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Bulgaria is one of European countries where trichinellosis continues to be regularly diagnosed and registered. The clinical and epidemiological features of 72 cases of trichinellosis associated with five outbreaks caused by Trichinella spiralis and Trichinella britovi between 2009 and 2011, are described. At hospital admission, patients were often initially treated with antibiotics, without any improvement. A range of signs and symptoms were recorded, including: myalgia, elevated temperature, arthralgia, difficulty with movement, facial oedema, conjunctival hyperaemia, ocular haemorrhages, diarrhoea, skin rash, headache, and fatigue. Due to the variable clinical course of the disease, the diagnostic process for trichinellosis is often complex and difficult. This means the diagnosis may be established late for an appropriate treatment, potentially leading to a severe course of the disease with complications. Laboratory abnormalities were expressed by marked eosinophilia (97.2%), leucocytosis (70.8%), elevated serum creatine phosphokinase levels (82%), and antibody-positive results by ELISA and indirect hemagglutination. Patients were treated with albendazole (Zentel) 10 mg/kg for 7-10 days. In two outbreaks, the aetiological agent was T. spiralis, in one outbreak T. britovi, and an unknown Trichinella species in the fourth outbreak. The sources of infection were domestic pigs, probably fed with scraps and offal of wild game. In one outbreak, T. spiralis was also detected in brown rats trapped close to where the pig had been raised in the backyard. These epidemiological factors are relevant in considering implementation of targeted control programmes.
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Surtos de Doenças , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/parasitologia , Trichinella spiralis , Triquinelose/epidemiologia , Adolescente , Adulto , Idoso , Albendazol/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Bulgária/epidemiologia , Criança , Creatina Quinase/sangue , Surtos de Doenças/prevenção & controle , Eosinofilia , Feminino , Humanos , Masculino , Carne/parasitologia , Produtos da Carne/parasitologia , Pessoa de Meia-Idade , Ratos , Sus scrofa/parasitologia , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/prevenção & controle , Trichinella/isolamento & purificação , Trichinella spiralis/isolamento & purificação , Triquinelose/sangue , Triquinelose/diagnóstico , Triquinelose/prevenção & controle , Ursidae/parasitologia , Adulto JovemRESUMO
Visceral leishmaniasis (VL) is a severe endemic disease with a fatal outcome if left untreated. The symptoms of patients are diverse and atypical. Against the background of anemia and pancytopenia, the condition of the patients gradually worsens with marked cachexia. Through sharing our experience, we aim to draw attention to this deadly disease. Clinical and laboratory data for 58 patients with VL treated over a forty-five-year period are presented. The diagnosis was established within a duration of 1 to 28 months of illness. Continuous fever (38-42 °C), splenomegaly, hepatomegaly, severe anemia (decreased hemoglobin to lowest values of 31 g/L), leucopenia (lowest values of leucocytes et 0.5 g/L), and thrombocytopenia (reduced thrombocyte count to 29 g/L) were observed. The diagnosis was made on the basis of microscopic evidence of amastigote forms in bone marrow smears and serological tests. The patients were treated with Glucantime for 17 to 21 days. Relapses were observed in seven patients (12.1%) and fatal outcome was observed in two patients (3.5%) during treatment, who developed acute respiratory and cardiovascular failure. In Bulgaria, Visceral leishmaniasis is primarily endemic in the southern regions and should be suspected not only in patients who have returned from tropical and subtropical countries, but also in those who have not traveled abroad. The challenges associated with VL stem from delayed diagnosis of patients, as this disease remains unrecognized by physicians.
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BACKGROUND: The real burden of human cystic echinococcosis (CE) remains elusive, due to the peculiar characteristics of the disease and the heterogeneous and incomplete data recording of clinical cases. Furthermore, official notification systems do not collect pivotal clinical information, which would allow the comparison of different treatment outcomes, and thus circumvent the difficulty of implementing clinical trials for CE. The Italian Register of CE (RIEC) was launched in 2012 and expanded in 2014 into the European Register of CE (ERCE). The primary aim of the ERCE was to highlight the magnitude of CE underreporting, through the recording of cases that were not captured by official records. We present an overview of data collated in the ERCE and discuss its future, five years after its inception. METHODS: The ERCE database was explored on March 31st 2019; data concerning participating centres and registered cases were descriptively analysed. RESULTS: Forty-four centres from 15 countries (7 non-European) were affiliated to the ERCE. Thirty-four centres (77%) registered at least one patient; of these, 18 (53%) recorded at least one visit within the past 18 months. A total of 2097 patients were registered, 19.9% of whom were immigrants. Cyst characteristics were reported for at least one cyst at least in one visit in 1643 (78.3%) patients, and cyst staging was used by 27 centres. In total, 3386 cysts were recorded at first registration; mostly located in the liver (75.5%). Data concerning clinical management could be analysed for 920 "cyst stage-location-management" observations, showing great heterogeneity in the implementation of the stage-specific management approach recommended by the WHO. CONCLUSIONS: The ERCE achieved its goal in showing that CE is a relevant but neglected public health problem in Europe and beyond, since a proportion of patients reaching medical attention are not captured by official notification systems. The ERCE may provide a valuable starting platform to complement hospital-derived data, to obtain a better picture of the epidemiology of clinical CE, and to collect clinical data for the issue of evidence-based recommendations. The ERCE will be expanded into the International Register of CE (IRCE) and restructured aiming to overcome its current criticalities and fulfil these aims.
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Equinococose/epidemiologia , Echinococcus , Animais , Bases de Dados Factuais , Equinococose/diagnóstico , Europa (Continente)/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Fígado/parasitologia , Pulmão/parasitologia , Masculino , Doenças Negligenciadas/diagnóstico , Doenças Negligenciadas/epidemiologia , Prevalência , Saúde Pública , Sistema de RegistrosRESUMO
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.
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Antígenos de Helmintos/imunologia , Equinococose/diagnóstico , Echinococcus granulosus/imunologia , Proteínas Recombinantes/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Estudos de Coortes , Reações Cruzadas , Equinococose/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Imunoensaio , Itália , Masculino , Estudos Retrospectivos , Sensibilidade e Especificidade , Testes Sorológicos/métodosRESUMO
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.
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Equinococose/diagnóstico por imagem , Equinococose/epidemiologia , População Rural/estatística & dados numéricos , Zoonoses/epidemiologia , Abdome/diagnóstico por imagem , Abdome/parasitologia , Animais , Estudos Transversais , Europa Oriental/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Prevalência , Fatores de Risco , Inquéritos e Questionários , Turquia/epidemiologia , Ultrassonografia , Zoonoses/parasitologia , Zoonoses/transmissãoRESUMO
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, 24â693 individuals presented to screening sessions and 24â687 underwent ultrasound screening. We excluded a further six indivduals due to missing data, leaving 24â681 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.
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Abdome/diagnóstico por imagem , Equinococose/diagnóstico por imagem , Equinococose/epidemiologia , População Rural/estatística & dados numéricos , Zoonoses/epidemiologia , Animais , Bulgária/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Vigilância da População , Prevalência , Romênia/epidemiologia , Turquia/epidemiologia , UltrassonografiaRESUMO
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.
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Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/imunologia , Equinococose/diagnóstico , Echinococcus granulosus/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Recombinantes/imunologia , Testes Sorológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos de Helmintos/genética , Reações Cruzadas , Feminino , Humanos , Imunoensaio/métodos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/genética , Estudos Retrospectivos , Sensibilidade e Especificidade , Espanha , Adulto JovemRESUMO
Cystic 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.
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Notificação de Doenças , Equinococose/epidemiologia , Sistema de Registros , Sociedades Científicas/organização & administração , Bases de Dados Factuais , Europa (Continente) , Humanos , Saúde PúblicaRESUMO
Sheep erythrocytes were stabilised with glutaraldehyde tanned and fixed with formalin in the indirect hemagglutination test (IHA-GF) and sensitised with hydatid antigen for the diagnosis of human cystic echinococcosis (CE). The sensitivity of this method was compared to that prepared with fresh tanned cells (IHA-TA) in 278 sera from hydatid patients. The sensitivity of IHA-GF (87.8%) was higher than that of IHA-TA (85.6%), the difference being insignificant. Higher geometric mean titres were obtained by IHA-GF (1:13300) than by IHA-TA (1:11600). The use of two sorts of aldehydes proved to be a satisfactory method, showing high sensitivity, a very good specificity and some advantages. The sensitised cells retained their diagnostic effectiveness for at least 15-18 months when stored at 4 degrees C. The technique is inexpensive and rapid, allowing the testing of a large number of sera. The method reduces the variation of the results and improves the reproducibility of the test. When the minimal diagnostic titre-1:400 is used the specificity of IHA-GF might increase by 2.9% while the sensitivity might decline by only 1.4%. The IHA-GF demonstrated better immunodiagnostic characteristics than enzyme linked immunosorbent assay (ELISA) and Latex agglutination test (LAT). The IHA-GF should be considered as an useful method in the range of classical diagnosis for the serology of CE. The clinical diagnostic potential should be increased by a combination of at least two tests: IHA-GF and ELISA or LAT.
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Equinococose/diagnóstico , Eritrócitos/imunologia , Formaldeído/farmacologia , Glutaral/farmacologia , Testes de Hemaglutinação/métodos , Animais , Anticorpos Anti-Helmínticos/sangue , Echinococcus/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Testes de Fixação do Látex , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , OvinosRESUMO
Over the past 30 years, benzimidazoles have increasingly been used to treat cystic echinococcosis (CE). The efficacy of benzimidazoles, however, remains unclear. We systematically searched MEDLINE, EMBASE, SIGLE, and CCTR to identify studies on benzimidazole treatment outcome. A large heterogeneity of methods in 23 reports precluded a meta-analysis of published results. Specialist centres were contacted to provide individual patient data. We conducted survival analyses for cyst response defined as inactive (CE4 or CE5 by the ultrasound-based World Health Organisation [WHO] classification scheme) or as disappeared. We collected data from 711 treated patients with 1,308 cysts from six centres (five countries). Analysis was restricted to 1,159 liver and peritoneal cysts. Overall, 1-2 y after initiation of benzimidazole treatment 50%-75% of active C1 cysts were classified as inactive/disappeared compared to 30%-55% of CE2 and CE3 cysts. Further in analyzing the rate of inactivation/disappearance with regard to cyst size, 50%-60% of cysts <6 cm responded to treatment after 1-2 y compared to 25%-50% of cysts >6 cm. However, 25% of cysts reverted to active status within 1.5 to 2 y after having initially responded and multiple relapses were observed; after the second and third treatment 60% of cysts relapsed within 2 y. We estimated that 2 y after treatment initiation 40% of cysts are still active or become active again. The overall efficacy of benzimidazoles has been overstated in the past. There is an urgent need for a pragmatic randomised controlled trial that compares standardized benzimidazole therapy on responsive cyst stages with the other treatment modalities.