Lights and shadows of the Taenia asiatica life cycle and pathogenicity.

Humans are definitive hosts of two well-known species of the Taenia genus, Taenia solium (the pig tapeworm) and Taenia saginata (the cattle tapeworm). In the 1990s, a third species, Taenia asiatica, was discovered, sharing features with the other two since the adult morphology is similar to that of T. saginata, but its life cycle is like that of T. solium. Human taeniasis usually is asymptomatic or displays mild symptoms, and only T. solium can cause other sometimes serious disorders when humans accidentally ingest the eggs and develop the larval stage in different organs (cysticercosis). In this review, we expose what we currently know (lights) and what we do not yet know (shadows) about the life cycle and pathogenicity of T. asiatica. Concerning its life cycle, the main uncertainty is whether humans can act as intermediate hosts of this species. We also suggest that due to its small size and location in pigs, the cysticerci probably escape veterinary inspection becoming a silent parasite. Concerning pathogenicity, it is still not known if T. asiatica can cause human liver cysticercosis, taking into account its principal hepatic tropism in pigs. To answer all these questions it would be essential to perform sensitive as well as specific diagnostic techniques for T. asiatica in humans and pigs. Currently, only molecular methods are able to determine the Taenia species, since morphology and immunology are useless, but unfortunately although largely used in research those methods are not employed in routine diagnosis.

INTRODUCTION

Three species of the Taenia genus are intestinal parasites of humans, Taenia solium, Taenia saginata and Taenia asiatica. However, only two of them, T. solium and T. saginata, have been considered for centuries, T. asiatica remained undiscovered until recently.[1]

The discovery of T. asiatica was based on the profound knowledge of the other two Taenia species. In a few words, the species that lives at the larval stage (cysticercus) in pigs (T. solium) possesses, at the adult stage, proglottids with a ramified uterus with fewer than 13 lateral branches (between 7 and 11), and the species whose cysticerci live in cattle (T. saginata) possesses proglottids, which include a ramified uterus with more than 13 lateral branches (between 14 and 32). The cysticerci of T. asiatica also live in pigs, as T. solium does, but the proglottids include a ramified uterus with more than 13 lateral branches, just like T. saginata [Figure 1].[2] Therefore, T. saginata and T. asiatica proglottids shed by humans are practically indistinguishable, and hence T. asiatica has been confounded with T. saginata for centuries.[3]

Figure 1

Human Taenia life cycles and gravid proglottids (uterus) morphology

Concerning pathogenicity, the intestinal adult stage of the three Taenia species usually does not cause relevant symptoms, while, apparently, only T. solium may cause another disorder since the eggs of this species can infect humans. The accidental ingestion of eggs released by human tapeworm carriers causes cysticercosis, i.e., the extra-intestinal development of T. solium larvae mainly in muscles, eyes and the central nervous system (neurocysticercosis). Approximately 50,000 infected individuals die annually due to neurocysticercosis.[4]

Before exposing the lights and shadows of T. asiatica, it would be worthwhile to briefly summarize some historical and phylogenetic remarks on the three human Taenia species.

LOOKING BACKWARD

Taenia infection has been recognized since biblical times. A detailed history on human Taenia is described by Grove,[5] Cox,[6] or Wadia and Singh,[7] among others.

The earliest reference to tapeworms was found in the works of ancient Egyptians dated almost 2000 BC. Hippocrates was one of the first who wrote on T. solium. The first report of T. saginata was made by Audry in 1700, but he was unable to distinguish the proglottids of the two tapeworms. Goeze in 1782 was the first who correctly described the worm in his treatise on helminthology.[8] It was not until the middle of the 19th century that Küchenmeister recognized the differences between T. solium and T. saginata based on the morphology of the scolex.[9] Leuckart was the first who experimentally showed that proglottids of T. saginata fed to cattle developed into cysticerci in calf muscles.[10] Finally, Oliver was the first who discovered that “bladder worms” developed into adult T. saginata when ingested by humans.[11]

The first person who demonstrated that pigs are the intermediate hosts of T. solium was the Belgian, van Beneden. In 1853, he gave T. solium eggs to a pig. When the pig was slaughtered at the abattoir four and a half months later, he found a large number of T. solium larvae (Cysticercus cellulosae) in the muscles.[12]

Cysticercosis in humans due to T. solium was described by Rumler in 1558;[13] however, the connection between tapeworms and cysticercosis had not been made at that time. Around 1850, Küchenmeister, largely criticized for his unethical practices, fed pork meat containing cysticerci of T. solium to humans awaiting execution in prison and after they had been executed, he recovered developing and adult tapeworms in their intestines.[14] By the middle of the 19th century, it was established that cysticercosis was caused by the ingestion of T. solium eggs.

The existence of a third Taenia species was not considered until the middle of the 20th century. In 1966, Huang and collaborators pointed out that the Taenia species present in Taiwan aborigines might not be the same as T. saginata.[15] This conclusion was based on the fact that although the morphology of the expelled proglottids indicated T. saginata, the patients had not eaten beef – cattle being the natural intermediate host of T. saginata, but their diet was exclusively based on wild boars and pigs.

In the 1980s Fan came up with the idea that the species found in several Asian countries (Taiwan, Korea, Indonesia) could be a new one.[16] This Taenia was known as Taiwan Taenia or the Asian Taenia until, in 1993, when Eom and Rim proposed to definitely consider it a new species, namely T. asiatica.[1] Lately, and due to its molecular similarities to T. saginata, Fan et al. proposed considering this Asian Taenia as a subspecies of T. saginata, i.e., T. saginata asiatica,[17] leading to contrary opinions on its systematic status until T. asiatica was finally considered a valid species.[18]

LOOKING BACK EVEN FURTHER

The host distribution for species of Taenia is related to historical ecology and food habits. African felids and canids are the most ancient definitive hosts of taeniids. Hunter-gatherer hominids would have acquired Taenia infections when they competed with hyaenids and felids for the same wild bovine and boar prey in the savannahs of sub-Saharan Africa during the past 1-2.5 MYBP. Taenia acquisition is consistent with the shift in the diet of hominids from herbivory to omnivory and facultative carnivory near 2.0-2.5 MYBP.[1819]

Phylogenetic resolution for human Taenia indicates independent origins for T. solium and T. asiatica + T. saginata. Hence, although discovered only 20 years ago, it is estimated that the divergence of T. saginata and T. asiatica took place 0.78-1.71 MYBP in Africa or Eurasia.[18] The biotic expansion from Africa into Eurasia may have resulted in isolation and later divergence of T. asiatica in Asia. A total of eight extant boar species have been identified in South-East Asia. This diversity of potential intermediate hosts in this area may have influenced the switch of intermediate host for T. asiatica from herbivore to swine. Therefore, the association of T. asiatica with swine may have been established in Asia following divergence of host populations that later expanded into Europe, being consistent with a dominant distribution of this species in Asian countries.[1819]

LIGHTS AND SHADOWS OF THE T. ASIATICA LIFE CYCLE

The two earlier known species of the Taenia genus, i.e., T. solium and T. saginata, are parasites that at the adult stage exclusively settle in the intestine of humans. However, there is a clear difference in the nature of their intermediate hosts. Cysticerci of T. saginata exclusively live in muscles and viscera of herbivorous hosts (cattle), while the T. solium larval stage is also able to live in muscles and viscera of a variety of omnivorous hosts such as pigs, dogs and also humans.

Facts such as, for instance, people in Sorok Island (southern Korea), where no cattle lived, were only infected by T. saginata-like tapeworms,[20] triggered the studies aimed at finding the true human source of that Taenia infection. During the 80s and early 90s, several articles were published concerning different experimental infections in domestic animals with eggs of Korean, Taiwanese, Indonesian or Thai strains of the Asian Taenia. In 1988, tiny cysticerci were found in the livers of pigs and wild boars in Taiwan, where, according to an old tradition, raw viscera of swine are eaten,[16] suggesting that pigs were the most suitable intermediate host for Taiwan Taenia.[21] Later on, the finding of the cysticerci of the Asian Taenia in the liver of natural infected pigs was also reported.[22] Then, the life cycle of T. asiatica was finally demonstrated thanks to a human experimental autoinfection with five cysticerci originating from the liver of a natural infected pig.[23] The volunteer was infected for two two years and after treatment with Niclosamide two strobilae were recovered. Precisely, these strobilae were used to describe the new species T. asiatica in 1993.[1]

The following are some of the known features (lights) of T. asiatica life cycle and also seven questions without answer yet (shadows) [Figure 2]:

Figure 2

Lights and shadows of the Taenia asiatica life cycle and pathogenicity

Hosts: In nature, humans are the only definitive and pigs and wild boars the intermediate hosts; calves, goats, monkeys and rodents have been experimentally infected although cysticerci infectivity has only been proven in Mongolian gerbils and severe combined immunodeficiency (SCID) mice;[1624252627] cysticerci recovered from experimentally infected older pigs are usually degenerated/calcified in contrast to mature cysticerci recovered from younger pigs, which are more susceptible to T. asiatica eggs;[21] partial development of the adult worm stage occurs in experimentally infected gerbils[27]

1. Do humans act as intermediate hosts of T. asiatica as they do in the case of T. solium?

Site of infection: Intestine in humans and liver in pigs and wild boars; naturally infected pigs in Korea presented 54% of cysticerci in the parenchyma (up to 88.9% in experimental infections) and the rest on the liver surface.[222324] The cysticerci are very small (2 mm) and when they are alive the host tissue capsules are transparent

Keeping in mind its small size and the fact that cysticerci are located more frequently in the liver parenchyma than in the surface,

2. Could T. asiatica be getting away from pig veterinary inspections around the world? And,

3. Could it then be considered a silent parasite in pigs?

Omentum, lungs, serosa of colon, diaphragm, abdominal muscles, gall bladder and abdominal and peritoneal cavities are alternative sites in experimentally infected pigs and abdominal cavity in an experimentally infected.[2428] Infectivity of cysticerci from extrahepatic origin has been proved in humans[24]

4. Are extrahepatic pig cysticerci a potential source of human infection?

Parasite development: Experimental human infections showed that the adult stage is reached by 2.5-4 months after infection, when gravid proglottids discharge begins;[2329] in experimentally infected pigs, cysticerci development is reached approximately after 4 weeks postinfection[16]

Life span: The adult life expectancy should be, at least, more than two years since one volunteer was treated after two years of infection;[23] infected people from endemic areas shed gravid proglottids for periods varying between 1 and 30 years;[30] eggs remained infective under laboratory conditions for about five months;[31] cysticerci life span (and size) depends on the host: from 1 to 5 months for 2 mm cysticerci in experimentally infected pigs,[23] up to one year in non-obese diabetic-SCID mice, reaching a size fivefold bigger (10 mm) than that in naturally infected pigs or wild boars (2 mm); cysticerci life span longer than one year probably reached in normal and immunosuppressed mice (C3H, C57and ICR strains)[2532]

In case T. asiatica eggs infect humans,

5. Could the cysticerci reach bigger sizes and live longer in immunocompromised hosts?

Mode of infection: Humans become infected by eating raw or undercooked pork liver or dishes; pigs and wild boars are infected by the accidental ingestion of the gravid proglottids/eggs eliminated in humans faeces that contaminate the environment; experimental infections showed that the more T. asiatica eggs the pig ingests the heavier the infection acquired.[21] In Vietnam, where people usually do not eat raw or undercooked pork liver or viscera, T. asiatica is the most common human Taenia species.[33] This point may suggest alternative location sites of cysticerci in pigs

In addition to liver,

6. Could pork meat also be a source of human infection?

Way of leaving definitive host: Apparently egg elimination can be independent of defecation since T. asiatica can leave the human intestine thanks to the active movement of its gravid proglottids,[16] although their presence in faeces is considered the most frequent sign of infection.[30] Single proglottids as well as fragments of strobila can pass with faeces.[1634]

LIGHTS AND SHADOWS OF T. ASIATICA PATHOGENICITY

When symptomatic, taeniasis due to T. solium or T. saginata is usually characterized by mild and non-specific symptoms. Abdominal pain, nausea, diarrhoea or constipation being the most frequent ones (http://www.who.int/mediacentre/factsheets/fs376/en/). Most of the people with taeniasis asiatica are also asymptomatic and only become aware of the infection when they pass proglottids in their stools. Although asymptomatic, patients infected with the tapeworm can suffer emotionally for a long period while expelling the proglottids.[35] When symptomatic, taeniasis asiatica shows practically the same mild and non-specific signs.

Table 1 shows the most frequent symptoms attributed to T. asiatica among around 500-1200 infected people.[163036] Other less frequent symptoms include weight loss, loss of appetite, muscular pain, stomach discomfort, gastric pain, somnolence, convulsion, anxiety, skin pruritus respiratory irregularity and hunger pains.[163036]

Table 1

Prevalence of the main clinical symptoms of taeniasis asiatica

At individual level, in a human experimental infection, the early onset of the patient's symptoms was mild abdominal pains after a week of getting infected. The following three months the main symptoms were diarrhoea, upper abdominal pain, increase or loss of appetite. Severe abdominal pain appeared later and subsequently the course of infection was subacute rather than chronic.[29]

Complications have also been reported since a naturally infected woman showed, in addition to nausea and vomiting (including fragments of strobila), acute epigastric pain due to an acute pancreatitis, probably caused by T. asiatica.[34]

At intermediate host level, T. asiatica causes hepatocyte degeneration that leads to a spotty necrosis in some local pig liver tissues. After about two months of infection, main damages are granulomatous reactions surrounding cysticercus and focal liver fibrosis.[37]

Considering its preferential site of infection in pigs,

7. Could T. asiatica produce human liver cysticercosis?[38]

DISCUSSION AND CONCLUSION

Currently, there is no way to answer any of the seven questions posed here about T. asiatica due to the lack of sensitivity and specificity of the available routine diagnostic procedures. Questions 2, 3, 4 and 6 concern pigs. For pork to be consumed by humans pigs have to undergo veterinary inspection, therefore direct diagnosis has to be performed, based on morphology, shape and size of the cysticerci. First of all, veterinarians have to be aware of the existence of T. asiatica and they must be familiar with its life cycle that includes pigs instead of cattle (authors who still call this species T. saginata asiatica induce error since T. saginata is a cattle parasite). Second, due to its name, T. asiatica is not usually considered in the differential diagnosis of pig cysticercosis out of Asia, when there are no reasons that could have impeded its world-wide spread, which was the case of the other two cosmopolitan Taenia species.[39] Precisely, T. asiatica has recently been detected in Nepal, and it would be very interesting to figure out if this species is present in India, where T. saginata-like tapeworms could be shed by non-beef but pork eaters.[40]

Third, due to its very small size, the cysticerci could frequently be overlooked. Unless slices of 2-3 mm were made, cysticerci could not be found in the liver (most of them are located in the parenchyma), as well as in other possible organs or tissues, and this procedure is not carried out in routine inspections.[222324]

There is no specific immunological diagnostic method for T. asiatica cysticercosis, which cross-reacts in the specific ones for T. solium.[39] The Taenia species can currently only be determined by means of molecular studies of the extracted cysticerci.[334142] These molecular methods, although largely used in research, are normally not employed in routine diagnosis.

Finally, questions 1 and 7 concern humans. The lack of a specific immunological diagnosis for T. asiatica cysticercosis leads to a troublesome situation when determining if humans can act or not as intermediate hosts. We have already proposed the use of imaging to determine possible liver cysticercosis at least in patients harbouring the adult stage and the subsequent molecular study of the extracted cysticerci.[43]

We conclude with a phrase written in 1860 by the French physician Casimir Davaine (1812-1882), who stated, “No animal has been responsible for more hypotheses, discussions and errors than the tapeworm”.[44] These words intended then for T. solium could perfectly be assigned today to T. asiatica as these enigmas cast a shadow on its conclusive life cycle and pathogenicity.