Epidemiology and surveillance of human (neuro)cysticercosis in Europe: is enhanced surveillance required?

OBJECTIVES: To report on relevant national surveillance systems of (N)CC and taeniasis (the infection with the adult tapeworm) in the European Union/European Economic Area and to assess the magnitude of (N)CC occurrence by retrieving information on cases for the period 2000-2016. METHODS: (N)CC cases were retrieved via national reporting systems, a systematic literature search, contact with clinicians and a search for relevant 'International Statistical Classification of Diseases and Related Health Problems' (ICD)-based data. RESULTS: Mandatory notification systems for (N)CC were found in Hungary, Iceland and Poland. Ten cases were reported in Poland and none in Hungary and Iceland. Through the systematic literature review and information given by clinicians, 263 individual and 721 aggregated (N)CC cases from 19 European countries were identified. ICD-based data were obtained from five countries. From 2000 to 2016, a total of 3489 cases (N)CC cases were coded: 832 in Italy, eight in Latvia, 357 in Portugal, 2116 in Spain and 176 in Sweden. CONCLUSION: Despite being classified as a possible eradicable disease, (N)CC is still diagnosed across Europe, yet its true extent and impact remain unclear.

OBJECTIFS: Rapporter sur les systèmes nationaux de surveillance pertinents de la (neuro)cysticercose (N)CC et de la téniase (infection par le ténia adulte) dans l'Union européenne/l'Espace économique européen, et évaluer l'ampleur de l'occurrence de la (N)CC en reprenant des informations sur les cas durant la période 2000-2016. MÉTHODES: Les cas de (N)CC ont été repris à partir des systèmes nationaux de notification, une recherche systématique de la littérature, des contacts avec des cliniciens et une recherche de données pertinentes basées sur la 'Classification Statistique Internationale des Maladies et Problèmes de Santé Connexes' (ICD). RÉSULTATS: Des systèmes de notification obligatoires pour la (N)CC ont été trouvés en Hongrie, en Islande et en Pologne. Dix cas ont été rapportés en Pologne et aucun en Hongrie et en Islande. Grâce à la revue systématique de la littérature et aux informations fournies par les cliniciens, 263 cas individuels et 721 cas agrégés de (N)CC de 19 pays européens ont été identifiés. Des données ICD ont été obtenues de cinq pays. De 2000 à 2016, un total de 3489 cas de (N)CC ont été codés: 832 en Italie, 8 en Lettonie, 357 au Portugal, 2116 en Espagne et 176 en Suède. CONCLUSION: Bien qu'elle soit classée comme une maladie pouvant être éradiquée, la (N)CC est toujours diagnostiquée à travers l'Europe, mais sa véritable ampleur et son impact restent incertains .

Clinical characteristics and management of neurocysticercosis patients: a retrospective assessment of case reports from Europe.

OBJECTIVES: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe. METHODS: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available. RESULTS: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases. CONCLUSIONS: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management.

Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease.

Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC.

One Health-ness Evaluation of Cysticercosis Surveillance Design in Portugal.

The increasing occurrence of human cysticercosis, a zoonotic neglected disease, is challenging the traditional prevention and control paradigm and calling for One Health (OH) solutions in industrialized countries. OH solutions for health interventions are increasingly being used to capture expected and unexpected outcomes across people, animals, and the environment. The Network for Evaluation of One Health (NEOH) proposes an evidence-based framework, relying on systems and mixed methods approaches to evaluate the One Health-ness. In this case study, this tool is used to evaluate the design of the Observatory of Taeniasis and Cysticercosis, as an example of intersectorial collaboration for surveillance in Portugal. The OH Initiative (drivers and expected outcomes) and its system (boundaries, aim, dimensions, actors, and stakeholders) were described. The different aspects of this Initiative were scored with values from 0 (=no OH approach) to 1 (=perfect OH approach). The OH index was 0.31. Its OH ratio is 1.98. Overall scores were as follows: OH thinking 0.75; OH planning 0.60; OH working 0.60; OH sharing 0.35; OH learning 0.50; and systemic organization 0.50. Operational levels of the Initiative are the main strengths, indicating a comprehensive multidimensional innovative approach and transdisciplinarity. Critical issues in the supporting infrastructure were observed, related to communication, learning and organizational gaps in the project, with the evaluation being conducted as the project is being designed and implemented. The strengths and weaknesses detected may be used to refine the Initiative. This case study therefore exemplifies and supports OH assessment also for ongoing projects, at design and early implementation stages for guiding and guaranteeing an OH-oriented perspective.

New approaches for education and training in veterinary public health: the SAPUVET projects.

Continued contact between humans and animals, in combination with the ever-increasing movement of human and animal populations that is one effect of globalization, contributes to the spread of diseases, often with detrimental effects on public health. This has led professionals involved in both animal health and public health to recognize veterinary public health (VPH) as a key area for their activities to address the human-animal interface. Veterinarians, a profession with major involvement in this field, are in need of specific knowledge and skills to prevent and control public-health problems. As a result, VPH must be directly integrated into veterinary educational programs. At present, only few veterinary schools have specific VPH programs; in most institutions, VPH does not feature as a specific subject in either undergraduate or post-graduate curricula. SAPUVET and SAPUVETNET II are network projects supported by the ALFA program of the European Union (EU). Their main objectives are to reach a common understanding between European and Latin American universities in the definition of the areas in which VPH is important in their respective countries, and to design a harmonized training program for veterinarians in VPH, by making use of new technological applications and innovative teaching methodologies. The elaboration of educational material in combination with case studies presenting real-life problems provides a basis to apply the knowledge acquired on VPH. It is envisaged that the material and modules developed during the two projects will be integrated into the veterinary curricula of the participating universities, as well as in other partner organizations.

Epidemiology of taeniosis/cysticercosis in Europe, a systematic review: Western Europe.

BACKGROUND: Taenia solium and Taenia saginata are zoonotic parasites of public health importance. Data on their occurrence in humans and animals in western Europe are incomplete and fragmented. In this study, we aimed to update the current knowledge on the epidemiology of these parasites in this region. METHODS: We conducted a systematic review of scientific and grey literature published from 1990 to 2015 on the epidemiology of T. saginata and T. solium in humans and animals. Additionally, data about disease occurrence were actively sought by contacting local experts in the different countries. RESULTS: Taeniosis cases were found in twelve out of eighteen countries in western Europe. No cases were identified in Iceland, Ireland, Luxembourg, Norway, Sweden and Switzerland. For Denmark, Netherlands, Portugal, Slovenia, Spain and the UK, annual taeniosis cases were reported and the number of detected cases per year ranged between 1 and 114. Detected prevalences ranged from 0.05 to 0.27%, whereas estimated prevalences ranged from 0.02 to 0.67%. Most taeniosis cases were reported as Taenia spp. or T. saginata, although T. solium was reported in Denmark, France, Italy, Spain, Slovenia, Portugal and the UK. Human cysticercosis cases were reported in all western European countries except for Iceland, with the highest number originating from Portugal and Spain. Most human cysticercosis cases were suspected to have acquired the infection outside western Europe. Cases of T. solium in pigs were found in Austria and Portugal, but only the two cases from Portugal were confirmed with molecular methods. Germany, Spain and Slovenia reported porcine cysticercosis, but made no Taenia species distinction. Bovine cysticercosis was detected in all countries except for Iceland, with a prevalence based on meat inspection of 0.0002-7.82%. CONCLUSIONS: Detection and reporting of taeniosis in western Europe should be improved. The existence of T. solium tapeworm carriers, of suspected autochthonous cases of human cysticercosis and the lack of confirmation of porcine cysticercosis cases deserve further attention. Suspected cases of T. solium in pigs should be confirmed by molecular methods. Both taeniosis and human cysticercosis should be notifiable and surveillance in animals should be improved.

The emergence of Taenia solium cysticercosis in Eastern and Southern Africa as a serious agricultural problem and public health risk.

Pig production has increased significantly in the Eastern and Southern Africa (ESA) region during the past decade, especially in rural, resource-poor, smallholder communities. Concurrent with the increase in smallholder pig keeping and pork consumption, there have been increasing reports of porcine cysticercosis in the ESA region. This article reviews the findings concerning the presence and impact of porcine cysticercosis in seven of the ESA countries. Most of the reported findings are based on surveys utilising lingual palpation and post-mortem examination, however, some also used serological assays. In Tanzania, community-based studies on porcine cysticercosis indicate a prevalence of 17.4% in the northern highlands district of Mbulu and a prevalence range of 5.1-16.9% in the southern highlands. In Kenya recent surveys in the southwestern part of the country where smallholder pig keeping is popular indicate that 10-14% of pigs are positive for cysticercosis by lingual examination. Uganda has the most pigs in Eastern Africa, most of which are kept under smallholder conditions. Preliminary surveys in 1998 and 1999 at slaughterhouses in Kampala indicated a prevalence of porcine cysticercosis between 0.12 and 1.2%, however, a rural survey in northern Uganda in 1999 indicated 34-45% of pigs slaughtered in selected villages were infected. Additionally, a new survey of 297 pigs slaughtered in Kampala in 2002 indicated that pigs from the central region of the country were negative for cysticercosis while 33.7% of the pigs coming from the rural Lira district in the north were positive. Interestingly 8 piglet foetuses removed from an infected slaughtered sow coming from Lira district were all found to harbour cysts of T. solium providing evidence of congenital transmission of porcine cysticercosis. In Mozambique, abattoir records indicate that porcine cysticercosis is present in all provinces of the country. A serological survey on pigs in rural Tete Province found 15% of pigs positive. In Zimbabwe, a retrospective study in official abattoirs around the country from 1994 to 2001 reported a mean prevalence of 0.34% which is in contrast to a post-mortem survey in 1999, which showed that the prevalence of porcine cysticercosis in rural west Zimbabwe where smallholder pig keeping is popular was 28.6%. In Zambia, abattoir records reported porcine cysticercosis in six of the nine provinces. Routine meat inspection of 1316 pigs at a slaughter slab in Lusaka showed that 20.6% of the pigs had cysticercosis whereas serological testing of 874 pigs at the same abattoir indicated that 56.6% were found to have circulating antigens of Taenia solium. Field surveys based on lingual palpation in Southern and Eastern Provinces of Zambia revealed prevalences of 8.2-28.4 and 5.2%, respectively. South Africa has the largest number of pigs in Southern Africa and cysticercosis has been recognised as a problem in the country for many decades. There is strong evidence supporting the high prevalence of neurocysticercosis infecting humans from resource-poor areas of the country where pigs are being raised under smallholder conditions. In spite of this community-based surveys on porcine cysticercosis have never been conducted in South Africa and the last slaughterhouse survey was conducted nearly 40 years ago. The prevalences of porcine cysticercosis found in these ESA countries rank among the highest in the world and the disease is emerging as an important constraint for the nutritional and economic well being of resource-poor smallholder farming communities. The current findings suggest the widespread presence of human tapeworm carriers and thus a high risk of human cysticercosis in both rural areas and urban centres in the ESA region. More research is required in the region to assess the extent and public health and economic impact of T. solium infection in order to determine whether and what prevention and control efforts are needed.

Quantitative study of Rickettsia massiliae in Rhipicephalus sanguineus organs.

Rickettsia massiliae, belonging to the spotted fever group of Rickettsia, is a human pathogen causing a similar course of disease to that caused by R. conorii, the originally recognized etiologic agent of Mediterranean spotted fever. In view of this similarity, we performed an ultrastructural study of R. massiliae in organs of Rhipicephalus sanguineus ticks, in order to advance knowledge of the complex dynamics at the tick-pathogen interface in rickettsioses. Adult R. massiliae-infected Rh. sanguineus ticks were fed on uninfected Hartley strain guinea pigs, and five females were collected daily throughout their feeding period up to day 6, and analyzed by quantitative real-time PCR and electron microscopy. An increase in rickettsial content was observed in the salivary glands, particularly in the first two days of feeding, and a plateau was observed between days 3 and 6. Rickettsial organisms were observed in all tick organs analyzed, in higher numbers in the fed state, and statistically significant differences were observed in measurements of the periplasmic layer of R. massiliae in salivary glands of fed and unfed Rh. sanguineus ticks, with increased thickness in the former case. This study provides insight into the interface between R. massiliae and Rh. sanguineus ticks, highlighting the need for analysis of R. massiliae to fully ascertain its place as an important pathogenic agent of a spotted fever rickettsiosis.