Biomedical subjects
Publications and source records attributed to A Flisser.
In human brain cysticercosis, there are three morphological types of cysticercus. Teresa Robielo, Angelica Rivas and Ana Flisser describe the appearance and possible taxonomic position of these forms, and discuss their relation to the various pathologies of neurocysticercosis.
In the computed tomography (CT) scans of five pigs with neurocysticercosis (Taenia solium), interesting lesions produced by the larvae were selected. The pigs were euthanized and the corresponding lesions in their brains identified and processed for histopathology. It was found that the hypodense areas in CT scans corresponded to vesicular larvae that are presumably viable. The hyperdense areas were either solid in nature or had formed a rim around a hypodense center and in the brain slice they were either solid granulomas or colloidal cysts with inflammatory reaction in the periphery, perivascular cuffing, and vasculitis. It was not always possible to classify larvae as meningeal or parenchymatous in the CT.
Mice infected heavily with Schistosoma mansoni cercariae were treated 6 days later with Praziquantel and the parasites studied 1 h post-treatment. Immunofluorescence experiments showed that parasite surface antigens became available for labelling in larvae harvested from Praziquantel-treated mice, but not from untreated mice. Red blood cell antigens acquired from the host were localized on all lung worms studied. The distribution of each set of antigens, as revealed by fluorescence-labelling was, however, quite different. The lungs of heavily infected, drug-treated mice, exhibited severe haemorrhages which occurred in a dose-dependent manner. Fewer haemorrhages were found when heavily infected mice were treated simultaneously with Praziquantel and Aprotinin, a proteinase inhibitor. These results indicate that Praziquantel treatment in vivo induces the exposure of parasite antigens on lung-stage worms and may cause the release of parasite-derived enzymes which induce haemorrhages in the lung tissue of the host.
Naive CBA/Ca mice and CBA/Ca mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni were challenged with normal cercariae and then treated with 500 mg/kg body weight of Praziquantel (Pzq). The drug was administered intramuscularly or intradermally on day 1, but intramuscularly only on day 6. The results show clearly that in naive mice skin-stage larvae were susceptible to Pzq provided the drug was given intradermally on day 1. Lung worms were susceptible to Pzq given intramuscularly on day 6. Drug efficacy in naive mice is thus dependent upon treatment being given at the correct time and via the optimal route. The efficiency of Pzq treatment was enhanced in vaccinated mice, but was again affected by the treatment regime. Analysis of the data revealed a highly significant synergistic effect between drug treatment and vaccination when Pzq was given intramuscularly on day 6. Synergy was detectable but only marginally significant when the drug was administered intradermally on day 1, and could not be demonstrated when Pzq was given via the intramuscular route on day 1. These findings are discussed in the light of known sites and mechanisms of vaccine resistance in mice, as well as in relation to the mode of action of Pzq against schistosome parasites.
Swines with cysticercosis are a useful model to study human disease. A multidisciplinary approach was undertaken to study in detail the effect of praziquantel treatment on hosts and parasites. Computerised tomographic scans showed changes in the number and size of parasites in treated pigs. These changes were more apparent in muscle than in brain cysticerci. Neurophysiologic data were normal in cysticercotic pigs before and after drug treatment. An increase in antibody response was seen immediately after treatment regarding the amount of antibodies and number of antigens recognised. A lower number of polyploid lymphocytes was seen after treatment in cysticercotic pigs as compared to untreated pigs. At different times after treatment pigs were humanely euthanised. Oxygen consumption rate of cysticerci decreased after treatment and evagination was abolished. The inflammatory reaction that surrounded parasites increased in number and type of cells. This was more apparent around cysticerci obtained from muscle than from the brain.
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The construction and antibody screening of Taenia solium cDNA libraries, generated in the Escherichia coli bacteriophage lambda gt11, with the identification of clones putatively expressing antigen B, T. solium-specific and other antigens is described. Lysogens were produced from a number of selected clones and beta-galactosidase fusion peptides ranging in Mr of approximately 135,000-150,000 were demonstrated. These proteins were shown by immunoblotting to be reactive with a pool of sera from cysticercotic patients originally used in the cDNA library screening. We report a method whereby Taenia (T. saginata and T. pisiformis) eggs can be detected with high sensitivity in a specific DNA dot-blot hybridisation assay using total parasite DNA as probe. We show also that intra-specific DNA variability occurs in T. solium isolates obtained from different geographical areas and discuss the potential significance of this heterogeneity.
In this paper we report the immunodiagnosis of cysticercosis by the detection of antibodies in the cerebrospinal fluid (CSF) of patients, by standard enzyme immunoassay (EIA) which gave 90% sensitivity. We are also showing the results obtained with a double homologous polyclonal or monoclonal antibody based EIA that detects parasite products: we analysed CSF of patients and obtained sensitivities ranging from 14% to 75% for single antibody systems and 90% when analysing the samples with two or three systems simultaneously. The sera of infected pigs were also evaluated; with one monoclonal antibody we could detect 79% of positive samples. The good results obtained encourage the standardization and improvement of the technique for diagnostic as well as for epidemiologic purposes.
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Human and porcine cases of neurocysticerosis were compared by computed tomography in regard to the morphological characteristics of the parasites and the impact of the infection on the brain. In pigs and young people many parasites were usually found, but this was seldom the case in adult humans. These parasites were small and located mainly in the parenchyma and the subarachnoid space; no calcified cysticerci were found. In contrast, in adult humans cysticerci were heterogeneous in appearance and distribution. The brain of the pigs showed no evidence of inflammatory reaction while young people had oedema, enhancement and hydrocephalus; in contrast, adults showed diverse tomographic characteristics of brain response. Thus, the disease has at least 2 different forms. It may be mild with short development and parasites of similar appearance, as occurs in young hosts. In contrast, a long lasting disease occurs in adults, with diverse tomographic, neurological and parasitological features.
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Cysticercosis is caused by the establishment of Taenia solium larvae (cysticerci), mainly in the central nervous system (CNS) and skeletal muscle of humans and pigs, after ingestion of eggs shed in human faeces by the adult tapeworm (see centrepage diagram). Human neurocysticercosis - often a life-threatening disease - is increasingly recognized as a public health problem, especially in developing countries. Clinical incidence of neurocysticercosis can reach 7% in Mexico and 18% in the Ekari population of New Guinea, while prevalence in autopsies ranges from 0.4% to 3.6% in several countries of Latin America, Asia and Africa. Many cases have also been recently reported in the USA, usually in immigrants. In this review, Ana Flisser focuses on the problems of cysticercosis in Mexico, where the disease is now recognized as a priority both in public health and economic terms. Recognition of the problem has been greatly aided in recent years by new developments in diagnosis - especially computed tomography (CT) to diagnose early stages of neurocysticercosis - and by improved drug treatment.
One hundred and twenty-four persons, nearly the entire population of a rural village in Hidalgo State, were screened for intestinal parasites and clinical or serologic (ELISA) evidence of Taenia solium cysticercosis. Heads of households were questioned about dietary and other practices that might lead to pork tapeworm transmission, and soil samples were examined for helminth eggs. Twenty-five percent of local pigs had cysticerci visible by examination of the undersurface of their tongues. Four persons passed taeniid eggs, 7 were seropositive, and 10 gave medical histories suggestive of neurodysticercosis. Most seropositive persons were not symptomatic and the reverse was also true. The clustered distribution of infected pigs, tapeworm carriers, and persons with serologic or clinical evidence of cysticercosis suggested intrahousehold transmission. Dietary and sanitary practices were generally optimal for transmission of pork tapeworm. No cattle were kept in the village and beef was rarely eaten. This preliminary report attempts to characterize T. solium transmission in communities with endemic disease in rural Mexico and illustrates some of the methodological problems faced by epidemiologists who study this disease.
The diagnosis of cysticercosis by enzyme-linked immunosorbent assay using serum and CSF was assessed in 61 cases of confirmed cysticercosis and in controls. A very high level of specificity and sensitivity was found.
An original technique for computed tomography (CT) of the pig's brain is described. Brains of 11 cysticercotic pigs were studied by CT and by macroscopic and microscopic examination after necropsy, in order to compare the tomographic images with the anatomic findings. By CT, cysticerci could be seen in all the brains except one which had only one parasite. Good correlation was found when the CT sections were compared with the anatomic slices, nevertheless not all cysticerci seen during necropsy examination could be identified in the CT images. Only two parasites were found in the ventricles. There were difficulties in differentiating submeningeal and parenchymal localization of the cysticerci. Most cysticerci had similar morphologic appearance; inflammatory reactions of different degrees and characteristics were observed around some of them.
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Cysticerci parasitize several mammalian species, including man, in which the parasitic disease shows unique characteristics since cysticerci are established mainly in immunologically privileged sites and can survive for many years. The study of the human immune response to cysticerci is helpful in diagnosis and could perhaps also aid in preventing or curing the disease. Anti-cysticercus IgG can be detected in serum and cerebrospinal fluid (CSF) of almost all patients with neurocysticercosis, by the enzyme-linked immunosorbent assay (ELISA); antibodies of the other classes are found less frequently. Antibodies react with up to eight Taenia solium cysticercus antigens, mainly with antigen B. This antigen has an affinity for collagen and is not commonly found in the CSF. It could therefore be participating in vasculitic processes spotted in the brain of neurocysticercotic patients. Immunoglobulins are also identified on the surface of the parasites: IgG is detected on parasites obtained from various tissues; IgM, IgA and IgE mostly on extracerebral cysticerci. We discuss the possibility of extraneural cysticerci being destroyed by the immune response of the host whereas natural aging may cause brain cysticerci death.