Unveiling the incidences and trends of the neglected zoonosis cystic echinococcosis in Europe: a systematic review from the MEmE project.

The neglected zoonosis cystic echinococcosis affects mainly pastoral and rural communities in both low-income and upper-middle-income countries. In Europe, it should be regarded as an orphan and rare disease. Although human cystic echinococcosis is a notifiable parasitic infectious disease in most European countries, in practice it is largely under-reported by national health systems. To fill this gap, we extracted data on the number, incidence, and trend of human cases in Europe through a systematic review approach, using both the scientific and grey literature and accounting for the period of publication from 1997 to 2021. The highest number of possible human cases at the national level was calculated from various data sources to generate a descriptive model of human cystic echinococcosis in Europe. We identified 64 745 human cystic echinococcosis cases from 40 European countries. The mean annual incidence from 1997 to 2020 throughout Europe was 0·64 cases per 100 000 people and in EU member states was 0·50 cases per 100 000 people. Based on incidence rates and trends detected in this study, the current epicentre of cystic echinococcosis in Europe is in the southeastern European countries, whereas historical endemic European Mediterranean countries have recorded a decrease in the number of cases over the time.

Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2-91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1-76.2), 2B2t (65.5%, 95% CI: 58.5-72.0), GST-Ag5t (64.5%, 95% CI: 57.5-71.1) and GST-DIPOL (63.1%, 95% CI: 56.0-69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3-99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6-50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.

Differences in larval survival and IgG response patterns in long-lasting infections by Trichinella spiralis, Trichinella britovi and Trichinella pseudospiralis in pigs.

BACKGROUND: Domesticated and wild swine play an important role as reservoir hosts of Trichinella spp. and a source of infection for humans. Little is known about the survival of Trichinella larvae in muscles and the duration of anti-Trichinella antibodies in pigs with long-lasting infections. METHODS: Sixty pigs were divided into three groups of 20 animals and infected with 10,000 larvae of Trichinella spiralis, Trichinella britovi or Trichinella pseudospiralis. Four pigs from each group were sacrificed at 2, 6, 12, 18 and 24 months post-infection (p.i.) and the number of larvae per gram (LPG) of muscles was calculated. Serum samples were tested by ELISA and western blot using excretory/secretory (ES) and crude antigens. RESULTS: Trichinella spiralis showed the highest infectivity and immunogenicity in pigs and larvae survived in pig muscles for up to 2 years p.i. In these pigs, the IgG level significantly increased at 30 days p.i. and reached a peak at about 60 days p.i., remaining stable until the end of the experiment. In T. britovi-infected pigs, LPG was about 70 times lower than for T. spiralis at 2 months p.i. and only very few infecting larvae were detected at 6 months p.i., whereas no larvae were detected at 12, 18 and 24 months p.i. At 6 months p.i., degenerated/calcified larvae and cysts were detected in the muscles by trichinoscopy and histology. The IgG pattern showed by T. britovi-infected pigs was similar to that of T. spiralis-infected pigs, although seroconversion occurred some days later. The larval burden of T. pseudospiralis was slightly greater than for T. britovi at 2 months p.i., but no larvae were detected at 6 and 12 months p.i. In T. pseudospiralis-infected pigs, seroconversion occurred slowly, as in T. britovi-infected pigs. The IgG level showed a significant drop at 6 months p.i. and declining to the cut-off value at 12 months p.i. CONCLUSIONS: The longer survival of T. spiralis in pigs in comparison with the other two species highlights its exceptional dissemination potential. These results provide an explanation of the controversial data collected by parasitological and serological tools in the course of epidemiological investigations.

Epidemiological factors associated with human cystic echinococcosis: a semi-structured questionnaire from a large population-based ultrasound cross-sectional study in eastern Europe and Turkey.

BACKGROUND: Cystic echinococcosis (CE) is a neglected parasitic zoonosis prioritized by the WHO for control. Several studies have investigated potential risk factors for CE through questionnaires, mostly carried out on small samples, providing contrasting results. We present the analysis of risk factor questionnaires administered to participants to a large CE prevalence study conducted in Bulgaria, Romania and Turkey. METHODS: A semi-structured questionnaire was administered to 24,687 people from rural Bulgaria, Romania and Turkey. CE cases were defined as individuals with abdominal CE cysts detected by ultrasound. Variables associated with CE at P < 0.20 in bivariate analysis were included into a multivariable logistic model, with a random effect to account for clustering at village level. Adjusted odds ratios (AOR) with 95% CI were used to describe the strength of associations. Data were weighted to reflect the relative distribution of the rural population in the study area by country, age group and sex. RESULTS: Valid records from 22,027 people were analyzed. According to the main occupation in the past 20 years, "housewife" (AOR: 3.11; 95% CI: 1.51-6.41) and "retired" (AOR: 2.88; 95% CI: 1.09-7.65) showed significantly higher odds of being infected compared to non-agricultural workers. "Having relatives with CE" (AOR: 4.18; 95% CI: 1.77-9.88) was also associated with higher odds of infection. Interestingly, dog-related and food/water-related factors were not associated with infection. CONCLUSIONS: Our results point toward infection being acquired in a "domestic" rural environment and support the view that CE should be considered more a "soil-transmitted" than a "food-borne" infection. This result helps delineating the dynamics of infection transmission and has practical implications in the design of specific studies to shed light on actual sources of infection and inform control campaigns.

Childhood vaccinations: knowledge, attitudes and practices of paediatricians and factors associated with their confidence in addressing parental concerns, Italy, 2016.

BackgroundPaediatrician recommendations are known to influence parental vaccine decisions.AimOur aim was to examine vaccination knowledge, attitudes and practices among paediatricians in Italy and identify factors associated with their confidence in addressing parental questions.MethodsAn electronic questionnaire survey was conducted from February to March 2016, among a sample of Italian paediatricians.ResultsThe survey was completed by 903 paediatricians (mean age: 56 years). Of 885 who responded to the specific question, 843 (95.3%) were completely favourable to vaccinations. Sixty-six per cent (570/862) felt sufficiently knowledgeable about vaccinations and vaccine-preventable diseases to confidently discuss them with parents. Paediatricians who were male, who were 55 years or older, who had participated in training courses in the last 5 years, who reported that taking courses and reading the scientific literature had contributed to their knowledge, or who had implemented vaccination promotion activities, felt more knowledgeable than other paediatricians. When asked to rate their level of agreement with statements about vaccine safety and effectiveness, only 8.9% (80/903) responded fully as expected. One third (294/878) did not systematically verify that their patients are up to date with the immunisation schedule. Only 5.4% (48/892) correctly identified all true and false contraindications.ConclusionsThe majority of paediatricians in Italy are favourable to vaccination but gaps were identified between their overall positive attitudes and their knowledge, beliefs and practices. Targeted interventions are needed aimed at increasing paediatricians' confidence in addressing parents' concerns, strengthening trust towards health authorities and improving systems barriers.

The overlap syndrome of urticaria and gastroesophageal reflux disease.

BACKGROUND: One-quarter of systemic symptoms associated with chronic spontaneous urticaria (CSU) are related to gastrointestinal complaints (GICs). OBJECTIVES: To investigate the prevalence and features of urticaria-overlapping GICs. METHODS: In this retrospective cross-sectional survey, 1426 consecutive outpatients were observed at our University Department. Only patients suffering from urticaria or GICs with a complete diagnostic work-up including serum total IgE level (Tot-IgE), differential blood count and urticaria activity score (UAS), were evaluated. RESULTS: Among different GICs, gastroesophageal reflux disease (GERD) was the most frequent syndrome observed (15.4%; 95%CI: 13.6-17.3). The prevalence of overlap syndrome for urticaria and GERD was 5.9% (95%CI: 4.7-7.2). In urticaria-patients, the prevalence of GERD was four-fold higher than in patients without hives (44% vs. 11%, p<0.001). UAS was significantly higher in urticaria and GERD overlap syndromes vs. isolated urticarias. In patients with GERD or acute/chronic urticaria or overlap syndrome, Tot-IgE and eosinophil blood count (EBC) differed significantly, with a stepwise increase in their values; from the subgroup of patients with GERD only, to that with overlap of CSU to GERD. Prevalence values for urticaria overlapping with GERD were three- and two-fold higher in CSU and in long-duration GERD cases respectively compared to acute urticaria or short-duration GERD cases. Similar to Th2 pathology models, CSU and GERD overlap syndrome was significantly and independently associated with Total-IgE ≥100IU/ml or EBC ≥250/mmc compared to CSU or GERD. Endoscopic/bioptic findings of non-erosive reflux disease (NERD) or Barrett's esophagus (BE) were more frequent in chronic overlap syndrome than in GERD-patients. CONCLUSIONS: GERD was the most frequent GIC in patients with urticaria. Overlap syndrome was more frequent among patients with CSU, where this syndrome was associated with higher values of UAS, Tot-IgE, EBC and frequencies of NERD and BE. These results suggest that overlap syndrome is frequently a chronic syndrome with a Th2-like profile.

Evaluation of the recombinant antigens B2t and 2B2t, compared with hydatid fluid, in IgG-ELISA and immunostrips for the diagnosis and follow up of CE patients.

Cystic echinococcosis (CE) is one of the most widespread helminthic zoonoses and is caused by the tapeworm Echinococcus granulosus complex. CE diagnosis and monitoring primarily rely on imaging techniques, complemented by serology. This is usually approached by the detection of IgG antibodies against hydatid fluid (HF), but the use of this heterogeneous antigenic mixture results in a variable percentage of false positive and negative results, and has shown to be useless for follow-up due to the long persistence of anti-HF antibodies in cured patients. To improve test performances and standardization, a number of recombinant antigens mainly derived from HF have been described, among them the B2t and 2B2t antigens. The performance of these antigens in the diagnosis and follow up of patients with CE has been so far evaluated on a limited number of samples. Here, we evaluated the performances of tests based on B2t and 2B2t recombinant antigens compared to HF in IgG-ELISA and immunochromatography (IC) for the diagnosis and follow-up of patients with CE in a retrospective cohort study. A total of 721 serum samples were collected: 587 from 253 patients with CE diagnosed by ultrasonography (US), 42 from patients with alveolar echinococcosis and 92 from healthy donors from Salamanca (Spain). The highest overall sensitivity was obtained with HF in ELISA (85.5%), followed by IC containing HF and 2B2t-HF (83.0% and 78.2%, respectively). The lowest sensitivity was obtained with B2t and 2B2t in ELISA (51.8%). The highest specificity was obtained with IC containing 2B2t-HF (100%), and the lowest with HF-ELISA (78.0%). The lowest cross-reactivity with sera from patients with alveolar echinococcosis was detected with the recombinant antigens in ELISA (9.5% - 16.7%) and the highest with the HF-IC (64.3%). The results of B2t and 2B2t-ELISA were influenced by cyst stage, as classified by US according to the WHO-Informal Working Group on Echinococcosis (WHO-IWGE), with low sensitivity for inactive (CE4 and CE5) cysts, and by the drug treatment, with higher sensitivity in patients after drug treatment compared with patients not subjected to drug treatment. The two recombinant antigens in ELISA provided promising results for monitoring patients in follow-up, although their use is limited to patients with positive serology against them at the beginning of the follow-up. Potential biological reasons behind the low sensitivity of the recombinant antigens and possible strategies to enhance the performance of CE serology are discussed.

Prevalence of abdominal cystic echinococcosis in rural Bulgaria, Romania, and Turkey: a cross-sectional, ultrasound-based, population study from the HERACLES project.

BACKGROUND: Cystic echinococcosis is a neglected zoonotic infection that is distributed worldwide and prioritised by WHO for control efforts. The burden of human cystic echinococcosis is poorly understood in most endemic regions, including eastern Europe. We aimed to estimate the prevalence of abdominal cystic echinococcosis in rural areas of Bulgaria, Romania, and Turkey. METHODS: We did a cross-sectional ultrasound-based survey that recruited volunteers from 50 villages in rural areas of Bulgaria, Romania, and Turkey. These villages were in provinces with annual hospital incidence of cystic echinococcosis within the mid-range for the respective countries. All people who attended a session were allowed to participate if they agreed to be screened. Abdominal ultrasound screening sessions were hosted in public community structures such as community halls, primary health-care centres, schools, and mosques. Lesions were classified using an adapted WHO classification. We reported the prevalence of abdominal cystic echinococcosis adjusted by sex and age through direct standardisation, using the country's rural population as a reference. FINDINGS: From July 1, 2014, to Aug 3, 2015, 24 693 individuals presented to screening sessions and 24 687 underwent ultrasound screening. We excluded a further six indivduals due to missing data, leaving 24 681 people in our analysis. Abdominal cystic echinococcosis was detected in 31 of 8602 people screened in Bulgaria, 35 of 7461 screened in Romania, and 53 of 8618 screened in Turkey. The age and sex adjusted prevalence of abdominal cystic echinococcosis was 0·41% (95% CI 0·29-0·58) in Bulgaria, 0·41% (0·26-0·65) in Romania, and 0·59% (0·19-1·85) in Turkey. Active cysts were found in people of all ages, including children, and in all investigated provinces. INTERPRETATION: Our results provide population-based estimates of the prevalence of abdominal cystic echinococcosis. These findings should be useful to support the planning of cost-effective interventions, supporting the WHO roadmap for cystic echinococcosis control. FUNDING: European Union Seventh Framework Programme.

Comparison of rubella immunization rates in immigrant and Italian women of childbearing age: Results from the Italian behavioral surveillance system PASSI (2011-2015).

BACKGROUND: International migration rapidly increased in the last decade, raising a renewed attention to its impact on public health. We evaluated differences in rubella immunization rate (RIR) between immigrant and Italian women of childbearing age and tried to identify the driving factors causing them. METHODS: We analyzed data from the Italian behavioral surveillance system PASSI collected in 2011-2015 in a nationally representative sample of residents in Italy. The analysis was performed using log-binomial models to compare RIR between 41,094 Italian women and 3140 regular immigrant women of childbearing age (18-49 years), stratifying the latter by area of origin and length-of-stay in Italy (recent: ≤ 5-years; mid-term: 6-10-years; long-term: > 10-years). RESULTS: Immigrant women showed a RIR of 36.0% compared to 60.2% among Italian women (RIR-ratio = 0.60, 95% confidence interval (CI): 0.57-0.63). Adjusting for demographic characteristics (i.e., sex, age and area of residence), socio-economic factors (i.e., education, occupation, family composition and economic status) and an indicator of the presence of at least one health-risk behavior (i.e., physical inactivity, current cigarette smoking, excessive alcohol consumption and excess weight) did not significantly change this difference (RIR-ratio = 0.56, 95% CI: 0.53-0.59). Recent immigrants (RIR-ratio = 0.47, 95% CI: 0.42-0.53) and immigrants from high migratory pressure countries (HMPC) in sub-Saharan Africa (RIR-ratio = 0.41, 95% CI: 0.31-0.56) and Asia (RIR-ratio = 0.42, 95% CI: 0.33-0.53) showed the greatest differences in RIR compared with Italian women. CONCLUSIONS: Differences in RIR between immigrant and Italian women were not explained by different demographic, socioeconomic and health-risk behaviors characteristics. As entitlement to free-of-charge immunization in Italy is universal, regardless of migration status, other informal barriers (e.g., cultural and barriers to information access) might explain lower RIRs in immigrant women, especially recent immigrants and those from HMPC in sub-Saharan Africa and Asia. Further investigations are needed to identify obstacles and appropriate promotion and access-enabling strategies for rubella immunization.

Screening for infectious diseases among newly arrived migrants in EU/EEA countries--varying practices but consensus on the utility of screening.

Screening is one possible tool for monitoring infectious diseases among migrants. However, there is limited information on screening programmes targeted for newly arrived migrants in EU/EEA countries. Our aim was to investigate the implementation, practices and usefulness of these programmes. We conducted a survey among country experts from EU/EEA countries and Switzerland, asking whether their countries had implemented screening programmes. We also estimated the association between the implementation of these programmes and the rate of asylum-seekers in the population. Of the countries, 16 (59%) had implemented screening programmes and 15 (56%) had national guidelines. The rate of asylum-seekers was associated with implementation of screening programmes (p = 0.014). Screening was performed most often for tuberculosis; most commonly on holding level, and was targeted to specific migrant groups in over half of the countries performing screening. Twenty-five of all the country experts (96%) considered screening among migrants useful, and 24 (92%) would welcome EU level guidelines for screening. The implementation of screening programmes varied, and the practices were different among countries. Our survey suggests, that establishing EU level guidelines for screening would be useful, although they would have to take into account differences between individual countries.

Differences in hospital admissions for males and females in northern Uganda in the period 1992-2004: a consideration of gender and sex differences in health care use.

To inform our understanding of male and female health care use, we assessed sex differences in hospital admissions by diagnosis and for in-patient mortality using discharge records for 210319 patients admitted to the Lacor Hospital in northern Uganda in the period 1992-2004. These differences were interpreted using a gender framework. The overall number of admissions was similar by sex, yet differences emerged among age groups. In children (0-14 years), malaria was the leading cause of admission, and the distribution of diseases was similar between sexes. Among 15-44 year olds, females had more admissions, overall, and for malaria, cancer and anaemia, in addition to delivery and gynaeco-obstetrical conditions (25.7% of female admissions). Males had more admissions for injuries, liver disease and tuberculosis in the same age group. In older persons (>or=45 years), women had more admissions for cancer, hypertension, malaria and diarrhoea, while, as for the previous age group, males had more admissions for injuries, liver disease and tuberculosis. This study provides insight into sex- and gender-related differences in health. The analysis and documentation of these differences are crucial for improving service delivery and for assessing the achievement of the dual goals of improving health status and reducing health inequalities.

Estimating HIV prevalence and the impact of HIV/AIDS on a Ugandan hospital by combining serosurvey data and hospital discharge records.

OBJECTIVE: To estimate the disease-specific HIV prevalence in a northern Ugandan hospital and to evaluate the impact of HIV/AIDS on hospital services. DESIGN: HIV serosurvey and analysis of routinely compiled hospital records. METHODS: The serosurvey was conducted among all 352 patients admitted to the medical ward of the Lacor Hospital in March 1999 (this ward consists of 3 units: general medicine, tuberculosis, and cancer). The impact on hospital services was estimated using the hospital discharge records for all 3447 patients admitted in 1999, in combination with serosurvey data, and was expressed as the percentage of bed-days attributable to HIV-positive patients. RESULTS: The overall HIV prevalence was 42.0% (52.6, 44.6, and 13.2% in the general medicine, tuberculosis, and cancer units, respectively). The disease-specific prevalence ranged from 45-65% for patients with tuberculosis, pneumonia, malaria, and enteritis. HIV-positive patients, compared with HIV-negative patients, had a higher in-hospital mortality (14.6 vs. 3.0%) and a lower average length of stay (41.4 vs. 48.9 days). AIDS cases accounted for 5.0% of hospital admissions, 4.1% of bed-days, and 11.5% of deaths. When considering all HIV-positive patients, these accounted for 37.2% of the bed-days. CONCLUSIONS: Knowledge of disease-specific HIV prevalence and of the patterns of HIV-related diseases is crucial for early case management. The impact of HIV-positive patients on hospital services is quite high, accounting for >1/3 of the bed-days in 1999. Providing a continuum of care through inpatient, outpatient, and outreach home care services probably represents the only means of relieving the pressure on overloaded hospitals.

New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions.

Vitiligo is a skin disease that is caused by selective destruction of melanocytes and is characterized by white spots. Melanocytes and keratinocytes seem to exhibit a functional close relationship, mediated at least in part by keratinocyte-derived cytokines, which seem important for survival and activity of melanocytic cells. We wanted to investigate the hypothesis that in vitiligo the expression of epidermal cytokines may be modified compared with normal skin. In 15 patients with active, non-segmental vitiligo, biopsies were obtained from lesional, perilesional and non-lesional skin; normal skin from five healthy donors was also tested. Tissue sections were tested using immunohistochemistry for the expression of keratinocyte-derived cytokines with stimulating activity, such as granulocyte-monocyte colony stimulating factor (GM-CSF), basic fibroblastic growth factor (bFGF), and stem cell factor (SCF) or with inhibiting activity, such as interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) on melanocytes. Cytokine receptors and specific melanocytic markers were also investigated. No melanocyte was identified in lesional skin by means of specific markers or c-kit receptor, whereas in perilesional, non-lesional and healthy skin, melanocytes were found in similar number. In vitiligo skin a significantly lower expression of GM-CSF, bFGF and SCF was found, and a significantly higher expression of IL-6 and TNF-alpha was detected, compared with perilesional, non-lesional and healthy skin. In conclusion, we provided evidence that a significant change of epidermal cytokines exists in vitiligo skin compared with perilesional, non-lesional and healthy skin, suggesting that the cytokine production of epidermal microenvironment may be involved in vitiligo.