Parasitology International 55 (2006) S99 – S103 www.elsevier.com/locate/parint

Laboratory animal models for human Taenia solium ´ vila a, Nancy Teran a, Laura Aguilar-Vega a, Pablo Maravilla b, Guillermina A Pilar Mata-Miranda b, Ana Flisser a,b,* a b

Departamento de Microbiologia y Parasitologia, Facultad de Medicina, UNAM, 04510 Mexico DF. Mexico Direccion de Investigacion, Hospital General ‘‘Dr. Manuel Gea Gonzalez’’, SSA, 14000 Mexico DF, Mexico Available online 13 December 2005

Abstract Human beings are the only hosts of adult Taenia solium; thus, many aspects of the host – parasite relationship are unknown. The development of successful experimental models of taeniasis allows in-depth investigations of the host – parasite relationship. We established experimental models in hamsters, gerbils and chinchillas. Here we review our findings regarding the characteristics of the tapeworms, their anchoring site and development, as well as the humoral and cellular immune response they elicit. We also used statistics to analyze the data obtained in different infections performed along several years. Furthermore, we compared the size of T. solium rostellum and strobila recovered from hamsters and gerbils to those obtained from humans. Our data indicate that these rodents are adequate experimental models for studying T. solium in its adult stage; that parasites induce immune responses and that hamsters seem to be more permissive hosts than gerbils, since parasites survive for longer times, grow longer and develop more, and the inflammatory response in the intestinal mucosa against T. solium is moderate. Finally, chinchillas are the most successful experimental definitive model for adult T. solium, since tapeworms with gravid proglottids are obtained, and the life cycle can be continued to the intermediate host. D 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Experimental animal models; Gerbils; Hamsters; Immune response; Taenia solium

1. General aspects of human taeniasis Until a few years ago the information on the host –parasite relationship in taeniasis has been acquired from patients, especially those infected with Taenia saginata. Attention was given to clinical aspects, diagnosis and treatment [1,2]. In general, taeniasis has a clinical benign state, or it is frequently even asymptomatic. In a study undertaken with 3100 people infected with T. saginata, only up to 35% had some clinical symptom and 93% discharged proglottids [3]. Other studies showed abnormalities in gastric mucosal secretion and hipochlorhidria in 58% and 50%, respectively; histological sections of biopsies of patients with taeniasis that suffered hipochlorhidria showed a lower amount of parietal cells and a mononuclear cell infiltrate. After cestocidal treatment, in most patients the secretory activity was regained, the cellular infiltrate * Corresponding author. Direccion de Investigacion, Hospital General ‘‘Dr. Manuel Gea Gonzalez’’, SSA, 14000 Mexico DF, Mexico. Tel.: +52 55 56232466; fax: +52 55 56232382. E-mail address: [email protected] (A. Flisser). 1383-5769/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.parint.2005.11.015

diminished and there was an increase in parietal cells in the mucosa [4]. An increase of IgE and IgA antibodies was shown in serum of persons harboring intestinal T. saginata, the specificity of the antibodies was not demonstrated but, after eliminating the worm, antibody levels returned to basal values. Similarly, a cellular immune response was detected in T. saginata carriers using inhibition of leukocyte and of macrophage migration, and a decrease in lymphocyte stimulation induced with phytohemaglutinin was seen while the tapeworm was in the intestine; once expelled, the response returned to normal values [5,6]. Diagnosis of taeniasis is usually performed by the identification of proglottids in sieved feces or by the observation of eggs in coproparasitoscopic studies (CPS). Sensitivity of CPS is around 60% and only allows identifying the genus, since T. solium and T. saginata eggs are morphologically identical. Gravid proglottids can be differentiated because T. solium has 7 –11 lateral branches when counted in the central uterus, while T. saginata has 12 or more branches; nevertheless, release of proglottids does not occur in a predefined pattern. Species identification is also achieved by microscopical observation of the scolex, which in

G. A´vila et al. / Parasitology International 55 (2006) S99 – S103

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Table 1 Overall data from all experimental T. solium infections performed in immunodepressed hamsters (1992 – 2001) Sex

Hosts used Infected Infected Total number Total Total (age 7 – hamsters hamsters of cysticerci tapeworms recovery 41 weeks) (number) (%) inoculateda recovered (%)

Female 89 Male 47 Total 136 a

65 45 110

73 94 80

455 301 756

220 176 396

48 58 52

Cysticerci (4 – 8) with 90 – 100% evagination.

T. solium has a double crown of hooks and in T. saginata is unarmed [1,2]. 2. Adult Taenia solium development in hamsters and gerbils Last decade, an enzyme-linked immunosorbent assay (ELISA) for coproantigen (CpAg) capture was developed for diagnosis of taeniasis. CpAg ELISA allows detection from prepatency; therefore, it is useful for the follow-up of infections and treatments [7– 10]. This assay has been mostly used in epidemiological studies (reviewed in [11] and in the article ‘‘Where are the tapeworms’’ published in this volume). The standardization of the CpAg ELISA was possible because of the development of T. solium experimental models, since tapeworm material and infected hamster feces have been obtained and used for this purpose. The first model was published long ago by Verster [12,13] in immunodepressed hamsters and sexually mature tapeworms were obtained. Our group evaluated different experimental models: macaques, pigs, dogs, cats and rabbits did not develop T. solium tapeworms in spite of being immunodepressed [14]. Mature and pre-gravid tapeworms have been obtained in Mongolian gerbils (Meriones unguiculatus) and in golden hamsters (Mesocricetus auratus). The latter host has been used along 15 years during which five infections were performed in over 100 hamsters in order to evaluate several tapeworm and host parameters as well as the reproducibility of the models [14 –16]. An overall analysis of all the results Table 2 Association between tapeworm recovery, sex, age, steroid dose and % evagination of cysticerci in immunodepressed hamsters infected with adult T. solium Variable

Sex Female Male Age (weeks)  25