Oxfendazole Nitazoxanide combination in experimental neurocysticercosis - Anti-inflammatory and cysticidal effects.

Neurocysticercosis (NCC) is a parasitic infection caused by the larval stage of the pork tapeworm, Taenia solium. The complications of NCC include seizures, headaches, cognitive impairment, and focal neurological deficits. In addition to antiparasitic drugs and surgery, the management of NCC includes the use of corticosteroids to reduce inflammation and control symptoms. The traditional treatment with albendazole and praziquantel has not been altered over 30 years and present several side effects. There are other anti-helminthic drugs such as oxfendazole and nitazoxanide that may show efficacy in NCC treatment. The aim of this study was to determine the histopathologic aspects of experimental NCC after in vivo treatment with the combination of oxfendazole and nitazoxanide. Balb/c mice were infected with T. crassiceps cysticerci and divided into groups of 10 animals each that received a single dose through gavage as follows: group treated with NaCl 0.9% (control group); group treated by monotherapy of the anti-helminthic drugs, 30 mg/kg in single dose of oxfendazole (OXF) or nitazoxanide (NTZ); and groups treated with the combination of the drugs (OXF/NTZ group). Macroscopic and microscopic analysis were performed. There was greater presence of final stage cysticerci after treatment. The microscopic analysis of the general pathological processes showed that the monotherapy with all treatment groups induced higher perivasculitis than what was observed in the control group. In contrast, the combination treatment showed a lower observation of PMN and MN inflammatory infiltration in comparison to the other treatments and to the control one. These results show that indeed the association of benzimidazole derivatives which present both anti-helminthic and anti-inflammatory properties with other cysticidal drugs are beneficial for the NCC treatment in which the aim is to destroy parasite without inducing inflammatory damage in the brain tissue.

Systematic review of the effectiveness of selected drugs for preventive chemotherapy for Taenia solium taeniasis.

BACKGROUND: Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations. METHODS: A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533. RESULTS: We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses. CONCLUSION: Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited.

Mathematical model of the life cycle of taenia-cysticercosis: transmission dynamics and chemotherapy (Part 1).

BACKGROUND: Taenia solium is the aetiological agent of human taeniasis, pig cysticercosis and human neurocysticercosis, which are serious public health problems, especially in developing countries. METHODS: A mathematical model of the transmission dynamics of taeniasis-cysticercosis is formulated. The model consists of a coupled system of differential equations, which are density-dependent equations for describing the flow of the parasite through the life cycle. The model is hybrid since it comprises deterministic equations with stochastic elements which describe changes in the mean parasite burden and incorporates the overall pattern of the parasites' distribution. RESULTS: Sensitivity and bifurcation analyses were carried out to determine the range of values of the model. The model can reproduce the observed epidemiological patterns of human taeniasis, pig and human cysticercosis. For example, for a wide range of parameter values, the mean intensity of adult worms tends to rapidly stabilize in one parasite per individual host. From this model, we also derived a Susceptible-Infected model to describe the prevalence of infection in humans and pigs. Chemotherapeutic interventions against pig cysticercosis or human taeniasis may reduce rapidly and effectively the mean intensity of human taeniasis, pig cysticercosis and human cysticercosis. This effect can be achieved even if the protective efficacy of the drug is of the order of 90% and the coverage rate is 90%. This means that health in humans infected either with adult worms or cysticerci may be achieved by the application of anthelmintic drugs against pig cysticercosis. However, treatment against human cysticercosis alone, does not influence neither human teniasis nor pig cysticercosis. This is because human cysticercosis infection does not influence the value of the basic reproductive number (Ro). CONCLUSIONS: Even coverage of 100% in the administration of anthelmintics did not eliminate the infection. Then elimination of the infection in all hosts does not seem a feasible goal to achieve by administering only chemotherapeutic interventions. Throughout the manuscript a discussion of our model in the context of other models of taeniasis-cysticercosis is presented.

A novel progesterone receptor membrane component (PGRMC) in the human and swine parasite Taenia solium: implications to the host-parasite relationship.

BACKGROUND: We have previously reported that progesterone (P4) has a direct in vitro effect on the scolex evagination and growth of Taenia solium cysticerci. Here, we explored the hypothesis that the P4 direct effect on T. solium might be mediated by a novel steroid-binding parasite protein. METHODS: By way of using immunofluorescent confocal microscopy, flow cytometry analysis, double-dimension electrophoresis analysis, and sequencing the corresponding protein spot, we detected a novel PGRMC in T. solium. Molecular modeling studies accompanied by computer docking using the sequenced protein, together with phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is from parasite origin. RESULTS: Our results show that P4 in vitro increases parasite evagination and scolex size. Using immunofluorescent confocal microscopy, we detected that parasite cells showed expression of a P4-binding like protein exclusively located at the cysticercus subtegumental tissue. Presence of the P4-binding protein in cyst cells was also confirmed by flow cytometry. Double-dimension electrophoresis analysis, followed by sequencing the corresponding protein spot, revealed a protein that was previously reported in the T. solium genome belonging to a membrane-associated progesterone receptor component (PGRMC). Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is related to a steroid-binding protein of Echinoccocus granulosus, both of them being nested within a cluster including similar proteins present in platyhelminths such as Schistocephalus solidus and Schistosoma haematobium. CONCLUSION: Progesterone may directly act upon T. solium cysticerci probably by binding to PGRMC. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.

Taenia solium infection in Peru: a collaboration between Peace Corps Volunteers and researchers in a community based study.

BACKGROUND: Neurocysticercosis is a leading cause of seizures and epilepsy in most of the world, and it occurs when Taenia solium larval cysts infect the central nervous system. T. solium tapeworm infection is endemic in much of Peru, but there are scarce data on the prevalence in many rural highland communities where it is likely to be hyper-endemic. Peace Corps Volunteers live and work in these communities; however, to our knowledge, they have not been used to facilitate public health research. MATERIALS AND METHODS: We utilized Peace Corps Volunteers to estimate the prevalence of T. solium tapeworm infection in seven rural communities in northern Peru. A convenience non-random sampling frame was used. Peace Corps Volunteers facilitated the collection of stool samples (N = 2,328), which were analyzed by sedimentation and microscopy. Niclosamide treatment and purgation preceded species identification, which was done by PCR-REA. RESULTS: Taenia sp. egg-positive stool samples were found in three of the seven communities we surveyed. The overall prevalence of Taenia sp. egg positivity was 2.1% (49/2,328) (95% CI = 1.6-2.8%) with prevalence up to 4.3% (42/977) (95% CI = 3.1-5.8%) by community. All 34 of the specimens tested by PCR-REA were T. solium. The overall prevalence of T. solium tapeworm infection was 1.5% (34/2,328) (95% CI = 1.0-2.0%). Prevalence up to 2.9% (28/977) (95% CI = 1.9-4.1%) by community was observed. CONCLUSION/SIGNIFICANCE: This study recorded high T. solium tapeworm prevalence, and identified hyper-endemic rural communities. It demonstrates that synergy between researchers and Peace Corps Volunteers can be an effective means to conducting large-scale, community-based studies in remote areas of Peru.

Disruption of the blood-brain barrier in pigs naturally infected with Taenia solium, untreated and after anthelmintic treatment.

Neurocysticercosis is a widely prevalent disease in the tropics that causes seizures and a variety into of neurological symptoms in most of the world. Experimental models are limited and do not allow assessment of the degree of inflammation around brain cysts. The vital dye Evans Blue (EB) was injected to 11 pigs naturally infected with Taenia solium cysts to visually identify the extent of disruption of the blood-brain barrier. A total of 369 cysts were recovered from the 11 brains and classified according to the staining of their capsules as blue or unstained. The proportion of cysts with blue capsules was significantly higher in brains from pigs that had received anthelmintic treatment 48 and 120h before the EB infusion, indicating a greater compromise of the blood-brain barrier due to treatment. The model could be useful for understanding the pathology of treatment-induced inflammation in neurocysticercosis.

Tamoxifen treatment in hamsters induces protection during taeniosis by Taenia solium.

Human neurocysticercosis by Taenia solium is considered an emergent severe brain disorder in developing and developed countries. Discovery of new antiparasitic drugs has been recently aimed to restrain differentiation and establishment of the T. solium adult tapeworm, for being considered a central node in the disease propagation to both pigs and humans. Tamoxifen is an antiestrogenic drug with cysticidal action on Taenia crassiceps, a close relative of T. solium. Thus, we evaluated the effect of tamoxifen on the in vitro evagination and the in vivo establishment of T. solium. In vitro, tamoxifen inhibited evagination of T. solium cysticerci in a dose-time dependent manner. In vivo, administration of tamoxifen to hamsters decreased the intestinal establishment of the parasite by 70%, while recovered tapeworms showed an 80% reduction in length, appearing as scolices without strobilar development. Since tamoxifen did not show any significant effect on the proliferation of antigen-specific immune cells, intestinal inflammation, and expression of Th1/Th2 cytokines in spleen and duodenum, this drug could exert its antiparasite actions by having direct detrimental effects upon the adult tapeworm. These results demonstrate that tamoxifen exhibits a strong cysticidal and antitaeniasic effect on T. solium that should be further explored in humans and livestock.

A new parasiticidal compound in T. solium cysticercosis.

The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis.

Medical management of neurocysticercosis.

INTRODUCTION: Neurocysticercosis (NCC) is considered to be the most common cause of acquired epilepsy worldwide. Formerly restricted to palliative measures, therapy for NCC has advanced with the advent of two drugs that are considered to be effective: praziquantel (PZQ) and albendazole (ALB). AREAS COVERED: All available articles regarding research related to the treatment of NCC were searched. Relevant articles were then reviewed and used as sources of information for this review. EXPERT OPINION: Anticysticercal therapy has been marked by intense controversy. Recent descriptions of spontaneous resolution of parenchymal cysticercosis with benign evolution, risks of complications and reports of no long-term benefits have reinforced the debate over the usefulness and safety of anticysticercal therapy. High interindividual variability and complex pharmacological interactions will require the close monitoring of plasma concentrations of ALB and PZQ metabolites in future trials. Given the relative scarcity of clinical trials, more comparative interventional studies - especially randomized controlled trials in long-term clinical evolution - are required to clarify the controversy over the validity of parasitic therapy in patients with NCC.

Progesterone induces scolex evagination of the human parasite Taenia solium: evolutionary implications to the host-parasite relationship.

Taenia solium cysticercosis is a health problem in underdeveloped and developed countries. Sex hormones are involved in cysticercosis prevalence in female and male pigs. Here, we evaluated the effects of progesterone and its antagonist RU486 on scolex evagination, which is the initial step in the development of the adult worm. Interestingly, progesterone increased T. solium scolex evagination and worm growth, in a concentration-independent pattern. Progesterone effects could be mediated by a novel T. solium progesterone receptor (TsPR), since RU486 inhibits both scolex evagination and worm development induced by progesterone. Using RT-PCR and western blot, sequences related to progesterone receptor were detected in the parasite. A phylogenetic analysis reveals that TsPR is highly related to fish and amphibian progesterone receptors, whereas it has a distant relation with birds and mammals. Conclusively, progesterone directly acts upon T. solium cysticerci, possibly through its binding to a progesterone receptor synthesized by the parasite.

In vitro anthelmintic activity of Melia azedarach naturalized in Argentina.

The anthelmintic activity of the drupe extracts of Melia azedarach L. (Meliaceae) growing in Argentina was tested against tapeworms, hookworms, nodular worms and earthworms, and was shown to be better than the standards piperazine phosphate and hexylresorcinol against tapeworms and hookworms, respectively.

[Effects of some chemical and physical agents on the metacestode Taenia solium in spicy meat and sausage]. / Efecto de algunos agentes físicos y químicos sobre el metacéstodo de Taenia solium presente en carne adobada y chorizo.

OBJECTIVE: To assess the effect of different cooking times and temperatures, as well as of some seasonings, on the viability of Taenia solium metacestodes in spicy meat and hot sausage. MATERIAL AND METHODS: This study was conducted by the Universidad Autónoma de Guerrero (Guerrero State Autonomous University), Mexico in 1999. Infected pork meat was bought in the community of Azacoaloya, in the municipality of Chilapa de Alvarez, Guerrero State. It was used to prepare spicy meat (adobada) and hot sausage (chorizo). Only the meat in which metacestode viability was proven was used. The products obtained underwent a) room temperature for 12 to 100 hours; b) temperatures of -10 to 37 degrees C for 24 hours; c) boiling (97 degrees C) from 1 to 15 minutes. To determine the effect of the seasonings, batches were prepared using twice the amount of a specific seasoning. Trials were done and assessed three times. Proportion differences were established using the chi-squared test. RESULTS: At room temperature the lowest evagination occurred after 100 hours for both products (p<0.05). After 24 hours, the lowest evagination occurred at -10 degrees C in spicy meat and at 37 degrees C in hot sausage (p<0.05). At boiling temperature there was no evagination after 10 minutes (p<0.05). In spicy meat, adding salt caused the most significant reduction; in hot sausage, thyme caused the most significant reduction (p<0.05). CONCLUSIONS: Meat with metacestodes should not be eaten, yet, it is being sold and used to prepare spicy meats. Adding spices can hide the metacestode, thus, adequate cooking of these meat products is necessary. These meats may be consumed at least four days after its preparation and spicy meat after a minimum of four days of refrigeration. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Efecto de algunos agentes físicos y químicos sobre el metacéstodo de Taenia solium presente en carne adobada y chorizo / Effects of some chemical and physical agents on the metacestode Taenia solium in spicy meat and sausage

OBJETIVO: Evaluar el efecto de diferentes temperaturas y tiempos, así como de algunos condimentos sobre la viabilidad de metacéstodos de Taenia solium en chorizo y carne adobada. MATERIAL Y MÉTODOS: Este trabajo se llevó a cabo en la Universidad Autónoma de Guerrero, en 1999. En la comunidad de Atzacoaloya, en el municipio de Chilapa de Alvarez, Guerrero, se compró carne de cerdo infectada, con la que se preparó carne adobada y chorizo; sólo se empleó aquélla en la cual se comprobó la viabilidad de los metacéstodos. Los productos obtenidos fueron sometidos a: a) temperatura ambiente durante 12 a 100 horas; b) temperaturas de -10 a 37 °C por 24 horas, y c) ebullición (97 °C) de 1 a 15 minutos. Para determinar el efecto de los condimentos se prepararon lotes con el doble de ingredientes de cada uno. Todas las evaluaciones se realizaron y evaluaron con tres repeticiones. Se establecieron diferencias de proporciones mediante c². RESULTADOS: A temperatura ambiente la menor evaginación fue a las 100 horas para ambos productos (p< 0.05). Por 24 horas a diferentes temperaturas la menor evaginación se dio a -10 °C en carne adobada y a 37 °C para el chorizo (p< 0.05). A temperatura de ebullición del agua se encontró que en ambos no hubo evaginación a partir de los 10 minutos (p< 0.05). En relación con los condimentos, la adición de sal generó la mayor reducción en carne adobada, y de tomillo, para el chorizo (p< 0.05). CONCLUSIONES: Si bien la carne con metacéstodos no debería consumirse, ante el hecho de su comercialización y de que la preparación de chorizos y la adición de pastas pueden ocultar al metacéstodo, es necesaria la cocción adecuada de los productos o consumir chorizo por lo menos cuatro días después de su elaboración y la carne adobada después de cuatro días de refrigeración.

Determinación de la actividad biológica de cinco especies vegetales: Talisia nervosa, Cyclanthus bipartitus, Selaginella artrítica, Tetragastris panamensis y Crisophila warscewiczii en Cisticercos de Taenia solium / Determination of the biological activity of five plant species: Talisia nervosa, Cyclanthus bipartitus, Selaginella arthritic, Tetragastris panamensis and Crisophila warscewiczii in Cysticercus of Taenia solium

Existen muchas clases o categorías de sustancias naturales producto del metabolismo vegetal que se han clasificado según su origen características químicas, similitud estructural, molecular o su acción farmacológica. Todo este potencial que las plantas han demostrado podemos desarrollarlo, no solo, como medio de subsistencia, si no, valorarlos sobre la disponibilidad de fuentes de conocimientos que conlleven a una ruta para nuevos y mejores medicamentos. De esta manera se justifica la búsqueda a través de la realización del ensayo, para determinar la actividad biológica en las especies vegetales a estudio, con el fin de encontrar una alternativa en favor de la disminución de la prevalencia de la enfermedad (Cisticercosis) y de esta manera contribuir a la salud de la población.

Chemotherapy of porcine cysticercosis with albendazole sulphoxide.

Cysticercosis is a zoonotic disease of humans produced by the larval stage of swine parasite, Taenia solium. Chemotherapy of infected pigs is a possible strategy for avoiding disease transmission and improving health programs in endemic areas of cysticercosis. In this preliminary study, seven naturally infected pigs from 6 to 12 months of age were allotted to treated (n = 4) and control groups (n = 3). The treated animals received a subcutaneous injection in their forelegs and thighs of 15 mg/kg per body weight of albendazole sulphoxide (ABZSO; Pisa, Mexico) once per day for 8 days. At the same time, the control group received a subcutaneous injection of saline solution (9% NaCl). After 12 weeks, all the animals were slaughtered and at least 200 metacestodes were isolated from the muscles and brain of each animal. Using histology and the metacestode viability criteria described in this study, treated animals had no viable cysts in their muscle (0/200), while 7 of 17 (41.1%) viable cysts were observed in those isolated from their brains. In the control group, 183/200 (91.5%) muscle metacestodes were viable and from brain, 22/29 (75.8%) metacestodes were viable. The 15 mg/kg per body weight dosage of ABZSO was 100% effective against muscular cysticercosis as shown by the lack of viable cysts and the micro-calcifications in meat from the treated pigs.