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In the past 50 years, enormous progress has been made in the diagnosis, treatment and control of taeniid cestode infections/diseases and in the scientific understanding thereof. Most interest in this group of parasites stems from the serious diseases that they cause in humans. It is through this lens that we summarize here the most important breakthroughs that have made a difference to the treatment of human diseases caused by these parasites, reduction in transmission of the taeniid species associated with human disease, or understanding of the parasites’ biology likely to impact diagnosis or treatment in the foreseeable future. Key topics discussed are the introduction of anti-cestode drugs, including benzimidazoles and praziquantel, and the development of new imaging modalities that have transformed the diagnosis and post-treatment monitoring of human echinococcoses and neurocysticercosis. The availability of new anti-cestode drugs for use in dogs and a detailed understanding of the transmission dynamics of Echinococcus granulosus sensu lato have underpinned successful programs that have eliminated cystic echinococcosis in some areas of the world and greatly reduced the incidence of infection in others. Despite these successes, cystic and alveolar echinococcosis and neurocysticercosis continue to be prevalent in many parts of the world, requiring new or renewed efforts to prevent the associated taeniid infections. Major advances made in the development of practical vaccines against E. granulosus and Taenia solium will hopefully assist in this endeavour, as might the understanding of the parasites’ biology that have come from an elucidation of the nuclear genomes of each of the most important taeniid species causing human diseases.

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.

The diagnosis of neurocysticercosis (NCC) is principally based on neuroimaging (magnetic resonance imaging or computed tomography), instrumentation that is scarcely available in the rural regions where Taenia solium transmission, primarily occurs due to poor sanitation conditions. Immunological assays for antigen or antibody detection complement the neuroimaging approach. However, no field-applicable assays to diagnose viable NCC or to guide the referral of cases for neuroimaging or for appropriate management are available. We performed an exploratory study on urine and serum samples using 1H-nuclear magnetic resonance (NMR)-based metabolomics to discriminate NCC patients (n = 14) from healthy control subjects (n = 22). Metabolic profiles demonstrated a discrimination between the urines of NCC patients and noninfected control subjects with a moderate predictive accuracy (R2 = 0.999, Q2 = 0.434). NMR metabolomics analysis has been proven useful in depicting biomarkers linked to other infectious diseases, various types of cancer, and other disorders. Our results, albeit preliminary, open a door to the development of better methods for detecting NCC through the identification of biomarkers participating in disturbed metabolic pathways.

Background Antigen tests for diagnosis and disease monitoring in some types of neurocysticercosis (NCC) are useful but access to testing has been limited by availability of proprietary reagents and/or kits. Methods/Principal findings Three previously identified IgM-secreting hybridomas whose IgM products demonstrated specificity to Taenia solium underwent variable heavy and light chain sequencing and isotype conversion to mouse IgG. Screening of these recombinantly expressed IgG anti-Ts hybridomas, identified one (TsG10) with the highest affinity to crude Taenia antigen. TsG10 was then used as a capture antibody in a sandwich antigen detection immunoassay in combination with either a high titer polyclonal anti-Ts antibody or with biotinylated TsG10 (termed TsG10*bt). Using serum, plasma, and CSF samples from patients with active NCC and those from NCC-uninfected patients, ROC curve analyses demonstrated that the TsG10-TsG10-*bt assay achieved a 98% sensitivity and 100% specificity in detecting samples known to be antigen positive and outperformed the polyclonal based assay (sensitivity of 93% with 100% specificity). By comparing levels of Ts antigen (Ag) in paired CSF (n = 10) or plasma/serum (n = 19) samples from well-characterized patients with extra-parenchymal NCC early in infection and at the time of definitive cure, all but 2 (1 from CSF and 1 from plasma) became undetectable. There was a high degree of correlation (r = 0.98) between the Ag levels detected by this new assay and levels found by a commercial assay. Pilot studies indicate that this antigen can be detected in the urine of patients with active NCC. Conclusions/Significance A newly developed recombinant monoclonal antibody-based Ts Ag detection immunoassay is extremely sensitive in the detection of extra-parenchymal NCC and can be used to monitor the success of treatment in the CSF, serum/plasma and urine. The ability to produce recombinant TsG10 at scale should enable use of this antigen detection immunoassay wherever NCC is endemic. Clinical Trial Registration ClinicalTrials.gov Identifiers: NCT00001205 - & NCT00001645.

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.

Neurocysticercosis (NCC), the infection of the nervous system by the cystic larvae of Taenia solium, is a highly pleomorphic disease because of differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response. Most patients with parenchymal brain NCC present with few lesions and a relatively benign clinical course, but massive forms of parenchymal NCC can carry a poor prognosis if not well recognized and inappropriately managed. We present the main presentations of massive parenchymal NCC and their differential characteristics.

Purpose of review This article reviews how parasites affect the human nervous system, with a focus on four parasitic infections of major public health importance worldwide, two caused by protozoa (malaria and toxoplasmosis) and two by helminths (neurocysticercosis and schistosomiasis). Recent findings Parasitic infections in humans are common, and many can affect the central nervous system where they may survive unnoticed or may cause significant pathology that can even lead to the death of the host. Neuroparasitoses should be considered in the differential diagnosis of neurologic lesions, particularly in individuals from endemic regions or those with a history of travel to endemic regions. Summary Cerebral malaria is a significant cause of mortality, particularly in African children, in whom infected red blood cells affect the cerebral vessels, causing severe encephalopathy. Neurocysticercosis is the most common cause of acquired epilepsy worldwide and has varied clinical presentations, depending on the number, size, and location of the parasites in the nervous system as well as on the host's inflammatory response. Toxoplasmosis is distributed worldwide, affecting a significant proportion of the population, and may reactivate in patients who are immunosuppressed, causing encephalitis and focal abscesses. Schistosomiasis causes granulomatous lesions in the brain or the spinal cord.

Background The pork tapeworm (Taenia solium) is a parasitic helminth that imposes a major health and economic burden on poor rural populations around the world. As recognized by the World Health Organization, a key barrier for achieving control of T. solium is the lack of an accurate and validated simulation model with which to study transmission and evaluate available control and elimination strategies. CystiAgent is a spatially-explicit agent based model for T. solium that is unique among T. solium models in its ability to represent key spatial and environmental features of transmission and simulate spatially targeted interventions, such as ring strategy. Methods/Principal findings We validated CystiAgent against results from the Ring Strategy Trial (RST)–a large cluster-randomized trial conducted in northern Peru that evaluated six unique interventions for T. solium control in 23 villages. For the validation, each intervention strategy was replicated in CystiAgent, and the simulated prevalences of human taeniasis, porcine cysticercosis, and porcine seroincidence were compared against prevalence estimates from the trial. Results showed that CystiAgent produced declines in transmission in response to each of the six intervention strategies, but overestimated the effect of interventions in the majority of villages; simulated prevalences for human taenasis and porcine cysticercosis at the end of the trial were a median of 0.53 and 5.0 percentages points less than prevalence observed at the end of the trial, respectively. Conclusions/Significance The validation of CystiAgent represented an important step towards developing an accurate and reliable T. solium transmission model that can be deployed to fill critical gaps in our understanding of T. solium transmission and control. To improve model accuracy, future versions would benefit from improved data on pig immunity and resistance, field effectiveness of anti-helminthic treatment, and factors driving spatial clustering of T. solium infections including dispersion and contact with T. solium eggs in the environment., Author summary Neurocysticercosis, caused by the ingestion of Taenia solium eggs, is a major cause of human epilepsy around the world. A wide spectrum of tools to fight T. solium is are now available and include antiparasitic treatment for pigs and humans, porcine vaccines, and sanitation improvements; however, the ideal combination of interventions applied to populations to maximize effectiveness and feasibility is not known. Transmission models are one tool that can be used to compare and evaluate different intervention strategies, but no currently available T. solium models have been tested for accuracy. In this research, we validated our model (“CystiAgent”) by comparing simulations of the model to the results of a large-scale trial testing a variety of T. solium control interventions. The model was calibrated using observed epidemiological data from these villages and evaluated for its ability to reproduce the effect of T. solium control interventions. The validation showed that the model was able to reproduce the baseline levels of disease, but generally overestimated the effect that each intervention would have on transmission. These results will allow us to identify limitations of the current model to improve future versions, and represent a step forward in the creation of a tool to design and evaluate future programs to control and eliminate T. solium.

BACKGROUND Subarachnoid neurocysticercosis (NCC) is associated with high morbidity and mortality rates. Conventional transcranial approaches and transventricular endoscopy have been previously reported for extraparenchymal NCC and ventricular NCC, respectively. By October 2019, endonasal endoscopic approaches had not been used for the treatment of NCC. OBSERVATIONS A 54-year-old-woman with NCC was admitted with acute neurological deterioration due to severe intracranial hypertension caused by massive subarachnoid NCC cysts, as evidenced on magnetic resonance imaging (MRI) with great brainstem compression. The case was discussed, and an endoscopic endonasal resection of the NCC cysts was scheduled. The diagnosis was confirmed by pathological anatomy. There were no complications in the surgery, with marked neurological improvement. Control MRIs demonstrated a significant reduction of NCC cysts. LESSONS Minimally invasive approaches are an excellent alternative for skull-base tumoral and infectious pathology. Prior knowledge of the pathophysiology and the authors’ experience in the management of patients with NCC allowed them to propose this approach, with optimal results.

BACKGROUND Neurocysticercosis, caused by the larval stage of Taenia solium, affects the cerebral ventricles in 20–30% of cases and may lead to hydrocephalus and other neurological morbidity. Conventional treatment for cysts in the 4th ventricle includes open surgery (suboccipital approach) and neuroendoscopy, with the latter being the option of choice. Stereotactic surgery, minimally invasive, offers a good alternative for this type of deep lesion. OBSERVATIONS The authors report the cases of two women, 30 and 45 years old, who presented with headache, dizziness, and ataxia and were diagnosed with 4th ventricle cysticercosis. Magnetic resonance imaging (MRI) revealed dilated 4th ventricles (approximately 2.5 cm in both cases, with cystic images inside the ventricular cavity). Both patients were treated with stereotactic surgery via a suboccipital transcerebellar approach. Cyst material was extracted, and the diagnosis was confirmed by pathological examination. The surgeries had no complications and resulted in clinical improvement. Control MRI scans showed reduction of the volume of the ventricle without residual cysts. LESSONS Minimally invasive stereotactic surgery provided a safe alternative for 4th ventricle neurocysticercosis cysts, with more benefits than risks in comparison with conventional techniques.

Objectives Neurocysticercosis (NCC) and human immunodeficiency virus (HIV) have 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 anti-retroviral 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.

Neurocysticercosis is endemic in most of the world and in endemic areas it accounts for approximately 30% of cases of epilepsy. Appropriate diagnosis and management of neurocysticercosis requires understanding the diverse presentations of the disease since these will vary in regards to clinical manifestation, sensitivity of diagnostic tests, and most importantly, therapeutic approach. This review attempts to familiarize tropical neurology practitioners with the diverse types of neurocysticercosis and the more appropriate management approaches for each.

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.

Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood–brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2). Also, two markers for BBB disruption, the endothelial barrier antigen and immunoglobulin G, were evaluated using immunohistochemical and immunofluorescence techniques. Brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. Both VEGF-A and FGF2 were overexpressed in the tissue surrounding the cysticerci, and VEGF-A was overexpressed in astrocytes. Vessels showed decreased immunoreactivity to endothelial barrier antigen marker and an extensive staining for IgG was found in the tissues surrounding the cysts. Additionally, an endothelial cell tube formation assay using human umbilical vein endothelial cells showed that excretory and secretory antigens of T. solium cysticerci induce the formation of these tubes. This in vitro model supports the hypothesis that angiogenesis in NCC might be caused by the parasite itself, as opposed to the host inflammatory responses alone. In conclusion, brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. This study also demonstrates that cysticerci excretory-secretory processes alone can stimulate angiogenesis. © 2018 Wiley Periodicals, Inc.

Background The parasite Taenia solium causes neurocysticercosis (NCC) in humans and is a common cause of adult-onset epilepsy in the developing world. Hippocampal atrophy, which occurs far from the cyst, is an emerging new complication of NCC. Evaluation of molecular pathways in brain regions close to and distant from the cyst could offer insight into this pathology. Methods Rats were inoculated intracranially with T. solium oncospheres. After 4 months, RNA was extracted from brain tissue samples in rats with NCC and uninfected controls, and cDNA was generated. Expression of 38 genes related to different molecular pathways involved in the inflammatory response and healing was assessed by RT-PCR array. Results Inflammatory cytokines IFN-γ, TNF-α, and IL-1, together with TGF-β and ARG-1, were overexpressed in tissue close to the parasite compared to non-infected tissue. Genes for IL-1A, CSF-1, FN-1, COL-3A1, and MMP-2 were overexpressed in contralateral tissue compared to non-infected tissue. Conclusions The viable cysticerci in the rat model for NCC is characterized by increased expression of genes associated with a proinflammatory response and fibrosis-related proteins, which may mediate the chronic state of infection. These pathways appear to influence regions far from the cyst, which may explain the emerging association between NCC and hippocampal atrophy., Author summary Taenia solium is a parasite that can infect human brain causing neurocysticercosis. Neurocysticercosis is a common cause of adult-onset epilepsy in the developing world. This infection elicits several cellular and molecular changes as a result of inflammation or parasite-host interaction, which can cause clinical symptoms, such as seizures. Most of these changes have been found in the tissue surrounding to the cysticercus, however, some pathologies, like hippocampal atrophy, which occurs in parts of the brain far from the cyst, are emerging as new complication in NCC patients. Using a rat model, the authors assessed the expression of genes related to different molecular pathways involved in the inflammatory response and healing by the RT-PCR array technique. They found increased expression of genes associated with inflammation and scar tissue formation in tissue surrounding the cyst, as well as tissue far from the cyst, when compared to non-infected brain tissue. This study provides new insights into the inflammatory changes that occur in brain tissue far from viable cysts and may provide evidence for the emerging association between NCC and hippocampal atrophy.

Between 1930 and 1960, 450 British soldiers who were being assessed for epilepsy and other neurological disease after returning from duty in India were found to be affected by neurocysticercosis (NCC), the infection of the human nervous system by the cystic larvae of the pork tapeworm Taenia solium. This unexpectedly frequent finding brought attention to a globally common but yet poorly known disease. Introduction of the computed tomography scan in the 1970s substantially improved the premortem diagnosis of NCC and slowly began to unveil the scope of the problem. T solium is now known to be endemic in wide areas of the world, including Latin America, sub-Saharan Africa, Eastern Europe, and parts of Asia, including the Indian subcontinent, Southeast Asia, and large regions of China. Endemicity of T solium is deeply rooted in poverty and involves domestic pig raising and poor sanitary conditions. As such, the burden of neurologic disease associated with continued transmission falls mainly on impoverished rural populations. However, NCC cases are diagnosed worldwide, even where transmission is not endemic...

Racemose neurocysticercosis is an aggressive disease caused by the aberrant expansion of the cyst form of Taenia solium within the subarachnoid spaces of the human brain and spinal cord resulting in a mass effect and chronic inflammation. Although expansion is likely caused by the proliferation and growth of the parasite bladder wall, there is little direct evidence of the mechanisms that underlie these processes. Since the development and growth of cysts in related cestodes involves totipotential germinative cells, we hypothesized that the expansive growth of the racemose larvae is organized and maintained by germinative cells. Here, we identified proliferative cells expressing the serine/threonine-protein kinase plk1 by in situ hybridization. Proliferative cells were present within the bladder wall of racemose form and absent from the homologous tissue surrounding the vesicular form. Cyst proliferation in the related model species Taenia crassiceps (ORF strain) occurs normally by budding from the cyst bladder wall and proliferative cells were concentrated within the growth buds. Cells isolated from bladder wall of racemose larvae were established in primary cell culture and insulin stimulated their proliferation in a dose-dependent manner. These findings indicate that the growth of racemose larvae is likely due to abnormal cell proliferation. The different distribution of proliferative cells in the racemose larvae and their sensitivity to insulin may reflect significant changes at the cellular and molecular levels involved in their tumor-like growth. Parasite cell cultures offer a powerful tool to characterize the nature and formation of the racemose form, understand the developmental biology of T. solium, and to identify new effective drugs for treatment., Author summary Racemose neurocysticercosis is the most aggressive and lethal form of the disease characterized by progressive expansion of the larval stage of Taenia solium within the subarachnoid spaces of the brain. Currently, the cellular or molecular events that promote its formation and development are unknown. Our observations, employing tissue samples, revealed the presence of mitotically active cells in the bladder wall of the racemose larvae. Finally, we isolated and established primary cell cultures and observed that these cells are sensitive (proliferate in response to insulin). These results suggest that the proliferative cells stimulated by host biomolecules like hormones would be responsible for the abnormal growth of racemose larvae. Further studies are needed to identify all genes and pathways altered in the racemose form. The primary cell cultures will be used as a therapeutic target and allow us in future works to understand the developmental biology of the parasite.

Neurocysticercosis (NCC) is endemic in many parts of the world, carrying significant neurological morbidity that varies according to whether lesions are located inside the cerebral parenchyma or in extraparenchymal spaces. The latter, in particular subarachnoid NCC, is assumed to be more severe, but no controlled studies comparing mortality between types of NCC exist. The aim of this study was to compare all-cause mortality between patients with intraparenchymal NCC and those with subarachnoid NCC. Vital status and sociodemographic characteristics were evaluated in patients with intraparenchymal viable, intraparenchymal calcified, and subarachnoid NCC attending a neurological referral hospital in Lima, Perú. Survival analyses using Kaplan–Meier curves and Cox proportional regression models were carried out to compare mortality rates between groups. From 840 NCC patients followed by a median time of 82.3 months, 42 (5.0%) died, six (1.8%) in the intraparenchymal viable group, four (1.3%) in the calcified group, and 32 (16.6%) in the subarachnoid group (P < 0.001). Older age and lower education were significantly associated with mortality. The age-adjusted hazard ratio for death in the subarachnoid group was 13.6 (95% CI: 5.6–33.0, P < 0.001) compared with the intraparenchymal viable group and 10.7 (95% CI: 3.7–30.8, P < 0.001) when compared with the calcified group. We concluded that subarachnoid disease is associated with a much higher mortality in NCC.

Neurocysticercosis (NCC) is considered a major cause of acquired epilepsy in most developing countries. Humans and pigs acquire cysticercosis ingesting T. solium eggs by the fecal-oral route. After ingestion, oncospheres disperse throughout the body producing cysts mainly in the central nervous system and striated muscles. The treatment is focused on antiparasitic, anti-inflammatory, and antiepileptic drugs; however, new drugs are being studied in animal models recently. The aim of this study was to perform histological image analysis of pig brains with NCC after antiparasitic treatment to develop future tools to study brain inflammation since usually the evaluation of fibrosis is obtained manually on microscopy images in a long, inaccurate, poorly reproducible, and tedious process. For this purpose, the slides of pig brains with NCC were stained with Masson's Trichrome, and high quality photographic images were taken. Then, image processing and machine learning were performed to detect the presence and extension of collagen fibers around the cyst as markers of fibrosis. The process includes the use of color normalization and probabilistic classification implemented in Java language as a plugin to the free access program ImageJ. This paper presents a new method to detect cerebral fibrosis, assessing the amount of fibrosis in the images with accuracy above 75% in 12 seconds. A manual editing tool allows us to raise the results above 90% faster and efficiently.

Taenia solium neurocysticercosis (NCC) is endemic in most of the world and contributes significantly to the burden of epilepsy and other neurological morbidity. Also present in developed countries because of immigration and travel, NCC is one of few diseases targeted for eradication. This paper reviews all aspects of its life cycle (taeniasis, porcine cysticercosis, human cysticercosis), with a focus on recent advances in its diagnosis, management, and control. Diagnosis of taeniasis is limited by poor availability of immunological or molecular assays. Diagnosis of NCC rests on neuroimaging findings, supported by serological assays. The treatment of NCC should be approached in the context of the particular type of infection (intra- or extraparenchymal; number, location, and stage of lesions) and has evolved toward combined symptomatic and antiparasitic management, with particular attention to modulating inflammation. Research on NCC and particularly the use of recently available genome data and animal models of infection should help to elucidate mechanisms of brain inflammation, damage, and epileptogenesis.

To report on relevant national surveillance systems of (N)CC and taeniasis (the infection with the adult tapeworm) in the European Union/European Economic Area and to assess the magnitude of (N)CC occurrence by retrieving information on cases for the period 2000-2016.(N)CC cases were retrieved via national reporting systems, a systematic literature search, contact with clinicians and a search for relevant 'International Statistical Classification of Diseases and Related Health Problems' (ICD)-based data.Mandatory notification systems for (N)CC were found in Hungary, Iceland and Poland. Ten cases were reported in Poland and none in Hungary and Iceland. Through the systematic literature review and information given by clinicians, 263 individual and 721 aggregated (N)CC cases from 19 European countries were identified. ICD-based data were obtained from five countries. From 2000 to 2016, a total of 3489 cases (N)CC cases were coded: 832 in Italy, eight in Latvia, 357 in Portugal, 2116 in Spain and 176 in Sweden.Despite being classified as a possible eradicable disease, (N)CC is still diagnosed across Europe, yet its true extent and impact remain unclear.Rapporter sur les systèmes nationaux de surveillance pertinents de la (neuro)cysticercose (N)CC et de la téniase (infection par le ténia adulte) dans l'Union européenne/l'Espace économique européen, et évaluer l'ampleur de l'occurrence de la (N)CC en reprenant des informations sur les cas durant la période 2000-2016. MÉTHODES: Les cas de (N)CC ont été repris à partir des systèmes nationaux de notification, une recherche systématique de la littérature, des contacts avec des cliniciens et une recherche de données pertinentes basées sur la ‘Classification Statistique Internationale des Maladies et Problèmes de Santé Connexes’ (ICD). RÉSULTATS: Des systèmes de notification obligatoires pour la (N)CC ont été trouvés en Hongrie, en Islande et en Pologne. Dix cas ont été rapportés en Pologne et aucun en Hongrie et en Islande. Grâce à la revue systématique de la littérature et aux informations fournies par les cliniciens, 263 cas individuels et 721 cas agrégés de (N)CC de 19 pays européens ont été identifiés. Des données ICD ont été obtenues de cinq pays. De 2000 à 2016, un total de 3489 cas de (N)CC ont été codés: 832 en Italie, 8 en Lettonie, 357 au Portugal, 2116 en Espagne et 176 en Suède.Bien qu'elle soit classée comme une maladie pouvant être éradiquée, la (N)CC est toujours diagnostiquée à travers l'Europe, mais sa véritable ampleur et son impact restent incertains .

Neurocysticercosis (NCC) is an infection prevalent in developing countries; however, it is neglected in the Democratic Republic of the Congo (DRC) and in sub-Saharan Africa. Here, we present three different cases seen in a consulting room in Lubumbashi. These cases are evidence that NCC is more common than it was previously thought in sub-Saharan Africa. Neurocysticercosis is a pathology-neglected and ignored infection, not only by the population but also by health professionals and health authorities in the DRC, and because of that, it is important to increase the research about NCC in the DRC to assess the prevalence and risk factors for NCC to assess the severity of the phenomenon and to help designing appropriate prevention and control measures.

Neurocysticercosis is the invasion of the human nervous system by larvae of the pork tapeworm Taenia solium; it is a major cause of seizures and neurologic morbidity worldwide. Parenchymal brain disease results in seizures and can follow a benign course, whereas extraparenchymal (intraventricular or subarachnoid) cysticercosis presents with hydrocephalus or intracranial hypertension, is progressive, and carries a poor prognosis. Diagnosis is based on brain imaging (computed tomography and magnetic resonance imaging) and supported by specific serology (Western blot with purified antigens). Management should be individualized and includes symptomatic treatment (analgesics, anti-epileptic drugs, anti-inflammatory drugs) and selected use of anti-parasitic therapy with albendazole and/or praziquantel.

Subarachnoid neurocysticercosis (SANCC) is a severe and progressive brain infection with Taenia solium. We performed a pilot study of noninvasive screening for SANCC in two endemic villages in northern Peru using a urine antigen screen followed by brain magnetic resonance imaging for participants with elevated levels of antigen. Among the 978 participants screened, we identified eight individuals with SANCC, many of whom were asymptomatic. This represents a minimum prevalence of 0.8% of SANCC, a level higher than expected based on prior studies, and a positive predictive value of 62% for our novel urine screening test. Future studies should confirm whether early detection and management improve clinical outcomes.

Infection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.

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.

Antiparasitic agents against Taenia solium cysticercosis have been in use since 1979, although its use has been questioned on the basis that cysts would die naturally and thus treatment-induced inflammation is unnecessary. In addition, isolated reports have also questioned whether neurocysticercosis (NCC) is a cause of epilepsy. After more than three and a half decades, a large body of evidence is available. Little if any doubt exists about NCC as a cause of seizures - NCC is consistently associated with seizures when appropriate groups are compared, and in a large subset of cases, seizure semiology correlates with the anatomical location of lesions. Cyst degeneration and the subsequent inflammatory reaction increase seizure expression, although patients with non-inflamed cysts may have seizures, as do patients with long-standing, not inflamed calcified scars. Assessment of the evidence on cysticidal efficacy, safety, and the impact of cyst destruction in decreasing seizures leads to the conclusion that the benefits of antiparasitic treatment in parenchymal brain cysticercosis clearly outweigh the risks, and have provided substantive evidence of the role of NCC as a cause of seizures and epilepsy. Antiparasitic therapy should be considered a primary option in the management of patients with live or degenerating brain NCC cysts. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy".

Background A unified set of criteria for neurocysticercosis (NCC) has helped to standardize its diagnosis in different settings. Methods Cysticercosis experts were convened to update current diagnostic criteria for NCC according to two principles: neuroimaging studies are essential for diagnosis, and all other information provides indirect evidence favoring the diagnosis. Recent diagnostic advances were incorporated to this revised set. Results This revised set is structured in absolute, neuroimaging and clinical/exposure criteria. Absolute criteria include: histological confirmation of parasites, evidence of subretinal cysts, and demonstration of the scolex within a cyst. Neuroimaging criteria are categorized as major (cystic lesions without scolex, enhancing lesions, multilobulated cysts, and calcifications), confirmative (resolution of cysts after cysticidal drug therapy, spontaneous resolution of single enhancing lesions, and migrating ventricular cysts on sequential neuroimaging studies) and minor (hydrocephalus and leptomeningeal enhancement). Clinical/exposure criteria include: detection of anticysticercal antibodies or cysticercal antigens by well-standardized tests, systemic cysticercosis, evidence of a household Taenia carrier, suggestive clinical manifestations, and residency in endemic areas. Besides patients having absolute criteria, definitive diagnosis can be made in those having two major neuroimaging criteria (or one major plus one confirmative criteria) plus exposure. For patients presenting with one major and one minor neuroimaging criteria plus exposure, definitive diagnosis of NCC requires the exclusion of confounding pathologies. Probable diagnosis is reserved for individuals presenting with one neuroimaging criteria plus strong evidence of exposure. Conclusions This revised set of diagnostic criteria provides simpler definitions and may facilitate its more uniform and widespread applicability in different scenarios.

Taenia solium (the pork tapeworm) is present in most developing countries, where it is a frequent cause of seizures and other neurological disease. Parasitic larvae invade the human brain, establish, and eventually resolve, leaving a calcified scar. While these lesions are common in endemic regions, and most of these are clinically silent, a proportion of individuals with calcified cysticerci develop seizures from these lesions, and 30-65% of these cases are associated with perilesional edema (PE), likely due to host inflammation. This manuscript summarizes the importance, characteristics, natural history, and potential prevention and treatments of symptomatic calcified neurocysticercosis (NCC).

Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case–control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6–14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop.

Taenia solium cysticercosis is difficult to eliminate without interventions or societal development. Atahualpa is a rural Ecuadorian village with documented low migration rate, where domestic pig raising is common and human cysticercosis is endemic. To assess neurocysticercosis (NCC) prevalence, 1,273 villagers aged ≥ 20 years underwent neuroimaging studies, which showed calcified lesions in 121 (9.5%) individuals, but no active disease. Likewise, positive reactions, apparently nonspecific, were found in only 3/200 subjects by the use of a monoclonal antibody-based enzyme-linked immunosorbent assay to detect T. solium antigens in urine. Only 2/418 pigs reacted to three antibody bands on serum western blot and none to more than three bands. This is the first time that spontaneously arrested T. solium transmission is documented in a known endemic village. Understanding why active transmission stopped could provide insights on potential targets for control interventions. Atahualpa could provide an optimal scenario for longitudinal studies on the consequences of calcified NCC.

Parasitic infections of the central nervous system are much more common than suspected, although most infections are asymptomatic. For example, parasites like the ubiquitous protozoa Toxoplasma gondii or the nematode larvae Toxocara canis infect significant proportions of the human population. Other parasitic infections such as malaria and neurocysticercosis are widespread in developing countries and become major causes of neurological morbidity in these regions as well in immigrants and travelers. This article reviews parasitic pathogens causing neurological morbidity and mortality, including an extensive list of less common parasitic infections of the human nervous system.

The pig is the natural intermediate host of Taenia solium, a parasite causing significant burden of disease in both humans and pigs. Porcine cysticercosis is traditionally detected via tongue palpation and slaughterhouse meat inspection, both with limited sensitivity. Serum antibody detection has a better performance; however, it does not discriminate past from present infection. Serum antigen detection can demonstrate viable infection and gives a good estimate of parasitic load. This study evaluated a sandwich antigen-detection ELISA using monoclonal antibodies (MoAbs) 158C11 and 60H8 for the diagnosis of viable cysticercosis in pigs. Serum samples were used from 35 naturally T. solium cysticerci–infected pigs, 31 cysticercosis-negative pigs, and 22 pigs with Taenia hydatigena infection (to assess cross-reactions). Positive cysticercosis samples were subcategorized at necropsy according to parasitic burden as mild (1–10 viable cysts, n = 10), moderate (11–100 cysts, n = 5), or severe infection (more than 100 cysts, n = 20). This Ag-ELISA showed a sensitivity of 82.9% and a specificity of 96.8% when not considering cross-reactions with T. hydatigena. Hundred percentage of severely infected, 80% of moderately infected, and 50% of mildly T. solium–infected pigs tested positive. Twenty of 22 pigs with only T. hydatigena infections were positive, with 13 reaching saturating levels in the ELISA. The Ag-ELISA revealed the presence of live cysts and is, thus, a fairly reliable test to monitor experimental infection, response to treatment, and follow-up in animal models of cysticercosis. It should, however, be carefully interpreted when used in regions where T. hydatigena is endemic in pigs.

BackgroundThe 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.MethodsASOX 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.ResultsThere 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.ConclusionsWe 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.

One-hundred and sixty-four migrants from Sub-Saharan Africa to Italy were screened with the Taenia solium specific enzyme-linked immunosorbent assay coproantigen (ELISA CoAg) and four (2.4%) were recorded as positive, but with optical density values near to the cut-off. No ELISA CoAg positive samples were confirmed by parasitological methods. Low positivity could be attributed to false positive result or cross-reaction with other Taenia species. Further studies are needed to assess the role of migration on sporadic autochthonous transmission of T. solium taeniasis/cysticercosis in Europe.

Neurocysticercosis (NCC), caused by Taenia solium larvae that reside in the central nervous system, results in serious public health and medical issues in many regions of the world. Current diagnosis of NCC is complex requiring both serology and costly neuroimaging of parasitic cysts in the brain. This diagnostic pipeline can be problematic in resource-constrained settings. There is an unmet need for a highly sensitive and clinically informative diagnostic test to complement the present diagnostic approaches. Here, we report that T. solium–derived cell-free DNA is readily detectable in the urine of patients with the subarachnoid and parenchymal forms of NCC, and discuss the potential utility of this approach in enhancing and refining T. solium diagnostics. Fil: Toribio, Luz. Universidad Peruana Cayetano Heredia; Perú Fil: Romano, Miryam de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentina. University Johns Hopkins; Estados Unidos Fil: Scott, Alan L.. University Johns Hopkins; Estados Unidos Fil: Gonzales, Isidro. Instituto Nacional de Ciencias Neurológicas; Perú Fil: Saavedra, Herbert. Instituto Nacional de Ciencias Neurológicas; Perú Fil: Garcia, Hector H.. Universidad Peruana Cayetano Heredia; Perú. Instituto Nacional de Ciencias Neurológicas; Perú Fil: Shiff, Clive. University Johns Hopkins; Estados Unidos

Reintroduction of Taenia solium into a region in Peru where it had been eliminated prompted evaluation of the possibility of reintroduction from an urban reservoir of taeniasis. In a cross-sectional study of an adjacent urban area, we found low prevalence of taeniasis (4/1,621; 0.25%), suggesting minimal risk of parasite reintroduction into rural areas through this route.

Single brain enhancing lesions (SEL) are the most common presentation of neurocysticercosis (NCC) observed on neuroimaging in people presenting with epileptic seizures not only on the Indian sub-continent and in travelers returning from cysticercosis-endemic regions, but are also present in other parts of the world. The aim of this study, which consisted of a systematic review (CRD42019087665), a meta-analysis and an expert group consultation, was to reach consensus on the best anti-seizure medication and anti-inflammatory treatment for individuals with SEL NCC. Standard literature review methods were used. The Cochrane risk of bias tool was used and random effects model meta-analyses were performed. The quality of the body of evidence was rated using GRADE tables. The expert committee included 12 gender and geographically balanced members and recommendations were reached by applying the GRADE framework for guideline development. The 1–1.5-year cumulative incidence of seizure recurrence, cyst resolution or calcification following anti-seizure medication (ASM) withdrawal was not statistically different between ASM of 6, 12 or 24 months. In contrast, in persons whose cyst calcified post treatment, longer ASM decreased seizure recurrence. The cumulative incidence ratio (CIR) 1–1.5 years after stopping ASM was 1.79 95% CI: (1.00, 3.20) for patients given 6 versus 24 months treatment. Anti-inflammatory treatment with corticosteroids in patients treated with ASM compared to patients treated with ASM only showed a statistically significant beneficial effect on seizure reduction (CIR 0.44, 95% CI 0.23, 0.85) and cyst resolution (CIR 1.37, 95%CI: 1.07, 1.75). Our results indicate that ASM in patients with SEL NCC whose cysts resolved can be withdrawn, while patients whose cysts calcified seem to benefit from prolonged anti-seizure medication. Additional corticosteroid treatment was found to have a beneficial effect both on seizure reduction and cyst resolution., Author summary Neurocysticercosis is an infection of the brain with the tapeworm Taenia solium. On the Indian sub-continent, the majority of people suffering from neurocysticercosis only show one cyst (larval form of the parasite) in their brain and often present at clinics with epileptic seizures. There is still some debate on the best way to treat these cases to reduce the risk for seizure recurrence. The goal of this study was to review the literature on how well different durations of treatment with anti-seizure medication (ASM), combined or not with corticosteroids, work in order to reduce the seizure recurrence and eliminate the cyst from the brain. The results show that ASM for 24 months compared to 6 months favors reduced seizure recurrence in patients whose cysts calcified post treatment. Concerning anti-inflammatory treatment, corticosteroids were also found to have beneficial effects on seizure reduction. However, further high-quality randomized controlled trials with adequately long follow-up time are required for better evidence on best drug(s), dose and duration of ASM and corticosteroids for individuals with SEL NCC.