Host-cell apoptosis in Taenia solium-induced brain granulomas in naturally infected pigs

To assess whether apoptosis occurs in pig brain granulomas due to Taenia solium cysticerci, brain tissues from 30 pigs naturally infected with T. solium cysticercosis were evaluated by terminal deoxynucleotidyl transferase-end labelling (TUNEL) staining. In addition, tissues were stained with CD3 marker to identify T lymphocytes. Examination of TUNEL-stained tissues showed apoptotic cells in early lesions that contained viable cysticerci. Apoptotic cells were primarily found interspersed with normal cell types, and were mostly located in the inflammatory infiltrate. Late or advanced granulomas with disintegrated scolices did not show TUNEL-positive cells. CD3+ cells were found in both early and advanced lesions and apoptosis mainly co-localized with CD3+ T lymphocytes. This suggests that these cells are constantly undergoing apoptosis and thus die as soon as they arrive at the site of infection. Apoptosis indeed may be one way by which T. solium cysticerci down-regulate the host's cellular immune response in early cysticercosis. Therefore, further research is needed to establish if other cells besides T-lymphocytes are also a target for destruction by cysticerci in early cysticercosis as well as studies to assess if cysteine protease is expressed by viable cysticerci in situ.     

Efficacy and Safety of Anthelmintics Tested against Taenia solium Cysticercosis in Pigs

Porcine cysticercosis, an infection caused by Taenia solium metacestodes, is continuously being reported in low-income countries of Latin America, Asia, and sub-Saharan Africa. The disease was declared eradicable by the International Task Force for Diseases Eradication (ITFDE) in 1993, and it is listed among the 17 WHO Neglected Tropical Diseases and Neglected Zoonoses that are potentially eradicable. In view of that, WHO has proposed a step-wise approach to its elimination, including chemotherapy of infected pigs. Different drugs have been tested on porcine cysticercosis with varying efficacies. These include flubendazole, fenbendazole, albendazole, albendazole sulphoxide, oxfendazole, praziquantel, and nitazoxanide. This review summarises available information on the efficacies and adverse effects shown by these drugs in pigs. Oxfendazole has shown to be effective for the control of porcine cysticercosis; however, it needs to be integrated with other control approaches. There is a need for standardised guidelines for evaluating the efficacy of anthelmintics against porcine cysticercosis, and more efficacy studies are needed since the conclusions so far are based on a limited number of studies using few infected pigs.

Key Learning Points

• Among the anthelmintics evaluated, oxfendazole has proven to be safe and efficacious against porcine cysticercosis.
• Limited intervention trials have shown oxfendazole to be effective for control of porcine cysticercosis; however, it needs to be integrated with other control approaches.
• Standardised protocols for assessment of anthelmintic efficacy and effectiveness for control of porcine cysticercosis are lacking, making inter-study comparison difficult.
• More studies are needed to fully assess the efficacy and effectiveness of oxfendazole and other anthelmintics against T. solium cysticercosis and other pig parasitoses.

Key References

• Gonzales AE, Garcia HH, Gilman RH, Gavidia CM, Tsang VCW, et al. (1996) Effective, single-dose treatment of porcine cysticercosis with oxfendazole. Am J Trop Med Hyg 54: 391-394.
• Gonzalez AE, Falcon N, Gavidia C, Garcia HH, Tsang VCW, et al. (1997) Treatment of porcine cysticercosis with oxfendazole: a dose-response trial. Vet Rec 141: 420-422.
• Moreno L, Lopez-Urbina MT, Faras C, Domingue G, Donadeu M, et al. (2012) A high oxfendazole dose to control porcine cysticercosis: Pharmacokinetics and tissue residue profiles. Food Chem Toxicol 50: 3819 – 3825.
• Sikasunge CS, Johansen MV, Willingham AL, III, Leifsson PS, Phiri IK (2008) Taenia solium porcine cysticercosis: viability of cysticerci and persistency of antibodies and cysticercal antigens after treatment with oxfendazole. Vet Parasitol 158: 57-66.
• Torres A, Plancarte A, Villalobos ANM, Aluja ASd, Navarro R, et al. (1992) Praziquantel treatment of porcine brain and muscle Taenia solium cysticercosis. 3. Effect of 1-day treatment. Parasitol Res 78: 161-164.

     

Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling

Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.     

Assessment of routine inspection methods for porcine cysticercosis in Zambian village pigs

The value of tongue and meat inspection as diagnostic tools for porcine cysticercosis was assessed in 65 Zambian village pigs by comparing the results with carcass dissections. In addition, the intensity of infections, distribution and viability of cysts in infected pigs were measured. Five pigs (7.7%) were positive on tongue examination, while routine meat inspection showed 12 (18.5%) positives. However, carcass dissections detected cysticerci in 31 (47.7%) pigs. The range in number of cysticerci was 1 to 14,662 per carcass. Cysticerci were distributed throughout the carcass with the highest concentration in the heart, tongue and hind legs. In one animal 13 viable cysts were detected only in the brain. Fourteen pigs had more than 100 viable cysts, six between 2 and 100, and four had single cyst infections. Seven animals harboured only calcified cysts. These findings demonstrate the serious shortcomings of routine detection methods for porcine cysticercosis. While the specificity of tongue palpation and meat inspection was 100%, these tests failed to detect the infection in 83.9% and 61.3% of infected pigs, respectively.