Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 https://doi.org/10.1186/s13023-020-01534-1 POSITION STATEMENT Open Access European expert network on rare communicable diseases and other rare diseases linked to mobility and globalisation focused on health care provision (EURaDMoG): a feasibility study Ana Requena-Méndez1,2* , Zeno Bisoffi3,4, Joan-Lluis Vives-Corrons5, Joaquim Gascon1 and Antoni Plasència1 Abstract Introduction: In the current mobility and globalization context, there is a growing need to identify potential changes on the pattern of diseases in the European Union (EU)/European Economic Area (EEA) and provide accurate diagnosis and treatment for the population. The pattern of rare communicable diseases that can affect people returning to EU/EEA from travel abroad, visiting EU/EEA or establishing in the EU/EEA is of special relevance. The objective of this manuscript is to give an overview about the EURaDMoG study and discuss the feasibility of establishing a European network on rare communicable diseases and other rare conditions linked to mobility and globalization. Methods: We undertook a three-steps process where we first conducted a narrative review to estimate the prevalence and incidence and to list rare communicable and non-communicable diseases linked to mobility and globalization in the EU/EEA; second, we organized an international consultation workshop with experts in the diseases previously selected; and finally, the feasibility study analysed how successful a European expert network on rare diseases linked to mobility and globalization focused on health care provision would be, accounting for different operational and also sustainability criteria. (Continued on next page) * Correspondence: ana.requena@isglobal.org 1 Barcelona Institute for Global Health (Hospital Clínic- Universitat de Barcelona), Barcelona, Spain 2 Department of Medicine, Karolinska Institutet, Solna, 17176 Stockholm, Sweden Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 2 of 14 (Continued from previous page) Results: First, considering the areas or topics that the network should cover, it was concluded that communicable and non-communicable rare diseases linked to mobility and globalization should be differentiated. Second, since all non-communicable rare diseases linked to mobility and globalization identified are already covered by different European Reference Networks (ERNs), there is no need for them to be included in a new European network. Three scenarios were considered for establishing a potential European network for rare communicable diseases linked to Mobility and Globalisation with a focus on Health Care provision: 1) To maintain the current situation “Status Quo” scenario; 2) to create a specific European expert network (EEN) on rare communicable diseases linked to mobility and globalisation; 3) to develop a new ERN on communicable rare diseases linked to mobility and globalisation. Conclusions: Since the focus is the provision of health care, an ERN could have the potential to better boost the quality of care being facilitated by technological tools and online platforms that permit the safe and ethically acceptable exchange of data. However, this potential new network should not eclipse current existing networks and they should be complementary. Keywords: Rare diseases, Mobility, Globalisation, Imported diseases, Communicable diseases, Rare infections Background have an impact on the health system (critical care for Population movements have had a major impact on dis- immunosuppressed migrant patients, transplant pro- ease epidemiology and public health [1]. There is a grams ...) [9]. Therefore, the risk of communicable dis- growing need to provide health care for “rare” diseases eases (CD) is in accordance to the country of origin and/ that are related to this context. The European Union or transit of migrants and refugees because prevalence (EU) /European Economic Area (EEA) countries are rates and burden of CD differ considerably by country tackling new emerging diseases not endemic in EU [10]. In this regard, additional work is needed to im- countries [2] which are not considered rare diseases at prove the knowledge gaps among different categories of the world-wide level, but which are rare conditions in health professionals [9]. Europe according to the definition of rare diseases from In the same way, the increase of global mobility related the European Commission (EC) [3] or are emerging due to tourism or trade has increased the risks of rare com- to climate change. municable diseases in travellers, particularly vector Such a definition of rare diseases was adopted by the borne diseases [11]. During the last century, invasive Community Action Programme on rare diseases 1999– mosquito species have become widely established across 2003 as those life-threatening or chronically debilitating Europe [12]. Although subsequent transmission and out- diseases presenting a prevalence less than 5 per 10,000 breaks of unfamiliar diseases such as Chikungunya and people in the EU [4]. Dengue are in part due to increased globalisation, with In addition to the limited number of patients, rare dis- intercontinental air travel and global shipping transport eases are characterised by by scarce knowledge and ex- [11], changes in vector distributions are also being pertise, single them out as a distinctive domain of very driven by climatic changes and changes in land use, in- high European added value [5]. European cooperation frastructure, and the environment [13]. can help to ensure that scarce knowledge can be shared Regarding rare CD, health professionals often lack the and resources combined as efficiently as possible, in necessary skills to correctly identify and treat unfamiliar order to tackle rare diseases effectively across the EU/ pathologies, due to their low prevalence in the countries EEA as a whole [4]. Classically, most rare diseases are where they are working or because they are newly emer- genetic disorders, that is, non-infectious inherited condi- ging diseases [14]. In the same way, the increase in glo- tions [6], but there are also other rare diseases like rare bal mobility for tourism or trade poses similar risks of cancers, auto-immune diseases, toxic disorders and com- rare diseases in travellers, often implying a particular municable diseases. Imported diseases which are not fa- challenge for diagnosis and management [11]. It is also miliar to European health professionals, have recently worth mentioning the effect of climate change on vector been recognized as a new challenge as they have been borne diseases [15]. Sharing medical knowledge and ex- found to be prevalent only in mobile populations coming pertise is an important strategy for developing the com- from tropical countries [7]. Although most migrants and petencies and skills of health professionals to address newly arriving refugees do not pose a special challenge patients’ needs and support change in health service for the autochthonous population in terms of commu- provision [16, 17]. It is clear that the focus here is the nicable diseases risk [8], they are disproportionately af- diagnosis and treatment, not the epidemiological surveil- fected by infectious diseases that at some point may lance of the diseases. Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 3 of 14 On the other hand, non-communicable diseases or not, or because of the risk of being introduced /rein- (NCD) may also represent a challenge in mobile popula- troduced or of changing their epidemiology in EU/EEA tions, particularly in migrants. Haemoglobin disorders countries due to environmental factors such as climate such as thalassemia or sickle cell disease (SCD) are change. We also conducted an online survey with ex- inherited disorders whose frequency varies by ethnic perts in CD to agree the preliminary of CD identified. group [18]. Due to population movements, the sickle cell The survey was distributed among European network trait has been spread to other places such as the Middle targeting most of the diseases identified in the list The East and Southern Europe [19], where thalassemia has European Network for Tropical Medicine and Travel also been endemic until now, also due to the historical Health (TROPNET) [22], the European Travel and endemic presence of malaria until recently. Most rare Tropical Medicine Network (EUROTRAVNET) [23] and non communicable diseases are already covered by the the European Expert laboratory network for emerging existing ERN [20]. viral diseases (EVDLABNET) [24]. The objective of this study was to evaluate the feasibil- Thereafter, the prevalence /incidence of these disor- ity of a European expert network on rare diseases linked ders were comprehensively reviewed through a narrative to mobility and globalization focused on Health Care review of the literature [25]. Concerning CD, we have provision. identified more than 130 infections that could be consid- ered “rare diseases” in EU/EEA countries and that are The EURaDMoG feasibility study linked to mobility and globalisation (See Table 1).. In This study analysed how successfully a European expert addition, many studies also highlight that most of these network on rare diseases linked to mobility and diseases do not have appropriate and widely available globalization focused on Health Care provision would be, diagnostic techniques and treatments. accounting for different factors or criteria that will be out- Concerning NCD, we have comprehensively reviewed the lined. Through this study, potential positive and negative literature to assess the association between traditional rare outcomes of the network have been envisaged. All these diseases (non CD) with mobility and globalization in EU/ factors have been separately assessed considering different EEA countries [25]. The online survey was also conducted scenarios and have been evaluated based on the results of with experts belonging to the 24 European Reference Net- a consultation workshop, with a combined three-step ap- works (ERN) in the EU/EEA to agree the preliminary of proach: [1] conducting a comprehensive review, a [2] con- rare non-CD identified. Some autosomal recessive disorders sultation workshop, [3] an overall feasibility assessment. have been particularly found to be associated with mobility The main results are described hereunder. and globalization, in part because co-sanguinity is more fre- quent in certain migrant populations. 1. A comprehensive review was carried out to assess Other results of the review also showed that most epidemiological, diagnostic and treatment aspects of studies were conducted in highly specialized units (par- rare diseases (both communicable and non- ticularly in Tropical diseases), suggesting a lack of know- communicable) linked to Mobility and Globalisation ledge among other health professionals regarding and to elaborate a list of rare diseases linked to mo- imported diseases. It was also concluded that the areas bility and globalisation. of expertise are quite different between rare NCD and CD. In the particular case of CD, a high expertise is re- The primary objective was to assess which rare dis- quired in some areas of infectious disease, particularly in eases (according to the EC definition of rare disease) Tropical Medicine, imported diseases and also tick- should be covered by a potential expert European net- borne diseases. Due to changes in the epidemiology of work of rare disease linked to mobility and Globalisa- rare CD (e.g. West Nile virus or Chikungunya), a net- tion, to review their prevalence and/or incidence in EU/ work including experts from countries where these dis- EEA countries as well as their epidemiological profile. eases are less rare would be helpful to clinicians working For that purpose, first a narrative review of the litera- in countries where cases are rarely diagnosed. In this re- ture has been conducted to explore which rare diseases gard, although a list of CD has been proposed (See Add- (both communicable and non-communicable) in EU/ itional file 1), the list should remain open to be updated EEA countries are linked to mobility and Globalization. in case new diseases are emerging. All these challenges For communicable diseases, first, we reviewed the should be considered when designing appropriate strat- Orphanet list if rare disease [21], selecting those that are egies to improve the health care provision related to associated with mobility and globalisation. This relation- these diseases in people living in EU/EEA countries. ship was established either because these diseases are more frequent in mobile populations (migrants and trav- 2. A consultation Workshop was conducted on the ellers) irrespective of whether they are imported diseases “Assessment of a European Expert Network on Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 4 of 14 Table 1 List of rare communicable diseases linked to mobility and globalisation identified throughout the euradmog study DISEASE related keywords MICROORGANISM related keywords BACTERIAL INFECTIONS Anaplasmosis Anaplasma phagocytophilum Ehrlichiosis Ehrlichia spp. Endemic typhus, Murine typhus /flea-borne typhus Rickettsia typhi Epidemic typhus Rickettsia prowazekii Mediterranean spotted fever Rickettsia conorii Rickettsialpox Rickettsia akari Scrub typhus, Tsutsugamushi disease Orientia tsutsugamushi Rocky mountain spotted fever Rickettsia rickettsii African tick typhus Rickettsia africae Relapsing fever Borrelia recurrentis Lyme disease Borrelia burgdoferi Other rickettsiosis Rickettsia spp. Anthrax Bacillus anthracis Tetanus Clostridium tetani Trachoma Chlamydia trachomatis Chancroid Haemophilus ducreyi Granuloma inguinale- Donovanosis Klebsiella granulomatis Actinomycosis Actinomyces israelii Treponema infections Yaws Treponema pallidum pertenue Buruli ulcer Mycobacterium ulcerans Hansen’s disease / Leprosy Mycobacterium leprae Leptospirosis Leptospira interrogans Bartonellosis, Oroya fever, Carrion disease Bartonella bacilliformis Bartonellosis, Trenchs fever Bartonella quintana Brucellosis, Malta fever Brucella spp. Melioidosis Burkholderia pseudomallei Paratyphoid fever Salmonella enterica serotype Paratyphi Typhoid fever Salmonella enterica serotype Typhi Rheumatic fever Streptococcus pyogenes Q fever, Nine mile fever, Quadrilateral fever, Query fever Coxiella burnetii Secondary non-tropical sprue - Whipple disease Tropheryma whipplei Cholera Vibrio cholerae Botulism Clostridium botulinum Tropical pyomyositis--- Tularemia Francisella tularensis Plague Yersinia pestis Diphtheria Corynebacterium diphtheriae FUNGAL INFECTIONS Chromomycosis/Chromoblastomycosis Fonsecaea pedrosoi, Phialophora verrucosa and Cladophialophora carrionii Madura foot /Eumycetoma Madurella mycetomatis Sporotrichosis Sporothrix schenckii Paracoccidioidomycosis Paracoccidioides brasiliensis Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 5 of 14 Table 1 List of rare communicable diseases linked to mobility and globalisation identified throughout the euradmog study (Continued) DISEASE related keywords MICROORGANISM related keywords Coccidioidomycosis, Desert fever, San Joaquin valley fever, California disease Coccidioides immitis Peniciliosis Penicillium marneffei Scedosporiosis Scedosporium spp. HELMINTH INFECTIONS Cystic echinococcosis, Echinococcosis Echinococcus granulosus Alveolar echinococcosis Echinococcus multilocularis Ancylostomiasis /Ankylostomiasis Ancylostoma duodenale /Necator americanus Angiostrongyliasis Angiostrongylus cantonensis Strongyloidiasis, Anguilluliasis Strongyloides stercoralis Anisakiasis Anisakis spp. Ascariasis Ascaris lumbricoides Bilharziasis, Schistosomiasis Schistosoma spp. Clonorchiasis Clonorchis sinensis Opisthorchiasis Opisthorchis viverrini Cutaneous larva migrans Ancylostoma spp. Cysticercosis Taenia solium Diphyllobothriasis Diphyllobothrium latum Dirofilariasis Dirofilaria immitis Distomatosis Other trematodes-Heterophyes heterophyes, Metagonimus spp. Dracunculiasis, Guinea Worm disease Dracunculus medinensis Fascioliasis Fasciola spp. Paragonimiasis Paragonimus spp. Gnathostomiasis Gnathostoma spp. Hymenolepiasis Hymenolepsis nana Loiasis Loa loa Lymphatic filariasis Wuchereria bancrofti / Brugia malayi Mansonelliasis Mansonella spp. Onchocerciasis Onchocerca volvulus Sparganosis Spirometra spp. Taeniasis Taenia spp. Trichinosis Trichinella spiralis Trichuriasis Trichuris trichiura PROTOZOAL INFECTIONS Acanthamoeba infection, Keratitis Acanthamoeba spp. African trypanosomiasis, Sleeping sickness Trypanosoma brucei Amebiasis Entamoeba histolytica Amebic meningoencephalitis Naegleria fowleri American trypanosomiasis, Chagas disease Trypanosoma cruzi Babesiosis Babesia spp. Cryptosporidiosis Cryptosporidium parvum Cyclosporiasis Cyclospora cayetanensis Isosporiasis Isospora belli Leishmaniasis Leishmania spp. Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 6 of 14 Table 1 List of rare communicable diseases linked to mobility and globalisation identified throughout the euradmog study (Continued) DISEASE related keywords MICROORGANISM related keywords Malaria Plasmodium spp. Sarcocystosis, Sarcosporidiosis Sarcocystis hominis VIRAL INFECTIONS Avian flu Avian influenza Brazilian haemorrhagic fever Sabia virus California encephalitis California encephalitis virus Chapare haemorrhagic fever Chapare virus Chikungunya Chikungunya virus Colorado tick-borne disease, Mountain fever, American mountain fever, Mountain Colorado tick fever (CTF) tick fever- Crimea-Congo haemorrhagic fever CCHF virus Dengue fever Dengue virus Ebola Ebola virus Hantavirosis, Haemorrhagic fever-renal syndrome Hantavirus Hepatitis D Hepatitis D virus Hepatitis E Hepatitis E virus Herpes B infection, B virus infection Herpesvirus simiae, monkey B virus Tropical spastic paraparesis Human T-lymphotropic virus 1 (HTLV-1) Japanese encephalitis Japanese encephalitis virus (JEV) Junin haemorrhagic fever, Argentine haemorrhagic fever Junin virus Kyasanur haemorrhagic fever, Kyasanur forest disease, Monkey fever, Monkey KFD virus (KFDV) disease La Crosse encephalitis La Crosse virus (LACV) Lassa haemorrhagic fever Lassa virus Lujo haemorrhagic fever, Zambian haemorrhagic fever Lujo virus Machupo haemorrhagic fever Machupo virus (MACV) Marburg haemorrhagic fever /Marburg virus disease Marburg virus Nipah encephalitis, Nipah fever /Nipah virus disease Nipah virus Omsk haemorrhagic fever Omsk haemorrhagic fever virus (OHFV) Poliomyelitis, Poliomyelitis in patients with immunodeficiency deemed at risk Poliovirus Rabies Rabies virus Rift valley fever Rift valley fever (RVF) virus Saint Louis encephalitis Saint Louis encephalitis (SLE) virus Tick-borne encephalitis Tick-borne encephalitis (TBE) virus Venezuelan haemorrhagic fever Guanarito virus Western equine encephalitis, Western equine encephalomyelitis Western equine encephalitis (WEE) virus West-Nile encephalitis, West-Nile fever West-Nile virus (WNV) Yellow fever Yellow fever virus Zika virus disease Zika virus Middle East respiratory syndrome coronavirus MERS-CoV OTHER CONDITIONS Tick paralysis Tick Cutaneous myiasis Dermatobia hominis, Cordylobia anthropophaga African iron overload Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 7 of 14 Table 1 List of rare communicable diseases linked to mobility and globalisation identified throughout the euradmog study (Continued) DISEASE related keywords MICROORGANISM related keywords Ciguatera fish poisoning Tropical calcific chronic pancreatitis Tropical pancreatitis Tropical pancreatic diabetes Tropical endomyocardial fibrosis (TEF) Acquired Creutzfeldt-Jakob disease prion disease Hyperreactive malarial splenomegaly Genital female mutilation Severe fever with thrombocytopenia syndrome INFECTIONS WITH PARTICULAR ASPECTS TO BE CONSIDERED Giardiasis Giardia duodenalis Shiga-like toxin-associated HUS E.coli (O157) Tuberculosis Mycobacterium tuberculosis communicable diseases and other rare pathologies  To promote the access to complex diagnostic tests in the context of Mobility and Globalization”. and also to drugs for neglected diseases in order to Participants of the online survey and belonging to reduce inequalities in health care. the networks TROPNET, EUROTRAVNET, EVDL  To give better advice to governments, or to be ABNET and the existing 24 ERN in the EU/EEA linking with the European regulatory bodies to were invited to participate to have a minimum of improve access to orphan drugs; and to act as a two health care professionals per country in the EU promoter of harmonized strategies and actions (e.g. (the countries participating the study) with to improve the standards of screening strategies of expertise on rare diseases linked to mobility and imported diseases across Europe for blood or globalisation. Whenever possible, they were selected transplant donors, pregnant women or as one member with expertise in rare-CD (imported immunosuppressed individuals) or vector-borne diseases) and the other one with  To supervise and improve online available data and expertise in rare NCD. The workshop was finally the registry of diseases that are not currently under attended by 57 people (health professionals with ex- surveillance, promoting the access to reliable pertise in rare CD and rare NCDs from EU coun- information on new developments. tries, Norway and from the EC) from 26 countries.  To enhance translation of research into practice by reinforcing research and epidemiological In the workshop, besides recognising the growing need surveillance and improve knowledge for to attend rare diseases related to mobility and physicians, healthcare providers, patients and globalization, the participants almost unanimously families. agreed to differentiate CD and NCD. The latter are  To promote clinical evidence-based guidelines on already covered by different ERNs and should not be in- imported diseases based on a robust methodology cluded in a new network. Concerning the benefit of a and exchange of healthcare professionals as well as having a network on rare CD with a focus on Health training and education activities (e.g. webinars, e- Care provision, several arguments were raised:. learning courses or summer schools among others) would be a countless benefit.  To find spaces to further enable the discussion of  Cross-linking mechanisms with other ERNs should clinical cases; and discussion between clinical and be promoted. Few examples of the types of laboratory experts (e.g. in terms of test results, how collaborations in this regard include among others: to deal with false-positives etc.); and also as a meet- ing point of needs, feedbacks and expertise for Health Care Providers (HCPs) and the external en- vironment (other networks, authorities, health sys- (i) To discuss and interact in some diseases that tems, private sectors, etc.). This may reduce require a multidisciplinary approach (e.g. inappropriate practice variation. cysticercosis may require a follow-up from an Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 8 of 14 Infectious diseases specialist but also from a 3) The governance coordination and management, Neurologist); including the establishment of a board of the (ii) To discuss with experts belonging to other ERNs network, the coordinator, the criteria that newly the specific problems and requirements of the formed HCP wishing to join an ERN must meet growing number of travellers to tropical and the involvement of patients’ associations. countries who are affected by chronic diseases, 4) The ability to promote a good quality and safe e.g. providing specific advice about the drug patient care by fostering timely and pertinent interaction with malaria chemoprophylaxis or diagnosis, treatment, follow-up and management about the contraindications of lived-attenuated across the Network. vaccine. 5) Continuous education, training and development, including the creation or participation in evidence- based guidelines/recommendations, the sharing of knowledge and technologies and other training ac- 3. The feasibility assessment was aimed at analysing tivities or education materials. how successful a European expert network on rare 6) The capacity of conducting and collaborating in communicable diseases linked to mobility and research activities (e.g. clinical trials) and the globalization focused on Health Care provision possibility of establishing shared registries and would be based on the results of the review and the databases aiming to integrate existing resources. Consultation Workshop, considering which are the 7) The good practice, outcome measures and quality options for building the network. control measures for the network. 8) The multidisciplinary approach. The options and conditions of creating a European ex- 9) The capacity of establishing further networking and pert network for rare CD linked to Mobility and Global- collaborations including the assessment of the isation (for diagnosis and treatment) were evaluated, added value that the network could bring to health considering three different scenarios: care providers, as well as to other existing networks related to the area of expertise (e.g. other ERNs) 1) “Status Quo” scenario, where current European 10) The funding sources including a management and networks identified would be enhanced but no new business plan. network would be built. 11) The evaluation of the sustainability considering the 2) To create a specific European expert network minimum of human resources required to maintain (EEN) on rare CD linked to mobility and the network; possible future funding sources; how globalisation with the governance and structure to to ensure a roster and regular turnover of available be defined. experts to work on the network tasks in the future; 3) To develop a new European Reference Network and how will the information be made available to (ERN) on CD linked to mobility and globalisation in wider audiences (e.g. establishment of a website, the same way as the current ERNs. organisation of seminars and conferences). To do the assessment, the operational criteria of a po- The detailed information about the results is summa- tential network were developed and adapted from the rized in Table 2. The main features of each scenario criteria established by the European Commission for were: ERN (Operational Criteria for the Assessment of Net- works) [26]. They were: 1. “Status Quo” scenario: there are several existing networks with some focus on health care provision 1) The establishment, including objectives and and patient care essentially improved through activities covered in the network, regulations of the exchange of information, continuous education and network that should comply with EU regulations, training of health professionals. They are but also the criteria and conditions to constitute the TROPNET, EUROTRAVNET and EVDLABNET. network. However, a proper system -according to EU data 2) The provision of highly specialized care in the areas protection regulations- has not been implemented of diagnosis, treatment and follow-up. This criterion to share health data. There are some diseases included an assessment of the thematic areas and (particularly endemic vector-borne diseases) not diseases covered by the network, the capability of covered by these networks. All current networks improving health care provision and the capacity to are functioning with low financial resources, most create data registries, of them private, and frequently informal and not Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 9 of 14 Table 2 Assessment of the three options for a potential network o rare Communicable diseases linked to Mobility and Globalisation Maintaining Status Quo Creation of a European Creation of a new ERN Other pending aspects to expert network (EEN) (ERN) be explored Operational criteria Establishment of + + + to ++ The proposed number of the network There are three existing The EC can set the basis but The EC and the Member required number of networks. there are not currently clear States set the basis. participants/ countries needs There are members from non- mechanisms to be supported The minimum of HCP to be reviewed and validated EU/EEA countries in the by EC (Health policy platform identified. networks. could be one). Health Care Provider status They comply the minimum of No clear mechanism on who might make difficult the HCP and countries required. should establish the expertise participation and enrolment The main goal of the of the HCP. of critical centres. networks is not exclusively A minimum of HCP identified It may partially overlap the focused on Health care The HCP criteria could be focus of those existing provision. more flexible compared with networks. an ERN. It may partially overlap the focus of those existing networks. Thematic areas ++ ++ ++ to be covered by All networks are focused on The network will be created The network will be created the network: Tropical and Travel related based on the findings, and based on the findings and diseases which are rare needs in terms of rare CD needs in terms of rare CD communicable diseases linked linked to Mobility and linked to Mobility and to Mobility and Globalisation Globalisation. Globalisation. (one of them with an exclusively focus on viral infections). Disease or + to ++ ++ ++ conditions The existing networks already The diseases to be included The diseases to be included covered cover most of the diseases. can be according to the can be according to the In TropNet and EVDLabNet, detected needs. detected needs. there is not a list of diseases. The list may not be a closed The list may not be a closed list since there are potential list since there are potential new public health threats for new public health threats for the EU/EEA countries in the the EU/EEA countries in the future. future. Improving the + + ++ Health Care TropNet has a forum for This criterion may be feasible This is the main guarantee of Provision discussion of clinical cases depending on the legal basis ERN, as well as its main goal, activity although ensuring the and cross-exchange mecha- to ensure a better access to compliance with the EU data nisms of the network al- highly specialized healthcare. protection policy is currently a though ensuring compliance challenge. with the data EU protection EVDLabNet has a directory of policy may be challenging. Laboratory capacities to improve the access to rare diagnostics tests. Data registry 0 to + + ++ TropNet and EuroTravNet do It is difficult to assess the This is the main guarantee of report number of cases yearly feasibility, as it will depend on ERN, as well as its main goal, as a sort of surveillance the rules, data definition and to ensure a better access to activity but do not register legal framework of the highly specialized healthcare. clinical cases. network. ERNs register clinical cases for The existing networks share This criterion may be feasible discussion and for a training data, but cannot be held depending on the legal basis purpose (CPMS system). responsible nor exchange and cross-exchange mecha- In addition, another ERNs’ personal patient data in a nisms of the network al- developments include online secure, safe and legally though ensuring compliance platform to safely and binding environment in with the EU data protection ethically share data, under the compliance with the data EU policy may be challenging. support of the EU in terms of protection policy, which is technological tools enabling currently a challenge. the sharing. Governance, 0 to + + ++ coordination Existing networks have A new network will mean The governance while and different governance and new structures and roles, but complex is aspect of the ERNs Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 10 of 14 Table 2 Assessment of the three options for a potential network o rare Communicable diseases linked to Mobility and Globalisation (Continued) Maintaining Status Quo Creation of a European Creation of a new ERN Other pending aspects to expert network (EEN) (ERN) be explored management of coordination structure. it does not have to be too has been already established. the network The networks might overlap complex. Patient’s associations could be in some aspects. It is currently It will depend on the organ potentially involved. foreseen to develop more (not necessarily the EC) to collaborations. support the network. Members of the networks Patient’s associations could may not necessarily be HCP. potentially be involved. Patients’ associations are not involved in these networks. Patient care + to ++ + to ++ ++ The role and involvement of The networks do not have The specialization of the The specialization of the patients within the network guidelines to promote quality network should enable the network should enable the needs to be clarified. and safe patient care. creation of formally accepted creation of formally accepted Networks also provide professionalized guidelines for professionalized guidelines for information for patients/ patient care. patient care. One of the key relatives within the network. The involvement of HCP will function of the ERNs is to EVDLabNet promotes the depend on the Governance of standardize care treatment, sharing of laboratory the network and the involvement of HCP capabilities. Discussion of individual directly connected to patients TropNet has available a clinical cases could be will ensure the direct repository with information proposed but the translation of improved on orphan drugs available in maintenance will be a treatments. the centres belonging to the challenge. A forum for discussion of network. ICT tools will depend on individual clinical cases will be No network has developed available funding. proposed. ICT-tools that could be devel- Most HCPs identified are from ICT-tools could be developed oped to provide care, access Western European countries. to provide care, access to to expertise, and support the Efforts should be done to expertise, and support the development, sharing and include more HCP from East development, sharing and spread of best practice. (E.g. European countries. spread of best practice. (E.g. Telemedicine, tele-expertise or Telemedicine, tele-expertise or remote consultation). remote consultation). Patient care is improved Most HCPs identified are from through continuous exchange Western European countries. of knowledge. Efforts should be done to Few centres from East include more HCP from East European countries are European countries. involved in the networks. The network complies with the legal framework of the EC in providing Health Care. Continuous ++ + ++ Training and educational education, Activities related to These activities would be very These activities would very activities are limited or not training and continuous education and close to the professionals close to the professionals for members of the network. development. training are currently being needs, and targeted to a very needs, and facilitated by the conducted (seminar, scientific specific field. Depending on exchange of information on meeting, conferences...). the resources available, they the official online platforms. They are very close to the will be implemented more Patients’ education material professional needs, as easily. are promoted by ERN. facilitated by the exchange and informal atmosphere. Research ++ ? + to ++ If external funding to fund activities of the The health professionals The creation of the network The main objective of the research is needed. network. already contribute to research itself is part of an R&I process. ERNs is to improve healthcare The amount of time to be by developing R&I projects The founders will need to services, and the research dedicated for research by together, including clinical decide the relevance of the activities, although secondary, clinicians trials, (particularly TropNet). research for the activities of are encouraged through the the network. consortium, and the individuals. Time is a constraint for clinicians involved. Good practice, 0 to + + ++ Define the set of Key outcome Although the networks Through the formalisation of ERNs are monitored and Performance Indicators to measures and promote the exchange of the network, a set of outcome controlled by both the HCP ensure monitoring and quality control good practices, it is not measures and monitoring and the funder (DG-Sante). A impact driven approach. Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 11 of 14 Table 2 Assessment of the three options for a potential network o rare Communicable diseases linked to Mobility and Globalisation (Continued) Maintaining Status Quo Creation of a European Creation of a new ERN Other pending aspects to expert network (EEN) (ERN) be explored measures for the mandatory to follow up and should be set, and agreed by series of Key Performance network monitor the concrete impact the founders, especially to Indicators (KPI) have to be of the exchanges, and the justify costs and impact, and established, and their uptake of new/improved obtain funding for their outcomes and impact is guidelines. activities. measured. Cross-border collaborations to However, to assure the ERN requires a quality control improve the health care compliance of the access to planning with clear objectives provision have been already medical records and clinical and measurable indicators for implemented (e.g. EVDLabNet information with the EU monitoring and evaluation, laboratory capacity sharing or regulations will be challenge particularly regarding the TROPNET – information access to create and maintain a compliance of the access to to Orphan drugs). system to assure the medical records and clinical There is not a defined quality confidentiality. information with the EU control planning with clear The network could also create regulations. objectives and measurable a standard procedure for The network would also indicators for monitoring and obtaining consent form. create a standard procedure evaluation, particularly for obtaining consent form. regarding the compliance of the access to medical records and clinical information with the EU regulations. Multidisciplinary + ? ++ Explore how to add social approach The existing networks have a The founders will need to ERN will ensure a and gender approach to the very open approach towards decide the relevance given to multidisciplinary approach to different networks. multidisciplinary collaboration, multi/trans-disciplinary treat the diseases/ affectations particularly EuroTravNet. approach, within the scheme at the core of the network. No clear rules within the decided and the concrete There is also 24 other ERNs, networks on the openness objectives/goals of the which meet and exchange at towards other disciplines is network. least on a bi-annual basis, established. summing up to the concrete specificities of each one of them. Networking and + to ++ + + to ++ Define better priority lines of collaboration Networks are already Although based on existing The general networking and collaboration. established, and although partnership, and related collaborations towards collaboration is well engaged, centres, the general external players would have both within and towards networking and collaborations to be developed. other networks, it is necessary towards external players However, collaboration with to establish it specifically on would have to be developed. other ERNs may be facilitated Health Care Provision. through the ERN structure. No official collaborations with other disciplines have been established (blood banks, transplant or antenatal care units among other). Funding and sustainability criteria Funding sources 0 to + ? ++ Funding sources need to be Networks are already Important funding is needed To start the activities, an ERN available in order to start functioning, although with to create a network. could receive resources from new activities, or consolidate low or non - financial The feasibility is very much EU Health programme. those already existing. resources. depending if a special A call for a new ERN would EVDLabNet is funded by the funding line is put in place to provide the necessary funding ECDC. support the new structure or to start the activity. Private funding sources: if the sources have to be EuroTravNet is currently identified and obtained funded by private institutions through standard competitive (International Society of Travel processes. Medicine and the Instituts Hospitalo-Universitaire Médi- terranée Infection Foundation, Marseille). TROPNET is not funded. Sustainability 0 to + ? + to ++ Define the basis of self- Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 12 of 14 Table 2 Assessment of the three options for a potential network o rare Communicable diseases linked to Mobility and Globalisation (Continued) Maintaining Status Quo Creation of a European Creation of a new ERN Other pending aspects to expert network (EEN) (ERN) be explored analysis of the For now, networks have been To ensure sustainability Sustainability is a key aspect sustained network, ensure network sustainable, as shown on their should be part of the basis of of the ERNs, although for sustainability through mul- existence overtime, and some the new network. If there is a now, the experience is too tiple funders, but also key collaborations or merger possibility to get the funds, a recent to have a concrete through clear and set en- are sought for. sustainability strategy should model (publicly funded, gagement of the stakeholders It is unclear though how be put in place, through the through European or National involved. sustainability is foreseen over engagement of the partners. schemes) that can be time if networks wish to grow replicated for this new ERN. and to strengthen the It is unclear yet how they will activities focused on Health become self-sustainable Care Provision. overtime. Full note: In the assessment of each scenario, each criterion was rated once for the overall network. Each criterion has been graded in the following way: “0” The scenario proposed does not fulfil the criterion; “+” The scenario proposed fulfil the criterion with limitations; “++” The scenario proposed fulfils the criterion; “?” Difficult to assess, (for the variables and knowledge limitations on the aspects assessed) necessarily recognised by the national health care prevalence of such diseases is low, or when a new dis- systems. ease is emerging as is the case for rare diseases linked to 2. A EEN would have the benefit of being created mobility and globalisation. This challenge is due both to based on the findings and detected needs. Focus the scarcity of expertise and to the scattering of small would be Health Care provision, and areas and patient populations across the EU, sometimes in isolated diseases to be included would be the ones identified locations where expertise does not exist or cannot be as rare diseases linked to mobility and globalisation. accessed. As a way of example, the evolution of the However, implementing a good system for data COVID-19 pandemic is affecting the European Member registry or discussion of clinical cases would be States (EU MS) with different levels of severity and with challenging in terms of sustainability. In addition, an epidemiological situation is evolving very quickly there is not a clear mechanism to guarantee the [28]. Although it is not a rare disease anymore in Eur- establishment of the EEN supported by the EC, and ope, and the level of knowledge is similar in all EU also the general networking and collaborations with countries, it is a novel emerging disease unknown for external players would have to be developed. most health professionals and to establish a proper sys- Finally, funding is needed and sources have to be tem for sharing information and to establish potential identified, also in order to sustain the network, collaborations across countries would be highly valuable. particularly if a special funding line is not put in Many patients are in the need of highly specialised place to support the new structure. care in third level hospitals. The practical experience on 3. The basis and the legal status for an ERN have how to manage the patients and in particular the severe already been established. Governance is a complex cases is scarce and scattered in Europe [27]. While the aspect for ERNs [26]. Health Care Provision and experience and the number of cases treated by some specialized care status is decided by national health Hospitals (and MS) is important, due the accumulated authorities and the participation and enrolment of expertise, other are still starting to deal with complex centres are decided at national level [5]. The areas patients. Following the previous example, the treatments and diseases covered would be based on the applied to the COVID-19 patients are in many cases ex- detected needs. The current ERNs are supported perimental and there are some limitations to reach the with technological tools and online platforms knowledge generated during the last months and weeks. facilitating the safe and ethically acceptable Therefore, a new ERN could help to integrate the ex- exchange of data, including the registries of cases. A pertise and competence of those that have already have call for a new ERN would provide the necessary them with the healthcare professionals that are directly funding to start the activity. Sustainability is a key in charge of the patients by facilitating a quick exchange aspect of the ERNs, although the experience is too of knowledge and experiences and assisting in the deci- recent to have a thorough model. sion making process and ultimately to benefit the pa- tients suffering the condition [27]. Discussion A European network on rare CD linked to mobility Providing highly specialised diagnosis, treatment and and globalisation may provide a unique opportunity for care for patients who have complex diseases can be a clinicians to work across borders in EU/EEA countries challenge [27]. This is especially true when the in healthcare provision in order to tackle this challenge. Requena-Méndez et al. Orphanet Journal of Rare Diseases (2020) 15:291 Page 13 of 14 Coordination strategies among EU/EEA countries to The manuscript does not contain personal data in any form. fight against new emerging communicable diseases may be facilitated if there is a network oriented to improve Authors’ contributions ARM coordinated the review, participated in the workshop and coordinated the the diagnosis capacity and treatment options for patient feasibility study, and wrote the manuscript; ZB participated in the workshop and learning from health professional experiences from and collaborated in the feasibility study and reviewed the manuscript; JLVC EU/EEA countries where the diseases have progressed participated in the review, in the workshop and reviewed the manuscript, JG coordinated the workshop, collaborated with the feasibility study and reviewed first. The network could also be well aligned with other the manuscript; AP coordinated the EURaDMoG project, supervised the European initiatives or programmes in place on commu- workshop and the feasibility study and supervised the manuscript. All authors nicable diseases such as the ECDC associated networks, read and approved the final manuscript. or the One Health European Joint Programme without Funding overlapping or eclipsing any function or role of such This work has been fully financed by the European Commission (Service programmes or initiatives. Contract 20177110). Open access funding provided by Karolinska Institute. On the other hand, the study has several limitations that need to be recognized. First, the heterogeneity of Availability of data and materials Supporting data will be available through request to the EC who are the the access to health care provision for individuals at risk owners of the data. of mobility associated infectious diseases across EU countries has not been properly evaluated. This is of Ethics approval and consent to participate particular importance for undocumented migrants who This study does not require an ethical approval or consent to participate. have restrictive access to health care services. This elem- Consent for publication ent needs to be considered and evaluated when the net- All authors have given consent for publication. work is implemented. Second, the connection with other initiatives or programmes with common objectives at Competing interests national and also at EU level need to be better evaluated No competing interest. to be complementary instead of overlapping activities. Author details Finally, the sustainability of is a key aspect as per the rest 1 Barcelona Institute for Global Health (Hospital Clínic- Universitat de of ERN that need a widespread assessment although for Barcelona), Barcelona, Spain. 2Department of Medicine, Karolinska Institutet, now, the experience of ERNs is too recent to have a con- Solna, 17176 Stockholm, Sweden. 3Department of Infectious - Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar crete model. (Verona) Italy. 4Department of Diagnostics and Public Health, University of Verona, Verona, Italy. 5Institute for Leukaemia Research Josep Carreras (IJC), Badalona (Barcelona), Spain. Conclusions If the focus is the health care provision, it could be con- Received: 16 December 2019 Accepted: 7 September 2020 cluded that an ERN could have the potential to better boost the quality of care. However, current existing net- References works should not be eclipsed by a potential new network 1. 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