Neotropical Echinococcosis: A Review

Abstract

Echinococcus vogeli (Rausch and Berstein, 1972) and Echinococcus oligarthra (Diesing, 1863) (Cestoda: Taeniidae) are the only two species known of Neotropical tapeworms, which cause Echinococcosis Polycystic (EP) and Echinococcosis Unicystic (EU), respectively, in humans and in wild rodents from Central and South America. This review applied a meta-analysis on published research about these diseases during the last decade (2010–2020) with the aim of finding out the new human cases reported on that decade on EP and EU. Several new human cases have been published in these 10 years, and important findings have been carried out on the phylogenetic taxonomy, on the genome of E. oligarthra, and on new molecular diagnostic techniques and imagenology applied upon this two neotropical echinococcosis, in particular in Argentina and Brazil. Finally, the life cycle of both Echinococcus species appears to be in a dynamic activity, apparently there is an expansion of both zoonotic diseases moving down to Southern zones of Argentina; therefore, a program of epidemiological surveillance on EP and EU is proposed to be carried out in those Patagonic regions.

1. Introduction

Neotropical echinococcosis is a parasitic disease caused by two species of cestodes: Echinococcus vogeli (Rausch and Berstein, 1972) and Echinococcus oligarthra (Diesing, 1863), which are parasites in the small intestine of their specific definitive hosts: for E. vogeli the “bush dog” (Speothos venaticus, Lund, 1842), so far the only known natural host (some colloquial names for S. venaticus are: “pitoco dog” or “vinager fox” in Argentina; “cachorro do moto” in Brazil; “guache dog” in Venezuela and Colombia), whereas several species of wild cats (Felidae) are hosts for E. oligarthra. The life cycle of these two tapeworms follows the “predator-prey” seylvatic patron; thus, a wild rodent the paca (Cuniculus paca, Linnaeus, 1776) is the main known intermediate host for E. vogeli (the paca is named “lapa” in Venezuela; “guagua” in Colombia) even though it has also been collected from agouties (Dasiprocta spp., and from spiny rats (Proechimis spp.). On the other hand, metacestodes of E. oligarthra¹ have been found in tissues of several intermediate hosts such as the agouties [1] (“picures” in Venezuela), spiny rats, pacas, opossums (Didelphis marsupialis), and in wild rabbits (Sylvilagus floridanus) [2] in tropical forests of Panama, Venezuela, Colombia, Chile, Brazil, and Argentina [3]. Proglotis and many eggs are shed from these tiny tapeworms into the gut lumen of their definitive hosts, passed out with the feces [4, 5], and next, eggs are accidentally ingested by the intermediate hosts, which become infected; in the case of E. vogeli, once in the intestine, the oncospheres stages are freed, invading organs such as the liver, lungs, small intestine, spleen, where develop they as protoscoleces, which asexually proliferate forming the hydatid polycystic cyst stage, polycystic for E. vogeli. The unicyst for E. oligarthra appears to be less erratic, and in three out of four cases diagnosed were found retrorbital. Echinococcus oligarthra was reported in its adult strobilar stage before 1860; nonetheless, more than 100 years (yr) have passed from the first report of the adult parasite to the recognition that this species infects humans causing the neotropical echinococcosis [6]. “Bush dogs” (Speothos venaticus) are less probably a direct source of infection for humans since it is a wild or seylvatic canid. On the contrary, hunting dogs (Canis familiaris), after being fed with raw viscera of pacas, are infected developing numerous Echinococcus vogeli cestodes in their small intestine, and thus in this way these dogs are the main responsible sources of infections for humans in rural zones. Therefore, E. vogeli and E. oligarthra metacestodes can have two transmission kinds of life cycles: (a) seylvatic and (b) rural or domestic to assure its survival as species [7].

A general taxonomic list for of these two Echinococcus tapeworms is as follows: Kingdom: Animalia; Phyum: Plathyelminthes; Class: Cestoda; Order: Cyclophylidea; Family: Taeniidae; Genus: Echinococcus (Rudolphi, 1801); and Neotropical species: Echinococcus vogeli and E. chinococcus oligarthra [6, 8]. On October 2019, the World Association of Echinococcosis (WAE) had its 28th World Cystic Echinococcosis Meeting at Lima, Peru, where it was updated the current nomenclature for the genus Echinococcus as follows: (a) it approved the names of Cystic Echinococcosis (for E. granulosus), Alveolar Echinococcosis (for E. multilocularis), and Neotropical Echinococcosis (for E. vogeli, and E. oligarthra), (b) the word “hydatid” from now on is used only for cysts caused by E. granulosus sensu lato, and (c) in the genus Echinococcus nine (09) species were officially recognized: E. granulosus, (sensu lato and sensu stricto), E. multilocularis, E. canadiensis, E. equinus, E. felidis, E. ortleppi, E. shiquicus, E. vogeli, and E. oligarthra [8].

The metacestodes of these two parasitic diseases are well documented and have been diagnosed in more than 200 people, mostly dwellers of tropical and subtropical areas from several Latin American Countries, (Nicaragua, Costa Rica, Panama, Colombia, Venezuela, Ecuador, Peru, Bolivia, Suriname, French Guiana, Paraguay, Brazil, Chile, Uruguay, and Argentina); these parasitoses are listed by the World Health Organization (WHO) among the 17 neglected tropical diseases and classified as zoonotic diseases [9]. The presence and impact of these neotropical parasitoses on humans in syelvatic and rural areas are directly related to different risk factors such as: (a) agricultural activities and deforestation, (b) continuing urbanization, (c) construction of new roads into syelvatic regions, (d) reduction of natural habits, (e) illegal hunting, plus capture and outlaw trade of wild animals, (f) infection in dogs due to their feeding with raw viscera, (g) possibility of scavenging dead animals, (h) lack of anthelmintic treatment, and (i) that these Neotropical Echinococcosis are not under surveillance and no compulsory official notification, because there is no obligation to report clinical cases in humans caused by these parasitic infections to health authorities in many countries of the region such as Colombia [10, 11] and also in other South American Countries [12, 13, 14, 15, 16]. The study of neotropical echinococcosis needs to follow and strengthen the holistic project of “One Health” following the WHO and the Pan American Health Organization (PAHO) plan of actions for hydatidosis for Latin American [9]. Therefore, a joint effort by veterinary and human medicine, environmental sciences, imagenology, and ecology is needed to improve our knowledge; in summary, it is a field that requires a multidisciplinary biomedical team to study its biology, diagnosis, treatment, surveillance, and control [3].

Few cases of human echinococcosis due to E. oligarthra infections have been diagnosed: the first case ever was a female patient from Venezuela who suffered a retroocular neotropical unicystic infection [17]; the second and third cases were diagnosed in Surinam showing one retroocular unicyst case, and another abdominal case [14, 18, 19]; the fourth case was a rural patient from Brazil who died of tetanus, and after necropsy an E. oligarthra unicystic stage was found at cardiac tissue [20]; and the fifth case was also in Brazil, and this patient had an hepatic neotropical unicyst infection [21]. On the contrary, in the period between 1979 and 2020. E. vogeli was responsible for causing more than 240 cases of human EP disease in several countries of Latin America [7, 22], and even few cases of EP have been diagnosed in the Netherlands from Suriname people who had moved to this European country [22]. The diagnosis of this neotropical echinococcosis originally has been carried out by the morphology of the cestodes shape, size, and length of the large and small rostellar hooks of these two Echinococcus cestodes [7]; however, the diagnosis has been widely improved in the last two decades: first, by the use of immunodiagnostic techniques such as ELISA, Western blot, or immunoeletrophoresis; second by molecular techniques (PCR) [22, 23, 24, 25, 26] and third by the use of imagenology equipment, i.e., ecography, including ultrasonography, Computerized Axial Tomography (CAT), Magnetic Resonance Imagenology (MRI), and conventional radiography; all are important for the diagnosis of CE; all these techniques are used not only for classification and identification of cysts, but also for monitoring the responses to treatments [7, 27, 28, 29, 30]; consequently, the number of human cases diagnosed has increased, not only in new cases, but it has also been reported in countries where it had not been diagnosed, i.e., Peru [30, 31] and Argentina [32, 33]. In addition, in the Peruvian Amazon, a study was carried out in wild pacas looking for EP, and 11.7% of pacas were found to be infected with metacestodes of E. vogeli, thus representing these pacas’ potential risks for humans living in that Peruvian region and for rural and urban dogs [3, 34].

2. Materials and methods

A meta-analysis was carried out as follows: articles search was performed by the author (RDM), since February 02, 2021, a systematic literature search was conducted on four databases to identify all publications reporting Echinococcus vogeli, Echinococcus oligarthra, Echinococcosis policystic, and Echinococcosis unicystic throughout the world in PubMed, Scopus, Research Gate, Google Scholar, and Medline, which were screened using those four (04) words without language restrictions.

Several inclusion criteria were required to meet articles to be selected: (a) should be scientific studies such as cross-sectional, longitudinal, case report or outbreak studies, published in indexed journals, reporting any natural infection of E. vogeli and/or E. oligarthra; (b) the study design, sample size, sample type, diagnostic methods, and number of Echinococcus infected animals; and (c) species of intermediate or definitive hosts animals for E. vogeli or/and E. oligarthra infections must be specified.

3. Results and discussion

The meta-analysis of scientific literature published between 2010 and 2020 showed that several new human cases of either neotropical EU and EP have been published during this decade, i.e.: (1) Echinococcus vogeli infection in a hunter from the rain forest of French Guiana was confirmed by imaging and mitochondrial Deoxyribonucleic Acid (DNA) sequence analysis [35]. (2) A case of infection by E. oligarthra in a Brazilian man was presented as a first case of Echinococcosis unicystic invasion of liver tissues [21]. (3) Two cases of liver EP were diagnosed by computerized tomography (CT) and ELISA in two female members of a Yanomani ethnic group located in the Amazonas State, Venezuela [36]. (4) Another human case of infection but by E. vogeli was reported from Argentina, the female patient was a Paraguayan immigrant who presented jaundice and abdominal pain in the right hypochondriac region. The diagnosis was achieved by abdominal CT, immunodiagnosis techniques (ELISA, immunoelectophoresis, Western blot), histopathologic studies, and molecular techniques (PCR) [37]. On the contrary, a review was recently published on the genus Echinococcus spp. [38], but new human clinical cases about neotropical EU and/or PE were not reported; the main information was about the life cycle and morphology of these two tapeworms [38].

The genus Echinococcus was recently studied through phylogenetic reconstructions of the relationship between several species using their mitochondrial DNA (mtDNA); moreover, molecular taxonomic analysis was also performed using short mtDNA sequences of genes for the cytochrome c oxidase subunit 1 (cox1) and for NAHD dehydrogenase subunit 1 (nad1) [39, 40, 41]. These studies concluded that the origin of the two species of Neotropical Echinococcus appears to be monophyletic; in other words, both share a common ancestor [42, 43]. This monophyletic result was more recently confirmed for E. vogeli after studies on its genetic diversity carried out in Western Brazilian Amazon [44, 45]. In addition, mitochondrial and nuclear sequence polymorphisms carried out with 38 isolates of E. vogeli from humans and wild animal hosts from Amazonian Regions revealed that E. vogeli is partially synanthropic, with a diverse population near or in association ecologically with humans [44, 45]. The use of molecular tools has shown differences in nucleic acid sequences that reflect phenotypic variation, and the phenotypic and genetic characteristics complement the previous observations published by the descriptive parasitologists years ago [20].

The genome of E. oligarthra was recently sequenced and assembled from hydatic unicysts obtained from tissues of an agouti (Dasyprocta azarae) [40], and it was estimated that its genome has a size of 86.2 megabases (Mb) and 8753 genes, which unexpectedly showed ~90% identity and 76.3% coverage with Echinococcus multilocularis, a tapeworm of Palearctic zones of the Northern hemisphere [46], and the phylogenetic work carried out on this E. oligarthra genome also showed that: (a) this neotropical genome is at a higher and farther distance from E. granulosus, and (b) E. oligarthra is one of the basal species of the genus Echinococcus. The genome size of E. granulosus was also recently estimated in 151.6 Mb, with 11,325 genes, and 9 pairs of chromosomes [47], therefore, the genome size of E. oligarthra is smaller, and almost half-size that of E. granulosus. The life cycle of E. oligarthra was also completed in the Upper Parana Atlantic Forest, Argentina, by microscopic, histological, and molecular techniques (PCR and nucleotide sequence of E. oligarthra DNA), and concluded that the agouti (D. azarae) is the main intermediate host (prey), and the felines Ocelot (Leopardus pardalis) and the puma (Felis concolor) are the definitive hosts of E. oligarthra [1, 32, 48].

It is considered that the number of human cases of neotropical unicystic and EP could be just “the tip of the iceberg” in relation to its real prevalence in Central and South America due to factors such as: (a) most infections occur to farmers, hunters, and rural people who lack medical assistance in those regions; (b) the development of these EP and EU cysts in human tissues or organs is slow and takes time, and during some years, patients are not aware of being parasitized by those polycysts; and (c) under those conditions patients are prone to suffer other infectious or organic diseases, which often might put an end to their lives. Therefore, the total number of human cases only for EP (232 for the year 2008) is perhaps only a small fraction of the real prevalence in South America countries, where there is lack of cumulative reports, of advanced diagnostic methods, and on-time treatment for EP [44]. In other clinical cases, parasitized farmers are able to obtain medical diagnosis and surgical treatment but with fatal results due to the advanced damage to organs such as the liver [21]. Previous publications showed that 172 human cases of Neotropical EU and EP were well documented from 12 countries in 2007 [7], whereas for the year 2008, a total of 232 similar cases were accounted, and from this last amount, 160 cases alone were diagnosed in Brazil (occurring in the States of Pará and Amapa, located in the Western Amazonian Region [44]. The difference between the 2007 and the 2008 data was 60 new cases, which means a 25.8% increment of new cases/year of Neotropical EU and EP per yr., if this percentage is taken as a reference point, then after 10 years (2010–2020), it may be estimated that at least more than 100 new cases of these parasitic diseases may have occurred in humans in seylvatic or rural regions, which were neither registered nor diagnosed.

The WHO included the EU and the EP among the 17 neglected tropical diseases and classified them as zoonotic diseases because these Echinococcus parasites infected humans in rural zones and seylvatic regions of Central and South America, where an early diagnosis and treatment for infected people are a difficult process. In this review it was stated that an exact cumulative annual number of human cases in the American Continent is lacking, due to the rural and remote origin of the patients, adults or teenagers, who get the fecal-oral infection from parasitized rural dogs or due to drinking water contaminated with feline feces. On the bases of the difference between the number of clinical cases of EP, published in 2007 and 2008 [7], it can be hypothesized that each year, between 2010 and 2020, may have occurred at least 10 new cases of human EP and of EU; unfortunately, none of those cases would have been registered in any hospital or medical services. Consequently, after a decade it may be estimated that no less than 100 humans were infected and suffered mainly EP. Nonetheless, a review of scientific literature for that decade shows that fewer than 100 human cases of these Neotropical echinococcoses have been published in journals, studied, diagnosed, and received medical services [20, 49].

4. Conclusions

It is important to underscore that E. oligarthra unexpectedly showed ~90% identity and 76.3% coverage with Echinococcus multilocularis, a tapeworm located in Palearctic zones of the Northern hemisphere, and this conclusion of genetic identity similarity can lead to hypothesize that E. oligarthra could have arrived to the American Continent through the Bering icy bridge. Next, it moved down this continent in the guts of some feline predators, then it crossed the Panama land isthmus millions of years ago arriving to Norther seylvatic lands of South America (now countries such as Colombia, Ecuador, and Venezuela), and nowadays, this E. oligarthra tapeworm appears to be still traveling down territories of the South Cone, perhaps heading toward Patagonia areas. The origin of the Neotropical echinococcosis showed that both tapeworms were brought to South America from North America. In the last year and for the first time, E. oligarthra was found, diagnosed, and its life cycle was completed in the Province of Misiones, north subtropical forest of Argentina. It may be hypothesized that both Neotropical Echinococcus still has a dynamic life cycle, which may be moving down toward some southern provinces of Argentina). Finally, a proposal would be to keep an epidemiological surveillance program in Southern provinces of Argentina as a public health action to figure out the presence or absence of these Neotropical echinococcoses in those Patagonic Regions.

Acknowledgments

Thanks to Consejo de Desarrollo Científico, Humanístico y Tecnológico (CDCHT) of Universidad Centroccidental Lisandro Alvarado (UCLA), Barquisimeto, Lara, Venezuela, for logistic and financial support upon this research.