen family); 2, positive to GP42-39 and GP24 (T24/42 family), with or without GP50; and 3 and 4, positive to GP50, GP42-39, and GP24 and reacting to bands in the 8-kDa family. Most cases in classes 3 and 4 had viable NCC (82% and 88%, respectively) compared to classes 2 and 1 (53% and 5%, respectively). Adding positive Ag-ELISA results to class 2 predicted all viable NCC cases (22/22 [100%]), whereas 11/40 patients (27.5%) Ag-ELISA negative had viable NCC (P < 0.001). Only 1/4 patients (25%) Ag-ELISA positive in class 1 had viable NCC, whereas 1/36 patients (2.8%) Ag-ELISA negative had viable NCC (P = 0.192). In classes 3 and 4, adding Ag-ELISA was not contributory. Combining Ag-ELISA with EITB banding patterns improves discrimination of viable from nonviable NCC, particularly for class 2 responses. Together, these complement neuroimaging more appropriately for the diagnosis of viable NCC.
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Neurocisticercosis , Taenia solium , Animales , Anticuerpos Antihelmínticos , Antígenos Helmínticos , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Neurocisticercosis/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Neurocysticercosis (NCC) is a common cause of late-onset epilepsy worldwide, but there is still minimal information regarding its impact on a patient's quality of life. This study evaluated quality of life in a series of patients with epilepsy secondary to NCC using the QOLIE (Quality of Life in Epilepsy)-31 questionnaire. METHODOLOGY: This cross-sectional study included 155 Peruvian patients between 16 and 70â¯years of age with epilepsy due to viable intraparenchymal NCC, who enrolled in two trials of anti-parasitic treatment during the period 2006-2011. The QOLIE-31 questionnaire was applied before the onset of anti-parasitic treatment. The associations between QOLIE-31 scores, sociodemographic characteristics, clinical, and neuroimaging data were analyzed with Kruskal-Wallis test and generalized linear models (GLM). RESULTS: The average QOLIE-31 score was 55.8 (SD⯱â¯7.6), with 119 individuals (76.8%) scoring in the poor quality-of-life category. Generalized tonic-clonic seizures and secondarily generalized epileptic seizures were associated with a lower QOLIE-31, as well as a low level of education with a value of pâ¯=â¯0.05. There were no associations between QOLIE-31 scores and other variables such as sex, age, antiepileptic medication, number of parasitic cysts, and number of compromised brain regions. On multivariate analysis, a greater number of generalized epileptic seizures maintained a statistically significant association with detrimental QOLIE-31 scores. CONCLUSION: Quality of life is affected in NCC, mainly in relation to the number of prior generalized epileptic seizures.
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Epilepsia , Neurocisticercosis , Estudios Transversales , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Humanos , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico por imagen , Calidad de Vida , Convulsiones/diagnóstico por imagen , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Encuestas y CuestionariosRESUMEN
Taenia solium neurocysticercosis (NCC) is endemic in most of the world and contributes significantly to the burden of epilepsy and other neurological morbidity. Also present in developed countries because of immigration and travel, NCC is one of few diseases targeted for eradication. This paper reviews all aspects of its life cycle (taeniasis, porcine cysticercosis, human cysticercosis), with a focus on recent advances in its diagnosis, management, and control. Diagnosis of taeniasis is limited by poor availability of immunological or molecular assays. Diagnosis of NCC rests on neuroimaging findings, supported by serological assays. The treatment of NCC should be approached in the context of the particular type of infection (intra- or extraparenchymal; number, location, and stage of lesions) and has evolved toward combined symptomatic and antiparasitic management, with particular attention to modulating inflammation. Research on NCC and particularly the use of recently available genome data and animal models of infection should help to elucidate mechanisms of brain inflammation, damage, and epileptogenesis.
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Cisticercosis/diagnóstico , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Teniasis/diagnóstico , Animales , Antiparasitarios/uso terapéutico , Cisticercosis/tratamiento farmacológico , Cisticercosis/parasitología , Cisticercosis/veterinaria , Humanos , Neurocisticercosis/parasitología , Porcinos/parasitología , Enfermedades de los Porcinos/parasitología , Taenia solium , Teniasis/tratamiento farmacológico , Teniasis/parasitologíaRESUMEN
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.
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COVID-19 , SARS-CoV-2 , Adulto , Ecuador/epidemiología , Humanos , América Latina , Población RuralRESUMEN
BACKGROUND: Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. METHODS: Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. RESULTS: The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02-1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05-1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08-1.46), mild antibody response (RR, 1.14; 95% CI, 1.002-1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14-1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02-1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08-1.93), or complete cure (RR, 1.48; 95% CI, 1.29-1.71) were associated with a increased risk of calcification. CONCLUSIONS: Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.
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Neurocisticercosis , Taenia solium , Albendazol/uso terapéutico , Animales , Antiparasitarios/uso terapéutico , Encéfalo , Humanos , Neurocisticercosis/complicaciones , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/epidemiología , Convulsiones/epidemiología , Convulsiones/etiologíaRESUMEN
Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p<0.001), despite a smaller proportion of population treated by targeted approaches (RS 1.4%, RT 19.3%, MT 88.5%). Our findings suggest multiple approaches can achieve rapid control of T. solium transmission.
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Cisticercosis , Taenia solium , Animales , Cisticercosis/tratamiento farmacológico , Cisticercosis/epidemiología , Cisticercosis/prevención & control , Humanos , Administración Masiva de Medicamentos , Perú/epidemiología , PorcinosRESUMEN
OBJECTIVES: Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have a high disease burden and are prevalent in overlapping low- and middle-income areas. Yet, treatment guidance for people living with HIV/AIDS (PLWH/A) co-infected with NCC is currently lacking. This study aims to scope the available literature on HIV/AIDS and NCC co-infection, focusing on epidemiology, clinical characteristics, diagnostics and treatment outcomes. METHODS: The scoping literature review methodological framework, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of 16,969 records identified through database searching, and 45 additional records from other sources were reduced to 52 included studies after a standardised selection process. RESULTS: Two experimental studies, ten observational studies, 23 case series/case reports and 17 reviews or letters were identified. Observational studies demonstrated similar NCC seroprevalence in PLWH/A and their HIV-negative counterparts. Of 29 PLWH/A and NCC co-infection, 17 (59%) suffered from epileptic seizures, 15 (52%) from headaches and 15 (52%) had focal neurological deficits. Eighteen (62%) had viable vesicular cysts, and six (21%) had calcified cysts. Fifteen (52%) were treated with albendazole, of which 11 (73%) responded well to treatment. Five individuals potentially demonstrated an immune-reconstitution inflammatory syndrome after commencing antiretroviral therapy, although this was in the absence of immunological and neuroimaging confirmation. CONCLUSIONS: There is a paucity of evidence to guide treatment of PLWH/A and NCC co-infection. There is a pressing need for high-quality studies in this patient group to appropriately inform diagnostic and management guidelines for HIV-positive patients with NCC.
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Coinfección , Infecciones por VIH/complicaciones , Neurocisticercosis/complicaciones , Salud Global , Infecciones por VIH/epidemiología , Humanos , Neurocisticercosis/epidemiologíaRESUMEN
Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, phase I multiple ascending dose and food effect studies were conducted. Thirty-six healthy adults were enrolled in an open-label study which evaluated (i) the pharmacokinetics and safety of oxfendazole following multiple ascending doses of oxfendazole oral suspension at 3, 7.5, and 15 mg/kg once daily for 5 days and (ii) the effect of food on oxfendazole pharmacokinetics and safety after a single 3-mg/kg dose administered following an overnight fast or the consumption of a fatty breakfast. Following multiple oral dose administration, the intestinal absorption of oxfendazole was rapid, with the time to maximum concentration of drug in serum (Tmax) ranging from 1.92 to 2.56 h. A similar half-life of oxfendazole (9.21 to 11.8 h) was observed across all dose groups evaluated, and oxfendazole exhibited significantly less than a dose-proportional increase in exposure. Oxfendazole plasma exposures were higher in female subjects than in male subjects. Following daily administration, oxfendazole reached a steady state in plasma on study day 3, with minimal accumulation. Food delayed the oxfendazole Tmax by a median of 6.88 h and resulted in a 49.2% increase in the maximum observed drug concentration in plasma (Cmax) and an 86.4% increase in the area under the concentration-time curve (AUC). Oxfendazole was well tolerated in all study groups, and there were no major safety signals identified in this study. (This study has been registered at ClinicalTrials.gov under identifier NCT03035760.).
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Bencimidazoles , Administración Oral , Adulto , Área Bajo la Curva , Bencimidazoles/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Semivida , Humanos , MasculinoRESUMEN
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.
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Mielitis/líquido cefalorraquídeo , Mielitis/diagnóstico por imagen , Toxocara canis , Toxocariasis/líquido cefalorraquídeo , Toxocariasis/diagnóstico por imagen , Adulto , Anciano , Animales , Autoanticuerpos/líquido cefalorraquídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mielitis/epidemiología , Estudios Retrospectivos , Sicilia/epidemiología , Toxocariasis/epidemiologíaRESUMEN
BACKGROUND: The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.
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Albendazol/análogos & derivados , Antihelmínticos/sangre , Antihelmínticos/uso terapéutico , Neurocisticercosis/sangre , Neurocisticercosis/tratamiento farmacológico , Praziquantel/sangre , Praziquantel/uso terapéutico , Adolescente , Adulto , Anciano , Albendazol/sangre , Albendazol/uso terapéutico , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Adulto JovenRESUMEN
Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).
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Bencimidazoles/farmacocinética , Administración Oral , Adolescente , Adulto , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Semivida , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS: We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS: Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS: We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).
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Cisticercosis/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Enfermedades Endémicas/prevención & control , Taenia solium , Adolescente , Adulto , Animales , Antihelmínticos/uso terapéutico , Cisticercosis/prevención & control , Cisticercosis/veterinaria , Estudios de Factibilidad , Femenino , Educación en Salud , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Perú , Sus scrofa/parasitología , Taenia solium/aislamiento & purificación , Teniasis/prevención & control , Teniasis/transmisión , Vacunas , Adulto JovenRESUMEN
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.
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Barrera Hematoencefálica/fisiopatología , Factores de Crecimiento de Fibroblastos/metabolismo , Neovascularización Patológica/metabolismo , Neurocisticercosis/fisiopatología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Vasos Sanguíneos/parasitología , Vasos Sanguíneos/patología , Barrera Hematoencefálica/parasitología , Barrera Hematoencefálica/patología , Encéfalo/parasitología , Células Endoteliales/metabolismo , Células Endoteliales/parasitología , Células Endoteliales/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunoglobulina G/metabolismo , Neovascularización Patológica/parasitología , Neurocisticercosis/parasitología , Ratas , Ratas Sprague-Dawley , Taenia soliumRESUMEN
Parasitic infections of the central nervous system are much more common than suspected, although most infections are asymptomatic. For example, parasites like the ubiquitous protozoa Toxoplasma gondii or the nematode larvae Toxocara canis infect significant proportions of the human population. Other parasitic infections such as malaria and neurocysticercosis are widespread in developing countries and become major causes of neurological morbidity in these regions as well in immigrants and travelers. This article reviews parasitic pathogens causing neurological morbidity and mortality, including an extensive list of less common parasitic infections of the human nervous system.
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Antiparasitarios/uso terapéutico , Infecciones Parasitarias del Sistema Nervioso Central/diagnóstico , Infecciones Parasitarias del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Malaria Cerebral/diagnóstico , Malaria Cerebral/tratamiento farmacológico , Neurocisticercosis/diagnóstico , Neurocisticercosis/tratamiento farmacológico , Toxoplasmosis Cerebral/diagnóstico , Toxoplasmosis Cerebral/tratamiento farmacológicoRESUMEN
The original version of this article contained a mistake.
RESUMEN
Several studies have been performed to determine specific antigens for the diagnosis of tapeworms. One of these antigens is Tso31, which is used to differentiate Taenia solium and Taenia saginata in human feces. The aim of the present work was the molecular characterization of this protein in different tapeworm specimens collected in Peru: T. omisa (n = 6), T. hydatigena (n = 7), T. taeniaeformis (n = 4), T. pisiformes (n = 1), T. multiceps (n = 7), and T. solium (n = 10). Total DNA was extracted from each proglottid using a commercial DNA kit for tissue. A nested PCR was used to amplify a fragment of the previously described oncosphere-specific protein Tso31 gene. The nested PCR products were analyzed by 1.5% agarose gel electrophoresis and visualized after ethidium bromide staining. All nested PCR-positive products were sequenced and their sequences were compared. Of all the tapeworms analyzed, only T. solium and T. multiceps amplified the Tso31 gene. All sequences were identical for each species. Our T. solium Tso31 showed 100% similarity when compared with published GenBank sequences. The difference between T. solium and T. multiceps Tso31 samples was 8.1%. In conclusion, our results show that the tsol31 gene is not exclusive to T. solium.
Asunto(s)
Antígenos Helmínticos/genética , Taenia saginata/genética , Taenia solium/genética , Teniasis/diagnóstico , Animales , Secuencia de Bases , ADN , ADN de Helmintos/genética , Heces/parasitología , Humanos , Perú , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Taenia , Taenia saginata/metabolismo , Taenia solium/metabolismo , Teniasis/parasitologíaRESUMEN
Background: The enzyme-linked immunoelectrotransfer blot (EITB) assay is the reference serological test for neurocysticercosis (NCC). A positive result on EITB does not always correlate with the presence of active infections in the central nervous system (CNS), and patients with a single viable brain cyst may be EITB negative. Nonetheless, EITB antibody banding patterns appears to be related with the expression of 3 protein families of Taenia solium, and in turn with the characteristics of NCC in the CNS (type, stage, and burden of viable cysts). Methods: We evaluated EITB antibody banding patterns and brain imaging findings of 548 NCC cases. Similar banding patterns were grouped into homogeneous classes using latent class analysis. The association between classes and brain imaging findings was assessed. Results: Four classes were identified. Class 1 (patients negative or only positive to the GP50 band, related to the protein family of the same name) was associated with nonviable or single viable parenchymal cysticerci; class 2 (patients positive to bands GP42-39 and GP24, related to the T24-42 protein family, with or without anti-GP50 antibodies) was associated with intraparenchymal viable and nonviable infections; classes 3 and 4 (positive to GP50, GP42-39, and GP24 but also responding to low molecular weight bands GP21, GP18, GP14, and GP13, related to the 8 kDa protein family) were associated with extraparenchymal and intraparenchymal multiple viable cysticerci. Conclusions: EITB antibody banding patterns correlate with brain imaging findings and complement imaging information for the diagnosis of NCC and for staging NCC patients.