Taenia solium life cycle: how does NCC come about?

The adult worm of T. solium is found in the small intestine of Homo sapiens, the only known definitive host of T. solium (White, Reference White2000) (Fig. 1). These worms can produce up to 2 00 000 and 4 00 000 infectious oncospheres (eggs) per day, which are excreted in the human feces (White, Reference White2000). If infected feces are ingested by a pig, the oncospheres become activated/mature in the presence of bile salts and intestinal enzymes, and force their way through the gut wall and into the bloodstream (White, Reference White2000). At blood vessel terminations, the activated oncospheres lodge in muscle, nervous, subcutaneous and ocular tissue (White, Reference White2000). There, each mature oncosphere evolves into a vesicular larva with an invaginated scolex (also known as a cysticercus) over a period of weeks or months (White, Reference White2000). These cysticerci have a lifespan of a few years (White, Reference White2000). If pork meat containing a viable cysticercus is ingested by a human, the scolex of the cysticercus evaginates in the small intestine (due to a change in osmotic pressure), and attaches to the intestinal wall. Here the larva develops once more into an adult worm (White, Reference White2000) (see Fig. 1).

Fig. 1.

Schematic representation illustrating the life cycle of Taenia solium and the process which results in human infection and neurocysticercosis.

NCC occurs when humans accidentally ingest the oncospheres of T. solium (Carpio, Reference Carpio2002). This may occur via food or water in areas where water sources are contaminated by human feces, or via accidental ingestion of tiny amounts of the feces of an adult tapeworm carrier in the household (Flisser, Reference Flisser1994). Oncospheres are also activated in the human gut as they would be in the pig gut, and are able to penetrate the gut wall and pass into the bloodstream (Carpio, Reference Carpio2002). The activated oncospheres may then lodge in muscle, ocular, subcutaneous or nervous tissue, with nervous system infection being of the greatest clinical concern (Carpio, Reference Carpio2002).

NCC disease progression and manifestation in humans

Following initial infection and the establishment of cysticerci in the brain parenchyma, sub-arachnoid space or ventricles, there is usually a lengthy period (months to years) in which the host shows little to no immune or inflammatory response to the infection and experiences no clinical symptoms (White, Reference White2000). This may be because the viable cysticerci employ various immune modulatory mechanisms to remain largely unaffected by the host immune system (White, Reference White2000). Viable cysticerci are also referred to as being in the vesicular stage (White, Reference White2000). At some point, however, the cysts appear to lose their ability to control the host immune response and the cyst wall and fluid become infiltrated by host inflammatory cells. This is termed the colloidal phase. Thereafter the cyst cavity collapses and the host response progresses to surrounding the cyst with fibrosis, resiulting in the granular–nodular phase. Together, cysts in the colloidal or granular–nodular phase are often termed as transitional phase cysts. Eventually the entire cyst is replaced with fibrosis and calcifies and is then said to be in the calcific stage (White, Reference White2000).

Manifestations of NCC are often studied and described in reference to the stage of the cyst (White, Reference White2000; Fleury et al., Reference Fleury, Cardenas, Adalid-Peralta, Fragoso and Sciutto2016; Gonzales et al., Reference Gonzales, Rivera and Garcia2016) (see Fig. 2). Cyst stages are largely determined using imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) scans, as well as post-mortem brain dissections (Carpio and Romo, Reference Carpio and Romo2014). A systematic review of the prevalence of different clinical manifestation of NCC reports seizures or epilepsy as the most common symptom, followed by headaches, intracranial hypertension, hydrocephalus and meningitis (Carabin et al., Reference Carabin, Ndimubanzi, Budke, Nguyen, Qian, Cowan, Stoner, Rainwater and Dickey2011). Seizures occur more commonly in patients with calcified cysts, although this symptom of NCC is still prevalent in those with transitional/active cysts. Intracranial hypertension, hydrocephalus and meningitis seem to be much more common in patients with transitional/active cysts (see Fig. 2). There are numerous other, extremely varied, symptoms secondary to NCC that have been reported (Patel et al., Reference Patel, Jha and Yadav2006; Mahanty and Garcia, Reference Mahanty and Garcia2010; Peon et al., Reference Peon, Ledesma-Soto and Terrazas2016). This diversity in symptoms has been attributed to the diversity in cyst antigens, numbers, stages, positions in the nervous system and the level of inflammation induced (Yakoleff-Greenhouse et al., Reference Yakoleff-Greenhouse, Flisser, Sierra and Larralde1982; Fleury et al., Reference Fleury, Dessein, Marie, Dumas, Tapia, Larralde and Sciutto2004).

Fig. 2.

Key differences in clinical, molecular and immune characteristics associated with Taenia solium cysts in neurocysticercosis [photographs sourced, with permission, from Carpio and Romo (Reference Carpio and Romo2014)].

Challenges to NCC research in humans and the necessity for animal models

A major challenge for the study of NCC in humans is that the disease can only be studied as it occurs naturally. This means that there are large numbers of variables which cannot be controlled for in human studies, making it hard to isolate conditions which lead to symptom onset. Additionally, when patients present with symptomatic NCC, there exists an ethical obligation to start treatment as soon as possible, which also obstructs the understanding of the disease processes underlying symptom development (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999). Study of the disease in humans is costly, as the only definitive diagnostic techniques are MRI or CT scans, which are typically not available in endemic areas with the highest prevalence rates. In addition, the large variability in human pathology and symptom presentation means that large sample sizes are required to obtain statistical significance. Longitudinal studies in humans are also challenging due to the lengthy time course of the disease, both in terms of symptom onset and progression of the cysts (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999).

Studies using human tissue are also limited, as most rely on specimens that are collected using only minimally invasive procedures such as the collection of blood samples. Beyond that, samples of brain tissue or cerebrospinal fluid can only be sourced in cases where these are sampled out of clinical or diagnostic need. This is fairly rare, making it difficult to obtain large sample sizes (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999). Taken together, these challenges greatly limit the exploration of the cellular and molecular processes underlying disease progression in NCC.

Animal models of NCC offer the potential to overcome many of these limitations: they allow for the experimental infection of animals in a controlled environment and for the study of disease progression both with and without treatment interventions. They are often much more cost-effective, as definitive infection can be confirmed post-mortem without neuroimaging, and smaller sample sizes can be used due to the controlled experimental environment. They facilitate longitudinal studies, as the time course of disease, especially in smaller animals, is much shorter and can be accelerated experimentally. Most importantly, animal models allow for unrestricted access to brain tissue and cerebrospinal fluid, thereby enabling more extensive cellular and molecular exploration. Although animal models have great utility in the study of disease processes in NCC, one should always bear in mind that findings from animal studies may not necessarily extrapolate to the human condition, as no animal model can fully recapitulate the human disease state.

In the section that follows, we review existing models of NCC, whilst describing their specific strengths and weaknesses.

Taenia solium

Taenia solium (T. solium) is the ‘gold standard’ organism in the study of NCC, as it is the cestode responsible for pathology in humans. Further, the genome of T. solium has recently been sequenced, allowing for the use of powerful genetic tools (Tsai et al., Reference Tsai, Zarowiecki, Holroyd, Garciarrubio, Sanchez-Flores, Brooks, Tracey, Bobes, Fragoso, Sciutto, Aslett, Beasley, Bennett, Cai, Camicia, Clark, Cucher, De Silva, Day, Deplazes, Estrada, Fernandez, Holland, Hou, Hu, Huckvale, Hung, Kamenetzky, Keane, Kiss, Koziol, Lambert, Liu, Luo, Luo, Macchiaroli, Nichol, Paps, Parkinson, Pouchkina-Stantcheva, Riddiford, Rosenvit, Salinas, Wasmuth, Zamanian, Zheng, Consortium, Cai, Soberon, Olson, Laclette, Brehm and Berriman2013). However, T. solium has numerous practical limitations for use within the laboratory setting. It is highly infectious to humans and its experimental use requires strict biosafety measures. It is also challenging to obtain T. solium larvae, and extremely hard to maintain a steady experimental supply of the larvae. Larvae (or cysticerci) can be obtained in three ways: they can be harvested directly from a naturally or experimentally infected pig; they can be produced experimentally by feeding oncospheres [obtained from gravid proglottids in the stool of infected human patients, or from experimentally infected, immunosuppressed, chinchillas or hamsters (Arora et al., Reference Arora, Tripathi, Kumar, Mondal, Mishra and Prasad2017)] to a host in which they will be activated and develop naturally into cysticerci (Nguekam et al., Reference Nguekam, Zoli, Vondou, Pouedet, Assana, Dorny, Brandt, Losson and Geerts2003); or they can be produced by activating oncospheres in vitro and then injecting the activated oncospheres into the brain to develop into cysts (Liu et al., Reference Liu, Li and Hao2002; Verastegui et al., Reference Verastegui, Mejia, Clark, Gavidia, Mamani, Ccopa, Angulo, Chile, Carmen, Medina, Garcia, Rodriguez, Ortega and Gilman2015). Taenia solium may also not be infectious to animals utilized in animal models, thus requiring direct intracranial application, but the larvae of T. solium are large, and may displace most of the brain tissue in small animals.

Taenia crassiceps

Taenia crassiceps (T. crassiceps) is the most commonly utilized model organism for T. solium. The two cestodes are closely related, belonging to the same genus, and have been shown to have significant antigenic similarity (Larralde et al., Reference Larralde, Montoya, Sciutto, Diaz, Govezensky and Coltorti1989; Sciutto et al., Reference Sciutto, Fragoso, Trueba, Lemus, Montoya, Diaz, Govezensky, Lomeli, Tapia and Larralde1990). Taenia crassiceps very rarely infect humans, making it a reasonably safe laboratory model, not requiring extensive biosafety measures (Willms and Zurabian, Reference Willms and Zurabian2010). This is particularly the case for the ORF strain of T. crassiceps, which has entirely lost the ability to infect a definitive host and mature into adult worms, meaning that it does not present an infection risk to animals (Willms and Zurabian, Reference Willms and Zurabian2010). A major advantage of T. crassiceps as a model organism for T. solium is that T. crassiceps larvae are able to rapidly asexually divide by budding in the intermediate host (usually mice), providing a simple way to maintain a steady experimental supply of the organism (Stringer et al., Reference Stringer, Marks, White and Robinson2003; Willms and Zurabian, Reference Willms and Zurabian2010). The larvae are also able to survive for several weeks in in vitro culture.

The use of T. crassiceps as a model organism in the study of NCC also has its limitations. The definitive hosts for T. crassiceps are carnivores, most often wild canines (Willms and Zurabian, Reference Willms and Zurabian2010), whilst that of T. solium is humans (see Fig. 3). Taenia crassiceps larvae are usually hosted by rodents and small moles (Willms and Zurabian, Reference Willms and Zurabian2010), whilst pigs host larval T. solium (see Fig. 3). As a result, there must exist differences in the antigens and species-specific immune responses induced by the two organisms (Sciutto et al., Reference Sciutto, Fragoso and Larralde2011). Another concern when utilizing T. crassiceps is that it has been found that many of the strains undergo morphological and genetic changes when they are maintained via serial intraperitoneal inoculation in mice, which may affect their immunogenicity and increase their dissimilarity to T. solium larvae (Zurabian et al., Reference Zurabian, Aguilar, Jiménez, Robert and Willms2008; Willms and Zurabian, Reference Willms and Zurabian2010). Lastly, T. crassiceps are difficult to use where intracranial inoculation of small model animals is desired (e.g. mice), as the cysticerci displace most of the brain tissue (Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010).

Fig. 3.

The intermediate and definitive hosts of Taenia solium, Taenia crassiceps and Mesocestoides corti.

Mesocestoides corti

Mesocestoides corti (M. corti) is thought to infect anthropods as the initial host, small mammals, birds, reptiles and amphibians in the larval form, and carnivores, such as dogs and cats, as an adult worm (Crosbie et al., Reference Crosbie, Padgett and Boyce2000) (see Fig. 3). Mesocestoides corti is not known to infect humans, making it a safe laboratory model not requiring extensive biosafety measures. Mesocestoides corti asexually divides both as cysticerci in the intermediate host (Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010) and as adult worms in the definitive host (Schmidt and Todd, Reference Schmidt and Todd1978). The larvae have also been shown to be able to survive and divide under the right in vitro culturing conditions (Voge and Coulombe, Reference Voge and Coulombe1966; Vendelova et al., Reference Vendelova, Hrckova, Lutz, Brehm and Komguep2016). A colony of M. corti can therefore be experimentally produced and maintained with relative ease (Schmidt and Todd, Reference Schmidt and Todd1978). Mesocestoides corti is closely related to T. solium, but is not of the same genus, which means that it may have greater antigenic difference to T. solium than does T. crassiceps (Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010). A major advantage of M. corti is that the cysticerci are significantly smaller than those of T. solium and T. crassiceps, which makes it easier to use for intracranial inoculation of small model animals such as rodents (Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010). However, unlike T. solium and T. crassiceps, M. corti has not been known to infect the CNS of any of its hosts during its natural cycle, which means that intracranial injection by the experimenter is the only way in which M. corti can enter the CNS (Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010).

Taenia crassiceps in mice

Mice are attractive model organisms for studying NCC due to their popularity across the life sciences. They are relatively cheap to maintain and have a rapid breeding cycle. Most importantly, the relative ease of modifying the mouse genome means that transgenic strains allowing molecular dissection of immunological and neurological pathways are now widely available.

NCC has been modelled in mice by intracranially injecting T. crassiceps larval extracts or intact early-stage larvae (Matos-silva et al., Reference Matos-silva, Reciputti, De Paula, Oliveira, Moura, Vinaud, Oliveira and Lino-Júnior2012; Robinson et al., Reference Robinson, Garza, Weinstock, Serpa, Goodman, Eckols, Firozgary and Tweardy2012; Leandro et al., Reference Leandro, Fraga, de Souza Lino and Vinaud2014). Different strains of mice show differing susceptibility to T. crassiceps intracranial infection (Matos-silva et al., Reference Matos-silva, Reciputti, De Paula, Oliveira, Moura, Vinaud, Oliveira and Lino-Júnior2012). There has been one report of T. crassiceps in the brain of a wild mouse (Kroeze and Freeman, Reference Kroeze and Freeman1982), which is suggestive that further experimentation on the oral administration of T. crassiceps oncospheres in mice (perhaps using immunocompromised individuals) may have potential for the development of a model somewhat more congruent to the condition in humans. One strength of this model is that intracranial injection of peritoneal granulomas can produce seizures in the host (Robinson et al., Reference Robinson, Garza, Weinstock, Serpa, Goodman, Eckols, Firozgary and Tweardy2012), although it is not known whether these seizures could persist chronically.

Intracranial administration of T. crassiceps in mice has provided some valuable insights: one study has shown that early-stage granuloma extracts containing substance P may be responsible for seizure activity; another has shown this model results in encephalitis closely resembling that in human NCC; and a third has shown that Taenia larvae in the brain are highly adaptable when faced with adverse conditions (Matos-silva et al., Reference Matos-silva, Reciputti, De Paula, Oliveira, Moura, Vinaud, Oliveira and Lino-Júnior2012; Robinson et al., Reference Robinson, Garza, Weinstock, Serpa, Goodman, Eckols, Firozgary and Tweardy2012; Leandro et al., Reference Leandro, Fraga, de Souza Lino and Vinaud2014).

Mesocestoides corti in mice

Mesocestoides corti (M. corti) can be utilized in conjunction with cultured mouse primary microglia to explore helminth-associated immunomodulation. One study utilizing this model system elucidated an immunosuppressive mechanism that may help to explain the delay in the onset of neuroinflammation seen in human NCC (Sun et al., Reference Sun, Chauhan, Sukumaran, Sharma, Singh and Mishra2014). More commonly, however, M. corti larvae are administered intracranially in mice (as they do not migrate to the CNS if administered orally) to model human NCC (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999, Reference Cardona, Gonzalez and Teale2003; Cardona and Teale, Reference Cardona and Teale2002; Alvarez and Teale, Reference Alvarez and Teale2007; Alvarez et al., Reference Alvarez, Mishra, Gundra, Mishra and Teale2010). This model presents with an initial relative lack of immune responsiveness, which is thought may be useful as a comparative model for the study of asymptomatic NCC (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999). Thus far no seizures have been reported in this model system of NCC, but it has provided much insight into potential mechanisms that dictate the severity of inflammation, blood–brain barrier breakdown, parasite burden and neuronal pathology (Cardona et al., Reference Cardona, Restrepo, Jaramillo and Teale1999, Reference Cardona, Gonzalez and Teale2003; Cardona and Teale, Reference Cardona and Teale2002; Alvarez and Teale, Reference Alvarez and Teale2006, Reference Alvarez and Teale2007).

Taenia crassiceps in rats

Extracts of T. crassiceps larvae have been administered intracranially in rats, but to date no studies have been performed where intact oncospheres/cysts are injected. Studies using this model have shown that the intracranial administration of early-stage granulomal extracts can induce seizures in the host (Stringer et al., Reference Stringer, Marks, White and Robinson2003; Robinson et al., Reference Robinson, Garza, Weinstock, Serpa, Goodman, Eckols, Firozgary and Tweardy2012). This is a very promising finding in terms of its potential use in the study of seizures secondary to NCC. It should be noted, however, that these studies are limited by the fact that the granulomas were produced peripherally in mice, and immune responses differ in different hosts, as well as peripherally as compared with the CNS, so the content of these granulomas may not be reflective of brain cysts. Brain activity was monitored acutely in these studies, so it is not yet known whether recurrent seizures would present in these rats.

Taenia solium in rats

Taenia solium does not naturally infect rodents, and as such very little research has been done using the T. solium–rat combination. In one study, however, activated oncospheres were intracranially injected into rats, and these were found to form cysts in roughly half of the rats after about 4 months (Verastegui et al., Reference Verastegui, Mejia, Clark, Gavidia, Mamani, Ccopa, Angulo, Chile, Carmen, Medina, Garcia, Rodriguez, Ortega and Gilman2015). Importantly, infection is much more successful in younger rats. The authors report that this model presents with many NCC characteristics typical of human infection and that 9% of infected rats present with chronic seizures (Verastegui et al., Reference Verastegui, Mejia, Clark, Gavidia, Mamani, Ccopa, Angulo, Chile, Carmen, Medina, Garcia, Rodriguez, Ortega and Gilman2015). Although this is not a very efficient model of epilepsy secondary to NCC, the induction of chronic seizures is intriguing, and it may be worth exploring whether this model could be optimized for seizure occurrence. The study further revealed diverse cyst distribution and immunopathology, similar to what is observed in humans. A major advantage of this model over other rodent models is the use of the parasite responsible for human disease.

Taenia solium in pigs

The study of T. solium NCC in pigs often involves the utilization of pigs reared for agricultural purposes that have naturally acquired the infection. Pigs can also be experimentally infected by oral administration of T. solium eggs to induce NCC, with between 20 and 100% of pigs dosed with high numbers of eggs developing NCC (de Aluja et al., Reference de Aluja, Villalobos, Plancarte, Rodarte, Hernandez and Sciutto1996; Santamaria et al., Reference Santamaria, Plancarte and de Aluja2002; Nguekam et al., Reference Nguekam, Zoli, Vondou, Pouedet, Assana, Dorny, Brandt, Losson and Geerts2003). Older pigs appear to be more resistant to infection than younger pigs (Santamaria et al., Reference Santamaria, Plancarte and de Aluja2002). Recently, a new model of pig NCC was developed whereby activated T. solium oncospheres are surgically implanted into the subarachnoid space (Fleury et al., Reference Fleury, Trejo, Cisneros, García-Navarrete, Villalobos, Hernández, Hernández, Hernández, Rosas, Bobes, de Aluja, Sciutto and Fragoso2015). All infected pigs developed brain cysts, although at very low infection efficiencies (Fleury et al., Reference Fleury, Trejo, Cisneros, García-Navarrete, Villalobos, Hernández, Hernández, Hernández, Rosas, Bobes, de Aluja, Sciutto and Fragoso2015). This model surprisingly did not result in any neurological signs (Fleury et al., Reference Fleury, Trejo, Cisneros, García-Navarrete, Villalobos, Hernández, Hernández, Hernández, Rosas, Bobes, de Aluja, Sciutto and Fragoso2015).

The pig model system of NCC has been extremely useful in characterizing immunopathological and proteomic changes in response to T. solium in the brain, both in the normal course of disease and after a vaccination or treatment protocol. Significant overlap between human and pig reactions has been found (Molinari et al., Reference Molinari, Meza and Tato1983; Sikasunge et al., Reference Sikasunge, Johansen, Phiri, Willingham and Leifsson2009; Guerra-Giraldez et al., Reference Guerra-Giraldez, Marzal, Cangalaya, Balboa, Orrego, Paredes, Gonzales-Gustavson, Arroyo, García, González, Mahanty and Nash2013; Singh et al., Reference Singh, Prasad, Prasad, Tripathi, Gupta and Husain2013; Mahanty et al., Reference Mahanty, Orrego, Mayta, Marzal, Cangalaya, Paredes, Gonzales-Gustavson, Arroyo, Gonzalez, Guerra-Giraldez, Garcia and Nash2015; Christensen et al., Reference Christensen, Trevisan, Leifsson and Johansen2016; Navarrete-Perea et al., Reference Navarrete-Perea, Isasa, Paulo, Corral-Corral, Flores-Bautista, Hernández-Téllez, Bobes, Fragoso, Sciutto, Soberón, Gygi and Laclette2017). A recent study reports severe seizures in naturally infected pigs, which could be extremely valuable in aiding progress towards understanding the most common symptomatic presentation in NCC (Trevisan et al., Reference Trevisan, Mkupasi, Ngowi, Forkman and Johansen2016). The pigs that presented with seizures in this study were much older than the others in the sample group, suggesting that a longer infection/experimental period may be necessary for neurological symptoms to present (Trevisan et al., Reference Trevisan, Mkupasi, Ngowi, Forkman and Johansen2016). NCC in pigs also presents with great variation in the infection characteristics and antibody response, which suggests that porcine models may be able, to some extent, to recapitulate the great variation in pathology and disease progression that is observed in infected humans (Prasad et al., Reference Prasad, Chawla, Prasad, Tripathi, Husain and Gupta2006; Saenz et al., Reference Saenz, Ramirez, Aluja, Escobar, Fragoso, Morales, Perez-Tamayo, Rosetti, Larralde, Sciutto and Fleury2008).

Limitations of the pig–T. solium model system includes that this model can prove very time and resource intensive, with T. solium cysts taking as long as 350 days to form in pigs (de Aluja et al., Reference de Aluja, Villalobos, Plancarte, Rodarte, Hernandez and Sciutto1996), pig handlers requiring training and larger animals requiring more resources to feed and keep (de Aluja et al., Reference de Aluja, Villalobos, Plancarte, Rodarte, Hernandez and Sciutto1996; Arora et al., Reference Arora, Tripathi, Kumar, Mondal, Mishra and Prasad2017).

Taenia solium in rhesus monkeys

Primate studies of neurological conditions are rare due to the significant ethical (Greene et al., Reference Greene, Schill, Takahashi, Bateman-House, Beauchamp, Bok, Cheney, Coyle, Deacon, Dennett, Donovan, Flanagan, Goldman, Greely, Martin, Miller, Mueller, Siegel, Solter, Gearhart, McKhann and Faden2005) and legal (Fox, Reference Fox2009) implications of using primates for research purposes. Many countries have laws in place either preventing primate research or restricting their use to cases where all other options have been exhausted or found unsuitable (Greene et al., Reference Greene, Schill, Takahashi, Bateman-House, Beauchamp, Bok, Cheney, Coyle, Deacon, Dennett, Donovan, Flanagan, Goldman, Greely, Martin, Miller, Mueller, Siegel, Solter, Gearhart, McKhann and Faden2005; Fox, Reference Fox2009).

Taenia solium has, however, been reported to infect several non-human primates in its larval form, although this is considered an ‘accidental infection’ since T. solium does not require infection of non-human primates to complete its life cycle (Kuntz, Reference Kuntz and Bourne1973; Johnston et al., Reference Johnston, Dyer, Madison-Antenucci, Mergen, Veeder and Brice2016). NCC can be reliably induced in rhesus monkeys by feeding them large doses of activated T. solium oncospheres. The infected monkeys present with seizures and clinical symptoms very similar to those in humans within a matter of days, and if not treated may eventually die from the infection (Saleque et al., Reference Saleque, Chowdhury, Iyer and Baruah1988; Chowdhury et al., Reference Chowdhury, Saleque, Sood and Singla2014). Symptom presentation is delayed and attenuated in monkeys receiving smaller numbers of oncospheres, which may more closely resemble the human condition (Chowdhury et al., Reference Chowdhury, Saleque, Sood and Singla2014). It is interesting to note that symptom onset could be induced within a matter of days, in contrast to a study reporting a case of naturally acquired NCC in an 8-year-old rhesus monkey, which presented with no symptoms (Johnston et al., Reference Johnston, Dyer, Madison-Antenucci, Mergen, Veeder and Brice2016). This could be explained by the high dosage of oncospheres used in the experimental studies and serves as a reminder of the importance of dose in eliciting disease phenotypes in models of NCC.