Agnès Fleury

Taenia solium disease in humans and pigs: an ancient parasitosis disease rooted in developing countries and emerging as a major health problem of global dimensions

This article reviews current knowledge on human and porcine cysticercosis caused by Taenia solium. It highlights the conditions favorable for its prevalence and transmission, as well as current trends in research on its natural history, epidemiology, immunopathology, diagnosis, treatment and prevention. Our opinions on the most urgent needs for further research are also presented.

High Prevalence of Calcified Silent Neurocysticercosis in a Rural Village of Mexico

Human neurocysticercosis (NC) is a parasitic disease caused by Taenia solium when its larvae lodge in the central nervous system. NC prevalence estimates are obscured by the variable and often asymptomatic clinical picture. While infection depends on exposure, severity is possibly related with various host factors (immunity, genes and gender). This epidemiological study of cranial CT scans in an endemic rural community found that 9.1% of apparently healthy subjects had calcified lesions and were completely asymptomatic. Silent NC cases did not correlate with the exposure factors tested but showed family aggregation and higher rates of positive serology. Thus, NC prevalence may be higher than currently considered and host-related factors appear to be involved in infection and pathogenesis.

Symptomatic human neurocysticercosis: Age, sex and exposure factors relating with disease heterogeneity

Abstract.Objective:To evaluate the relevance of exposure and host biological factors in the heterogeneity of the clinical, radiological and inflammatory picture of neurocysticercosis (NCC).Methods:105 Mexican symptomatic NCC patients confirmed by imaging were studied before they received any specific treatment. The relationships studied were those between a) the patients’ characteristics (gender, age and level of exposure), b) the type of clinical picture and c) the radiological and inflammatory characteristics of the disease (number, aspect, localization of the parasites, and CSF leukocytecounts).Results:Results Seizures were the most frequent symptom and multiple subarachnoid cysticerci the most frequent localization. Symptomatology related to the developmental stage, number and localization of the parasites as well as the CSF leukocyte-counts. The total number of cysticercal lesions and of vesicular cysticerci increased with age,whereas the number of colloidal cysticerci decreased. CSF leukocyte-counts were higher in women than in men. Levels of exposure did not correlate with the clinical and radiological pictures.Conclusions:The variability found in the number, stage, localization and inflammation in the parasite lesions is strongly associated with the heterogeneity of NCC symptoms. The increased number of vesicular cysticerci and the decreased number of degenerating cysticerci with aging, as well as the prominence of inflammation in women suggest that immuno-endocrinological factors may play a role in susceptibility and pathogenesis. The data also show that with increasing age and exposure there is no increment in severity, a suggestion that there might be ways of regulating pathogenicity.

Subarachnoid basal neurocysticercosis: a focus on the most severe form of the disease

Neurocysticercosis is an endemic disease in Latin America, Asia and Africa with growing occurrence in industrialized countries due to the increase in migration from low- and middle-income to high-income countries. The most severe clinical presentation is when the parasite is located in the subarachnoid space at the base of the brain (NCSAB). Aside from its clinical presentation, the severity of this form of the disease is due to the difficulties in diagnosis and treatment. Although NCSAB frequency is lower than that reported for the parenchymal location of the parasite, its clinical relevance must be emphasized. We provide a critical review of the central epidemiological, clinical, diagnostic and therapeutic features of this particular form of the disease, which is still associated with unacceptably high rates of morbidity and mortality.

Castration and pregnancy of rural pigs significantly increase the prevalence of naturally acquired Taenia solium cysticercosis

Cuentepec is a rural village of central Mexico, where 1300 pigs were bred at the time of the study in conditions that favor Taenia solium transmission. The tongues of 1087 (84%) of these pigs were visually examined and 33% were found to be cysticercotic. Castration of male pigs increased prevalence from 23 to 50% (P < 0.001) and pregnancy in sows also increased their prevalence from 28 to 59% (P < 0.001). Thus, endocrinological conditions characterized by low levels of androgens or high levels of female hormones probably influence the susceptibility of pigs to T. solium cysticercosis as observed in mice infected with Taenia crassiceps. Delaying castration of male pigs and confinement of sows during pregnancy might significantly decrease the prevalence of pig-cysticercosis and help curb transmission without much cost or difficulty.

Population genetic structure of Taenia solium from Madagascar and Mexico: implications for clinical profile diversity and immunological technology.

Taenia solium is a cestode parasitic of humans and pigs that strongly impacts on public health in developing countries. Its larvae (cysticercus) lodge in the brain, causing neurocysticercosis, and in other tissues, like skeletal muscle and subcutaneous space, causing extraneuronal cysticercosis. Prevalences of these two clinical manifestations vary greatly among continents. Also, neurocysticercosis may be clinically heterogeneous, ranging from asymptomatic forms to severely incapacitating and even fatal presentation. Further, vaccine design and diagnosis technology have met with difficulties in sensitivity, specificity and reproducibility. Parasite diversity underlying clinical heterogeneity and technological difficulties is little explored. Here, T. solium genetic population structure and diversity was studied by way of random amplified polymorphic DNA in individual cysticerci collected from pigs in Madagascar and two regions in Mexico. The amplification profiles of T. solium were also compared with those of the murine cysticercus Taenia crassiceps (ORF strain). We show significant genetic differentiation between Madagascar and Mexico and between regions in Mexico, but less so between cysticerci from different localities in Mexico and none between cysticerci from different tissues from the same pig. We also found restricted genetic variability within populations and gene flow was estimated to be low between populations. Thus, genetic differentiation of T. solium suggests that different evolutionary paths have been taken and provides support for its involvement in the differential tissue distribution of cysticerci and varying degrees of severity of the disease. It may also explain difficulties in the development of vaccines and tools for immunodiagnosis.

Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors

Human neurocysticercosis (NC) is endemic in most countries of Latin America, Asia and Africa and is re-emerging in some industrialized nations. Both within and among endemic countries, NC is very variable in its clinical and radiological features, as well as in the intensity of the immuno-inflammatory reactions of the hosts. This review, focusing on the Mexican experience, describes and interprets the heterogeneity of NC as the result of different combinations among factors associated with the parasite, host and environment. The review may serve to foster similar descriptive efforts in other endemic areas of the world in order to facilitate the identification of the distinct factors that participate in the complex pathogenesis and diverse clinical outcomes of NC. In particular, it is necessary to understand the precise physiopathology of the inflammatory reaction associated with NC, as inflammation is one of the characteristics of those NC cases that are clinically more severe and less responsive to current treatments. Devising new medical interventions through the use of molecular regulators of the innate and adaptive immune responses of the host is a largely unexplored approach that could improve the existing forms of treatment.

TH2 profile in asymptomatic Taenia solium human neurocysticercosis

Neurocysticercosis (NC), a parasitic disease caused by Taenia solium, may be either asymptomatic or have mild to severe symptoms due to several factors. In this study, the immunological factors that underlie NC pleomorphism were studied. Ten of the 132 inhabitants of a rural community in Mexico (Tepez) had a computerized tomography (CT) scan compatible with calcified NC, and all were asymptomatic. Their immunological profiles were compared with those of 122 CT scan negative (non-NC) subjects from the same village. NC was associated with a TH2 response (IgG4, IL-4, IL-5, IL-13). Subjects from Tepez had higher levels of specific antibodies (IgG1, IgG2, IgG4, IgE) and specific cell proliferation than subjects from an area with low exposure (Ensenada). This suggests that non-NC subjects from Tepez had been exposed to T. solium and resisted infection in the brain. Distinct immunological profiles in equally exposed individuals differing in outcome of infection support the hypothesis of host-related factors in resistance to and pathogenesis of NC. This is the first study reporting the immunological profile associated with the asymptomatic form of NC.

Human Neurocysticercosis: Comparison of Different Diagnostic Tests Using Cerebrospinal Fluid

ABSTRACT Neurocysticercosis (NC), caused by the larval stage of Taenia solium, is one of the most common parasitic diseases of the central nervous system. The diagnosis of NC is mostly based on costly brain neuroimaging (computed tomography and/or nuclear magnetic resonance), which is rarely accessible in most affected areas. The most sensitive and specific tools for NC diagnosis are imagery techniques. The identification of specific antibodies and antigens is currently used only to support NC diagnosis due to their limited specificity and sensitivity. This study was performed to compare immunodiagnostic assays (antibody detection by enzyme-linked immunosorbent assay [ELISA] and enzyme-linked immunoelectrotransfer blotting [EITB] and HP10 antigen detection by ELISA) with the detection of parasite DNA by PCR amplification of a repetitive element of the parasite genome in the cerebrospinal fluid (CSF) of 121 radiologically and clinically characterized NC patients. Patients were divided into six groups according to the stage of the parasites and their localization. The CSF cellularity of each patient was also recorded. When all patients were considered, PCR exhibited the highest sensitivity (95.9%) and variable specificity (80% or 100%) depending on the controls used. The sensitivities of antibody detection by ELISA and EITB were not significantly different, and ELISA identified HP10 antigen mostly when vesicular cysticerci were located in the subarachnoideal basal cisterns. These results can help in the selection of different individual assays or combinations of assays to be used in NC diagnosis according to different requirements.

The immune response in Taenia solium cysticercosis: protection and injury

This article reviews current knowledge on the innate and acquired immune responses in human Taenia solium neurocysticercosis, highlighting the conditions that appear to be favourable for the survival or destruction of the parasite and for the benefit or injury to its host.