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Cystic echinococcosis control in South American countries requires a comprehensive integrative ‘One Health’ approach. While insular nations have seen successful in their elimination programmes, South American countries face persistent challenges in hostile environments, with Echinococcus granulosus s.l., posing a significant public health concern. Vaccination of intermediate hosts has demonstrated the efficacy of the EG95 vaccine in reducing transmission rates. For example, since 2009, Rio Negro Province in Argentina has added, with marked success, the EG95 vaccine to the control programme, supplementing dog deworming. The Aysen Region of Chile has also reported encouraging preliminary results in reducing cyst prevalence in vaccinated sheep after 3 years of vaccination. The challenges in aligning control strategies with socio-cultural factors, especially in indigenous communities, underlines the need for context-specific strategies. The Rio Negro programme demonstrated commendable compliance, underlining the importance of community engagement in achieving lasting success. The most promising strategies for effective echinococcosis control involved dog deworming and the routine vaccination of sheep and/or goats, underscoring the importance of sustained implementation until all grazing animals have been replaced. For lasting success, these interventions need to be combined with a robust surveillance system.
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
Echinococcosis lacks sensitive serological diagnostic tools. The echinococcosis-specific antigens Eg95, AgB8/1 and the Em18 gene sequences were fused and expressed as the novel recombinant antigens rAgB8/1-Em18-Eg95 (T3) and rEm18-Eg95 (T2), used for the diagnosis of hydatid disease, prepared into an enzyme-linked immunosorbent reaction (ELISA) kit, and evaluated for their serological diagnostic value. The relative molecular weight of the T3 protein was 88.1 kDa, the purified concentration was 1.5 mg mL−1, and the purity was 80%. The relative molecular weight of T2 protein was 79.9 kDa, the total protein concentration was 0.5 mg mL−1, and the purity was less than 50%. The overall coincidence rate of T2 protein was low, and it was impossible to distinguish between negative and positive sera. The T3 antigen was coated at 1.0 μg mL−1, the cutoff value was 0.5271, and the serum dilution ratio was 1:400. A T3 ELISA kits (96 tests) was constructed to detect the serum of 272 clinically and pathologically confirmed cases. The sensitivity of T3 was 93.8%, and the specificity was 83.3%. The parasite cross-reaction was 30%. Satisfactorily, the Pearson correlation coefficient between the T3 OD value and lesion diameter was 0.707, showing a strong correlation. T3 exhibits better antigenicity than T2, and the prepared T3 ELISA diagnostic kits reached the laboratory diagnostic level of a commercial kits. T3 can distinguish human cystic echinococcosis (CE) and alveolar echinococcosis (AE) more significantly and predict the diameter of lesions according to the OD value, which provides practical value for drug or surgical efficacy.
Cystic echinococcosis (CE), caused by Echinococcus granulosus s.l. is a neglected zoonosis posing a significant public health challenge. Little is known about human CE in Bhutan. This study was conducted to gain an understanding of the burden, distribution, and potential risk factors of CE in Bhutan. From January 2015 to December 2019 data from Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) and 6 other district-level hospitals were reviewed. Descriptive statistics were used to summarize the data. DALYs and Poisson regression models were used to estimate the burden and explore the relationship between cases and possible risk factors. A total of 159 cases were recorded. Most cases (145) were admitted to the surgical ward and 14 cases were referred to India. The average annual incidence was 4.4 cases per 100 000 population. The burden of disease was estimated to be approximately 39 DALYs per year for treatment-seeking cases, or possibly 80 DALYs per year including non-treatment seeking cases. This translates to approximately to 5.2 DALYs and 10.2 per 100 000 per year respectively. The commonest sites of infection were the liver (78%) and lungs (13%). Most cases were treated with surgery (>82%), and more than 47% were admitted to the hospital for >4 days. Policy interventions targeting community engagement, awareness, education, high risk occupational groups, females, and those living in the endemic districts of the central and western regions may yield larger gains. More studies and the institution of a surveillance system can help better guide policy interventions.
The study aimed to assess the heterogeneity in the distribution of disease awareness, attitudes, and practices related to cystic echinococcosis (CE) in different subgroups and inform health authorities regionally and globally for future evidence-based tailored prevention practices in the region. A cross-sectional study was conducted with 242 participants from Kyrgyz Republic (KR), Issyk-Kul oblast, and utilized survey data to analyse demographics, household information, echinococcosis-related practices, and knowledge. Participants in high-risk environments (HRE) and engaging in high-risk behaviours (HRB) linked to CE contracting were identified. Out of 242 participants, 39% lived in HRE, with 22% engaging in HRB of contracting CE. 13% lived in HRE and engaged in HRB. Only 6% followed all preventive measures, while 56% followed some. 97.5% of participants had heard about CE, but only 6% identified all transmission routes, and 63.4% were unaware of dog contact as a route. Education reduced the odds of being in the highest risk group (HRE&HRB) (OR 0.5, 95% CI 0.23–0.80). The study's findings are alarming, emphasizing factors contributing to regional endemicity. We anticipated a similar pattern in the neighbouring countries, given the shared nomadic customs and historical parallels. Examination of the heterogeneity of disease awareness and practices allows tailored prevention strategies. Urgent prevention programmes focusing on echinococcosis awareness in the KR are crucial to addressing challenges posed by nomadic habits.
This study aimed to explore extracellular microRNA derived from Echinococcus multilocularis (EM) in the plasma of patients with alveolar echinococcosis (AE) and assess its potential as a diagnostic biomarker. EM-derived miRNAs were identified in plasma samples from 20 AE patients through miRNA sequencing. Three novel miRNA molecules (emu-miR-novel 1, 2 and 3) were predicted through bioinformatic analysis to elucidate their chromosomal locations, secondary structures and precursor forms. Subsequently, plasma samples from 30 AE patients and 30 controls were utilized to establish an assay via stem-loop reverse transcription PCR, optimizing primers, reaction systems, and conditions to assess cross-reactivity and sensitivity. Clinical validation revealed that emu-miR-novel 1 had the highest diagnostic accuracy, with an area under the curve (AUC) of 0.8994, a P value of less than 0.0001, a sensitivity of 83.3%, and a specificity of 86.7%. Statistically significant differences were observed between the groups for emu-miR-novel 1 (P < 0.05), whereas emu-miR-novel 2 and 3 showed AUC values of 0.7922 and 0.6883, with P values of 0.0001 and 0.012, respectively, indicating no significant difference between groups (P > 0.05). Furthermore, the assay showed no cross-reactivity with samples from 18 common viruses, 4 parasitic infections, and miRNAs from AE sequenced from 8 species, confirming its high specificity. Emu-miR-novel 1 exhibited a sensitivity of 1 femtomolar. Emu-miR-novel 1 holds promise as a key diagnostic tool for AE, offering a novel perspective and approach for disease diagnosis.
Cystic and alveolar echinococcosis are considered the second and third most significant foodborne parasitic diseases worldwide. The microscopic eggs excreted in the feces of the definitive host are the only source of contamination for intermediate and dead-end hosts, including humans. However, estimating the respective contribution of the environment, fomites, animals or food in the transmission of Echinococcus eggs is still challenging. Echinococcus granulosus and E. multilocularis seem to have a similar survival capacity regarding temperature under laboratory conditions. In addition, field experiments have reported that the eggs can survive several weeks to years outdoors, with confirmation of the relative susceptibility of Echinococcus eggs to desiccation. Bad weather (such as rain and wind), invertebrates and birds help scatter Echinococcus eggs in the environment and may thus impact human exposure. Contamination of food and the environment by taeniid eggs has been the subject of renewed interest in the past decade. Various matrices from endemic regions have been found to be contaminated by Echinococcus eggs. These include water, soil, vegetables and berries, with heterogeneous rates highlighting the need to acquire more robust data so as to obtain an accurate assessment of the risk of human infection. In this context, it is essential to use efficient methods of detection and to develop methods for evaluating the viability of eggs in the environment and food.
The diagnosis of cystic echinococcosis (CE) is based on imaging. Detection of a focal lesion with morphological characteristics of Echinococcus granulosus sensu lato metacestode is the starting point for the diagnostic workup. In organs explorable with ultrasound (US), this is the method of choice for both aetiological diagnosis of CE and staging of the CE cyst. Staging in terms of lesion morphology is also needed when serology is added to the diagnostic workflow when imaging alone is inconclusive. Finally, staging guides the clinical management of uncomplicated CE, especially in the liver. This commentary provides an overview of the most up-to-date evidence backing the above-mentioned role of US in the diagnosis and clinical management of CE. Finally, we outline future perspectives for the improvement of CE diagnosis.