Project description:To estimate the lifetime prevalence of neurocysticercosis (NCC)-associated epilepsy and the proportion of NCC among people with epilepsy in three Burkina Faso villages.Three villages were selected to represent three types of pig-rearing methods: (1) Batondo, where pigs are left to roam; (2) Pabré, where pigs are mostly tethered or penned; and (3) Nyonyogo, where the majority of residents are Muslim and few pigs are raised. In Batondo and Nyonyogo, all concessions (a group of several households) were included. Half of the concessions in Pabré were randomly chosen. All households of selected concessions were included, and one person per household was randomly selected for epilepsy screening and serologic testing for cysticercosis. Self-reported cases of epilepsy were also examined and confirmed cases included in analyses other than the estimate of NCC-associated epilepsy prevalence. Epilepsy was defined as ever having had more than one episode of unprovoked seizures. Individuals with medically confirmed epilepsy had a computerized tomography (CT) scan of the brain before and after contrast medium injection. The diagnosis of NCC was made using a modification of the criteria of Del Brutto et al.Thirty-nine (4%) of 888 randomly selected villagers and 33 (94%) of 35 self-reported seizures cases were confirmed to have epilepsy by medical examination. Among the 68 participants with epilepsy who had a CT scan, 20 patients were diagnosed with definitive or probable NCC for a proportion of 46.9% (95% confidence interval [CI] 30.2-64.1) in Batondo and 45.5% (95% CI 19.0-74.1) in Pabré. No cases of NCC were identified in Nyonyogo.All the definitive and probable cases of NCC were from the two villages where pig breeding is common. Prevention policies intended to reduce the burden of epilepsy in this country should include measures designed to interrupt the life cycle of Taenia solium.
Project description:Zambia is endemic for Taenia solium taeniosis and cysticercosis. In this single-centered, cross-sectional, community-based study, the role of neurocysticercosis (NCC) as a cause of epilepsy was examined. People with epilepsy (PWE, n = 56) were identified in an endemic area using a screening questionnaire followed by in-depth interviews and neurological examination. Computed tomography (CT) was performed on 49 people with active epilepsy (PWAE) and their sera (specific antibody and antigen detection, n = 56) and stools (copro-antigen detection, n = 54) were analyzed. The CT scan findings were compared to a group of 40 CT scan controls. Of the PWE, 39.3% and 23.2% were positive for cysticercal antibodies and antigens, respectively, and 14.8% for coproantigens (taeniosis). Lesions highly suggestive of NCC were detected in 24.5% and definite NCC lesions in 4.1% of CT scans of PWAE. This compares to 2.5% and 0%, respectively, in the control CT scans. Using the Del Brutto diagnostic criteria, 51.8% of the PWAE were diagnosed with probable or definitive NCC and this rose to 57.1% when the adapted criteria, as proposed by Gabriël et al. (adding the sero-antigen ELISA test as a major criterion), were used. There was no statistically significant relationship between NCC, current age, age at first seizure and gender. This study suggests that NCC is the single most important cause of epilepsy in the study area. Additional large-scale studies, combining a community based prevalence study for epilepsy with neuroimaging and serological analysis in different areas are needed to estimate the true impact of neurocysticercosis in endemic regions and efforts should be instituted to the control of T. solium.
Project description:Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa.
Project description:BackgroundNeurocysticercosis (NCC) is a common parasitic infection of the central nervous system, caused by the tapeworm Taenia solium. It is endemic to certain parts of the world, including Central America, South America, Asia, and Africa. The racemose form, characterized by extraparenchymal location, increased morbidity and mortality, and large loculated cystic lesions, is rarely seen in industrialized countries, such as the United States. The management of racemose neurocysticercosis (RNCC) differs from that of the typical parenchymal variant. The ideal course of treatment is debated by experts, but typically includes either surgical intervention with subsequent medical therapy or medical therapy alone.Case descriptionWe present the case of a 34-year-old male diagnosed with RNCC and treated successfully with surgical cyst drainage, resection, and subsequent medical therapy.ConclusionCurrently, no standardized evidence-based protocol exists that dictate appropriate treatment for extraparenchymal or racemose NCC. We present a case of RNCC treated successfully with surgical and medical intervention. Further research encompassing well-designed clinical trials is necessary to delineate appropriate and standardized protocols for treatment of this disease.
Project description:Neurocysticercosis is the most common parasitic disease affecting the human central nervous system, with protean clinical manifestations. During the last 17 years, 153 cases of neurocysticercosis were histopathologically diagnosed on surgically resected and autopsied material. Variable number of cysts, from a solitary one to multiple were found invading different parts of the neuraxis (118 cases). These cestode larval forms had a prediliction for locating in the cerebral grey matter (98 cases), followed by subcortical nuclear area (12), cerebral ventricles and subarachnoid cisterns (26 cases). Patients harbouring parenchymal cysts manifested predominantly with seizures and encephalitis (113 cases) whereas those with ventricular and/or cisternal cysts presented with features of chronic meningitis and hydrocephalus. The unusual clinical presentations were psychiatric symptoms with behavioural abnormalities and stroke in the young as a result of cysticercal meningitis with associated arteritis. Primary cysticercal abscess in the brain parenchyma was an interesting pathological feature noted in 3 cases. In the endemic areas, the co-existence of neurocysticercosis appears to enhance the morbidity and mortality due to Japanese encephalitis (31 cases). The surface glycoprotein of the cysticercal cyst has been identified to be the antigenic component to which the host immune system responds by forming antibody in the CSF.
Project description:Intestinal helminth infections of livestock and humans are predominantly controlled by treatment with three classes of synthetic drugs, but some livestock nematodes have now developed resistance to all three classes and there are signs that human hookworms are becoming less responsive to the two classes (benzimidazoles and the nicotinic acetylcholine agonists) that are licensed for treatment of humans. New anthelmintics are urgently needed, and whilst development of new synthetic drugs is ongoing, it is slow and there are no signs yet that novel compounds operating through different modes of action, will be available on the market in the current decade. The development of naturally-occurring compounds as medicines for human use and for treatment of animals is fraught with problems. In this paper we review the current status of cysteine proteinases from fruits and protective plant latices as novel anthelmintics, we consider some of the problems inherent in taking laboratory findings and those derived from folk-medicine to the market and we suggest that there is a wealth of new compounds still to be discovered that could be harvested to benefit humans and livestock.
Project description:Drug repositioning is defined as a process to identify a new application for drugs. This approach is critical as it takes advantage of well-known pharmacokinetics, pharmacodynamics, and toxicity profiles of the drugs; thus, the chance of their future failure decreases, and the cost of their development and the required time for their approval are reduced. Anthelmintics, which are antiparasitic drugs, have recently demonstrated promising anticancer effects in vitro and in vivo. This literature review focuses on the potential of anthelmintics for repositioning in the treatment of cancers. It also discusses their pharmacokinetics and pharmacodynamics as antiparasitic drugs, proposed anticancer mechanisms, present development conditions, challenges in cancer therapy, and strategies to overcome these challenges.
Project description:Movement disorders are uncommon manifestations of neurocysticercosis. When present, most are secondary to parenchymal lesions in the basal ganglia. Rarely, movement disorders can occur in racemose/extraparenchymal neurocysticercosis, an aggressive variant frequently associated with cerebrospinal fluid outflow obstruction and hydrocephalus. Appropriate treatment can reverse neurological manifestations.
Project description:Prolonged use of broad-spectrum antibiotics disrupts the indigenous gut microbiota, which consequently enables toxigenic Clostridium difficile species to proliferate and cause infection. The burden of C. difficile infections was exacerbated with the outbreak of hypervirulent strains that produce copious amounts of enterotoxins and spores. In recent past, membrane-active agents have generated a surge of interest due to their bactericidal property with a low propensity for resistance. In this study, we capitalized on the antimicrobial property and low oral bioavailability of salicylanilide anthelmintics (closantel, rafoxanide, niclosamide, oxyclozanide) to target the gut pathogen. By broth microdilution techniques, we determined the MIC values of the anthelmintics against 16 C. difficile isolates of defined PCR-ribotype. The anthelmintics broadly inhibited C. difficile growth in vitro via a membrane depolarization mechanism. Interestingly, the salicylanilides were bactericidal against logarithmic- and stationary-phase cultures of the BI/NAP1/027 strain 4118. The salicylanilides were poorly active against select gut commensals (Bacteroides, Bifidobacterium and Lactobacillus species), and were non-hemolytic and non-toxic to mammalian cell lines HepG2 and HEK 293T/17 within the range of their in vitro MICs and MBCs. The salicylanilide anthelmintics exhibit desirable properties for repositioning as anti-C. difficile agents.
Project description:Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of Taenia solium causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were treated with extended cysticidal and anti-inflammatory regimens and followed up a median of 4.2 years posttreatment (range: 15 for ? 4 years, 20 ? 2 years, 26 > 1 year, and 3 < 1 year). The median ages at the time of first symptom, diagnosis, and enrollment were 29.7, 35.6, and 37.9 years, respectively; 58.8% were male and 82.4% were Hispanic. The median time from immigration to symptoms (minimum incubation) was 10 years and the estimated true incubation period considerably greater. Fifty percent also had other forms of NCC. Common complications were hydrocephalus (56%), shunt placement (41%), infarcts (18%), and symptomatic spinal disease (15%). Thirty patients (88.2%) required prolonged treatment with albendazole (88.2%, median 0.55 year) and/or praziquantel (61.8%; median 0.96 year), corticosteroids (88.2%, median 1.09 years), methotrexate (50%, median 1.37 years), and etanercept (34.2%, median 0.81 year), which led to sustained inactive disease in 29/30 (96.7%) patients. Three were treated successfully for recurrences and one has continuing infection. Normalization of cerebral spinal fluid parameters and cestode antigen levels guided treatment decisions. All 15 patients with undetectable cestode antigen values have sustained inactive disease. There were no deaths and moderate morbidity posttreatment. Corticosteroid-related side effects were common, avascular necrosis of joints being the most serious (8/33, 24.2%). Prolonged cysticidal treatment and effective control of inflammation led to good clinical outcomes and sustained inactive disease which is likely curative.