ABSTRACT
Neurocysticercosis (NCC) is the most common helminthic infection of the human central nervous system. The antibody detection assay of choice is the enzyme-linked immunoelectrotransfer blot assay using lentil-lectin purified parasite antigens (LLGP-EITB, Western blot), an immunoassay with exceptional performance in clinical samples. However, its use is mainly restricted to a few research laboratories because the assay is labor-intensive and requires sophisticated equipment, expertise, and large amounts of parasite material for preparation of reagents. We report a new immunoprint assay (MAPIA) that overcomes most of these barriers. We initially compared the performance of five different antigen combinations in a subset of defined samples in the MAPIA format. After selecting the best-performing assay format (a combination of rGP50 + rT24H + sTs14 antigens), 148 archived serum samples were tested, including 40 from individuals with parenchymal NCC, 40 with subarachnoid NCC, and 68 healthy controls with no evidence of neurologic disease. MAPIA using three antigens (rGP50 + rT24H + sTs14) was highly sensitive and specific for detecting antibodies in NCC. It detected 39 out of 40 (97.5%) parenchymal NCC cases and 40/40 (100%) subarachnoid cases and was negative in 67 out of 68 (98.53%) negative samples. MAPIA using three recombinant and synthetic antigens is a simple and economical tool with a performance equivalent to the LLGP-EITB assay for the detection of specific antibodies to NCC. The MAPIA overcomes existing barriers to adoption of the EITG LLGP and is a candidate for worldwide use.
Subject(s)
Neurocysticercosis , Taenia solium , Animals , Humans , Neurocysticercosis/diagnosis , Neurocysticercosis/parasitology , Peru , Antigens, Helminth , Sensitivity and Specificity , Immunoassay , Enzyme-Linked Immunosorbent Assay , Antibodies, HelminthABSTRACT
A single enhancing lesion in the brain parenchyma, also called an inflammatory granuloma, is a frequent neurologic diagnosis. One of the commonest causes of this lesion is human neurocysticercosis, the infection by the larvae of the pork tapeworm, Taenia solium. Following the demonstration that viable cysticercosis cysts survive in good conditions for several years in the human brain, single cysticercal granulomas have been consistently interpreted as representing late degeneration of a long-established parasite. On the basis of epidemiologic, clinical, and laboratory evidence detailed in this article, we hypothesize that in most cases these inflammatory lesions correspond to parasites that die in the early steps of infection, likely as the natural result of the host immunity overcoming mild infections.
Subject(s)
Granuloma/etiology , Neurocysticercosis/complications , Animals , Brain/microbiology , Brain/pathology , Granuloma/epidemiology , Granuloma/immunology , Humans , Magnetic Resonance Imaging/methods , Neurocysticercosis/epidemiology , Neurocysticercosis/immunology , Taenia solium/pathogenicity , Tomography, X-Ray Computed/methodsABSTRACT
Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.
Subject(s)
Anticonvulsants/therapeutic use , Antiplatyhelmintic Agents/therapeutic use , Biomedical Research/trends , Neurocysticercosis/diagnosis , Neurocysticercosis/therapy , Neurosurgical Procedures/methods , Practice Patterns, Physicians'/trends , Forecasting , Humans , Needs Assessment , Practice Guidelines as TopicABSTRACT
Neurocysticercosis is responsible for increased rates of seizures and epilepsy in endemic regions. The most common form of the disease, chronic calcific neurocysticercosis, is the end result of the host's inflammatory response to the larval cysticercus of Taenia solium. There is increasing evidence indicating that calcific cysticercosis is not clinically inactive but a cause of seizures or focal symptoms in this population. Perilesional edema is at times also present around implicated calcified foci. A better understanding of the natural history, frequency, epidemiology, and pathophysiology of calcific cysticercosis and associated disease manifestations is needed to define its importance, treatment, and prevention.
Subject(s)
Epilepsies, Partial/etiology , Neurocysticercosis/complications , Animals , Brain Edema/etiology , Brain Edema/parasitology , Calcinosis/complications , Calcinosis/parasitology , Cysticercus/isolation & purification , Cysticercus/physiology , Epilepsies, Partial/parasitology , Epilepsies, Partial/physiopathology , Food Parasitology , Humans , Latin America/epidemiology , Neurocysticercosis/epidemiology , Neurocysticercosis/parasitology , Neurocysticercosis/prevention & control , Neurocysticercosis/transmission , Taenia solium/physiologyABSTRACT
End stages of neurocysticercosis include residual intraparenchymal brain calcifications and hydrocephalus. Although brain calcifications alone have a benign prognosis, hydrocephalus is frequently associated with chronic inflammation and intracranial hypertension, together with a protracted clinical evolution, and may lead to patient deaths. By using a monoclonal-based antigen detection enzyme-linked immunosorbent assay, we measured the levels of circulating parasite antigen in the sera of 56 patients with neurocysticercosis: 27 with calcifications only and 29 with hydrocephalus. The assay gave positive results in 14 of 29 patients with hydrocephalus but was consistently negative in patients with calcifications. Circulating parasite antigen in hydrocephalus secondary to neurocysticercosis indicates the presence of live parasites in these patients and thus a potential benefit from antiparasitic therapy.
Subject(s)
Antigens, Helminth/blood , Hydrocephalus/parasitology , Neurocysticercosis/complications , Neurocysticercosis/parasitology , Taenia/isolation & purification , Adult , Aged , Animals , Antibodies, Helminth/immunology , Antibodies, Monoclonal/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Taenia/immunologyABSTRACT
A recently described one-day regimen of praziquantel (PZQ) therapy for neurocysticercosis (NCC), three doses of 25 mg/k given at 2 h intervals, was applied in eight patients with viable NCC cysts without any evidence of inflammation. Resolution of lesions in computed tomography (CT) was observed in all five patients with a single cyst, whereas all cysts survived in three patients with multiple brain parasites. One-day praziquantel is a good regimen for patients with a single viable brain cysticercus but is poorly effective for multiple cysts.
Subject(s)
Anthelmintics/therapeutic use , Brain Diseases/drug therapy , Neurocysticercosis/drug therapy , Praziquantel/therapeutic use , Adult , Animals , Brain Diseases/diagnostic imaging , Cysticercus/drug effects , Female , Humans , Male , Middle Aged , Neurocysticercosis/diagnostic imaging , Tomography, X-Ray Computed , Treatment Failure , Treatment OutcomeABSTRACT
Twenty-six patients with single enhancing brain lesion (SEL) were openly assigned to receive single-day praziquantel therapy (n=14), or not (n=12). From 14 treated patients, complete resolution was found in 11, partial resolution in two, and the remaining case was later diagnosed as an arteriovenous malformation. Side effects presented in only one patient and remitted in the same day with symptomatic treatment. Conversely, the lesions persisted unchanged in six of 12 patients in the non-treatment group. Untreated patients with persisting lesions were prescribed praziquantel treatment. After this, SELs disappeared in three cases, other diagnoses (brain tuberculoma and arteriovenous malformation) were made in two, and one was not evaluated. When analyzed in regard to the baseline serology, resolution of lesions on computed tomography was found in 13 (complete=12, partial=1) of 14 seropositive patients, whereas it only happened in six (complete=5, partial=1) of 12 seronegative patients. Serological screening defines a subset of SEL patients with good prognosis. If antiparasitic therapy is to be used in patients with SEL, and we cannot find a strong argument against it, single-day praziquantel is the regimen of choice based on duration, costs, and minimal side effects.