RESUMO
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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Neurocisticercose , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , Humanos , Antiparasitários/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêuticoRESUMO
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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Cisticercose , Cistos , Hidrocefalia , Hipertensão Intracraniana , Neurocisticercose , Teníase , Animais , Cisticercose/diagnóstico , Cisticercose/epidemiologia , Humanos , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , Suínos , Teníase/diagnóstico , Teníase/epidemiologiaRESUMO
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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Neurocisticercose , Taenia solium , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Neurocisticercose/diagnóstico , Sensibilidade e EspecificidadeRESUMO
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 , Neurocisticercose , Estudos Transversais , Epilepsia/tratamento farmacológico , Epilepsia/etiologia , Humanos , Neurocisticercose/complicações , Neurocisticercose/diagnóstico por imagem , Qualidade de Vida , Convulsões/diagnóstico por imagem , Convulsões/tratamento farmacológico , Convulsões/etiologia , Inquéritos e QuestionáriosRESUMO
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 , Equador/epidemiologia , Humanos , América Latina , População RuralRESUMO
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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Neurocisticercose , Taenia solium , Albendazol/uso terapêutico , Animais , Antiparasitários/uso terapêutico , Encéfalo , Humanos , Neurocisticercose/complicações , Neurocisticercose/tratamento farmacológico , Neurocisticercose/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologiaRESUMO
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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Coinfecção , Infecções por HIV/complicações , Neurocisticercose/complicações , Saúde Global , Infecções por HIV/epidemiologia , Humanos , Neurocisticercose/epidemiologiaRESUMO
PURPOSE OF REVIEW: Neurocysticercosis is the most common helminthic infection of the central nervous system caused by the larval stage of the pork tapeworm, Taenia solium. Endemic regions include Latin American countries, sub-Saharan Africa, and large regions of Asia, including the Indian subcontinent and is a global health problem. Seizures are the most common manifestation and approximately 30% of adult-onset seizures in endemic regions are attributable to NCC. Calcifications because of neurocysticercosis is the most common finding on imaging in endemic regions and are important seizure foci contributing to the burden of epilepsy. RECENT FINDINGS: After treatment with antiparasitics for multiple viable parenchymal disease, approximately 38% of cysts that resolved after 6 months of therapy will result in residual calcifications, which represents a significant burden of residual disease. Calcified disease has been referred to as 'inactive disease', but there is accumulating evidence to suggest that calcified granulomas are actually dynamic and substantially contribute to the development and maintenance of seizures. SUMMARY: Calcified parenchymal neurocysticercosis contributes significantly to the development and maintenance of seizures in endemic regions. Understanding the pathogenesis of the role of calcified NCC in seizure development and risk factors for development of calcifications after treatment is critical to decreasing the burden of symptomatic disease in endemic regions.
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Encéfalo/patologia , Calcinose/epidemiologia , Neurocisticercose/epidemiologia , Adulto , Animais , Antiparasitários/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Calcinose/diagnóstico por imagem , Calcinose/etiologia , Saúde Global , Humanos , Neurocisticercose/tratamento farmacológico , Neurocisticercose/parasitologia , Fatores de Risco , Convulsões/epidemiologia , Convulsões/etiologia , Taenia solium/isolamento & purificação , Tomografia Computadorizada por Raios X/métodosRESUMO
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 , Anti-Helmínticos/sangue , Anti-Helmínticos/uso terapêutico , Neurocisticercose/sangue , Neurocisticercose/tratamento farmacológico , Praziquantel/sangue , Praziquantel/uso terapêutico , Adolescente , Adulto , Idoso , Albendazol/sangue , Albendazol/uso terapêutico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
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Anticorpos Anti-Helmínticos/análise , Encéfalo/patologia , Neurocisticercose/patologia , Taenia solium/imunologia , Adulto , Idoso , Animais , Encéfalo/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , NeuroimagemRESUMO
OBJECTIVE: To evaluate the diagnostic performance of two commercially available ELISA kits, Novalisa® and Ridascreen® , for the detection of antibodies to Taenia solium, compared to serological diagnosis of neurocysticercosis (NCC) by LLGP-EITB (electro-immunotransfer blot assay using lentil-lectin purified glycoprotein antigens). METHODS: Archive serum samples from patients with viable NCC (n = 45) or resolved, calcified NCC (n = 45), as well as sera from patients with other cestode parasites (hymenolepiasis, n = 45 and cystic hydatid disease, n = 45), were evaluated for cysticercosis antibody detection using two ELISA kits, Novalisa® and Ridascreen® . All NCC samples had previously tested positive, and all samples from heterologous infections were negative on LLGP-EITB for cysticercosis. Positive rates were calculated by kit and sample group and compared between the two kits. RESULTS: Compared to LLGP-EITB, the sensitivity of both ELISA assays to detect specific antibodies in patients with viable NCC was low (44.4% and 22.2%), and for calcified NCC, it was only 6.7% and 4.5%. Sera from patients with cystic hydatid disease were highly cross-reactive in both ELISA assays (38/45, 84.4%; and 25/45, 55.6%). Sera from patients with hymenolepiasis cross-reacted in five cases in one of the assays (11.1%) and in only one sample with the second assay (2.2%). CONCLUSIONS: The performance of Novalisa® and Ridascreen® was poor. Antibody ELISA detection cannot be recommended for the diagnosis of neurocysticercosis.
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Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Separação Imunomagnética/métodos , Neurocisticercose/diagnóstico , Taenia solium/isolamento & purificação , Animais , Antígenos de Helmintos/sangue , Testes Imunológicos , Neurocisticercose/sangue , Neurocisticercose/parasitologia , Sensibilidade e Especificidade , Taenia solium/imunologiaRESUMO
BACKGROUND: The efficacy of current antiparasitic treatment for cerebral Taenia solium cysticercosis with either albendazole (ABZ) or praziquantel (PZQ) is suboptimal. A recent study demonstrated that combining these 2 antiparasitic drugs improves antiparasitic efficacy. We present here the parasiticidal efficacy data obtained during a previous phase II pharmacokinetic study that compared combined ABZ plus PZQ with ABZ alone. METHODS: The study was a randomized, double-blinded, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ (15 mg/k/d, for 10 days) and PZQ (50 mg/k/d, for 10 days) in intraparenchymal brain cysticercosis. Patients received the usual concomitant medications, including an antiepileptic drug (phenytoin or carbamazepine), dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug. Patients underwent safety laboratory evaluations at days 4, 7, and 11, as well as magnetic resonance (MR) imaging at 6 months to assess parasiticidal efficacy. RESULTS: Thirty-two patients were included, 16 in each arm. All of them completed antiparasitic treatment and underwent follow-up brain MR imaging. Cysticidal efficacy was strikingly higher in the combined ABZ-plus-PZQ group than in the ABZ-alone group (proportion of cysts resolved, 78 of 82 [95%] vs 23 of 77 [30%] [relative risk {RR}, 3.18; 95% confidence interval {CI}, 2.08-4.88; P < .001]; patients with complete cyst clearance, 12 of 16 [75%] vs 4 of 16 [25%] [RR, 3.00; 95% CI, 1.23-7.34; P = .005]). CONCLUSIONS: The combination of ABZ plus PZQ is more effective in destroying viable brain cysticercosis cysts than ABZ alone. CLINICAL TRIALS REGISTRATION: NCT00441285.
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Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Encefalopatias/tratamento farmacológico , Neurocisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Taenia solium/efeitos dos fármacos , Adolescente , Adulto , Albendazol/farmacologia , Animais , Anticestoides/farmacologia , Encefalopatias/parasitologia , Feminino , Humanos , Masculino , Neurocisticercose/parasitologia , Praziquantel/farmacologia , Adulto JovemRESUMO
OBJECTIVE: Neurocysticercosis (NCC) is a major cause of seizures and epilepsy in endemic countries. Antiparasitic treatment of brain cysts leads to seizures due to the host's inflammatory reaction, requiring concomitant steroids. We hypothesized that increased steroid dosing will reduce treatment-associated seizures. METHODS: Open-label randomized trial comparing 6 mg/day dexamethasone for 10 days (conventional) with 8 mg/day for 28 days followed by a 2-week taper (enhanced) in patients with NCC receiving albendazole. Follow-up included active seizure surveillance and brain imaging. Study outcomes were seizure days and patients with seizures, both measured in days 11-42. Additional analyses compared days 1-10, 11-21, 22-32, 33-42, 43-60, and 61-180. RESULTS: Thirty-two individuals were randomized into each study arm; two did not complete follow-up. From days 11 to 42, 59 partial and 6 generalized seizure days occurred in 20 individuals, nonsignificantly fewer in the enhanced arm (12 vs. 49, p = 0.114). The numbers of patients with seizures in this period showed similar nonsignificant differences. In the enhanced steroid arm there were significantly fewer days and individuals with seizures during antiparasitic treatment (days 1-10: 4 vs. 17, p = 0.004, and 1 vs. 10, p = 0.003, number needed to treat [NNT] 4.6, relative risk [RR] 0.1013, 95% confidence interval [CI] 0.01-0.74) and early after dexamethasone cessation (days 11-21: 6 vs. 27, p = 0.014, and 4 vs. 12, p = 0.021, NNT 4.0, RR 0.33, 95% CI 0.12-0.92) but not after day 21. There were no significant differences in antiparasitic efficacy or relevant adverse events. SIGNIFICANCE: Increased dexamethasone dosing results in fewer seizures for the first 21 days during and early after antiparasitic treatment for viable parenchymal NCC but not during the first 11-42 days, which was the primary predetermined time of analysis.
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Antiparasitários/uso terapêutico , Cisticercose/complicações , Dexametasona/uso terapêutico , Convulsões/tratamento farmacológico , Convulsões/etiologia , Adolescente , Adulto , Cisticercose/tratamento farmacológico , Eletroencefalografia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Neurocysticercosis is a parasitic disease of major public health importance. Definitive diagnosis requires neuroimaging, which is typically unavailable in rural impoverished regions of endemicity. Screening immunoassays can support diagnosis in this setting by identifying individuals most likely to have severe forms of disease for referral to imaging. Urine sampling is convenient, painless, and generally well accepted. We developed a rapid point-of-care (POC) assay to detect urinary antigens and assessed concordance with a standard antigen ELISA (Ag-ELISA), both using monoclonal antibodies TsW8/TsW5. From 28,145 stored community samples with Ag-ELISA results, we selected 843 for comparison, 281 each from nonreactive (ratio <1), reactive-below-cutoff (ratio 1:3), and positive (ratio ≥3) samples. Overall agreement was 73.6%, with strong agreement observed in the nonreactive (280/281, 99.6%) and positive (255/281, 90.8%) groups. This affordable noninvasive POC test can be applied to identify individuals in the community most at risk of developing severe disease.
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Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de Helmintos/urina , Animais , Cisticercose/diagnóstico , Cisticercose/urina , Sensibilidade e Especificidade , Neurocisticercose/diagnóstico , Neurocisticercose/urina , Taenia solium/imunologia , Feminino , Masculino , Adulto , CriançaRESUMO
Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapeworm Taenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.
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Neurocisticercose , Espaço Subaracnóideo , Taenia solium , Animais , Taenia solium/genética , Neurocisticercose/parasitologia , Neurocisticercose/genética , Espaço Subaracnóideo/metabolismo , Humanos , Perfilação da Expressão Gênica , Transcriptoma , Proliferação de Células , Cistos/genética , Cistos/parasitologia , Cistos/metabolismoRESUMO
Despite being a leading cause of acquired seizures in endemic regions, the pathological mechanisms of neurocysticercosis are still poorly understood. This study aims to investigate the impact of anthelmintic treatment on neuropathological features in a rat model of neurocysticercosis. Rats were intracranially infected with Taenia solium oncospheres and treated with albendazole + praziquantel (ABZ), oxfendazole + praziquantel (OXF), or untreated placebo (UT) for 7 days. Following the last dose of treatment, brain tissues were evaluated at 24 h and 2 months. We performed neuropathological assessment for cyst damage, perilesional brain inflammation, presence of axonal spheroids, and spongy changes. Both treatments showed comparable efficacy in cyst damage and inflammation. The presence of spongy change correlated with spheroids counts and were not affected by anthelmintic treatment. Compared to white matter, gray matter showed greater spongy change (91.7% vs. 21.4%, p < 0.0001), higher spheroids count (45.2 vs. 0.2, p = 0.0001), and increased inflammation (72.0% vs. 21.4%, p = 0.003). In this rat model, anthelmintic treatment destroyed brain parasitic cysts at the cost of local inflammation similar to what is described in human neurocysticercosis. Axonal spheroids and spongy changes as markers of damage were topographically correlated, and not affected by anthelmintic treatment.
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Anti-Helmínticos , Encéfalo , Neurocisticercose , Taenia solium , Animais , Neurocisticercose/tratamento farmacológico , Neurocisticercose/patologia , Ratos , Anti-Helmínticos/uso terapêutico , Encéfalo/patologia , Encéfalo/parasitologia , Albendazol/uso terapêutico , Albendazol/farmacologia , Praziquantel/uso terapêutico , Modelos Animais de Doenças , Masculino , Feminino , BenzimidazóisRESUMO
We explored the association between serological status for hepatitis E and neurocysticercosis (NCC) in neurologic patients attending a national neurological referral center in Lima, Perú, between the years 2008 and 2012. Anti-hepatitis E antibodies were evaluated in patients with and without NCC, and a control group of rural general population. Anti-hepatitis E IgG was found in 23.8% of patients with NCC, compared with 14.3% in subjects without NCC from a general rural population (P = 0.023) and 14.4% in subjects with neurological complaints without NCC (P = 0.027). Seropositive patients had a median age of 44 years compared with 30 years in seronegative patients (P <0.001). No significant differences in sex, region of residence, or liver enzyme values were found. Seropositivity to hepatitis E was frequent in this Peruvian population and higher in patients with NCC, suggesting shared common routes of infection.
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Vírus da Hepatite E , Hepatite E , Neurocisticercose , Humanos , Neurocisticercose/epidemiologia , Neurocisticercose/imunologia , Neurocisticercose/complicações , Masculino , Adulto , Feminino , Hepatite E/epidemiologia , Hepatite E/imunologia , Vírus da Hepatite E/imunologia , Pessoa de Meia-Idade , Peru/epidemiologia , Adulto Jovem , Prevalência , Imunoglobulina G/sangue , Anticorpos Anti-Hepatite/sangue , Estudos Soroepidemiológicos , Adolescente , IdosoRESUMO
Background: Cystic echinococcosis (CE) is a widespread neglected zoonotic disease caused by Echinococcus granulosus sensu lato (EG) with a global burden of control in the billions of dollars. E. granulosus' life cycle involves definitive, intermediate, and humans as dead-end hosts. Echinococcosis control programs use strategies that focus on any of these hosts. We aimed to provide a comprehensive and up-to-date overview of the EG control interventions worldwide. Methods: We conducted a scoping review by mapping all studies on interventions for EG control following the Arksey and O'Malley Framework. We screened identified articles, and charted and coded selected papers. We classified the data based on target host, type of study, and control mechanism. We described the efficacy or safety outcomes, and the associated barriers/facilitators for the intervention. Critical appraisal was conducted. Results: From 7,853 screened studies, we analyzed 45: seven centered on human interventions, 21 on animals, and 17 on both. Studies on humans focused on educational strategies and human CE monitoring. The studies on animals were field trials and most were based on Praziquantel (PZQ) for dogs. Studies focused on both animals and humans had, in general, more participants, lasted longer, and covered larger geographical areas. Overall, the quality of studies was moderate to low. Conclusions: Available evidence suggests that long-term interventions aimed at both animals and humans can achieve significant reduction in EG transmission, particularly when PZQ treatment for dogs is included. Higher quality evidence, standardization of methodologies, and better reporting on post-intervention outcomes are necessary for drawing stronger conclusions. Further evidence is needed to assess the sustainability and scalability of control measures. Nonetheless, an integrative One Health approach is essential for overcoming the multiple challenges associated with sustaining long-term control efforts for Echinococcosis.
RESUMO
We report a proof-of-concept study using a dipstick assay to detect Taenia solium antigen in urine samples of 30 patients with subarachnoid neurocysticercosis and 10 healthy control subjects. Strips were read in blind by two readers. The assay detected antigen in 29 of 30 cases and was negative in all 10 control samples. Although this study was performed in samples from individuals with subarachnoid neurocysticercosis who likely had high circulating antigen levels, it provides the proof of concept for a functional urine antigen point-of-care assay that detects viable cysts. Such an assay could serve to support a clinical diagnosis of suspect neurocysticercosis or to identify patients at risk of developing severe disease in areas where medical resources are limited, providing evidence to refer these individuals for imaging and specialized care as needed.
Assuntos
Cisticercose , Neurocisticercose , Taenia solium , Humanos , Animais , Neurocisticercose/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Ensaio de Imunoadsorção Enzimática/métodos , Antígenos de HelmintosRESUMO
Patients with subarachnoid neurocysticercosis (NCC) are usually older than those with parenchymal disease. Whether this difference reflects a prolonged presymptomatic period or a delay in diagnosis is not clear. From 408 eligible patients, we retrospectively compared the age at symptom onset in 140 patients diagnosed with parenchymal (pure viable or pure calcified) and subarachnoid NCC who had a confirmatory image available not more than 2 years after the beginning of symptoms. Patients with mixed (parenchymal and subarachnoid) NCC or those with parenchymal cysts at different stages (viable and/or degenerating and/or calcified) were not included. After controlling by sex and residence in rural endemic regions, the mean age at symptom onset in patients with subarachnoid disease was 13.69 years older than those with viable parenchymal disease. A long incubation period is a major contributing factor to older age at presentation in subarachnoid NCC, independent of delayed diagnosis or access to care.