Active Neurocysticercosis Research Articles

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n = 212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n = 35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p = 0.097), consumed more pork (97.1% vs. 73.6%, p = 0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p = 0.005) than PWE without NCC (n = 177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p = 0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa.

Neurocysticercosis and its impact on crude prevalence rate of epilepsy in an Indian community

Community-based studies of epilepsy in India have reported variable prevalence rates, 5-10/1000 population. Reasons for this wide variation in the prevalence rates are uncertain. Most of the earlier studies had not done appropriate investigations to establish the possible etiology. To study the prevalence and etiological profile of active epilepsy in the rural population of Uttarakhand. In this rural community-based study in the state of Uttarakhand, a door-to-door survey was conducted using validated questionnaire. All the suspected cases of epilepsy were examined by a neurologist to confirm the diagnosis of epilepsy and all the confirmed cases underwent contrast computed tomography (CT) scan and electroencephalography (EEG). Epilepsy and epilepsy syndromes were classified using the classifications proposed by the International League Against Epilepsy. Of the 14,086 population studied, 141 cases of active epilepsy were detected giving a crude prevalence rate of 1%. After clinical evaluation and scanning, 35 (24.8%) were found to have seizure disorder active neurocysticercosis (NCC) and 14 (9.9%) had remote symptomatic seizures related to calcified granuloma. After excluding acute and remote symptomatic cases related to NCC, prevalence rate of epilepsy was 6.5/1000. The study suggests that the region-specific prevalence rates of epilepsy in India are partly dependent on the prevalence of NCC in the given community. To some extent, this may be responsible for variable rates of epilepsy prevalence reported from different regions of the country.

Seizure in people with newly diagnosed active or transitional neurocysticercosis

Purpose The aim of this study is to describe seizure as a presenting symptom in individuals with recently diagnosed neurocysticercosis (NCC). Methods Using logistic regression, we examined the probability of having seizures as a presenting symptom among those with active or transitional NCC by host age and gender, and by number of cysts, location of the cysts in the brain, and phase of evolution of the encysted parasite. Results We found that the odds of having seizures as presenting symptom for those in the youngest age group (3–24 years old) were 12.9 times that of the oldest participants (age 55–82 years) ( p = 0.006). People with cysts in parenchymal locations had a significantly higher odds of seizures compared to those with all their cysts elsewhere (ventricles or subarachnoid) (OR = 6.2, p = 0.028); and the number of cysts was significantly associated with having seizures (OR = 1.1, p = 0.026). Host gender and cyst phase were not significantly associated with having seizures after adjusting for confounders and covariates. Conclusion Children, those with cysts in parenchymal locations, and those with a higher number of cysts appear to be more likely to experience seizure when they have NCC cysts in the active or transitional stage.

PAF64 Evaluation of a cysticidal treatment regime in an Indian population with neurocysticercosis

Aims and ObjectiveTo evaluate efficacy and safety of a specific cysticidal treatment regime in Indian patients with neurocysticercosis (NCC).Materials and MethodsWe prospectively studied patients referred to us at the neurology...

Cognitive impairment and dementia in neurocysticercosis

Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health.

High-dose praziquantel for neurocysticercosis: serum and CSF concentrations

Serum and CSF concentrations of praziquantel were analyzed in 8 patients with active neurocysticercosis aged 35 +/- 16 (mean +/- sd) years, in order to determine factors that may improve the therapeutic ratio. Praziquantel was given orally at 6-h intervals for 10 days at a daily dose of 100 mg/kg. Serum concentrations were determined at 1, 2 and 4 h, and CSF concentrations at 2 h after the morning dose. Peak serum concentrations occurred between 1 and 2 h after administration. There was a trend towards a drop in serum concentration from Days 1 through 5 to 10 of therapy. A fourfold increase in oral dose led to an eightfold rise in serum and CSF concentration, indicating saturation of hepatic metabolism. There were linear correlations (p less than 0.01) between serum and CSF concentrations of praziquantel, indicating free flow across the blood-brain barrier, above an apparent threshold, which may be related to occupation of plasma protein-binding sites. The results indicate that monitoring of serum concentrations may be clinically useful.

Crude antigen from Taenia crassiceps cysticercus used as heterologous antigen in ELISA and in EITB for neurocysticercosis diagnosis of patients from Paraná-Brazil

Neurocysticercosis (NCC), the cerebral presence of Taenia solium metacestode (Cysticercus cellulosae), is responsible for neurological disorders worldwide. In order to validate an immunodiagnosis for public-health patients in the State of Parana-Brazil, crude antigen of Taenia crassicepsmetacestode (Cysticercus longicollis) was used as an alternative heterologous antigen to be used in ELISA and in electroimmunotransfer blotting (EITB) for active and inactive NCC diagnosis. Indirect ELISA was able to discriminate between active and inactive samples and presented high specificity and sensitivity. Any immunodominant band was able to distinguish the NCC stages, although the EITB showed 100% specificity. The immunological results proved to be an important auxiliary toll for NCC diagnosis, mainly for public-health systems in developing countries, where either the neuroimage techniques are not accessible or the resources are scarce.

First case report of pharyngeal cysticercosis

An 86-year-old woman with pharyngeal cysticercosis presented to Victoria Hospital, Cape Town, South Africa in February 2007 with active neurocysticercosis and subcutaneous tissue involvement. Diagnosis was based on clinical, radiological and histopathological grounds. The patient was successfully managed with surgical excision of the oropharyngeal cyst and subsequent chemotherapy with albendazole. This was a rare case of pharyngeal cysticercosis and illustrates that Taenia solium can invade the upper aerodigestive tract. The occurrence of cysticercosis in pharyngeal tissue adds a new dimension to the manifestation of this disease and should alert to more severe generalised disease.

Anticysticercal and antitoxocaral antibodies in people with epilepsy in rural Tanzania

In developing countries, especially Latin America, neurocysticercosis (NCC) is a common cause of epilepsy. Recently, neurotoxocariasis has also been implicated in the pathogenesis of epilepsy. In sub-Saharan Africa data on parasitic disease and epilepsy are scarce. We therefore conducted a study in a rural hospital in northern Tanzania and analysed serum samples for anticysticercal and antitoxocaral antibodies for 40 people with epilepsy (PWE), 20 of whom had confirmed NCC on cranial computed tomography (CT) and 20 healthy individuals. Cerebrospinal fluid (CSF) of 11 PWE with NCC lesions on cranial CT was also investigated. Antibodies were determined using ELISA and Western blot. Six PWE with NCC lesions showed anticysticercal antibodies in serum. Of those, five had active lesions. Anticysticercal antibodies were significantly more frequent in PWE with active NCC than in those with inactive NCC (P<0.01). CSF samples were positive for anticysticercal antibodies in five patients, of whom four had active lesions on cranial CT. Antitoxocaral antibodies were detected in sera of 11 (55%) PWE with NCC lesions, of eight (40%) PWE without lesions on cranial CT and of eight (40%) controls. In our study anticysticercal antibodies in both serum and CSF were associated with active NCC in PWE, whereas there was no relationship between antitoxocaral antibodies and epilepsy.

Taenia solium metacestode immunodominant peptides recognized by IgG antibodies in cerebrospinal fluid and serum paired samples from patients with active and inactive neurocysticercosis

The aim of this study was to test if serological distinction between patients with active and inactive neurocysticercosis (NCC), could be accomplished by the recognition of immunodominant peptides in total saline antigenic extract of Taenia solium metacestodes by IgG antibody in cerebrospinal fluid (CSF) and serum paired samples. CSF and serum samples of 10 each, active NCC patients, inactive NCC, and individuals with other neurological disorders, were used to recognize the antigenic peptides by western blot (WB). In the active NCC the 28-32 and 39-42 kDa peptides were more frequently detected in CSF than in sera (p < 0.05). The 47-52, 64-68, and 70 kDa antigens showed high frequencies in both samples from patients with active NCC. All the CSF samples of inactive NCC and other neurological disorder (control) patients tested negative, while serum samples from these last two groups recognized mainly the 80, 86, 95, and 98 kDa bands. This finding eliminates the use of the high molecular weigh bands (> 80 kDa) for diagnosis of NCC. The final conclusions were that the difference between active and inactive NCC may be done with the detection of peptides only in the CSF samples and that the 47-52, 64-68, and 70 kDa bands may be included as specific markers for active NCC when detected in CSF samples by WB using total saline extract of T. solium metacestode.

Taenia solium metacestode immunodominant peptides recognized by IgG antibodies in cerebrospinal fluid and serum paired samples from patients with active and inactive neurocysticercosis

The aim of this study was to test if serological distinction between patients with active and inactive neurocysticercosis (NCC), could be accomplished by the recognition of immunodominant peptides in total saline antigenic extract of Taenia solium metacestodes by IgG antibody in cerebrospinal fluid (CSF) and serum paired samples. CSF and serum samples of 10 each, active NCC patients, inactive NCC, and individuals with other neurological disorders, were used to recognize the antigenic peptides by western blot (WB). In the active NCC the 28-32 and 39-42 kDa peptides were more frequently detected in CSF than in sera (p < 0.05). The 47-52, 64-68, and 70 kDa antigens showed high frequencies in both samples from patients with active NCC. All the CSF samples of inactive NCC and other neurological disorder (control) patients tested negative, while serum samples from these last two groups recognized mainly the 80, 86, 95, and 98 kDa bands. This finding eliminates the use of the high molecular weigh bands (>or= 80 kDa) for diagnosis of NCC. The final conclusions were that the difference between active and inactive NCC may be done with the detection of peptides only in the CSF samples and that the 47-52, 64-68, and 70 kDa bands may be included as specific markers for active NCC when detected in CSF samples by WB using total saline extract of T. solium metacestode.

Hippocampal sclerosis in association with neurocysticercosis

To discuss the possible mechanisms underlying a dual pathology combining neurocysticercosis and hippocampal atrophy, illustrated by the observation of four patients with epilepsy. The first patient presented at the age of four years with a first episode of status epilepticus, presumably due to an inflamed, calcified, parenchymal cysticercus granuloma. Thereafter, he had occasional seizures. Routine MRI undertaken several years later revealed unilateral hippocampal atrophy and sclerosis. Two other patients with initial imaging evidence of active neurocysticercosis located close to the hippocampus, and occasional seizures, developed ipsilateral hippocampal sclerosis. The seizure disorder of our fourth patient, with medically intractable epilepsy, was initially attributed to a calcified cysticercus granuloma. Clinical description, video-EEG telemetry and imaging work-up suggested a diagnosis of mesial temporal lobe epilepsy due to hippocampal sclerosis. Definitive conclusions as to the underlying mechanisms cannot be derived from the present, retrospective series of only four patients. However, the following suggestions can be made: 1) seizures due to neurocysticercosis may constitute the initial precipitating illness for the development of hippocampal sclerosis, 2) the hippocampus may be involved in host brain inflammation and gliosis in response to a nearby, degenerating cysticercus, 3) the seizure focus formed by the degenerating cysticercus, engenders epileptogenic changes in the hippocampus through kindling, and 4) the two conditions may coexist purely by chance. Systematic and prospective, serial MRI evaluations of hippocampal structures in patients with neurocysticercosis should contribute to further clarify the underlying mechanisms.

Evaluation of recombinant HP6-Tsag, an 18 kDa Taenia saginata oncospheral adhesion protein, for the diagnosis of cysticercosis

With the objective of providing inexpensive and reproducible assays for the detection of antibodies indicating exposure to Taenia saginata and Taenia solium, we have evaluated the diagnostic utility of the T. saginata oncosphere adhesion protein (HP6-Tsag), expressed in baculovirus (HP6-Bac) and bacteria (HP6-GST [glutathione S-transferase]), employing enzyme-linked immunosorbent assays (ELISAs) and sera from T. saginata infected cattle, T. solium infected pigs and serum and cerebrospinal fluid (CSF) samples from clinically defined T. solium neurocysticercosis (NCC) patients. The two recombinant proteins were antigenic in all three systems, with the signal to background ratio of the HP6-Bac ELISA slightly higher than that for the HP6-GST ELISA. Assay performance in cattle was similar to previously described peptide-based ELISA assays, although NCC sample sensitivity/specificity was marginally better. The sensitivity of the HP6-Bac and HP6-GST ELISAs was close for active human NCC (77.4 and 80.6% for serum and 76.9 and 73.1% for CSF samples, respectively). In inactive human NCC, however, the sensitivity of the HP6-Bac ELISA was almost twice that of the HP6-GST ELISA. Because peptides are relatively expensive and recombinant proteins are simple and economical to produce, the latter may provide useful reagents for antibody detection in countries with endemic cysticercosis/NCC.

Feasibility of baculovirus-expressed recombinant 10-kDa antigen in the serodiagnosis of Taenia solium neurocysticercosis

Bacterially expressed recombinant 10-kDa protein of Taenia solium metacestode (TsM) was previously found to be reliable in the diagnosis of active stage neurocysticercosis (NCC) by immunoblotting but not by ELISA. In this study, we evaluated the diagnostic feasibility of detecting eukaryote-expressed recombinant 10-kDa protein of TsM by ELISA (rTsM10-ELISA) in the serum and cerebrospinal fluid (CSF) from NCC patients. In 45 cases of active NCC, 91.1 and 97.8% cases showed positive reactions for serum and CSF by rTsM10-ELISA. ELISA employing the crude cyst fluid antigen (CF-ELISA) also revealed a similar result. Negligible cross-reactions were observed in serum samples from control subjects and from subjects with other helminthic diseases by rTsM10-ELISA (5/139 cases, 3.6%). By contrast, CF-ELISA demonstrated a high degree of cross-reactivity (24/139, 17.3%) especially from those patients with alveolar and cystic echinococcoses. The overall sensitivity and specificity of rTsM10-ELISA were 94.3 and 96.4%; and those of CF-ELISA were 95.7 and 84.5%, for serum and CSF, respectively. Antibody responses to rTsM10 were detected as early as 3 months after experimental infection of T. solium eggs in pigs. Our results show that ELISA with rTsM10 could be highly applicable in the serodiagnosis of NCC from early stage of infection.

Use of the paired samples (cerebrospinal fluid and serum) in immunodiagnostic of active and inactive human neurocysticercosis

Paired samples of cerebrospinal fluid (CSF) and serum of 30 patients--10 with active, 10 with inactive neurocysticercosis (NCC), and 10 control subjects--were evaluated by enzyme-linked immunosorbent assay (ELISA) using two Taenia crassiceps metacestode extracts as antigen in order to detect IgG antibodies. In active NCC, high levels of IgG were detected (p < 0.05). The CSF samples showed 80% (CI 72-88) of reactivity in the saline extract (S) and 90% (CI 84-95) in sodium dodecyl sulphate (SDS) and the serum samples were reactive in 90% (CI 84-95) and 100% (CI 98-100) in the S and SDS antigenic extracts, respectively. The use of the paired samples of CSF and serum in active NCC showed equivalent results suggesting that the serum samples could be used as a screening in those patients whose CSF puncture is counter-indicated.

Antigenic Proteins Associated with Calcareous Corpuscules of Taenia solium: Partial Characterization of a Calcium-Binding Protein

A protein fraction was isolated from calcareous corpuscles of Taenia solium cysticerci. The antigens in this fraction were recognized in ELISA and Western blot assays by all sera from a group of patients with active neurocysticercosis (NC) and were not recognized by the sera from patients with other neurological disorders. Western blot analysis also showed that several high molecular weight proteins were strongly recognized by antibodies in all the neurocysticercotic patient sera, suggesting a potential for serological diagnosis of neurocysticercosis. In order to characterize these antigenic proteins, we used a monoclonal antibody raised against a high MW calcium-binding protein associated with calcareous corpuscles of Echinococcus granulosus (EgCaBP1). Western blot assays revealed the recognition of a protein band of about 260 kDa, appearing within the range of the high MW antigens recognized by the NC sera. Several cDNA clones were isolated through screening of a T. solium metacestode library with a DNA probe for EgCaBP1, containing partial coding sequences showing about 88% identity with the protein of E. granulosus. Moreover, a recombinant product expressed in bacteria from the partial coding sequence of T. solium showed the ability to bind Ca2+ and was recognized by the monoclonal antibody. This recombinant calcium-binding protein of T. solium was not recognized by the NC patient sera by ELISA and Western blot. Antigenic proteins in the calcareous corpuscles of T. solium metacestodes deserve further analysis as candidates in the development of diagnostic tools for neurocysticercosis.

PREVALENCE OF ANTIBODIES TO UNIQUE TAENIA SOLIUM ONCOSPHERE ANTIGENS IN TAENIASIS AND HUMAN AND PORCINE CYSTICERCOSIS

The presence of two oncosphere antigens (OAs) of 22.5 and 31.3 kD in whole and excretory/secretory (ES) OA preparations of both Taenia solium and T. saginata or in antigen preparations from T. solium metacestodes or immature tapeworms was assessed. This included an evaluation of whether antibodies to other cestodes cross-reacted to these OAs. The OAs were present in whole oncosphere extract and E/S antigens of T. solium, but were not present in other stages (immature tapeworm or metacestode) or in OAs of T. saginata. The majority (95%) of T. solium tapeworm carriers had antibodies to these OAs, while only 20% of active neurocysticercosis cases were positive. No antibodies to the OAs were found in healthy controls, subjects infected with Hymenolepis nana, patients with hydatid disease, T. saginata tapeworm carriers, hamsters infected with immature T. solium tapeworms, or dogs infected with Echinococcus granulosus. The OAs are stage and species specific to T. solium and antibodies to OAs are usually present in tapeworm carriers.

SIMILAR DIAGNOSTIC PERFORMANCE FOR NEUROCYSTICERCOSIS OF THREE GLYCOPROTEIN PREPARATIONS FROM TAENIA SOLIUM METACESTODES

The detection of antibodies to Taenia solium metacestodes is very important in the differential diagnosis of neurocysticercosis (NCC). In this study, an electroimmunotransfer blot (EITB) assay that uses an elaborate protocol with metacestode glycoproteins as antigens was compared with two other Western blots that use glycoproteins obtained using simpler methods, including an eluate from a lectin column, or the vesicular fluid (VF) of the parasite. The concordance between the three assays was 91% in patients with active NCC and 100% in patients with suspected NCC and previous documentation of negative serology. The specificities for the Western blots and the EITB assay were 98% and 100%, respectively (98% concordance). These data suggest that the simplest of these immunoassays, the one that uses the VF of T. solium metacestodes in a Western blot format, can be reliably used for the serologic diagnosis of NCC in developing countries where access to the EITB assay is difficult.

Discrimination between active and inactive neurocysticercosis by metacestode excretory/secretory antigens of Taenia solium in an enzyme-linked immunosorbent assay.

To detect IgG antibodies to Taenia solium, a controlled double-blind study was conducted using 91 coded cerebrospinal fluid samples from patients with neurocysticercosis (NCC) and other neurologic disorders. Samples were tested in an enzyme-linked immunosorbent assay (ELISA) using metacestode excretion/secretion antigens. The results were correlated with data from medical records on the diagnosis of NCC (based on computed tomography and magnetic resonance imaging criteria) and other neurologic disorders. The ELISA results were positive in 22 of the 24 cases with active NCC. In contrast, six cases with calcified cysts (inactive NCC), as well as one case in a transitional stage, were negative. One case with a calcified granuloma and another with a granuloma plus calcifications (classified as inactive NCC) had positive results. The remaining negative results corresponded to other neurologic disorders (58 cases). The results of the ELISA showed a significant difference between active and inactive NCC (P = 0.0034).

Taenia solium: identification of specific antibody binding regions of metacestode 10-kDa protein

Taenia solium neurocysticercosis (NCC) represents one of the major public health problems associated with several neurological manifestations worldwide. We previously identified a recombinant 10-kDa protein of T. solium metacestode (CyDA) specific to active NCC. Immunoblottings with sera from active NCC patients and from animals experimentally infected with larval T. solium (pig), T. saginata (pig), T. asiatica (pig), and T. crassiceps (mouse) strongly recognized CyDA, while sera from patients infected only with adult worms did not. Mapping of antigenic sites using deletion mutants revealed that amino acids (aa) residues 30–34, Asn-Met-Thr-Val-Met (NMTVM), reacted only with sera from active stage T. solium cysticercosis cases. Recognition of CyDA aa 30–34 resided almost exclusively in the IgG4 isotype. Competitive immunoprecipitation with synthetic peptides confirmed the specificity of anti-sera for this penta-peptide. These results demonstrated that aa residues NMTVM in CyDA comprise the core sequence for an active stage NCC-related antigenic determinant. Index Descriptors and Abbreviations: Taenia solium metacestode; Cestode; Neurocysticercosis; Specific antigen; Epitope; Larval stage; Genus-/species-specificity; Hydrophobic ligand binding protein; Neurocysticercosis, NCC; T. solium metacestode, TsM; 10-kDa protein of TsM, CyDA; Amino acids, aa; Central nervous system, CNS; Hydrophobic ligand binding protein, HLBP; Cyst fluid, CF; Pooled serum of 10 active NCC patients, serum-pool.