Exploring the Potential of Flubendazole in Filariasis Control: Evaluation of the Systemic Exposure for Different Pharmaceutical Preparations

The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-β-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CD_oral and FLBZ-CD_sc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEEN_sc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMC_oral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC_0-LOQ) was significantly (P<0.05) higher after the FLBZ-CD treatments, both oral (4.8±0.9 µg.h/mL) and subcutaneous (7.3±0.6 µg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.93±0.2 µg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CD_oral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.     

Echinococcus granulosus:An Intraperitoneal Diffusion Chamber Model of Secondary Infection in Mice

Breijo, M., Spinelli, P., Sim, R.B., and Ferreira, A. M. 1998.Echinococcus granulosus:An intraperitoneal diffusion chamber model of secondary infection in mice.Experimental Parasitology90, 270–276. The present work describes a new experimental model of secondary infection which allows, through the recovery of the parasite together with its localin vivoenvironment, examination of the local nonadaptive immune response of the infected host and the differentiation of the parasite from protoscoleces to cysts. In this model we administered protoscoleces within silicone diffusion chambers, previously implanted into the peritoneal cavities of mice. The process of designing the model involved, first, determination of the optimal time postimplantation to infect the mice and, second, evaluation of the parasite's ability to establish infection within the chambers. The optimal time for infection was considered to be after the inflammation caused by implantation of the chambers had subsided. Our results showed that by day 20 postsurgery, three parameters used as indications of inflammation (complement C3, serum amyloid P protein, and polymorphonuclear cells in the peritoneum and in the chamber contents) had reverted to their normal levels. In our study of parasite differentiation, we found that 2–3% of the total number of parasites inoculated into the chambers were recovered as viable cysts after 100 days. Throughout the infection period, the population of parasites recovered was heterogeneous; certain parasite morphologies that have not been described previously were observed. In conclusion, the use of intraperitoneal diffusion chambers offers a potential tool for investigating thein vivodifferentiation process of secondary cysts ofEchinococcus granulosusin mice and the early local interactions between host and parasite during this process.     

Post-treatment follow-up study of abdominal cystic echinococcosis in tibetan communities of northwest Sichuan Province, China

Background

Human cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, with the liver as the most frequently affected organ, is known to be highly endemic in Tibetan communities of northwest Sichuan Province. Antiparasitic treatment with albendazole remains the primary choice for the great majority of patients in this resource-poor remote area, though surgery is the most common approach for CE therapy that has the potential to remove cysts and lead to complete cure. The current prospective study aimed to assess the effectiveness of community based use of cyclic albendazole treatment in Tibetan CE cases, and concurrently monitor the changes of serum specific antibody levels during treatment.

Methodology/Principal Findings

Ultrasonography was applied for diagnosis and follow-up of CE cases after cyclic albendazole treatment in Tibetan communities of Sichuan Province during 2006 to 2008, and serum specific IgG antibody levels against Echinococcus granulosus recombinant antigen B in ELISA was concurrently monitored in these cases. A total of 196 CE cases were identified by ultrasound, of which 37 (18.9%) showed evidence of spontaneous healing/involution of hepatic cyst(s) with CE4 or CE5 presentations. Of 49 enrolled CE cases for treatment follow-up, 32.7% (16) were considered to be cured based on B-ultrasound after 6 months to 30 months regular albendazole treatment, 49.0% (24) were improved, 14.3% (7) remained unchanged, and 4.1% (2) became aggravated. In general, patients with CE2 type cysts (daughter cysts present) needed a longer treatment course for cure (26.4 months), compared to cases with CE1 (univesicular cysts) (20.4 months) or CE3 type (detached cyst membrane or partial degeneration of daughter cysts) (9 months). In addition, the curative duration was longer in patients with large (>10 cm) cysts (22.3 months), compared to cases with medium (5–10 cm) cysts (17.3 months) or patients with small (<5 cm) cysts (6 months). At diagnosis, seven (53.8%) of 13 cases with CE1 type cysts without any previous intervention showed negative specific IgG antibody response to E. granulosus recombinant antigen B (rAgB). However, following 3 months to 18 months albendazole therapy, six of these 7 initially seronegative CE1 cases sero-converted to be specific IgG antibody positive, and concurrently ultrasound scan showed that cysts changed to CE3a from CE1 type in all the six CE cases. Two major profiles of serum specific IgG antibody dynamics during albendazole treatment were apparent in CE cases: (i) presenting as initial elevation followed by subsequent decline, or (ii) a persistent decline. Despite a decline, however, specific antibody levels remained positive in most improved or cured CE cases.

Conclusions

This was the first attempt to follow up community-screened cystic echinococcosis patients after albendazole therapy using ultrasonography and serology in an endemic Tibetan region. Cyclic albendazole treatment proved to be effective in the great majority of CE cases in this resource-poor area, but periodic abdominal ultrasound examination was necessary to guide appropriate treatment. Oral albendazole for over 18 months was more likely to result in CE cure. Poor drug compliance resulted in less good outcomes. Serology with recombinant antigen B could provide additional limited information about the effectiveness of albendazole in CE cases. Post-treatment positive specific IgG antibody seroconversion, in initially seronegative, CE1 patients was considered a good indication for positive therapeutic efficacy of albendazole.     

氟苯达唑对人急性髓系白血病HL-60细胞的增殖抑制作用研究

目的:研究氟苯达唑对人急性髓系白血病HL-60细胞增殖的抑制作用,明确氟苯达唑对HL-60细胞周期,凋亡发生的作用机制。方法:噻唑蓝法(MTT)检测氟苯达唑对人急性髓系白血病HL-60细胞的生长抑制作用,流式细胞术检测氟苯达唑对HL-60细胞周期,DNA片段化的影响,免疫印迹法检测Caspase, Raf, Bcl-2家族蛋白表达。结果:氟苯达唑抑制人急性髓系白血病HL-60细胞生长,HL-60细胞G2/M期增加,与阴性对照组相比,在一定的剂量和时间内,差别具有显著统计学意义;DNA片段化上升,0.25,0.5,1μM组与对照组相比差别具有显著统计学意义,促使Cleaved PARP,Cleaved-caspase 3,Cleaved-caspase 9蛋白表达量趋势增加;Bag-1和Bcl-2蛋白表达量降低;b-raf,c-raf磷酸化蛋白表达水平逐渐降低。结论:氟苯达唑通过诱导HL-60细胞阻滞于G2/M期,增加DNA片段化水平,激活Caspase, Raf, Bcl-2家族介导的凋亡相关通路抑制人急性髓系白血病HL-60细胞增殖,诱导人急性髓系白血病HL-60细胞发生凋亡而发挥抗肿瘤作用。     

Echinococcosis in China,a Review of the Epidemiology of <Emphasis Type="Italic">Echinococcus</Emphasis> spp.

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly significant infectious diseases occurring worldwide and caused by metacestodes of tapeworms Echinococcus granulosus and E. multilocularis, respectively. Both human CE and AE have highest prevalence rates in western and northwestern China. Livestock is the main intermediate host of E. granulosus, and wild small mammal are the main intermediate hosts of E. multilocularis. Since they range freely in pastoral areas, prey on wild small mammals and offal of livestock after slaughter, and have close relationships with humans, domestic dogs are the most important definitive host of both Echinococcus spp. with the highest risk of transmitting CE and AE to humans. Pastoralism is the occupation with the highest risk of being infected with the both kinds of echinococcosis due to the proximity of livestock, dogs, and wildlife host species. In this review, we summarize the epidemiology of human echinococcosis, the situation of parasite transmission in animal hosts, and possible transmission patterns in China. In addition, human activities and their potential influence on the transmission of echinococcosis are also discussed.     

Clinical and Demographic Characteristics of Patients with Urinary Tract Hydatid Disease

Background

Human cystic echinococcosis (CE) is caused by flatworm larvae of Echinococcus granulosus and is endemic in many parts of the world. In humans, CE cysts primarily affect the liver and pulmonary system, but can also affect the renal system. However, the clinical manifestations of renal CE can be subtle, so healthcare professionals often overlook renal CE in differential diagnosis. In this study, we examined the clinical and demographic characteristics of patients with urinary tract CE and analyzed the diagnosis and treatment procedures for this disease.

Methods

The records of 19 consecutive renal CE patients who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 1983 to April 2011 were retrospectively reviewed. In all cases, CE of the urinary tract was confirmed by pathological examination and visual inspection during surgery.

Results

Fifteen patients were males and 4 were females. The most common symptoms were non-specific lower back pain and percussion tenderness on the kidney region. All patients were followed up for 9–180 months after surgery. None of the patients experienced a recurrence of renal CE, but 4 patients experienced non-renal recurrence of hydatid disease.

Conclusions

Hydatid cysts from E. granulosus are structurally similar in the liver and urinary tract. Thus, the treatment regimen for liver CE developed by the World Health Organization/Informal Working Group on Echinococcosis (WHO/IWGE) could also be used for urinary tract CE. In our patients, the use of ultrasound, computed tomography, serology, and clinical characteristics provided a diagnostic accuracy of 66.7% to 92.3%.     

Recombinant antigens for immunodiagnosis of cystic echinococcosis

Three cDNAs, termed EpC1, TPxEg and EgG5, were isolated by immunoscreening from an Echinococcus granulosus cDNA library. The recombinant phages exhibited strong reactivity with sera from humans with confirmed cystic echinococcosis (CE) and with sera from mice infected with E. granulosus oncospheres. The cDNAs were subcloned into a pET vector, expressed as fusion proteins tagged with GST and affinity purified against the GST tag. Of the three recombinant proteins, EpC1 achieved the highest performance for serodiagnosis of CE in Western blot analysis using a panel of clinically defined human sera to initially address the sensitivity and specificity of the molecules. The protein yielded an overall sensitivity of 92.2% and specificity of 95.6%, levels unprecedented taking into account the large panel of 896 human sera that were tested. The strategy used may also prove suitable for improved immunodiagnosis of other parasitic infections.     

Design of a liquid nano-sized drug delivery system with enhanced solubility of rivaroxaban for venous thromboembolism management in paediatric patients and emergency cases

Abstract

The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests, in vitro dissolution, particle size, and zeta potential were executed to optimize the formulations. The optimized formulation, that composed of Capryol 90:Tween 20:PEG 300 (5:45:50), increased RIVA solubility (285.7-fold than water), it formed nanoemulsion with a particle size of 16.15?nm, PDI of 0.25 and zeta potential of ?21.8. It released 100.83?±?2.78% of RIVA after 5?min. SNEDDS was robust to dilution with oral and parenteral fluids and showed safety to human RBCs. SNEDDS showed enhanced bioavailability after oral and intravenous administration than the oral drug suspension (by 1.25 and 1.26-fold, respectively). Moreover, it exhibited enhanced anticoagulant efficacy in the prevention and treatment of carrageenan-induced thrombosis rat model.     

Infection Status of Hydatid Cysts in Humans and Sheep in Uzbekistan

Uzbekistan is endemic of cystic echinococcosis (CE). In order to estimate endemicity of CE, we collected data from emergency surgery due to CE in 2002-2010 and also investigated the prevalence of hydatid cysts in the liver and lungs of sheep at an abattoir in Uzbekistan from July 2009 to June 2010. In 14 emergency hospitals, 8,014 patients received surgical removal or drainage of CE during 2002-2010, and 2,966 patients were found in 2010. A total of 22,959 sheep were grossly examined of their liver and lungs, and 479 (2.1%) and 340 (1.5%) of them were positive for the cyst in the liver and lungs, respectively. Echinococcus granulosus is actively transmitted both to humans and sheep, and CE is a zoonotic disease of public health priority in Uzbekistan.     

Molecular Characterization of Echinococcus granulosus Cysts in North Indian Patients: Identification of G1, G3, G5 and G6 Genotypes

Background

Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India.

Methodology/Principal Findings

To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype.

Conclusions/Significance

These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis.     

Studies on anthelmintic effects of flubendazole and mebendazole on the rat lungworm Angiostrongylus cantonensis in mice and rats

Flubendazole and mebendazole given orally at 10 mg/kg/day 5-7 days post-infection (total 30 mg/kg) were found to eliminate 93-100% of Angiostrongylus cantonensis larvae in mice and rats. No significant difference was observed between the effects of the 2 drugs. The effectiveness of the drugs decreased with the increase in days post-infection on which medication was administered. It was found possible to treat A. cantonensis adults in rats by administering flubendazole or mebendazole at 10 mg/kg/day for 10 consecutive days. The drugs exhibited better anthelmintic efficacy in a divided dosing regimen than in a single dosing regimen.     

In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst

Cystic echinococcosis (CE) is caused by the larval stage of Echinococcus granulosus, which in this disease the metacestode develop in visceral organs especially liver and lungs. The disease is present worldwide and affects humans as well as herbivores including cattle, sheep, camels, horses and others. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE in inoperable patients and have to be applied in high doses for extended periods of time, and therefore adverse side effects are frequently observed. This study was designed to evaluate and compare the in vivo effects of 0.5 mg/kg, BID, albendazole sulfoxide (ricobendazole) and two different therapeutic regimens of 0.5 mg/kg BID and 2 mg/kg every 48 h of albendazole sulfoxide loaded solid lipid nanoparticles. Albendazole sulfoxide loaded solid lipid nanoparticles was prepared by solvent diffusion–evaporation method. Fifty Balb/c mice were infected by intraperitoneal injection of protoscoleces and 8 months post infection, the infected mice were treated for 15 days with the above mentioned regimens. They were then euthanized and the size and weight of the cysts as well as their ultrastructural changes were investigated. Although the cysts showed reduced size and weight in the treated animals but these reductions were not statistically significant. The cysts in the animals which received albendazole sulfoxide loaded SLN every 48 h showed more ultrastructural modification. However, these ultrastructural changes should be supported by further biochemical and molecular studies before introducing it as an efficient therapeutic regimen for treatment of human and animal hydatid disease.     

Control of cystic echinococcosis in the Middle Atlas,Morocco: Field evaluation of the EG95 vaccine in sheep and cesticide treatment in dogs

BackgroundCystic echinococcosis (CE) is an important cause of human morbidity and mortality worldwide, particularly in Morocco and other North African countries.Methodology/Principal findingsWe investigated the potential of three strategies to reduce Echinococcus granulosus transmission: (1) 4-monthly treatment of dogs with praziquantel, (2) vaccination of sheep with the EG95 vaccine and (3) a combination of both measures. These measures were implemented during four consecutive years in different areas of the Middle Atlas Mountains in Morocco. The outcome of the interventions was assessed through hydatid cyst (viable and non-viable) counts in liver and lungs using necropsy or in vivo ultrasound examination of the liver. A total of 402 lambs were recruited for annual vaccination with the EG95 anti-E. granulosus vaccine and 395 similar lambs were selected as non-vaccinated controls.At approximately four years of age the relative risk (estimated as odds ratio) for vaccinated sheep to have viable hydatid cysts compared with non-vaccinated controls was 3% (9.37% of the vaccinated sheep were found infected while 72.82% of the controls were infected; p = 0.002). The number of viable cysts in vaccinated animals was reduced by approximately 97% (mean counts were 0.28 and 9.18 respectively; p<0.001). An average of 595 owned dogs received 4-monthly treatment during the 44 months trial, corresponding to 91% of the owned dog population. Approximately, 5% of them were examined for E. granulosus adult worms by arecoline purge or eggs in feces (confirmed by PCR). The proportion of infected dogs significantly decreased after treatment (12% versus 35%; p<0.001). Post-treatment incidence of re-infestation corresponded to a monthly risk of 4% (95% CI: 3–6%). Treatment of owned dogs on a 4-monthly basis did not reduce the level of transmission of E. granulosus to sheep, nor did it enhance the level of control generated by vaccination of sheep with EG95, possibly because of unowned dogs and wild canids were not treated.Conclusions/SignificanceThese data suggest that vaccination of sheep with EG95 has the potential to reduce the level of CE in Morocco and in other parts of the world with similar transmission dynamics. Under the epidemiological circumstances existing in the trial area, 4-monthly treatment of owned dogs with praziquantel was insufficient to have a major impact of E. granulosus transmission to sheep.     

Age‐related dystrophic changes in corneal endothelium from DNA repair–deficient mice

The corneal endothelium (CE) is a single layer of cells lining the posterior face of the cornea providing metabolic functions essential for maintenance of corneal transparency. Adult CE cells lack regenerative potential, and the number of CE cells decreases throughout life. To determine whether endogenous DNA damage contributes to the age‐related spontaneous loss of CE, we characterized CE in Ercc1^?/Δ mice, which have impaired capacity to repair DNA damage and age prematurely. Eyes from 4.5‐ to 6‐month‐old Ercc1^?/Δ mice, age‐matched wild‐type (WT) littermates, and old WT mice (24‐ to 34‐month‐old) were compared by spectral domain optical coherence tomography and corneal confocal microscopy. Histopathological changes in CE were further identified in paraffin tissue sections, whole‐mount immunostaining, and scanning electron and transmission electron microscopy. The CE of old WT mice displayed polymorphism and polymegathism, polyploidy, decreased cell density, increased cell size, increases in Descemet's thickness, and the presence of posterior projections originating from the CE toward the anterior chamber, similar to changes documented for aging human corneas. Similar changes were observed in young adult Ercc1^?/Δ mice CE, demonstrating spontaneous premature aging of the CE of these DNA repair–deficient mice. CD45⁺ immune cells were associated with the posterior surface of CE from Ercc1^?/Δ mice and the tissue expressed increased IL‐1α, Cxcl2, and TNFα, pro‐inflammatory proteins associated with senescence‐associated secretory phenotype. These data provide strong experimental evidence that DNA damage can promote aging of the CE and that Ercc1^?/Δ mice offer a rapid and accurate model to study CE pathogenesis and therapy.     

Field efficacy of two netobimin oral suspensions (5% and 15%) in sheep naturally infected with Dicrocoelium dendriticum

This study was carried out to compare the efficacy of two suspensions (5% and 15%) of netobimin against Dicrocoelium dendriticum in naturally infected sheep. Fifteen Merino sheep, 4 to 7 years old, were used in this survey. Animals were divided into three equal groups each of five sheep on the basis of bodyweights and D. dendriticum egg counts in per gram faeces. Group A and group B sheep were treated orally with 5% and 15% suspension of netobimin, respectively; both at a dose rate of 20 mg kg⁻¹. Group C sheep were left untreated as controls. Twenty-one days post-treatment all sheep were slaughtered for post-mortem examination. All D. dendriticum from the liver and gall bladder were recovered and counted. The results showed that the efficacy of 5% and 15% suspension of netobimin was 90.80% and 91.50%, respectively, and the use of 15% suspension in sheep is discussed.     

Genetic diversity of Echinococcus granulosus sensu stricto in Sardinia (Italy)

Cystic echinococcosis (CE) is a severe parasitic zoonosis caused by the metacestode of the tapeworm Echinococcus granulosus sensu lato (s.l.). The disease has a global distribution representing a significant public health concern. Based on mitochondrial DNA analysis E. granulosus s.l. has been subdivided into five species: E. granulosus sensu stricto (s.s.) (G1, G3 genotype), E. equinus (G4 genotype), E. ortleppi (G5 genotype), E. canadensis (G6-G8, G10 genotype) and E. felidis. E. granulosus s.s., and in particular G1, is the most widespread genotype and the major responsible of human CE cases worldwide. In Italy G1 genotype is higly represented with larger percentages in some hyperendemic areas such as Sardinia. Molecular studies represent a valuable tool to improve our understanding of the E. granulosus epidemiology and CE control strategies. In the present study we investigated genetic variability of E. granulosus s.s. in Sardinia. To this purpose 83 hydatid cysts were collected from different animal species including humans and the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene was partially sequenced (720 bp). Nucleotide sequences from Mediterranean basin were also analyzed for comparison. The phylogenetic network revealed 30 haplotypes grouped around a predominant isolate that had been already reported from other world regions. Haplotype diversity (0.8495 ± 0.0336) and nucleotide diversity (0.003305 ± 0.002014) were similar in Sardinia respect to other Mediterranean countries. Neutrality indices obtained by Tajima's D and Fu's Fs test were significantly negative (p ≤ .01) suggesting expansion of Sardinian population. Low Fixation indices (Fst), ranging from negative values (Algeria, Greece, Spain, other part of Italy) to 0.089 (Albania, France), indicated absence of genetic differentiation, and gene flow between Sardinia and other Mediterranean countries.     

Cystic Echinococcoses in Mongolia: Molecular Identification,Serology and Risk Factors

Background

Cystic echinococcosis (CE) is a globally distributed cestode zoonosis that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.) is the major causative agent of CE worldwide, recent molecular epidemiological studies have revealed that E. canadensis is common in countries where camels are present. One such country is Mongolia.

Methodology/Principal Findings

Forty-three human hepatic CE cases that were confirmed histopathologically at the National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by analysis of mitochondrial cox 1 gene as being caused by either E. canadensis (n = 31, 72.1%) or E. granulosus s.s. (n = 12, 27.9%). The majority of the E. canadensis cases were strain G6/7 (29/31, 93.5%). Twenty three haplotypes were identified. Sixteen of 39 CE cases with data on age, sex and province of residence were citizens of UB (41.0%), with 13 of the 16 cases from UB caused by E. canadensis (G6/7) (81.3%). Among these 13 cases, nine were children (69.2%). All pediatric cases (n  =  18) were due to E. canadensis with 17 of the 18 cases (94.4%) due to strain G6/7. Serum samples were available for 31 of the 43 CE cases, with 22 (71.0%) samples positive by ELISA to recombinant Antigen B8/1 (rAgB). Nine of 10 CE cases caused by E. granulosus s.s. (90.0%) and 13 of 20 CE cases by E. canadensis (G6/7) (65.0%) were seropositive. The one CE case caused by E. canadensis (G10) was seronegative. CE cases caused by E. granulosus s.s. showed higher absorbance values (median value 1.131) than those caused by E. canadensis (G6/7) (median value 0.106) (p  =  0.0137).

Conclusion/Significance

The main species/strains in the study population were E. canadenis and E. granulossus s.s. with E. canadensis the predominant species identified in children. The reason why E. canadensis appears to be so common in children is unknown.     

The permeability of the membranes of experimental secondary cysts of Echinococcus granulosus to [14C]mebendazole

The permeability of secondary E. granulosus cysts to [¹⁴C]mebendazole was studied. The cysts were obtained by transplanting secondary cysts raised in mice into rats. The permeability to [¹⁴C]mebendazole was established by two different experiments: uptake and washout of the drug. The cyst wall permeability to [¹⁴C]mebendazole was found to be 1·33 × 10^?4 cm s^?1, which is of the same order as the diffusion permeability coefficient to water (1·88 × 10^?4 cm s^?1, Rotunno, Kammerer, Perez Esandi & Cereijido, 1974).The drug readily permeates through the cyst wall and experimental data suggest that it moves across the barrier by simple diffusion.     

Prevalence rate and risk factors of human cystic echinococcosis: A cross-sectional,community-based,abdominal ultrasound study in rural and urban north-central Chile

BackgroundCystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a neglected and underdiagnosed parasitic zoonosis that has a significant socioeconomic impact on rural communities relying on livestock farming. CE is endemic across Latin America, including Chile, where the Coquimbo region exhibits a relatively high record of hospital-based human cases and infected animals. However, the incidence of hospitalized CE cases may underestimate the real burden of infection in a population, since the majority of cases never reach medical attention or official disease records.Methodology/Principal findingsIn 2019, a cross-sectional, community-based study was conducted with the objectives of estimating for the first time the prevalence of human abdominal CE using abdominal ultrasound (US) screening in volunteers residing in urban and rural localities of the Monte Patria municipality located in Limarí province, Coquimbo region, Chile, and identifying the risk factors associated with human infection. Pre-screening activities included a 16-h lecture/hands-on training aimed at rural physicians that focused on the diagnosis of CE by US, based on current WHO recommendations. A total of 2,439 (~8% of municipality inhabitants) people from thirteen target localities were screened by abdominal US in June-July 2019. We found an overall CE prevalence of 1.6% (95% CI 1.1–2.2) with a significantly higher likelihood of infection in rural localities, older age classes and people drinking non-potable water; 84.6% of infected volunteers were newly diagnosed with CE. Cysts were either in active or inactive stages in equal proportions; active cysts were detected in all age classes, while 95.7% of inactive cysts occurred in >40 years-old subjects.Conclusions/SignificanceThis is the first US survey aimed at detecting human infection caused by Echinococcus granulosus s.l. in Chile. Our findings indicate a high CE prevalence in the area, and contribute to define the demographic and behavioral risk factors promoting the transmission of the parasitic infection within target communities. Our results support the implementation of cost-effective strategies for the diagnosis, treatment and control of CE, and the need to improve the epidemiological surveillance system in Chile.