Treatment of a giant hepatic echinococcal cyst with percutaneous drainage and in vivo assessment of the protoscolicidal effect of praziquantel.

Therapy choices for cystic echinococcisis (CE) are stage-specific: surgical, minimally invasive, medical or observation without intervention. PAIR (percutaneous aspiration, instillation of a scolicide, and re-aspiration) has been considered the treatment of choice for uncomplicated echinococcal liver cysts. However, PAIR carries the risk of toxic cholangitis or hypernatremia and that the cyst frequently refills with bile after withdrawing the catheter. We treated a patient with a giant CE 1 liver cyst with puncture drainage (PD) under albendazole coverage. Drainage enabled us to monitor the morphology of protoscolices under praziquantel (PZQ) co-medication. Protoscolices degenerated within 5 days of PZQ 50 mg/kg/d. The cyst cavity solidified with no evidence of reactivation or secondary spread. Percutaneous treatments can replace surgery in a significant number or cases with hepatic CE. PD allows to assess microscopically the viability of protoscolices under co-medication with PZQ-albendazole and to avoid the instillation of topical scolicides.

Role of microRNAs in host defense against Echinococcus granulosus infection: a preliminary assessment.

Cystic echinococcosis (CE) is a neglected helminthic zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus s.l. MicroRNAs (miRNAs) are regulators of gene expression that have been linked with the pathogenesis of several human diseases, but little exists in the available literature about miRNAs in CE. Here, we investigate the expression profiles of 84 microRNAs relevant to the function of lymphocytes and other immune cells during CE infection in the peripheral blood of patients with cysts in active and inactive stages. We applied the microRNA PCR array technology to blood samples from 20 patients with a single hepatic CE cyst in either the active (CE3b) or inactive (CE4-CE5) stage. Our results show a significant upregulation of eight miRNAs (let-7g-5p, let-7a-5p, miR- 26a-5p, miR- 26b-5p, miR- 195-5p, miR- 16-5p, miR- 30c-5p, and miR- 223-3p) in patients with active cysts compared to those with inactive cysts. The high expression of these miRNAs in patients with active cysts suggests their role in a specific host immune response against the infection. Further work in this direction may help shed light on the pathogenesis of human CE.

Correction to: Role of microRNAs in host defense against Echinococcus granulosus infection: a preliminary assessment.

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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.

Preliminary assessment of the diagnostic performances of a new rapid diagnostic test for the serodiagnosis of human cystic echinococcosis.

Rapid diagnostic tests for cystic echinococcosis (CE) are convenient to support ultrasound diagnosis in uncertain cases, especially in resource-limited settings. We found comparable diagnostic performances of the experimental Hyd Rapid Test and the commercial VIRapid HYDATIDOSIS Test, used in our diagnostic laboratory, using samples from well-characterized hepatic CE cases.

Structural and Immunodiagnostic Characterization of Synthetic Antigen B Subunits From Echinococcus granulosus and Their Evaluation as Target Antigens for Cyst Viability Assessment.

Background: Several tools have been proposed for serodiagnosis of cystic echinococcosis (CE), but none seems promising for cyst viability assessment. Antigens with stage-specific diagnostic value have been described, but few studies with well-characterized antigens and human serum samples have been performed. Antigen B (AgB) proteoforms hold promise as markers of viability, due to their differential stage-related expression and immunoreactivity. Methods: Four AgB subunits (AgB1, AgB2, AgB3, AgB4) were synthesized and structurally characterized. Based on the preliminary evaluation of the subunits by western immunoblotting and enzyme-linked immunosorbent assay (ELISA), AgB1 and AgB2 were further tested in two ELISA setups and extensively validated on 422 human serum samples. Results: All subunits showed a high degree of spontaneous oligomerization. Interacting residues within oligomers were identified, showing that both the N-terminal and C-terminal of each subunit are involved in homo-oligomer contact interfaces. No hetero-oligomer was identified. AgB1 and AgB2 ELISAs revealed different sensitivities relative to cyst stage. Of note, besides high specificity (97.2%), AgB1 revealed a higher sensitivity for active-transitional cysts (100% for CE1, 77.8% for CE2, 81.5% for CE3a, and 86.3% for CE3b) than for inactive cysts (41.7% for CE4 and 11.1% for CE5) and postsurgical patients (44%). Interestingly, 19 of 20 patients with spontaneously inactive cysts and 6 of 9 treated with albendazole >5 years earlier were negative on the AgB1 assay. Conclusions: The structural characterization of subunits provides insights into the synthetic antigen conformation. The stage-related sensitivity of synthetic AgB1 holds promise as part of a multiantigen setting and deserves further longitudinal evaluation as marker of cyst viability.

Costs Associated with Surgically Treated Cases of Abdominal Cystic Echinococcosis: A Single Center's Experience from 2008 to 2014, Pavia, Italy.

Cystic echinococcosis (CE) is a globally distributed zoonosis caused by the Echinococcus granulosus sensu lato species complex. Four approaches are available for treatment of abdominal CE: surgery, percutaneous aspiration, chemotherapy with albendazole, and watch-and-wait. Allocation of patients to these different treatment options mainly depends on the stage of the cystic lesion. However, as available guidelines are not widely followed, surgery is often applied even without the correct indication outside referral centers. This is not only a disadvantage for the patient, but also a waste of money. In this study, we evaluated the cost of the surgical approach for abdominal CE by analyzing hospitalization costs for 14 patients admitted to the General Surgery Ward at the "San Matteo" Hospital Foundation in Pavia, Italy, from 2008 through 2014. We found that the total cost of a single hospitalization, including hospital stay, surgical intervention, personnel, drugs, and administrative costs ranged from €5,874 to 23,077 (median €11,033) per patient. Our findings confirm that surgery can be an expensive option. Therefore, surgical intervention should be limited to cyst types that do not benefit from nonsurgical therapies and appropriate case management can best be accomplished by using a cyst stage-specific approach.

Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases--A Review of Applications and Perspectives.

The development of good quality and affordable ultrasound machines has led to the establishment and implementation of numerous point-of-care ultrasound (POCUS) protocols in various medical disciplines. POCUS for major infectious diseases endemic in tropical regions has received less attention, despite its likely even more pronounced benefit for populations with limited access to imaging infrastructure. Focused assessment with sonography for HIV-associated TB (FASH) and echinococcosis (FASE) are the only two POCUS protocols for tropical infectious diseases, which have been formally investigated and which have been implemented in routine patient care today. This review collates the available evidence for FASH and FASE, and discusses sonographic experiences reported for urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS protocols are suggested and technical as well as training aspects in the context of resource-limited settings are reviewed. Using the focused approach for tropical infectious diseases will make ultrasound diagnosis available to patients who would otherwise have very limited or no access to medical imaging.

Focused assessment with sonography for HIV-associated tuberculosis (FASH): a short protocol and a pictorial review.

BACKGROUND: Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings. METHODS: A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed. RESULTS: The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high. CONCLUSION: FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future.

Performance of real-time strain elastography, transient elastography, and aspartate-to-platelet ratio index in the assessment of fibrosis in chronic hepatitis C.

OBJECTIVE: The purpose of this article is to evaluate the diagnostic performance of transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index in assessing fibrosis in patients with chronic hepatitis C by using histologic Metavir scores as reference standard. SUBJECTS AND METHODS: Consecutive patients with chronic hepatitis C scheduled for liver biopsy were enrolled. Liver biopsy was performed on the same day as transient elastography and real-time strain elastography. Transient elastography and real-time strain elastography were performed in the same patient encounter by a single investigator using a medical device based on elastometry and an ultrasound machine, respectively. Diagnostic performance was assessed by using receiver operating characteristic curves and area under the receiver operating characteristic curve (AUC) analysis. RESULTS: One hundred thirty patients (91 men and 39 women) were analyzed. The cutoff values for transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index were 6.9 kPa, 1.82, and 0.37, respectively, for fibrosis score of 2 or higher; 7.3 kPa, 1.86, and 0.70, respectively, for fibrosis score of 3 or higher; and 9.3 kPa, 2.33, and 0.70, respectively, for fibrosis score of 4. AUC values of transient elastography, real-time strain elastography, aspartate-to-platelet ratio index were 0.88, 0.74, and 0.86, respectively, for fibrosis score of 2 or higher; 0.95, 0.80, and 0.89, respectively, for fibrosis score of 3 or higher; and 0.97, 0.80, and 0.84, respectively, for fibrosis score of 4. A combination of the three methods, when two of three were in agreement, showed AUC curves of 0.93, 0.95, and 0.95 for fibrosis scores of 2 or higher, 3 or higher, and 4, respectively. CONCLUSION: Transient elastography, real-time strain elastography, and aspartate-to-platelet ratio index values were correlated with histologic stages of fibrosis. Transient elastography offered excellent diagnostic performance in assessing severe fibrosis and cirrhosis. Real-time elastography does not yet have the potential to substitute for transient elastography in the assessment of liver fibrosis.

Short course for focused assessment with sonography for human immunodeficiency virus/tuberculosis: preliminary results in a rural setting in South Africa with high prevalence of human immunodeficiency virus and tuberculosis.

In Africa, human immunodeficiency virus (HIV)-associated extrapulmonary tuberculosis (TB) is common and poses diagnostic difficulties. Ultrasound is useful to find suggestive signs such as effusions or abdominal lymphadenopathy. Because trained radiologists are scarce in resource-poor settings, even this simple and relatively inexpensive diagnostic tool is frequently unavailable to patients in district hospitals in sub-Saharan Africa. We developed a focused protocol for assessment with sonography for HIV/TB and trained physicians in a rural district hospital in South Africa. In this pilot study, high levels of confidence in identifying specific signs were rapidly achieved and ultrasound was introduced into routine clinical practice.

Metabolic viability assessment of cystic echinococcosis using high-field 1H MRS of cyst contents.

Cystic echinococcosis is a worldwide disease caused by larval stages of the parasite Echinococcus granulosus (canine tapeworm). In clinical practice, staging of cyst development by ultrasonography (US) has allowed treatment options to be tailored to individual patient needs. However, the empirical correlation between cyst morphology and parasite viability is not always dependable and has, until now, required confirmation by invasive assessment of cyst content by light microscopy (LM), for example. Alternatively, high-field 1H MRS may be used to examine cyst fluid ex vivo and prepare detailed quantitative metabolite profiles, enabling a multivariate metabolomics approach to cyst staging. One-dimensional and two-dimensional 1H and 1H/13C MRS at 600 MHz (14.1 T) was used to analyze 50 cyst aspirates of various US and LM classes. MR parameters and concentrations relative to internal valine were determined for 44 metabolites and four substance classes. The high concentrations of succinate, fumarate, malate, acetate, alanine, and lactate found in earlier studies of viable cysts were confirmed, and additional metabolites such as myo-inositol, sorbitol, 1,5-anhydro-D-glucitol, betaine, and 2-hydroxyisovalerate were identified. Data analysis and cyst classification were performed using univariate (succinate), bivariate (succinate vs fumarate), and multivariate partial least squares discriminant analysis (PSL-DA) methods (with up to 48 metabolite variables). Metabolic classification of 23 viable and 18 nonviable cysts on the basis of succinate alone agreed with LM results. However, for seven samples, LM and MRS gave opposing results. Reclassification of these samples and two unclassified samples by PLS-DA prediction techniques led to a set of 50 samples that could be completely separated into viable and nonviable MRS classes with no overlap, using as few as nine variables: succinate, formate, malate, 2-hydroxyisovalerate, acetate, total protein content, 1,5-anhydro-D-glucitol, alanine, and betaine. Thus, future noninvasive in vivo applications of MRS would appear promising.

Coarse vs. fine needle aspiration biopsy for the assessment of diffuse liver disease from hepatitis C virus-related chronic hepatitis.

BACKGROUND/AIMS: Liver biopsy is crucial in defining natural history and therapeutic choices in chronic hepatitis C and it is usually performed with coarse (>1 mm) needles (CN). As fine needles (FN) do not require anaesthesia, are used over a wider range of coagulation values and allow multiple passes, we compared the diagnostic yield of FN vs. CN biopsies. METHODS: Paired samples obtained with FN (0.8 mm) and CN (1.2 mm) on 149 consecutive outpatients from a tertiary care institution were evaluated prospectively. Histologic variables were quantitatively scored. Sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were calculated as measures of diagnostic ability assuming CN as reference. RESULTS: FN biopsy was adequate in 83 cases, CN in 140 cases (P<0.001). Considering the 83 paired adequate specimens, the best sensitivity of FN vs. CN was for portal inflammation (0.95%) and the worst for cirrhosis (0.33%). Overall discriminant ability of FN was unsatisfactory and histologic variables were systematically underscored. Tolerability was good for both procedures. CONCLUSIONS: The advantages of FN biopsy are lost on its inferior diagnostic performance. Its use in diffuse liver diseases should be restricted to early non-fibrotic lesions.