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Background The onset of anthelmintic treatment of neurocysticercosis (NCC) provokes an acute immune response of the host, which in human cases is associated with exacerbation of neurological symptoms. This inflammation can occur at the first days of therapy. So, changes in the brain cysts appearance may be detected by medical imaging. We evaluated radiological changes in the appearance of brain cysts (enhancement and size) on days two and five after the onset of antiparasitic treatment using naturally infected pigs as a model for human NCC. Methods and results Contrast T1-weighted magnetic resonance imaging with gadolinium was performed before and after antiparasitic treatment. Eight NCC-infected pigs were treated with praziquantel plus albendazole and euthanized two (n = 4) and five (n = 4) days after treatment; another group of four infected pigs served as untreated controls. For each lesion, gadolinium enhancement intensity (GEI) and cyst volume were measured at baseline and after antiparasitic treatment. Volume and GEI quantification ratios (post/pre-treatment measures) were used to appraise the effect of treatment. Cysts from untreated pigs showed little variations between their basal and post treatment measures. At days 2 and 5 there were significant increases in GEI ratio compared with the untreated group (1.32 and 1.47 vs 1.01, p = 0.021 and p = 0.021). Cyst volume ratios were significantly lower at days 2 and 5 compared with the untreated group (0.60 and 0.22 vs 0.95, p = 0.04 and p = 0.02). Cysts with lower cyst volume ratios showed more marked post-treatment inflammation, loss of vesicular fluid and cyst wall wrinkling. Conclusion/Significance A significant and drastic reduction of cyst size and increased pericystic enhancement occur in the initial days after antiparasitic treatment as an effect of acute perilesional immune response. These significant changes showed that early anthelmintic efficacy (day two) can be detected using magnetic resonance imaging., Author summary Neurocysticercosis (NCC) is a frequent parasitic infection of the human brain and the most common cause of adult onset epilepsy in developing countries. Acute inflammatory response in NCC plays an important role in the pathogenesis of symptoms by anthelminitic therapies. The anthelmintic recommended therapy for NCC has drawbacks as the exacerbation of inflammation around degenerating cysts provokes the appearance of symptoms at the first days of treatment. Radiological changes in the appearance of cysts usually are seen after months of therapy. To evaluate if significant radiological changes (enhancement and size) occur in the first days of therapy, we used a porcine NCC model and magnetic resonance imaging (MRI) with contrast solution. The major radiological changes observed after treatment with albendazole and praziquantel were an increase in enhancement and the significant reduction in cyst size by day 2 and more evident on day 5. Cysts with greater changes also experienced exacerbated inflammation, loss of vesicular fluid and wrinkling of the cyst wall. These results show an early therapeutic effect and the possible utility of repeat MRI imaging within a few days after starting treatment. Finally, these findings contribute to our understanding of the treatment induced early exacerbation of symptoms.

Background Infections with Taenia solium are the most common cause of adult acquired seizures worldwide, and are the leading cause of epilepsy in developing countries. A better understanding of the genetic diversity of T. solium will improve parasite diagnostics and transmission pathways in endemic areas thereby facilitating the design of future control measures and interventions. Microsatellite markers are useful genome features, which enable strain typing and identification in complex pathogen genomes. Here we describe microsatellite identification and characterization in T. solium, providing information that will assist in global efforts to control this important pathogen. Methods For genome sequencing, T. solium cysts and proglottids were collected from Huancayo and Puno in Peru, respectively. Using next generation sequencing (NGS) and de novo assembly, we assembled two draft genomes and one hybrid genome. Microsatellite sequences were identified and 36 of them were selected for further analysis. Twenty T. solium isolates were collected from Tumbes in the northern region, and twenty from Puno in the southern region of Peru. The size-polymorphism of the selected microsatellites was determined with multi-capillary electrophoresis. We analyzed the association between microsatellite polymorphism and the geographic origin of the samples. Results The predicted size of the hybrid (proglottid genome combined with cyst genome) T. solium genome was 111 MB with a GC content of 42.54%. A total of 7,979 contigs (>1,000 nt) were obtained. We identified 9,129 microsatellites in the Puno-proglottid genome and 9,936 in the Huancayo-cyst genome, with 5 or more repeats, ranging from mono- to hexa-nucleotide. Seven microsatellites were polymorphic and 29 were monomorphic within the analyzed isolates. T. solium tapeworms were classified into two genetic groups that correlated with the North/South geographic origin of the parasites. Conclusions/Significance The availability of draft genomes for T. solium represents a significant step towards the understanding the biology of the parasite. We report here a set of T. solium polymorphic microsatellite markers that appear promising for genetic epidemiology studies., Author Summary Taenia solium, the pork tapeworm, is an important pathogen as it is a major cause of acquired epilepsy in developing countries. The parasite was eliminated from most developed countries decades ago due to improvement in sanitary conditions but it remains a common infection across Asia, Africa and Latin America. Identification of genetic variants within T. solium will enable to study the genetic epidemiology, distribution and movement of this parasite within endemic communities, which will ultimately facilitate the design of control strategies to reduce the health and economic burden of disease. Microsatellites have been used in other parasites to identify genetic variants. In this study, we partially sequenced the genome of T. solium and identified microsatellites widely distributed in the genome using bioinformatics tools. We evaluated the distribution of these microsatellites collected from 20 tapeworms from the north and 20 tapeworms from the south of Peru. We identified seven polymorphic microsatellites, and evaluated their capacity to differentiate genetic variants of T. solium. Interestingly, tapeworms from the North and South of Peru showed different genotypes, suggesting its use as a potential marker to differentiate geographic origin.

Background Neurocysticercosis (NCC), infection of the central nervous system by Taenia solium cysticerci, is a pleomorphic disease. Inflammation around cysticerci is the major cause of disease but is variably present. One factor modulating the inflammatory responses may be the location and characteristics of the brain tissue adjacent to cysticerci. We analyzed and compared the inflammatory responses to cysticerci located in the parenchyma to those in the meninges or cysticerci partially in contact with both the parenchyma and the meninges (corticomeningeal). Methodology/Principal Findings Histological specimens of brain cysticerci (n = 196) from 11 pigs naturally infected with Taenia solium cysticerci were used. Four pigs were sacrificed after 2 days and four after 5 days of a single dose of praziquantel; 3 pigs did not receive treatment. All pigs were intravenously injected with Evans Blue to assess disruption of the blood-brain barrier. The degree of inflammation was estimated by use of a histological score (ISC) based on the extent of the inflammation in the pericystic areas as assessed in an image composed of several photomicrographs taken at 40X amplification. Parenchymal cysticerci provoked a significantly greater level of pericystic inflammation (higher ISC) after antiparasitic treatment compared to meningeal and corticomeningeal cysticerci. ISC of meningeal cysticerci was not significantly affected by treatment. In corticomeningeal cysticerci, the increase in ISC score was correlated to the extent of the cysticercus adjacent to the brain parenchyma. Disruption of the blood-brain barrier was associated with treatment only in parenchymal tissue. Significance Inflammatory response to cysticerci located in the meninges was significantly decreased compared to parenchymal cysticerci. The suboptimal inflammatory response to cysticidal drugs may be the reason subarachnoid NCC is generally refractory to treatment compared to parenchymal NCC., Author Summary The cystic larvae of the pork tapeworm Taenia solium may affect the human brain causing neurocysticercosis (NCC), a very frequent cause of neurological symptoms in developing countries. The clinical expression and response to treatment of human NCC are related to the location of cysticerci inside (intraparenchymal) or outside the brain parenchyma (extraparenchymal NCC). We used a naturally infected pig model to assess the characteristics of inflammation around brain cysticerci of parenchymal, meningeal and mixed locations. There were no major differences in inflammation without treatment. After antiparasitic treatment with praziquantel, inflammation around parenchymal brain cysticerci increased in comparison to meningeal located cysticerci. Cysticerci partially surrounded by both brain parenchyma and meninges showed increased inflammation in relation to the extent of the cysticercus in the brain parenchyma. The location of cysticerci within the brain is a factor that determines the extent and degree of the immune response following anticysticidal treatment. Similar changes may occur in treated human infections. Our work could contribute to explain the differences in response to antiparasitic treatment in different forms of human neurocysticercosis.

Objective Neurocysticercosis, an infection with the larval form of the tapeworm, Taenia solium, is the cause of 29% of epilepsy in endemic regions. Epilepsy in this population is mostly associated with calcified granulomas; at the time of seizure recurrence 50% of those with calcifications demonstrate transient surrounding perilesional edema. Whether edema is consequence of the seizure, or a result of host inflammation directed against parasite antigens or other processes is unknown. To investigate whether perilesional edema is due to inflammation, we imaged a marker of neuroinflammation, translocater protein (TSPO), using positron emission tomography (PET) and the selective ligand 11C-PBR28. Methods In nine patients with perilesional edema, degenerating cyst or both, PET findings were compared to the corresponding magnetic resonance images. Degenerating cysts were also studied because unlike perilesional edema, degenerating cysts are known to have inflammation. In three of the nine patients, changes in 11C-PBR28 binding were also studied over time. 11C-PBR28 binding was compared to the contralateral un-affected region. Results 11C-PBR28 binding increased by a mean of 13% in perilesional edema or degenerating cysts (P = 0·0005, n = 13 in nine patients). Among these 13 lesions, perilesional edema (n=10) showed a slightly smaller increase of 10% compared to the contralateral side (P = 0·005) than the three degenerating cysts. In five lesions with perilesional edema in which repeated measurements of 11C-PBR28 binding were done, increased binding lasted for 2-9 months. Conclusions Increased TSPO in perilesional edema indicates an inflammatory etiology. The long duration of increased TSPO binding after resolution of the original perilesional edema and the pattern of periodic episodes is consistent with intermittent exacerbation from a continued baseline presence of low level inflammation. Novel anti-inflammatory measures may be useful in the prevention or treatment of seizures in this population.