RESUMEN
Neurocysticercosis is one of the main risk factors of seizures and epilepsy in many regions of the world, which are Taenia solium-endemic but resource-constrained to control the parasite. The nosology of seizures and the classification of epilepsy in the context of neurocysticercosis are somewhat uncertain. Many seizures associated with the infection are customarily referred to as "acute symptomatic seizures." The term, however, seems unsuitable. Neither is the condition acute nor does it allow the avoidance of long-term antiseizure medications, as is the case with acute symptomatic seizures, for instance, associated with traumatic brain injury. We propose that seizures be classified according to the evolutionary stage of parenchymal cysticercosis in addition to the conventional classification of seizures and epilepsy and identification of the epileptogenic zone. An often-ignored aspect is the identification of comorbidities, many of which are specific to neurocysticercosis.
Asunto(s)
Epilepsia , Neurocisticercosis , Convulsiones , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico por imagen , Humanos , Convulsiones/etiología , Epilepsia/etiología , Epilepsia/complicaciones , Taenia solium , AnimalesRESUMEN
Transcription regulation in cestodes has been little studied. Here, we characterize the Taenia solium TATA-binding protein (TBP) gene. We found binding sites for transcription factors such as NF1, YY1, and AP-1 in the proximal promoter. We also identified two TATA-like elements in the promoter; however, neither could bind TBP. Additionally, we mapped the transcription start site (A+1) within an initiator and identified a putative downstream promoter element (DPE) located at +27 bp relative to the transcription start site. These two elements are important and functional for gene expression. Moreover, we identified the genes encoding T. solium TBP-Associated Factor 6 (TsTAF6) and 9 (TsTAF9). A Western blot assay revealed that both factors are expressed in the parasite; electrophoretic mobility shift assays and super-shift assays revealed interactions between the DPE probe and TsTAF6-TsTAF9. Finally, we used molecular dynamics simulations to formulate an interaction model among TsTAF6, TsTAF9, and the DPE probe; we stabilized the model with interactions between the histone fold domain pair in TAFs and several pairs of nucleotides in the DPE probe. We discuss novel and interesting features of the TsTAF6-TsTAF9 complex for interaction with DPE on T. solium promoters.
Asunto(s)
Regiones Promotoras Genéticas , Factores Asociados con la Proteína de Unión a TATA , Taenia solium , Animales , Taenia solium/genética , Taenia solium/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Unión Proteica , Sitios de Unión , Proteínas del Helminto/genética , Proteínas del Helminto/metabolismo , Proteína de Unión a TATA-Box/metabolismo , Proteína de Unión a TATA-Box/genética , Sitio de Iniciación de la Transcripción , Simulación de Dinámica Molecular , Regulación de la Expresión GénicaRESUMEN
BACKGROUND: The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood. This study aimed to identify the potential impact of HIV coinfection in CC and NCC patients. METHODOLOGY: A nested study within a cross-sectional analysis in two Tanzanian regions was performed and 234 participants (110 HIV+ and 124 HIV-) were tested for cysticercosis antibodies, antigens, CD4 counts and serum Th1 and Th2 cytokines via multiplex bead-based immunoassay. 127 cysticercosis seropositive individuals underwent cranial computed tomography (CCT) and clinical symptoms were assessed. Multiple regression analyses were performed to identify factors associated with cytokine modulation due to HIV in CC and NCC patients. RESULTS: Serologically, 18.8% tested positive for cysticercosis antibodies, with no significant difference HIV+ and HIV+. A significantly higher rate of cysticercosis antigen positivity was found in HIV+ individuals (43.6%) compared to HIV- (28.2%) (p = 0.016). CCT scans revealed that overall 10.3% had active brain cysts (NCC+). Our study found no significant changes in the overall cytokine profiles between HIV+ and HIV- participants coinfected CC and NCC, except for IL-5 which was elevated in HIV+ individuals with cysticercosis. Furthermore, HIV infection in general was associated with increased levels of pro-and some anti-inflammatory cytokines e.g. TNF-α, IL-8, and IFN-γ. However, based on the interaction analyses, no cytokine changes were observed due to HIV in CC or NCC patients. CONCLUSIONS: In conclusion, while HIV infection itself significantly modulates levels of key cytokines such as TNF-α, IL-8, and IFN-γ, it does not modulate any cytokine changes due to CC or NCC. This underscores the dominant influence of HIV on the immune system and highlights the importance of effective antiretroviral therapy in managing immune responses in individuals coinfected with HIV and CC/NCC.
Asunto(s)
Coinfección , Citocinas , Infecciones por VIH , Neurocisticercosis , Taenia solium , Humanos , Masculino , Neurocisticercosis/inmunología , Neurocisticercosis/complicaciones , Adulto , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Estudios Transversales , Citocinas/sangre , Coinfección/inmunología , Taenia solium/inmunología , Persona de Mediana Edad , Tanzanía/epidemiología , Anticuerpos Antihelmínticos/sangre , Animales , Recuento de Linfocito CD4 , Adulto Joven , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/sangreRESUMEN
BACKGROUND: Geographically targeted Taenia solium ring approaches consisting of treating individuals within a radius of 100-meter of a cysticercosis positive pig have been trialled in Peru. This study explored if a similar approach could be proposed to control T. solium transmission in a post elimination setting in Zambia, focussing on community members' willingness to be sampled and treated. METHODOLOGY AND PRINCIPAL FINDINGS: The study was conducted in a community where elimination of active T. solium transmission was achieved. All eligible pigs and people were sampled, at 4- to 6-monthly intervals, followed by implementation of the ring treatment approach. This implied that whenever a pig was seropositive for cysticercosis during sampling, every human and pig residing in a radius of 50-meters of the seropositive pig would be treated. The results of the positive human stool samples were used to create the rings, whenever no pigs were positive. From June 2018 to October 2019, four samplings, followed by ring treatments were conducted. Between 84% and 91% of the willing people provided a stool sample, covering 46% to 59% of the total population living in the study area. Between 78% and 100% of the eligible pigs got sampled. Three ring treatments were based on porcine seropositivity and one on taeniosis results. Two to four rings were opened per sampling. During the ring treatments, between 89% and 100% of the eligible human and pig population living within a ring was treated. CONCLUSIONS: Participants were willing to participate and get treatment, once the rings were opened. However, the utility of ring treatment approaches in a post elimination setting needs further evaluation, given the lack of highly accurate diagnostic tools for porcine cysticercosis and the challenges in obtaining stool samples. The ring treatment approach adopted should be further improved before recommendations to public health authorities can be given.
Asunto(s)
Cisticercosis , Heces , Enfermedades de los Porcinos , Taenia solium , Animales , Zambia/epidemiología , Taenia solium/aislamiento & purificación , Humanos , Proyectos Piloto , Porcinos , Enfermedades de los Porcinos/transmisión , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/prevención & control , Heces/parasitología , Cisticercosis/transmisión , Cisticercosis/veterinaria , Cisticercosis/prevención & control , Femenino , Masculino , Adulto , Adolescente , Persona de Mediana Edad , Adulto Joven , Teniasis/transmisión , Teniasis/prevención & control , Teniasis/parasitología , Teniasis/veterinaria , Niño , Erradicación de la Enfermedad/métodos , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificaciónRESUMEN
BACKGROUND: Epilepsy poses a significant public health problem in many parts of the world. The majority of people with epilepsy (PWE) are from low-income and middle-income countries (LMICs). Taenia solium neurocysticercosis (NCC) is estimated to cause 30% of preventable epilepsy in PWE in areas of T. solium endemicity. This study was conducted to assess the prevalence of NCC in PWE, evaluate the presence of cognitive impairment in PWE and assess potentially contributing factors. METHODS: PWE were recruited within a mental health clinic-based cross-sectional study in rural Southern Tanzania. PWE underwent a detailed neurological examination, including mental state, and a blood sample was collected for T. solium cysticercosis (CC) serology testing. Patients who were serologically positive for CC and those detected to have prominent neurological deficits apart from epilepsy were invited to receive a cerebral computed tomography (CT) examination. RESULTS: Out of the 223 people with epilepsy (PWE) recruited, 221 underwent clinical examination. Among these, 26 (11.8â¯%) had cognitive impairment, and 2 had neurological signs or symptoms without cognitive impairment. Twenty-five of the 223 PWE (11.2â¯%) tested positive for CC, of which 4 had cognitive impairment. One hundred and ninety-eight (88.8â¯%) tested negative for CC, of which 22 had cognitive impairment. A total of 36 participants underwent CT scans, with 18 testing positive and 18 testing negative for CC. Of the 36 who had CT scans, 8 (22.2â¯%) were diagnosed with NCC; 7 were CC positive, and 1 was CC negative; only the latter had cognitive impairment. Multivariate logistic regression confirmed that cognitive impairment in PWE was 8.62 times higher for Kongwa participants than Chunya, with a statistically significant association (95â¯% CI: 1.75, 156; pâ¯=â¯0.037). Additionally, having and education was associated with a 91â¯% reduction in the odds of cognitive impairment (ORâ¯=â¯0.09) compared to no education, which was also statistically significant (95â¯% CI: 0.01, 0.33; pâ¯=â¯0.002). There was no association between cognitive impairment and NCC. CONCLUSION: Our study found a 22.2â¯% prevalence of NCC among PWE. Cognitive impairment was present in 11.8â¯% of PWE but was not significantly associated with NCC. Socioeconomic and educational factors may play a larger role in cognitive impairment among PWE.
Asunto(s)
Disfunción Cognitiva , Epilepsia , Neurocisticercosis , Población Rural , Taenia solium , Humanos , Neurocisticercosis/epidemiología , Neurocisticercosis/complicaciones , Tanzanía/epidemiología , Epilepsia/epidemiología , Epilepsia/complicaciones , Estudios Transversales , Masculino , Femenino , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Adulto , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Animales , Adulto Joven , Prevalencia , Adolescente , AncianoRESUMEN
We report a case of Taenia solium taeniasis in a 10-year-old child in Timor-Leste, confirmed by molecular analysis, suggesting T. solium transmission to humans is occurring in Timor-Leste. Proactive measures are needed to improve public understanding of prevalence, geographic spread, and health implications of human taeniasis and cysticercosis in Timor-Leste.
Asunto(s)
Taenia solium , Teniasis , Animales , Niño , Humanos , Cisticercosis/parasitología , Cisticercosis/diagnóstico , Taenia solium/genética , Taenia solium/aislamiento & purificación , Teniasis/parasitología , Teniasis/diagnóstico , Timor Oriental/epidemiologíaRESUMEN
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.
Asunto(s)
Antígenos Helmínticos , Ensayo de Inmunoadsorción Enzimática , Sistemas de Atención de Punto , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos Helmínticos/orina , Animales , Cisticercosis/diagnóstico , Cisticercosis/orina , Sensibilidad y Especificidad , Neurocisticercosis/diagnóstico , Neurocisticercosis/orina , Taenia solium/inmunología , Femenino , Masculino , Adulto , NiñoRESUMEN
Human cysticercosis caused by Taenia soliun (T. soliun) is endemic in certain areas of Latin America, Asia and Sub-Saharan Africa. Neurocysticercosis (NCC) is mainly diagnosed by neuroimaging, which, in most cases, is unavailable in endemic areas. Due to their high sensitivity and specificity, serological tests such as enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) based on the glycosylated fraction of the cyst CS50 are widely used for the detection of the anti-cysticercus IgG antibodies despite their significant cost and the need of cysticercus material. Given their cost-effectivess and simplicity, immunoassays based on recombinant proteins could provide new alternatives for human cysticercosis diagnosis: such tests would be aimed at screening those people living in remote areas who need further examination. To date, however, no test using recombinant antigens is commercially available. Herein, five recombinant proteins (R14, R18, R93.1, R914.1, and R915.2) were produced, three of which (R93.1, R914.1, and R915.2) were newly identified from the cyst fluid. Evaluation of the diagnostic performance of these recombinant antigens by ELISA was done using sera from 200 epileptic and non-epileptic individuals in comparison with the WB-CS50 as the reference serological method. Recombinant proteins-based ELISA showed a level of diagnostic performance that is inferior than the reference serological method, but similar to that of the native antigen ELISA for human cysticercosis (commonly used for screening). Further optimization of expression conditions is still needed in order to improve proteins solubility and enhance diagnostic performance for human cysticercosis detection. However, this preliminary evaluation of the recombinant antigens has shown their potential valuable use for screening cysticercosis in patients with epilepsy attending dispensaries in remote areas. Future studies should be conducted to evaluate our recombinant antigens in a large group of patients with different stages of NCC, and in correlation with imaging findings.
Asunto(s)
Anticuerpos Antihelmínticos , Antígenos Helmínticos , Western Blotting , Cisticercosis , Ensayo de Inmunoadsorción Enzimática , Proteínas Recombinantes , Sensibilidad y Especificidad , Taenia solium , Humanos , Proteínas Recombinantes/inmunología , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/genética , Cisticercosis/diagnóstico , Animales , Taenia solium/inmunología , Taenia solium/genética , Anticuerpos Antihelmínticos/sangre , Inmunoglobulina G/sangre , Neurocisticercosis/diagnóstico , Neurocisticercosis/inmunología , Epilepsia/diagnóstico , Adulto , Masculino , Pruebas Serológicas/métodos , FemeninoRESUMEN
BACKGROUND: This study aimed at describing the epidemiology of (neuro)cysticercosis as well as its clinical and radiological characteristics in a Taenia solium endemic district of Zambia. METHODS: This was part of a cross-sectional community-based study conducted in Sinda district to evaluate an antibody-detecting T. solium point-of-care (TS POC) test for taeniosis and (neuro)cysticercosis. All TS POC cysticercosis positive (CC+) participants and a subset of the TS POC cysticercosis negative (CC-) received a clinical evaluation and cerebral computed tomography (CT) examination for neurocysticercosis (NCC) diagnosis and staging. RESULTS: Of the 1249 participants with a valid TS POC test result, 177 (14%) were TS POC CC+ . Cysticercosis sero-prevalence was estimated to be 20.1% (95% confidence intervals [CI] 14.6-27.0%). In total, 233 participants received a CT examination (151 TS POC CC+ , 82 TS POC CC-). Typical NCC lesions were present in 35/151 (23%) TS POC CC+ , and in 10/82 (12%) TS POC CC- participants. NCC prevalence was 13.5% (95% CI 8.4-21.1%) in the study population and 38.0% (95% CI 5.2-87.4%) among people reporting epileptic seizures. Participants with NCC were more likely to experience epileptic seizures (OR = 3.98, 95% CI 1.34-11.78, p = 0.01) than those without NCC, although only 7/45 (16%) people with NCC ever experienced epileptic seizures. The number of lesions did not differ by TS POC CC status (median: 3 [IQR 1-6] versus 2.5 [IQR 1-5.3], p = 0.64). Eight (23%) of the 35 TS POC CC+ participants with NCC had active stage lesions; in contrast none of the TS POC CC- participants was diagnosed with active NCC. CONCLUSION: NCC is common in communities in the Eastern province of Zambia, but a large proportion of people remain asymptomatic.
Asunto(s)
Neurocisticercosis , Humanos , Zambia/epidemiología , Neurocisticercosis/epidemiología , Neurocisticercosis/diagnóstico , Estudios Transversales , Masculino , Femenino , Prevalencia , Adulto , Adolescente , Persona de Mediana Edad , Animales , Adulto Joven , Niño , Taenia solium/aislamiento & purificación , Tomografía Computarizada por Rayos X , PreescolarRESUMEN
Neurocysticercosis (NCC), a major cause of global acquired epilepsy, results from Taenia solium larval brain infection. T. solium adult worms release large numbers of infective eggs into the environment contributing to high levels of exposure in endemic areas. This study identifies T. solium proteins in the sera of individuals with and without NCC using mass spectrometry to examine exposure in endemic regions. Forty-seven patients (18-51 years), 24 parenchymal NCC (pNCC), 8 epilepsy of unknown aetiology, 7 glioma, 8 brain tuberculoma, and 7 healthy volunteers were studied. Trypsin digested sera were subject to liquid chromatography-tandem mass spectrometry and spectra of 375-1700 m/z matched against T. solium WormBase ParaSite database with MaxQuant software to identify T. solium proteins. Three hundred and nineteen T. solium proteins were identified in 87.5% of pNCC and 56.6% of non-NCC subjects. Three hundred and four proteins were exclusive to pNCC sera, seven to non-NCC sera and eight in both. Ten percent, exhibiting immune-modulatory properties, originated from the oncosphere and cyst vesicular fluid. In conclusion, in endemic regions, T. solium proteins are detected in sera of individuals with and without pNCC. The immunomodulatory nature of these proteins may influence susceptibility and course of infection.
Asunto(s)
Proteínas del Helminto , Neurocisticercosis , Taenia solium , Humanos , Neurocisticercosis/sangre , Neurocisticercosis/parasitología , Taenia solium/inmunología , Adulto , Adolescente , Animales , Persona de Mediana Edad , Adulto Joven , Masculino , Femenino , Proteínas del Helminto/sangre , Cromatografía Liquida , Espectrometría de Masas en Tándem , Espectrometría de Masas , Suero/químicaRESUMEN
BACKGROUND: Porcine cysticercosis, a serious zoonotic parasitic disease, is caused by the larvae of Taenia solium and has been acknowledged by the World Organization for Animal Health. The current detection methods of Cysticercus cellulosae cannot meet the needs of large-scale and rapid detection in the field. We hypothesized that the immunofluorescence chromatography test strip (ICS) for detecting Cysticercus cellulosae, according to optimization of a series of reaction systems was conducted, and sensitivity, specificity, and stability testing, and was finally compared with ELISA. This method utilizes Eu3+-labeled time-resolved fluorescent microspheres (TRFM) coupled with TSOL18 antigen to detect TSOL18 antibodies in infected pig sera. RESULTS: ICS and autopsy have highly consistent diagnostic results (n = 133), as determined by Cohen's κ analysis (κ = 0.925). And the results showed that the proposed ICS are high sensitivity (0.9459) with specificity (0.9792). The ICS was unable to detect positive samples of other parasites. It can be stored for at least six months at 4â. CONCLUSIONS: In summary, we established a TRFM-ICS method with higher sensitivity and specificity than indirect ELISA. Results obtained from serum samples can be read within 10 min, indicating a rapid, user-friendly test suitable for large-scale field detection.
Asunto(s)
Anticuerpos Antihelmínticos , Antígenos Helmínticos , Cisticercosis , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente , Sensibilidad y Especificidad , Enfermedades de los Porcinos , Animales , Porcinos , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/sangre , Cisticercosis/veterinaria , Cisticercosis/diagnóstico , Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/sangre , Antígenos Helmínticos/inmunología , Técnica del Anticuerpo Fluorescente/veterinaria , Técnica del Anticuerpo Fluorescente/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Ensayo de Inmunoadsorción Enzimática/métodos , Cysticercus/inmunología , Taenia solium/inmunologíaRESUMEN
Taenia solium is a widespread zoonotic tapeworm that predominantly affects regions of Latin America, South and South-East Asia, and Sub-Saharan Africa. Neurocysticercosis (NCC), the presence of T. solium cysts in the brain is associated with diverse clinical manifestations, such as epilepsy, seizures, and neurological deficits. It is a significant cause of preventable epilepsy globally, accounting for approximately 30% of cases in endemic regions. The diagnosis of neurocysticercosis relies on neuroimaging techniques, but these resources are often limited in low-income countries, resulting in an underestimation of the disease burden. The present study enrolled 141 patients who were clinically suspected and radiologically confirmed for NCC at the Neurology OPD of PGIMER, Chandigarh. Additionally, 98 control subjects attending the PGIMER OPD for investigation were also included. Plasma and urine samples were collected from all participants for further analysis. Cell-free DNA extraction was performed using specific kits, and the quality of the extracted DNA was assessed. The RT-LAMP assay targeted the cox1 gene. Real-time RT-LAMP results were evaluated using a fluorescence graph obtained with the Genei III fluorimeter. Among a group of patients diagnosed with NCC, the gene was identified in 74.4% of plasma samples and 67.3% of urine samples. In comparison, the T. solium cox1 gene was found in 6.1% of control subjects in plasma and urine samples using the LAMP assay. In conclusion, the study emphasises the need for improved diagnostic methods for NCC and presents promising alternatives, such as RT-LAMP and urine-based cell-free DNA analysis. These approaches offer advantages in terms of cost-effectiveness, simplicity, and diagnostic accuracy.
Asunto(s)
Biomarcadores , Ácidos Nucleicos Libres de Células , Neurocisticercosis , Humanos , Neurocisticercosis/diagnóstico , Neurocisticercosis/sangre , Neurocisticercosis/genética , Masculino , Femenino , Adulto , Biomarcadores/sangre , Persona de Mediana Edad , Ácidos Nucleicos Libres de Células/sangre , Adulto Joven , Taenia solium/genética , Taenia solium/aislamiento & purificación , Adolescente , Técnicas de Diagnóstico Molecular/métodosRESUMEN
Neurocysticercosis is the leading cause for acquired epilepsy worldwide, and it is caused by the larval stage of the parasite Taenia solium. Several proteins of this stage have been characterized and studied to understand the parasite-host interaction, however, the proteins from the early cysticercus stages (the postoncospheral form) have not yet been characterized. The study of the postoncospheral form proteins is important to understand the host-parasite relationship in the early stages of infection. The aim of this work was to identify postoncospheral form antigenic proteins using sera from neurocysticercosis patients. T. solium activated oncospheres were cultured in HCT-8 cells to obtain the postoncospheral form. Soluble total and excretory/secretory proteins were obtained from the postoncospheral form and were incubated with both pool sera and individual serum of neurocysticercosis positive human patients. Immunoblotting showed target antigenic proteins with apparent molecular weights of 23â¯kDa and 46-48â¯kDa. The 46-48â¯kDa antigen bands present in soluble total and excretory/secretory postoncospheral form proteins were analyzed by LC-MS/MS; proteins identified were: nuclear elongation factor 1 alpha, enolase, unnamed protein product/antigen diagnostic GP50, calcium binding protein calreticulin precursor and annexin. The postoncospheral form expresses proteins related to interaction with the host, some of these proteins are predicted to be exosomal proteins. In conclusion, postoncospheral proteins are consistent targets of the humoral immune response in human and may serve as targets for diagnosis and vaccines.
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Antígenos Helmínticos , Proteínas del Helminto , Neurocisticercosis , Taenia solium , Taenia solium/inmunología , Taenia solium/genética , Antígenos Helmínticos/inmunología , Animales , Humanos , Neurocisticercosis/inmunología , Neurocisticercosis/parasitología , Neurocisticercosis/diagnóstico , Proteínas del Helminto/inmunología , Proteínas del Helminto/genética , Proteínas del Helminto/química , Espectrometría de Masas en Tándem , Anticuerpos Antihelmínticos/sangre , Anticuerpos Antihelmínticos/inmunología , Cromatografía Liquida , Peso MolecularRESUMEN
The excretory-secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30-150-nm-sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto-lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV-treated macrophages. Due to this, both macro-autophagy and caspase-linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT-mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV-mediated immune suppression revealed that the EV can protect the mice from DSS-induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential.
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Colitis , Vesículas Extracelulares , Diana Mecanicista del Complejo 1 de la Rapamicina , Proteínas Proto-Oncogénicas c-akt , Taenia solium , Animales , Ratones , Apoptosis , Colitis/metabolismo , Colitis/parasitología , Sulfato de Dextran , Modelos Animales de Enfermedad , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismo , Macrófagos/parasitología , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Neurocisticercosis/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Taenia solium/metabolismoRESUMEN
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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Neurocisticercosis , Espacio Subaracnoideo , Taenia solium , Animales , Taenia solium/genética , Neurocisticercosis/parasitología , Neurocisticercosis/genética , Espacio Subaracnoideo/metabolismo , Humanos , Perfilación de la Expresión Génica , Transcriptoma , Proliferación Celular , Quistes/genética , Quistes/parasitología , Quistes/metabolismoRESUMEN
The pork tapeworm Taenia solium causes human taeniasis and cysticercosis when ingested as viable cysts and eggs, respectively. Despite its high health burden in low-income countries, knowledge of the parasite in endemic areas such as Rwanda is often limited. Here, we assess whether The Vicious Worm education software can increase knowledge in endemic areas of Rwanda. A cross-sectional mixed-methods study was conducted to evaluate knowledge about T. solium among community health workers trained using the Vicious Worm education software. Knowledge was assessed before, immediately after, and four weeks after the training. The health workers perceptions of the software were analysed thematically. A total of 207 community health workers were recruited from Nyamagabe district in Southern Province, Rwanda. Participants were composed of males (33.5%) and females (66.5%), aged between 22 and 68 years, and most (71%) had only completed primary education. Knowledge of cysticercosis at baseline was low, particularly knowledge of human cysticercosis and neurocysticercosis. The overall knowledge score increased significantly after training and was maintained four weeks after the training. Overall, insufficient knowledge was associated with neurocysticercosis-related questions, which after the training, remained relatively lower compared to questions of other categories. Participants reported the software to be user-friendly and educational. Digital illiteracy and the lack of smartphones were among the critical challenges highlighted in responses. This study has shown gaps in knowledge regarding T. solium infections within rural Rwanda, particularly neurocysticercosis. Health education using the Vicious Worm education software should be considered in integrated control programs.
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Agentes Comunitarios de Salud , Cisticercosis , Conocimientos, Actitudes y Práctica en Salud , Taenia solium , Humanos , Agentes Comunitarios de Salud/educación , Adulto , Animales , Rwanda/epidemiología , Femenino , Masculino , Taenia solium/aislamiento & purificación , Estudios Transversales , Cisticercosis/epidemiología , Cisticercosis/prevención & control , Cisticercosis/parasitología , Persona de Mediana Edad , Adulto Joven , Anciano , Educación en Salud/métodos , Programas InformáticosRESUMEN
Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after in vivo treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with T. crassiceps cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.
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Bencimidazoles , Encéfalo , Ratones Endogámicos BALB C , Neurocisticercosis , Nitrocompuestos , Tiazoles , Animales , Neurocisticercosis/tratamiento farmacológico , Neurocisticercosis/patología , Ratones , Tiazoles/uso terapéutico , Tiazoles/farmacología , Tiazoles/administración & dosificación , Nitrocompuestos/uso terapéutico , Bencimidazoles/uso terapéutico , Bencimidazoles/farmacología , Encéfalo/parasitología , Encéfalo/patología , Femenino , Quimioterapia Combinada , Antiinflamatorios/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antihelmínticos/uso terapéutico , Antihelmínticos/farmacología , Antihelmínticos/administración & dosificación , Taenia solium/efectos de los fármacosAsunto(s)
Cisticercosis , Enfermedades de los Porcinos , Taenia solium , Animales , Cisticercosis/veterinaria , Cisticercosis/epidemiología , Cisticercosis/parasitología , Taenia solium/aislamiento & purificación , Enfermedades de los Porcinos/parasitología , Enfermedades de los Porcinos/epidemiología , Porcinos , Humanos , PrevalenciaRESUMEN
BACKGROUND: Antigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA. METHODS: We report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland-Altman (BA) analysis and Lin's concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA. RESULTS: The TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin's CCC: 0.69, 0.92, and 0.96, respectively, all P < 0.001). In pigs infected with T. hydatigena, almost all paired log-OD differences were within the LoA in the BA analysis, whereas the concordance of log-ODs between assays was low at baseline (Lin's CCC: 0.24) but increased on days 28 and 90 PI (Lins' CCC: 0.88 and 0.98, P < 0.001). CONCLUSIONS/SIGNIFICANCE: The TsW8/TsW5 Ag-ELISA recognizes antigens in pigs with T. solium cysticercosis and is highly concordant with the B158/B60 Ag-ELISA. However, its diagnostic use is hampered by cross-reactions with T. hydatigena, as in other mAb-based Ag-ELISAs.
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Cisticercosis , Quistes , Enfermedades de los Porcinos , Taenia solium , Taenia , Animales , Humanos , Porcinos , Cysticercus , Anticuerpos Monoclonales , Enfermedades de los Porcinos/diagnóstico , Cisticercosis/veterinaria , Ensayo de Inmunoadsorción Enzimática/veterinaria , Antígenos , Antígenos Helmínticos , Anticuerpos AntihelmínticosRESUMEN
Neurocysticercosis, a parasitic infection of the central nervous system (CNS), is a significant public health issue globally, including in Brazil. This article presents a case report of a 44-year-old male patient residing in the rural area of Roraima, the northernmost region of Brazil within the Amazon Forest. The patient, with chronic HIV infection, acquired the Taenia solium helminth, resulting in neurocysticercosis development. Remarkably, the diagnosis of neurocysticercosis was not initially apparent but emerged through meticulous analysis following a motorcycle accident. The absence of seizures, a common clinical manifestation, complicated the diagnostic process, making it an uncommon case of NCC, which may be related to co-infection. As the patient's condition progressed, multiple complications arose, requiring additional medical attention and interventions. This case underscores the immense challenges faced by healthcare teams in managing neurocysticercosis effectively. It emphasizes the critical need for a comprehensive, multidisciplinary approach to provide optimal care for such complex cases. The study's findings underscore the importance of raising awareness and implementing improved strategies for tackling neurocysticercosis, particularly in regions where it remains a prevalent concern.