Cysticidal Drugs Research Articles

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.

Human Neurocysticercosis: An Overview.

Human cysticercosis is caused by ingestion of T. solium eggs from taenia carriers. Neurocysticercosis (NCC), defined as the infection of the CNS and the meninges by the larval stage of Taenia solium, is the most common helminthic infection of the CNS worldwide. Parasites may lodge in brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing pathological changes that account for the pleomorphism of this disease. Seizures/epilepsy are the most common clinical manifestation, but other patients present with headache, focal deficits, intracranial hypertension, or cognitive decline. Accurate diagnosis of NCC is possible after interpretation of clinical data together with findings of neuroimaging studies and results of immunological tests. However, neuroimaging studies are fundamental for diagnosis because immunological test and clinical manifestations only provide circumstantial evidence of NCC. The introduction of cysticidal drugs changed the prognosis of most NCC patients. These drugs have been shown to reduce the burden of infection and to improve the clinical course of the disease in many patients. Efforts should be directed to eradicate the disease through the implementation of control programs against all the steps in the life cycle of T. solium, including carriers of the adult tapeworm, infected pigs, and eggs in the environment.

Taenia solium Cysticercosis: Present Scenario: A Review

Cysticercosis is one of the most important neglected parasitic diseases caused by the larval stage of the tapeworm Taenia solium. It is the most common cause of epilepsy in the areas with improper pig husbandry practices and poor sanitary conditions. In pig the larvae lodges in the muscle and subcutaneous tissue and seldom manifests any clinical sign. In human beings the larval stage resides in the CNS thus leading to the condition Neurocysticercosis. The disease can be diagnosed by using various neuroimaging techniques and immunodiagnostic methods. Available therapeutic options include cysticidal drugs, steroids, anti-epileptic drugs etc. The disease can be controlled by anti-parasitic treatment of the pig and humans residing in endemic areas, vaccinating the pigs, creating awareness and other measures.

Extensive Neurocysticercosis with Diffuse Leukoencephalopathy

In Central nervous system (CNS), neurocysticercosis (NCC) is the most common parasitic infection that affects the CNS. Cysticidal drugs are used for its treatment, and they can precipitate an inflammatory response, which results in worsening of symptoms. We report 2 cases of extensive neurocysticercosis that show diffuse white matter edema that involves both cerebral hemispheres. Of the 2 patients, one showed disseminated cysticercosis that involved the tongue, scalp muscles, and skeletal muscles of the extremities.

Evaluation of New Benzimidazole Derivatives as Cysticidal Agents: In Vitro, in Vivo and Docking Studies.

Based on our previous research on cysticidal drugs, we report the synthesis and evaluation of three new benzimidazole derivatives. In these compounds, the amido group was used as a bioisosteric replacement of the ester group. The molecular docking on β-tubulin revealed that the derivatives interacted through hydrogen bonding with N165, E198 and V236. All compounds showed in vitro activity against Taenia crassiceps cysts. Among them, benzimidazole 3 was found to be the most potent of the series (EC50 0.86 µM). This compound also exhibited the highest probability of binding and the lowest binding free energy score and was therefore selected for in vivo evaluation. Results indicated that the efficacy of compound 3 was comparable to that of the reference drug, albendazole (50.39 vs. 47.16% parasite reduction). Animals treated with compound 3 seemed to tolerate this benzimidazole well, with no changes in behavior, or food and water consumption. These findings are consistent with the in silico prediction results, which indicated low toxicity risks. The pharmacokinetic study showed that the half-life and mean residence time (6.06 and 11.9 h, respectively) were long after oral administration. Together, these results indicate that this new benzimidazole derivative represents a promising structure with cysticidal activity.

Effect of dexamethasone on albendazole cysticidal activity in experimental cysticercosis by Taenia crassiceps in BALB/c mice: In vitro and in vivo evaluation

Taenia solium is a parasite whose larvae (cysticerci) can locate in the central nervous system of humans and cause neurocysticercosis (NC). The introduction of cysticidal drugs such as albendazole (ABZ) for the treatment of NC has significantly improved its prognosis. However, treatment is not always effective, and the high levels of corticosteroids used to prevent inflammatory complications in this disease could be, partly, the cause of this observation. In this context, this study investigated, using the experimental mouse model of intraperitoneal infection with Taenia crassiceps, the influence of corticosteroid administration on the therapeutic efficacy of ABZ. We evaluated and compared the effects of ABZ, dexamethasone (DXM) and their combination (ABZ + DXM) on cyst viability, both in vitro and in vivo. Serum levels of IL-4, IFN-gamma, IL-6 and IL-10 were evaluated in the in vivo study. Results showed that the treatment with ABZ, in vitro and in vivo, was associated with a high number of parasites deaths. Concomitant treatment with DXM did not alter ABZ in vitro cysticidal activity but reduced its effectiveness significantly in the in vivo experimental model. Cytokine serum levels did not change significantly in treated mice compared to the controls. The results of this study are relevant as they indicate a negative effect of corticosteroids on the efficacy of cysticidal therapy. In human neurocysticercosis, control of inflammation is of great importance to most patients in order to avoid complications. Corticosteroids are generally used for this purpose and the results of this study demonstrate the need to find other therapeutic strategies. Further studies are needed to better understand the mechanisms involved.

Pediatric Neurocysticercosis

Neurocysticercosis is the most common helminth infection of nervous system in humans caused by the encysted larvae of Taenia solium. It is a major cause of epilepsy in tropical areas and the most common cause of focal-onset seizures in North Indian children. Children with neurocysticercosis have pleomorphic manifestations depending on the location, number and viability of the cysts and host response. In endemic areas, neurocysticercosis should be clinically suspected in any child with recent-onset seizures, headache or focal motor deficits where there is no other suggestion of an underlying neurological disorder. Diagnosis of neurocysticercosis is essentially based on neuroimaging; visualization of a scolex is diagnostic. Management includes use of cysticidal drugs usually albendazole, which seems to be effective for lesion resolution and seizure remission, use of steroids and anti-epileptic drugs. Single lesions portend good prognosis with resolution of lesions in >60% of the cases within 6 mo and good seizure control. Prognosis is guarded in cysticercus encephalitis, racemose and extraparenchymal neurocysticercosis.

In vitro and in vivo cysticidal activity of extracts and isolated flavanone from the bark of Prunus serotina: A bio-guided study

Currently, neurocysticercosis treatment involves two drugs: albendazole and praziquantel; however, their efficacy is suboptimal and new cysticidal drugs are needed. The present paper reports the cysticidal activity of extracts of the bark from Prunus serotina against Taenia crassiceps cysts and the isolation and identification of the main components of the most active extract. Results showed that all extracts displayed in vitro cysticidal activity (EC50=17.9–88.5μg/mL), being the methanolic the most active and selective. Also, methanolic extract exhibited in vivo efficacy at 300mg/kg which was similar to that obtained with albendazole. Bio-guided fractionation of methanolic extract led the isolation of 2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one (naringenin, NGN), 3,4,5-trimethoxybenzoic acid and 1,3,5-trimethoxybenzene. NGN exhibited in vitro activity, in a time-concentration-dependent manner (EC50=89.3μM]. Furthermore, NGN at a dose of 376.1μmol/kg displayed similar in vivo efficacy than those obtained with albendazole at 188.4μmol/kg. NGN also caused a high level of damage in all parasite tissue in a similar manner than that observed with the methanolic extract. This study represents the first report of the cysticidal properties of the bark of P. serotina. NGN was identified as the main active compound of this specie and other studies are required to explore the potential of this flavanone as cysticidal agent.

Clinical and etiological evaluation of secondary seizures by computed tomography and electroencephalogram

This study was conducted to determine the clinical evaluation and various etiological factors of secondary seizures in patients admitted to Government Medical College, Nagpur. We evaluated 58 patients of secondary seizures from Dec 2011 to Oct 2013. Secondary seizures were defined as case of seizure with CT (brain) or MRI (brain) abnormality1. Out of 58 cases 35 were males and 23 were females. Mean age of study subjects was 34.85. The commonest presenting feature was generalized tonic clonic convulsions (42 patients) followed by focal seizures (16 patients). Todd’s palsy was observed in 4 cases. Aura was present in 24 cases. According to CT brain scan the aetiology was – neurocysticercosis (34.48%), post stroke (27.59%), tuberculoma (24.14%). Space occupying lesions(SOLs) were present in 8 patients, out of whom 4 had brain tumour, 2 patients had brain abscess, 1 had hydatid cyst and 1 had metastasis. Majority of lesions were located in frontal region (58.62%), followed by in parietal region (44.83%), in temporal region (25.86%) and in occipital region (13.79 % patients). In our study neurocysticercosis was found to be the commonest cause of secondary seizures. As in a meta-analysis it was found that cysticidal drugs result in better outcome in patients of neurocysticecosis, we recommend that the patients of secondary seizures should be identified for the aetiology and treated at the earliest2.

Neurocysticercosis: A case report and brief review.

Neurocysticercosis (NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization. It is considered a common infection of the nervous system caused by the Taenia solium and is known to be the primary cause of preventable epilepsy in many developing countries. NCC is commonly resulted by the ingestion of Taenia solium eggs after consuming undercooked pork, or contaminated water. The parasite can grow in the brain and spinal cord within the nervous system, causing severe headache and seizures beside other pathological manifestations. Immigration and international travel to endemic countries has made this disease common in the United States. NCC can be diagnosed with computed tomography and magnetic resonance imaging of the brain. The treatment of the NCC including cysticidal drugs (e.g., albendazole and praziquantel), and neurosurgical procedure, depending upon the situation. A patient of Asian origin came to our clinic with complaints of dizziness, headaches and episodes seizures for the past twelve years without proper diagnosis. The computed tomography and magnetic resonance imaging scans indicated multilobulated cystic mass in the brain with the suspicion of neurocysticercosis.

Neurocisticercosis racemosa subaracnoidea gigante y ventricular: a propósito de un caso

Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.

A case report on subarachnoid and intraventricular neurocysticercosis

Neurocysticercosis is the most common central nervous system helminthic infection in humans. We hereby present a case combining two rare manifestations of neurocysticercosis: the subarachnoid and intraventricular forms. The patient presented with hydrocephalus and neurologic deficits and although endoscopic removal of the cysts and two cycles of postoperative cysticidal drugs resulted in resolution of symptoms, they later recurred. Ventriculoperitoneal shunt placement and a further cycle of albendazole plus dexamethasone led to substantial clinical improvement. Extraparenchymal neurocysticercosis may be challenging to diagnose and treat and is usually associated with a poorer prognosis. Clinicians should be aware of this condition.

Clinical, sociodemographic, radiological profile and response to albendazole therapy in children with neurocysticercosis in Uttarakhand

Background: Overall neurocysticercosis (NCC) is identified as a major cause of active epilepsy in the developing world. Most of the studies focus on adults with limited studies in children. A pilot study from Garhwal region of Uttarakhand had reported a high incidence. Conflicting reports regarding the clinical presentation and response of cysticidal drugs have created a controversy regarding disease and outcome. This prospective observational study in Kumaon region of Uttarakhand aims to study clinical features, sociodemographic profile, radiological findings and response to 28 days albendazole therapy in children with NCC. Materials and Methods: Seventy nine patients with various neurological complaints, were diagnosed to have NCC on basis of computed tomography scan head. Other differential diagnoses were excluded by chest X-ray, Mantoux, erythrocyte sedimentation rate and magnetic resonance imaging where needed. The clinical, sociodemographic profile was recorded, and radiological and clinical response at 3 months after 28 days albendazole therapy was observed. Results: Seizures (93.9%) followed by vomiting (62%) and headache (30.4%) were the chief complaints. Complex partial seizures (70.3%) and generalized (17.6%) were the main seizure type. Most NCC were single (72.2%) out of which 26.3% disappeared on follow-up, 17.7% were multiple out of which 7% resolved and eight were calcified of which all persisted. Electroencephalography was abnormal in 62% patients. Conclusion: NCC in children is a relatively benign disease in Kumaon region with significant morbidity in the form of epilepsy with no mortality. Better prognosis was seen in single NCC in comparison to multiple or calcified lesions, but response to albendazole therapy was much less than in previous studies.

Neurocysticercosis.

Neurocysticercosis, the most common helminthic infection of the nervous system, is a major cause of acquired epilepsy worldwide. The disease occurs when humans become intermediate hosts of the tapeworm Taenia solium after ingesting its eggs by contagion from an asymptomatic Taenia carrier. Within the nervous system, parasites may locate in brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing several pathological changes that are responsible for the clinical pleomorphism of the disease. Seizures are the most common clinical manifestation, but a sizable proportion of patients develop focal deficits, intracranial hypertension, or cognitive decline. Preoperative diagnosis of neurocysticercosis is possible after proper integration of data from neuroimaging studies and immunological tests. Cysticidal drugs (albendazole and praziquantel) have changed the prognosis of most patients with neurocysticercosis. The use of these drugs has shown to reduce the parasite load within the central nervous system and to improve the clinical prognosis of the disease in many cases. Future studies should focus on disease eradication through the implementation of control programs against all the interrelated steps in the life cycle of T solium, including human carriers of the adult tapeworm, infected pigs, and eggs in the environment.

Disseminated neurocysticercosis presenting as affective mood disorder with chronic tension type headache

Neurocysticercosis is a common parasitic infection in India presenting usually with seizues, headache, focal neurological deficits. Neurocysticercosis presenting as a psychiatric illness is rare. Disseminated cysticercosis with involvement of central nervous system and head and neck muscles is rare even in endemic areas. We present a case of disseminated cysticercosis, which presented with chronic tension type headache and affective mood disorder. Treatment with cysticidal drugs led to complete remission of psychiatric complaints. In endemic areas history suggestive of mood disorder should not be used as supportive evidence of a primary headache syndome like tension type headche without ruling out secondary causes. Making an early diagnosis can prevent morbidity.

Intramedullary cysticercosis of the spinal cord: A review of patients evaluated with MRI

ObjectiveReview of cases of intramedullary spinal cord cysticercosis diagnosed with MRI to outline the features and outcome of this overlooked form of presentation of neurocysticercosis. MethodsMEDLINE, LILACS, and manual search of case reports or case series of patients with intramedullary cysticercosis evaluated with MRI. Abstracted data included: demographic profile, clinical manifestations, neuroimaging findings, therapy, and follow-up. ResultsForty-three patients were reviewed. Mean age was 36years, and 65% were men. Most patients (67%) had parasites located at the thoracic spinal cord. All but two patients had a single cyst. The most common form of presentation was a subacute or chronic transverse myelopathy. On MRI, all lesions had signal properties paralleling that of CSF, and most were surrounded by edema and had a “ring-like” pattern of abnormal enhancement. The scolex of the parasite was visualized in 16 (37%) cases. Twenty-nine patients underwent surgical resection of the lesion, and 14 were medically-treated. Follow-up data was available in 20 surgically-treated and 13 medically-treated patients. Twelve (60%) of the 20 surgically-treated patients recovered completely, and the remaining were left with sequelae or did not improve. In contrast, all the 13 medically-treated patients recovered completely after the use of cysticidal drugs plus corticosteroids (11 cases) or corticosteroids alone (two cases). ConclusionsIntramedullary cysticercosis is rare. Clinical and neuroimaging findings may resemble those of other intramedullary lesions, but the visualization of the scolex or the incidental discovery of intracranial lesions provide helpful diagnostic clues. Prognosis is benign provided the correct diagnosis is suspected and patients receive prompt therapy.

Intrasellar cysticercosis: a systematic review

The objective of this study was to review patients with intrasellar cysticercosis to outline the features of this form of neurocysticercosis. A MEDLINE and manual search of patients with intrasellar cysticercosis were done. Abstracted data included clinical manifestations, neuroimaging findings, therapy, and outcome. Twenty-three patients were reviewed. Ophthalmological disturbances, including diminution of visual acuity and visual field defects following a chiasmatic pattern, were recorded in 67 % of cases. Endocrine abnormalities were found in 56 % of patients (panhypopituitarism, hyperprolactinemia, diabetes insipidus, and isolated hypothyroidism). In addition, some patients complained of seizures or chronic headaches. Neuroimaging studies showed lesions confined to the sellar region in 47 % of cases. The remaining patients also had subarachnoid cysts associated or not with hydrocephalus, parenchymal brain cysts, or parenchymal brain calcifications. Thirteen patients underwent surgical resection of the sellar cyst through a craniotomy in nine cases and by the transsphenoidal approach in four. Visual acuity or visual field defects improved in only two of these patients. Five patients were treated with cysticidal drugs without improvement. Intrasellar cysticercosis is rare and probably under-recognized. Clinical manifestations resemble those caused by pituitary tumors, cysts, or other granulomatous lesions. Neuroimaging findings are of more value when intrasellar cysts are associated with other forms of neurocysticercosis, such as basal subarachnoid cysts or hydrocephalus. Prompt surgical resection is mandatory to reduce the risk of permanent loss of visual function. There seems to be no role for cysticidal drug therapy in these cases.

Evidence-based guideline: Treatment of parenchymal neurocysticercosis [RETIRED

Objective:To review the evidence base for different treatment strategies in intraparenchymal neurocysticercosis in adults and children.Method:A literature search of Medline, EMBASE, LILACS, and the Cochrane Database from 1980 to 2008, updated in 2012, resulted in the identification of 10 Class I or Class II trials of cysticidal drugs administered with or without corticosteroids in the treatment of neurocysticercosis.Results:The available data demonstrate that albendazole therapy, administered with or without corticosteroids, is probably effective in decreasing both long-term seizure frequency and the number of cysts demonstrable radiologically in adults and children with neurocysticercosis, and is well-tolerated. There is insufficient information to assess the efficacy of praziquantel.Recommendations:Albendazole plus either dexamethasone or prednisolone should be considered for adults and children with neurocysticercosis, both to decrease the number of active lesions on brain imaging studies (Level B) and to reduce long-term seizure frequency (Level B). The evidence is insufficient to support or refute the use of steroid treatment alone in patients with intraparenchymal neurocysticercosis (Level U).

Neurocysticercosis: A disease of neglect

Neurocysticercosis (NCC) is a neglected tropical disease caused by larval forms of the parasite Taenia solium lodging in central nervous system (CNS). There is a huge morbidity and debilitation due to CNS manifestations of NCC in developing and underdeveloped regions of the globe, mainly Asian, African and Latin American countries. It is the cause of epilepsy in about 1% of the population of endemic countries and is the underlying etiology in about 15-50% persons with epilepsy, depending upon the geographical region. There is no perfect diagnostic method and the diagnosis relies on a combination of clinical, radio-imaging, immunologic and epidemiologic data. Treatment includes anti-parasitic treatment by cysticidal drugs and management of associated symptoms and complications. The disease is eradicable and control depends on an integrated and coordinated involvement of international bodies like the World Health Organization along with scientific institutions and political and administrative strata of the endemic countries to provide the essential tools such as adequate sanitation, live-stock management, health education and improved socio-economic conditions.

Single parenchymal brain cysticercus: relationship between age of patients and evolutive stage of parasites

Background: A recent hypothesis suggested that in many cases cysticercal granulomas represent recently established Taenia solium metacestodes rapidly destroyed by the host’s immune system. Here, we attempted to determine whether patients with cysticercal granulomas are younger than those with other forms of parenchymal brain cysticercosis.Methods: Series of 185 patients with single parenchymal brain cysticercus, classified according to the stage of the parasite at the moment of diagnosis in cysts without inflammation, cysts with inflammation, granular lesions, and calcifications. We correlated the age of the patients with the parasite evolutive stage.Results: Patients with cysticercus granulomas were significantly younger than those with vesicular cysts (17·7±12·9 versus 36·8±15·1 years, P<0·005) or calcifications (17·7±12·9 versus 40·8±19·7 years, P<0·0001). There was also a non-significant trend for patients with granulomas to be younger than those with coloidal cysts (17·7±12·9 versus 26·7±15·6 years, P = 0·367).Conclusions: Results from this study argued against the classical hypothesis that granulomas are the end result from long-established vesicular cysts destroyed by the host’s immune system. Vesicular (viable) cysticerci must be treated with cysticidal drugs as it is unlikely that they will be spontaneously destroyed.