Spinal cystic echinococcosis - a systematic analysis and review of the literature : part 2. treatment, follow-up and outcome

Bone involvement in human cystic echinococcosis (CE) is rare, but affects the spine in approximately 50% of cases. Despite significant advances in diagnostic imaging techniques, surgical treatment and introduction of pharmacological therapy, spinal echinococcosis remains associated with a high degree of morbidity, disability and mortality. We systematically reviewed the published literature of the last five decades to update and summarize the currently existing data on treatment, follow-up and outcome of spinal CE

Serum Cytokine Profile by ELISA in Patients with Echinococcal Cysts of the Liver: A Stage-Specific Approach to Assess Their Biological Activity

To investigate the usefulness of serum cytokine dosage in the clinical management of cystic echinococcosis (CE), we analyzed serum levels of Th1 and Th2 cytokines in patients with hepatic CE in different cyst stages, CE1-2 (active), CE3a-3b (transitional), and CE4-5 (inactive). Ex vivo assessment of Th1 (IFN-γ) and Th2 (IL-4, IL-13, and IL-10) cytokines in sera was carried out using ELISA. IL-10 was undetectable in all serum samples of patients and controls, while a few sera contained measurable amounts of IFN-γ, IL-4, and IL-13. No statistically significant difference was found between the percentages of positive samples for each cytokine and the different groups analyzed (patients/controls, stage, number, location, and size of the cyst, serology, and sex of patients), with the exception of the association of IL-4 and IL-13 with the cyst stage. Overall, this investigation showed many limits of serum cytokine dosage as a marker of biological activity of echinococcal cysts. Because of low sensitivity and lack of specificity of this test, we believe that other ways to evaluate ex vivo biological activity of the cysts should be explored

The first meeting of the European Register of Cystic Echinococcosis (ERCE)

6 páginas, 3 figuras, 1 tablaCystic echinococcosis (CE) is a zoonotic parasitic disease endemic in southern and eastern European countries. The true prevalence of CE is difficult to estimate due to the high proportion of asymptomatic carriers who never seek medical attention and to the underreporting of diagnosed cases, factors which contribute to its neglected status. In an attempt to improve this situation, the European Register of Cystic Echinococcosis (ERCE), was launched in October 2014 in the context of the HERACLES project. ERCE is a prospective, observational, multicentre register of patients with probable or confirmed CE. The first ERCE meeting was held in November 2015 at the Italian National Institute of Health (Istituto Superiore di Sanita, ISS) in Rome, to bring together CE experts currently involved in the Register activities, to share and discuss experiences, and future developments. Although the Register is still in its infancy, data collected at the time of writing this report, had outnumbered the total of national cases reported by the European endemic countries and published by the European Centre for Disease Prevention and Control in 2015. This confirms the need for an improved reporting system of CE at the European level. The collection of standardized clinical data and samples is expected to support a more rational, stage-specific approach to clinical management, and to help public authorities harmonize reporting of CE. A better understanding of CE burden in Europe will encourage the planning and implementation of public health policies toward its control.This research received funding from the European Community’s Seventh Framework Programme under the grant agreement 602051 (Project HERACLES: Human cystic Echinococcosis ReseArch in CentraL and Eastern Societies; http:// www.heracles-fp7.eu/).Peer reviewe

Treatment of uncomplicated hepatic cystic echinococcosis (hydatid disease).

Background Cystic echinococcosis is a parasitic infection mainly impacting people living in low‐ and middle‐income countries. Infection may lead to cyst development within organs, pain, non‐specific symptoms or complications including abscesses and cyst rupture. Treatment can be difficult and varies by country. Treatments include oral medication, percutaneous techniques and surgery. One Cochrane review previously assessed the benefits and harms of percutaneous treatment compared with other treatments. However, evidence for oral medication, percutaneous techniques and surgery in specific cyst stages has not been systematically investigated and the optimal choice remains uncertain. Objectives To assess the benefits and harms of medication, percutaneous and surgical interventions for treating uncomplicated hepatic cystic echinococcosis. Search methods We searched CENTRAL, MEDLINE, two other databases and two trial registries to 4 May 2023. We searched the reference lists of included studies, and contacted experts and researchers in the field for relevant studies. Selection criteria We included randomized controlled trials (RCTs) in people with a diagnosis of uncomplicated hepatic cystic echinococcosis of World Health Organization (WHO) cyst stage CE1, CE2, CE3a or CE3b comparing either oral medication (albendazole) to albendazole plus percutaneous interventions, or to surgery plus albendazole. Studies comparing praziquantel plus albendazole to albendazole alone prior to or following an invasive intervention (surgery or percutaneous treatment) were eligible for inclusion. Data collection and analysis We used standard Cochrane methods. Our primary outcomes were symptom improvement, recurrence, inactive cyst at 12 months and all‐cause mortality at 30 days. Our secondary outcomes were development of secondary echinococcosis, complications of treatment and duration of hospital stay. We used GRADE to assess the certainty of evidence. Main results We included three RCTs with 180 adults and children with hepatic cystic echinococcosis. Two studies enrolled people aged 5 to 72 years, and one study enrolled children aged 6 to 14 years. One study compared standard catheterization plus albendazole with puncture, aspiration, injection and re‐aspiration (PAIR) plus albendazole, and two studies compared laparoscopic surgery plus albendazole with open surgery plus albendazole. The three RCTs were published between 2020 and 2022 and conducted in India, Pakistan and Turkey. There were no other comparisons. Standard catheterization plus albendazole versus PAIR plus albendazole The cyst stages were CE1 and CE3a. The evidence is very uncertain about the effect of standard catheterization plus albendazole compared with PAIR plus albendazole on cyst recurrence (risk ratio (RR) 3.67, 95% confidence interval (CI) 0.16 to 84.66; 1 study, 38 participants; very low‐certainty evidence). The evidence is very uncertain about the effects of standard catheterization plus albendazole on 30‐day all‐cause mortality and development of secondary echinococcosis compared to open surgery plus albendazole. There were no cases of mortality at 30 days or secondary echinococcosis (1 study, 38 participants; very low‐certainty evidence). Major complications were reported by cyst and not by participant. Standard catheterization plus albendazole may increase major cyst complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 10.74, 95% CI 1.39 to 82.67; 1 study, 53 cysts; very low‐certainty evidence). Standard catheterization plus albendazole may make little to no difference on minor complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 1.03, 95% CI 0.60 to 1.77; 1 study, 38 participants; very low‐certainty evidence). Standard catheterization plus albendazole may increase the median duration of hospital stay compared with PAIR plus albendazole, but the evidence is very uncertain (4 (range 1 to 52) days versus 1 (range 1 to 15) days; 1 study, 38 participants; very low‐certainty evidence). Symptom improvement and inactive cysts at 12 months were not reported. Laparoscopic surgery plus albendazole versus open surgery plus albendazole The cyst stages were CE1, CE2, CE3a and CE3b. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on cyst recurrence in participants with CE2 and CE3b cysts compared to open surgery plus albendazole (RR 3.00, 95% CI 0.13 to 71.56; 1 study, 82 participants; very low‐certainty evidence). The second study involving 60 participants with CE1, CE2 or CE3a cysts reported no recurrence in either group. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on 30‐day all‐cause mortality in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole. There was no mortality in either group (2 studies, 142 participants; very low‐certainty evidence). The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on major complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.50, 95% CI 0.13 to 1.92; 2 studies, 142 participants; very low‐certainty evidence). Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.13, 95% CI 0.02 to 0.98; 2 studies, 142 participants; low‐certainty evidence). Laparoscopic surgery plus albendazole may reduce the duration of hospital stay compared with open surgery plus albendazole (mean difference (MD) −1.90 days, 95% CI −2.99 to −0.82; 2 studies, 142 participants; low‐certainty evidence). Symptom improvement, inactive cyst at 12 months and development of secondary echinococcosis were not reported

A lack of confirmation with alternative assays questions the validity of IL-17A expression in human neutrophils using immunohistochemistry

We identified IL-17A-positive neutrophils in Wolbachia-positive Onchocerca volvulus nodules using an antibody that has previously reported IL-17A-positive neutrophils in several inflammatory conditions. However, we could not detect IL-17A using a range of alternative assays. Our data question the IL-17A antibody specificity and the ability of human neutrophils to express IL-17A

Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, were functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterised. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism

Ultrasound and intestinal lesions in Schistosoma mansoni infection: A case-control pilot study outside endemic areas

Infection with Schistosoma mansoni is a major cause of morbidity and mortality in endemic areas, and is increasingly diagnosed in migrants and travellers outside transmission areas. Markers for the assessment of morbidity and impact of control programs in endemic areas and for the clinical management of patients in the clinical setting are scant, especially for intestinal involvement. Ultrasonography is well established to evaluate hepatosplenic pathology; on the contrary, ultrasound evaluation of intestinal schistosomiasis is virtually unexplored. In this pilot study, we aimed to describe and evaluate the accuracy of unenhanced intestinal ultrasound for morbidity due to intestinal S. mansoni infection

Epidemiologic-economic models and the One Health paradigm: echinococcosis and leishmaniasis, case studies in Veneto region, Northeastern Italy

Epidemiology and health economics have systemic interdependencies. The identification of the economic outcomes of any disease is operated by overlapping its epidemiology with the economic functions of the impacted entities. This communication presents two epidemiologic-economic models designed to evaluate the economic burden of cystic echinococcosis and leishmaniasis in Veneto (Northeastern Italy). Following a One Health approach, the research integrates expertise from different disciplines and institutions and fulfilled its first stage by defining the relevant cost categories and the data collection strategy for the two diseases in the study area. The two models identify the relevant epidemiological factors and the economic outcomes of infections in both animals and humans. The results, visualized in flow charts indicating the types of costs associated with these zoonoses, will guide data collection and the epidemiologic and economic assessment in the next research stages. This experience shows that One Health methods, although still innovative or unusual in many scientific and professional contexts, can be applied by using relatively limited resources and already available professional skills

Shortage of Albendazole and Its Consequences for Patients with Cystic Echinococcosis Treated at a Referral Center in Italy

Albendazole (ABZ) is the best drug available to treat cystic echinococcosis (CE), a neglected tropical disease. Cystic echinococcosis patients often receive a continuous course of the drug for 6-12 months. In Italy, ABZ shortages occur almost on a yearly basis. We searched clinical records at the World Health Organization Collaborating Center for the Clinical Management of CE in Pavia, Italy, to estimate the amount of ABZ prescribed to patients between January 2012 and February 2017. The cost of ABZ was estimated at €2.25 per tablet based on the current market price in Italy. Patients to whom ABZ had been prescribed were contacted to determine if they had experienced difficulties in purchasing the drug and to assess how such problems affected their treatment. Of 348 identified CE patients, 127 (36.5%) were treated with ABZ for a total of 20,576 days. This led to an estimated cost of €92,592. Seventy-five patients were available for follow-up, 42 (56%) reported difficulties in obtaining ABZ. Of these patients, four (9.5%) had to search out of their region and 10 (23.8%) had to go out of the country. A total of 27 patients (64%) had to visit more than five pharmacies to locate the drug and 10 patients (23.8%) interrupted treatment because of ABZ nonavailability. Shortages in ABZ distribution can disrupt CE treatment schedules and jeopardize patient health

A large case series of travel-related Mansonella perstans (vector-borne filarial nematode): a TropNet study in Europe

Mansonella perstans; Travel; TreatmentMansonella perstans; Viaje; TratamientoMansonella perstans; Viatge; TractamentBackground Infection with Mansonella perstans is a neglected filariasis, widely distributed in sub-Saharan Africa, characterized by an elusive clinical picture; treatment for mansonellosis is not standardized. This retrospective study aimed to describe the clinical features, treatment schemes and evolution, of a large cohort of imported cases of M. perstans infection seen in four European centres for tropical diseases. Methods Mansonella perstans infections, diagnosed by identification of blood microfilariae in migrants, expatriates and travellers, collected between 1994 and 2018, were retrospectively analysed. Data concerning demographics, clinical history and laboratory examinations at diagnosis and at follow-up time points were retrieved. Results A total of 392 patients were included in the study. Of the 281 patients for whom information on symptoms could be retrieved, 150 (53.4%) reported symptoms, abdominal pain and itching being the most frequent. Positive serology and eosinophilia were present in 84.4% and 66.1%, respectively, of those patients for whom these data were available. Concomitant parasitic infections were reported in 23.5% of patients. Treatment, administered to 325 patients (82.9%), was extremely heterogeneous between and within centres; the most commonly used regimen was mebendazole 100 mg twice a day for 1 month. A total of 256 (65.3%) patients attended a first follow-up, median 3 months (interquartile range 2–12) after the first visit; 83.1% of patients having received treatment based on mebendazole and/or doxycycline, targeting Wolbachia, became amicrofilaremic, 41.1–78.4% of whom within 12 months from single treatment. Conclusions Lack of specific symptoms, together with the inconstant positivity of parasitological and antibody-based assays in the infected population, makes the clinical suspicion and screening for mansonellosis particularly difficult. Prospective studies evaluating prevalence of infection in migrants from endemic areas, infection-specific morbidity, presence of Wolbachia endosymbionts in M. perstans populations from different geographical areas and efficacy of treatment regimens are absolutely needed to optimize the clinical management of infection.The publication of this study was funded by Italian Ministry of Health Fondi Ricerca Corrente–L2 to IRCCS Sacro Cuore Don Calabria Hospital