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Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo.

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Most human cystic echinococcosis (CE) cases worldwide are attributed to Echinococcus granulosus sensu stricto (s.s), followed by the G6 and G7 genotypes. While E. granulosus s.s. has a cosmopolitan distribution, the G6 genotype is restricted to areas where camels and goats are present. Goats are the primary livestock in the Neuquén province in Argentina where the G6 genotype has been reported to be responsible for a significant percentage of CE human cysts genotyped. In the present study, we genotyped 124 Echinococcus cysts infecting 90 CE-confirmed patients. Echinococcus granulosus s.s. was identified in 51 patients (56.7%) with 81 cysts and the G6 genotype in 39 patients (43.3%) harbouring 43 cysts. Most CE cases ≤18 years were male suggesting pastoral work could be a risk factor for the infection. Echinococcus granulosus s.s. was significantly found more frequently in the liver (32/51 patients) and the G6 genotype in the lungs and extrahepatic localizations (27/39). The patients infected with E. granulosus s.s., presented up to 6 cysts while patients infected with G6 presented a maximum of 2. The diameter of lung cysts attributed to E. granulosus s.s. was significantly larger compared to lung cysts from G6. Following the WHO ultrasound classification of liver cysts, we observed inactive cysts in 55.6% of G6 cysts and only 15.3% of E. granulosus s.s cysts. In conclusion, we provide evidence of differences in clinical aspects of CE caused by E. granulosus s.s. and the G6 genotype of E. granulosus s.l. complex infecting humans.

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Two domestic cats from the Patagonia rural area in Argentina were found to be naturally infected with Echinococcus granulosus sensu stricto/G1 genotype; so far, the only species/genotype of E. granulosus sensu lato complex described to infect domestic cats. The felines developed abdominal disseminated larval disease; the diagnosis was performed by ultrasound, exploratory laparotomy, and molecular techniques. These results indicate that cystic echinococcosis must be considered for differential diagnosis of felines with abdominal distension and/or observation of vesicles through ultrasound, from endemic areas. Even though cats and dogs are carnivores, differences in digestive physiology and immunological characteristics between them could allow the development of larval or adult worm parasites. Domestic cats with cystic echinococcosis show to be environmentally infected with E. granulosus s. s./G1 eggs.

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Abstract Hepatopulmonary hydatidosis in young children is a rare and atypical presentation of Echinococcus granulosus infection. We report the first case of cystic echinococcosis caused by a microvariant of E. granulosus sensu stricto. Chemotherapy and systemic corticoids were administered before curative surgery was performed. Recurrence was not observed for more than 24 months of follow-up.

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Human cystic echinococcosis is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato (s. l.). Although benzimidazole compounds such as albendazole (ABZ) and mebendazole have been the cornerstone of chemotherapy for the disease, there is often no complete recovery after treatment. Hence, new strategies are required to improve treatment of human cystic echinococcosis. The goals of the current study were as follows: (i) to evaluate the in vitro efficacy of the 5-fluorouracil (5-FU) and ABZ combination against E. granulosus s. l. protoscoleces and cysts, (ii) to compare the clinical efficacy of 5-FU alone or in combination with ABZ in infected mice. The combination of 5-FU+ABZ had a stronger in vitro effect against larval stage than that did both drugs alone. Even at the lowest concentration of 5-FU+ABZ combination (1µg/ml), the reduction of the viability of protoscoleces and cysts was greater than that observed with drugs alone at 10µg/ml. The results were confirmed at the ultrastructural level by scanning electron microscopy. These data helped to justify the in vivo investigations assessing the therapeutic potential of the combination of 5-FU and ABZ suspension in CF-1 mice infected with E. granulosus sensu stricto (s. s.) metacestodes. Treatment with 5-FU (10mg/kg) or 5-FU (10mg/kg) + ABZ suspension (5mg/kg) reduced the weight of cysts recovered from mice compared with control groups. Interestingly, the effect of 5-FU given weekly for 5 consecutive weeks was comparable to that observed with ABZ suspension under a daily schedule during 30days. Co-administration of 5-FU with ABZ did not enhance the in vivo efficacy of drugs alone calculated in relation to cysts weights. However, the combination provoked greater ultrastructural alterations compared to the monotherapy. In conclusion, we demonstrated the efficacy of 5-FU either alone or co-administrated with ABZ against murine experimental cystic echinococcosis. Since 5-FU treatments did not cause toxic effect in mice, further in vivo studies will be performed by adjusting the dosage and the frequency of treatments.

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Cystic echinococcosis, a zoonotic disease caused by Echinococcus granulosus sensu lato (s. l.), is a significant global public health concern. Echinococcus granulosus s. l. is currently divided into numerous genotypes (G1-G8 and G10) of which G1-G3 are the most frequently implicated genotypes in human infections. Although it has been suggested that G1-G3 could be regarded as a distinct species E. granulosus sensu stricto (s. s.), the evidence to support this is inconclusive. Most importantly, data from nuclear DNA that provide means to investigate the exchange of genetic material between G1-G3 is lacking as none of the published nuclear DNA studies have explicitly included G2 or G3. Moreover, the commonly used relatively short mtDNA sequences, including the complete cox1 gene, have not allowed unequivocal differentiation of genotypes G1-G3. Therefore, significantly longer mtDNA sequences are required to distinguish these genotypes with confidence. The main aim of this study was to evaluate the phylogenetic relations and taxonomy of genotypes G1-G3 using sequences of nearly complete mitogenomes (11,443bp) and three nuclear loci (2984bp). A total of 23 G1-G3 samples were analysed, originating from 5 intermediate host species in 10 countries. The mtDNA data demonstrate that genotypes G1 and G3 are distinct mitochondrial genotypes (separated by 37 mutations), whereas G2 is not a separate genotype or even a monophyletic cluster, but belongs to G3. Nuclear data revealed no genetic separation of G1 and G3, suggesting that these genotypes form a single species due to ongoing gene flow. We conclude that: (a) in the taxonomic sense, genotypes G1 and G3 can be treated as a single species E. granulosus s. s.; (b) genotypes G1 and G3 should be regarded as distinct genotypes only in the context of mitochondrial data; (c) we recommend excluding G2 from the genotype list.

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BACKGROUND: Echinococcus granulosus (sensu lato) (s.l.) and Echinococcus vogeli are causative agents of chronic zoonotic diseases such as cystic and polycystic echinococcosis, respectively. In Brazil, polycystic echinococcosis has a restricted geographical distribution in the North Region, while cystic echinococcosis is observed in the South Region. Domestic dogs (Canis familiaris) fed with raw viscera represent a risk factor for E. granulosus (s.l.) infection in the South Region. Although this practice is frequent, it remains unclear whether domestic dogs are infected with E. vogeli in the state of Acre, located in the Amazon basin in the North Region of Brazil. The aim of this study was to investigate this gap in the polycystic echinococcosis epidemiology. METHODS: Sixty-five fecal samples were collected from the ground in five municipalities (Sena Madureira, n = 14; Rio Branco, n = 06; Bujari, n = 06; Xapuri, n = 30; and Epitaciolândia, n = 09) located in the state of Acre, northern Brazil. The samples were screened for parasites by copro-PCR using the cox1 gene associated with automated sequencing. RESULTS: Echinococcus vogeli was molecularly confirmed in a sample from Sena Madureira and E. granulosus (sensu stricto) (s.s.) (G1) in a sample from Rio Branco. CONCLUSIONS: These findings indicate that molecular assays are useful in typing Echinococcus taxa from fecal samples of dogs in northern Brazil. The present study is the first molecular record of E. vogeli in domestic dogs found in the state of Acre, reinforcing their role as a source of infection for humans. Because E. granulosus (s.s.) (G1) was detected for the first time in the North Region, from the epidemiological standpoint this finding is highly relevant, because it expands the known geographical distribution, which was previously restricted to the South Region of Brazil.

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Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas.

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The cystic echinococcosis (CE) is an important zoonotic disease caused by the parasite Echinococcus spp. In Brazil, this parasite is present in Rio Grande do Sul (RS) state, border with Argentina and Uruguay, causing several damages to human and animal health. This study aimed to identify Echinococcus spp. in hydatid cysts of swine and evaluate the similarity of the genotypes through the phylogenetic analysis. A total of 3,101,992 swine were slaughtered in the central/northern region of RS/Brazil, during 2008-2012. Five isolates were characterized as hydatid cyst by molecular analysis, based on the mitochondrial gene cytochrome c oxidase subunit I (cox-I). The genotypes E. granulosus sensu stricto (G1) (n=2) and E. canadensis (G7) (n=3) were identified in the hydatid cysts. The swine represents a potential intermediate host for different genotypes of Echinococcus spp., besides it can contribute to the perpetuation of the parasite's life cycle in rural areas.

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