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1.
PLoS Comput Biol ; 18(5): e1010118, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35587497

RESUMO

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.


Assuntos
Cisticercose , Cistos , Hidrocefalia , Hipertensão Intracraniana , Neurocisticercose , Teníase , Animais , Cisticercose/diagnóstico , Cisticercose/epidemiologia , Humanos , Neurocisticercose/diagnóstico , Neurocisticercose/epidemiologia , Suínos , Teníase/diagnóstico , Teníase/epidemiologia
2.
J Clin Microbiol ; 60(2): e0155021, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34851685

RESUMO

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.


Assuntos
Neurocisticercose , Taenia solium , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Neurocisticercose/diagnóstico , Sensibilidade e Especificidade
3.
Epilepsy Behav ; 131(Pt A): 108668, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35483205

RESUMO

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 70 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 p = 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.


Assuntos
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 Questionários
4.
Clin Infect Dis ; 73(2): 314-317, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32717052

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Equador/epidemiologia , Humanos , América Latina , População Rural
5.
Clin Infect Dis ; 73(9): e2592-e2600, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-32556276

RESUMO

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.


Assuntos
Neurocisticercose , Taenia solium , Albendazol/uso terapêutico , Animais , Antiparasitários/uso terapêutico , Encéfalo , Humanos , Neurocisticercose/complicações , Neurocisticercose/tratamento farmacológico , Neurocisticercose/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologia
6.
Trop Med Int Health ; 26(10): 1140-1152, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34228854

RESUMO

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.


Assuntos
Coinfecção , Infecções por HIV/complicações , Neurocisticercose/complicações , Saúde Global , Infecções por HIV/epidemiologia , Humanos , Neurocisticercose/epidemiologia
7.
Curr Opin Infect Dis ; 33(5): 334-338, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32868513

RESUMO

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.


Assuntos
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/métodos
8.
Clin Infect Dis ; 69(11): 1996-2002, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30715265

RESUMO

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.


Assuntos
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 Jovem
9.
Clin Infect Dis ; 66(2): 282-288, 2018 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-29020381

RESUMO

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.


Assuntos
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 , Neuroimagem
10.
Trop Med Int Health ; 23(1): 101-105, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29160912

RESUMO

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.


Assuntos
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/imunologia
11.
Clin Infect Dis ; 62(11): 1375-9, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26984901

RESUMO

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.


Assuntos
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 Jovem
12.
Epilepsia ; 55(9): 1452-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25092547

RESUMO

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.


Assuntos
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 Jovem
13.
Sci Rep ; 14(1): 11833, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782926

RESUMO

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.


Assuntos
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/metabolismo
14.
Brain Pathol ; : e13237, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212958

RESUMO

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.

15.
Am J Trop Med Hyg ; 110(6): 1210-1213, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38653231

RESUMO

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.


Assuntos
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 , Idoso
16.
Am J Trop Med Hyg ; 108(3): 578-580, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36746658

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 Helmintos
17.
Am J Trop Med Hyg ; 108(6): 1188-1191, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37127275

RESUMO

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.


Assuntos
Cistos , Neurocisticercose , Humanos , Idoso , Adolescente , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/epidemiologia , Estudos Retrospectivos , Espaço Subaracnóideo , População Rural
18.
Pathogens ; 12(11)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-38003778

RESUMO

(1) Background: This study presents the baseline characteristics of a community-level population of people with epilepsy (n = 1975) living in an area endemic for Taenia solium, the pathogen responsible for neurocysticercosis (NCC). (2) Methods: Participants were sequentially enrolled in a clinical cohort from 2007 to 2020 in Tumbes, Peru. All participants provided demographic and clinical history and received clinical evaluations. Diagnostics, including neuroimaging, cysticercosis serologies, and EEG, were obtained where possible. The data presented are from the cross-sectional baseline assessment of cohort participants. (3) Results: Approximately 38% of participants met the criteria for NCC. Those with NCC were more likely to have adult-onset epilepsy, as well as a longer duration of epilepsy, as compared to their counterparts without NCC. Overall, the data indicate a large treatment gap, with only approximately a quarter of the baseline population with prescriptions for anti-seizure medications. (4) Conclusions: These data reveal a high proportion of NCC among people living with epilepsy in these communities, with limited health care resources. At baseline, 74% of the population were not receiving anti-seizure treatments. Further analyses of these data will clarify the natural history of the disease for this population.

19.
Pathogens ; 12(4)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37111451

RESUMO

Monoclonal antibody (mAb)-based enzyme-linked immunosorbent assay (ELISA) is a complementary diagnosis technique for neurocysticercosis (NCC), which detects circulating parasite antigen (Ag) indicative of viable infection and Ag levels that correlate well with the parasite burden. In this study, we compared the performance of two Ag-ELISA techniques for the detection of NCC. We assessed the agreement between our in-house TsW8/TsW5 Ag-ELISA and the widely used B158/B60 Ag-ELISA for measuring T. solium antigen levels in the sera from 113 patients with calcified, parenchymal, and subarachnoid NCC. Concordance was demonstrated evaluating the limits of agreement (LoAs) stratified by the type of NCC. Both ELISA's detected 47/48 (97.8%) subarachnoid NCC cases. In parenchymal and calcified NCC, the B158/B60 Ag-ELISA detected 19/24 (79.2%) and 18/41 (43.9%) cases, while the TsW8/TsW5 Ag-ELISA detected 21/24 (87.5%) and 13/41 (31.7%), respectively. Parenchymal and calcified NCC obtained a perfect agreement (100%), indicating that all sample results were within the predicted LoA, while for subarachnoid NCC, the agreement was 89.6%. The high concordance between the assays was confirmed by Lin's concordance coefficient (LCC = 0.97). Patients with viable parenchymal NCC (LCC = 0.95) obtained the highest concordance between assays, followed by subarachnoid NCC (LCC = 0.93) and calcified NCC (LCC = 0.92). The TsW8/TsW5 Ag-ELISA and B158/B60 Ag-ELISA showed high Ag measurement correlations across diverse types of NCC.

20.
Pathogens ; 13(1)2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38251334

RESUMO

Neurocysticercosis (NCC), the infection of the central nervous system caused by Taenia solium larvae (cysticerci), is a major cause of acquired epilepsy worldwide. Calcification in NCC is the most common neuroimaging finding among individuals with epilepsy in T. solium-endemic areas. We describe the demographic, clinical, and radiological profiles of a large hospital cohort of patients with calcified NCC in Peru (during the period 2012-2022) and compared profiles between patients with and without a previous known diagnosis of viable infection. A total of 524 patients were enrolled (mean age at enrollment: 40.2 ± 15.2 years, mean age at symptom onset: 29.1 ± 16.1 years, 56.3% women). Of those, 415 patients (79.2%) had previous seizures (median time with seizures: 5 years, interquartile range (IQR): 2-13 years; median number of seizures: 7 (IQR: 3-32)), of which 333 (80.2%) had predominantly focal to bilateral tonic-clonic seizures; and 358 (68.3%) used antiseizure medication). Patients had a median number of three calcifications (IQR: 1-7), mostly located in the frontal lobes (79%). In 282 patients (53.8%) there was a previous diagnosis of viable infection, while 242 only had evidence of calcified NCC since their initial neuroimaging. Most patients previously diagnosed with viable infection were male, had previous seizures, had seizures for a longer time, had more calcifications, and had a history of taeniasis more frequently than patients without previously diagnosed viable infection (all p < 0.05). Patients with calcified NCC were heterogeneous regarding burden of infection and clinical manifestations, and individuals who were diagnosed after parasites calcified presented with milder disease manifestations.

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