Epidemiological challenges for blood supply in Europe. 8th IFBDO seminar, 02 October 2015, Copenhagen Dragoslav Domanovic ECDC, Stockholm, Sweden

Transcription

1 Epidemiological challenges for blood supply in Europe 8th IFBDO seminar, 02 October 2015, Copenhagen Dragoslav Domanovic ECDC, Stockholm, Sweden 1

2 The battle has been won but not the war

3 Donor Derived Infections Infection of SoHO recipient Graft/produc t related Recipient related Donor derived Contaminati ons Nosocomial Community based The donor-derived infectious disease is defined as an infection which has been transmitted to a patient through transfusion or transplantation of SoHO donated by an infected donor.

4 Characteristics of donor derived infections Pathogen Donor Donation Host Transmissibility Imputability Severity Expectedness Cluster of transmissions

5 Infectious threats to the safety of transfusion and transplantation Established infections Risk reduction interventions implemented Risk is not completely eliminated - residual risk HBV, HCV, HIV, HTLV-1, CMV.. Emerging and re-emerging infections

6 Reporting of transfusion transmitted infections in EU

7 Serious adverse reactions and transfusion transmitted infections in EU Year Issued blood components SAR Frequency TTI Bacterial Viral Parasitic / (1.9%) 15 (60%) 10 (40%) 0 (0%) / (1.2%) 18 (90%) 1(5%) 1 (5%) / (1.9%) 24 (68%) 10 (29%) 1 (4%) / (1,7%) 16 (52%) 14 (45%) 1 (3%) Source: EU Commission. Annual SARE reports

8 Emerging and re-emerging infections "infections that have newly appeared in a population or have existed but are rapidly increasing in incidence or geographic range. Newly identified diseases previously known microorganism (Strept. A toxic shock syndrome) previously unknown or unrecognized microorganism (AIDS) Known diseases newly recognized etiology by known microorganism (HBP) in new geographic areas (WNV) markedly increased in incidence (TB, malaria) Microorganisms Drug resistance (MRSA) Evolution (E. coli, O157:H7) Extended host range to humans (Avian Influenza)

9 Appearance and spread of EIDs Human demographics & behaviour Technology & industry Economic development & land use International travel & commerce Microbial adaptation & change Breakdown of public health measures

10 Emerging diseases currently notifiable under EU legislation National contact points for surveillance Emerging and vectorborne diseases Malaria + Yersinia pestis infection 0 Q fever + Severe acute respiratory syndrome (SARS) 0 Smallpox 0 Hantavirus infections + Crimean Congo haemorrhagic fever 0 Rift Valley fever 0 Ebola and Marburg virus 0 Lassa fever 0 Dengue fever + Chikungunya fever + West Nile fever + Yellow fever 0 Ref: ECDC. Annual Epidemiological Report Available at

11 West Nile virus WNV infection Disease Agent Characteristics Family: Flaviviridae; Genus: Flavivirus Morphology: Enveloped, nm in diameter Nucleic acid: a positive-sense, single strand of RNA, between 11,000 an 12,000 nucleotides West Nile virus can be destroyed by many disinfectants,uv light and gamma irradiation, as well as heat 30 min. at 56 C (133 F).

12 WNV vector, infection transmission cycle, clinical picture. Incubation Period: 2 to 14 days. Clinical Signs (humans) West Nile fever : (relatively mild and flu-like) West Nile neuroinvasive disease, (cases with neurological signs). 80 % WNV infections are asymptomatic.

13 Reported cases of West Nile fever for EU and neighbouring countries Culicidae spp. EU MS EU -neighbuors Type of SoHO Transmission Cells & Tissues + Organs Blood & blood comp. + 13

14 Case TT WNV infection Greece /07/ First case reported blood safety measures applied 31/07/2012 Transfusion transmitted case reported

15 Dengue - Disease Agent Characteristics Dengue viruses (DENV-1, DENV-2, DENV-3, DENV-4) Family: Flaviviridae; Genus: Flavivirus Morphology: Enveloped, ~50 nm in diameter Nucleic acid: RNA, Linear, positive-sense, single-stranded RNA, ~10.7 kb in length Susceptible to common disinfectants; low ph and heat. Dengue virus is stable in dried blood and exudates up to several days at room temperature.

16 Dengue vectors in Europe Aedes aegypti Aedes albopictus

17 Number of cases Cases/ Dengue Number and rate of reported cases , ,7 0,6 0, , , ,2 0, Year Reported cases Confirmed cases Conf.case rate Overall case rate (2012): 0.26 / Type of SoHO Cells & Tissues Transmission + (bone marrow) Organs + Source: Country reports (18) from Austria, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Malta, Poland, Portugal, Spain, Sweden, Slovakia and Slovenia Blood & blood comp. +

18 Crude rate per population Dengue Age and gender distribution 2012 Seasonality 0,50 0,45 0,40 0,35 0,30 0,25 0,20 0,15 0,10 0,05 Male Female 0, Age Group Limited foci of local transmission of DENV : Nice, France, and Croatia, Madeira, Portugal Bouches-du-Rhône, France

19 Number of cases Incidence of probable and confirmed cases of dengue in Madeira Start: 3 October 2012 Indigenous Cases reported: 2164 (as of ) ECDC Mission Madeira outbreak Imported cases in EU ECDC Mission 18 March WEEKS Imported cases travellers from Madeira (78): Portugal-11;UK 23; Germany 19;France 3; Sweden 5; Finland 7; Poland - 2; Austria 2; Norway 2; Croatia 1; Slovenia 1;Spain 1; Switzerland 1.

20 Dengue transmission through SoHO transfusion of erythrocytes, platelets and plasma (2) transplantation of kidney (1) and bone marrow (1) Reasons for low number of reported transmissions: Difficult to differentiate between non-mosquito transmission and mosquitoborne infection in endemic areas where the vector is widespread Transmission results in mild or asymptomatic illness that is not recognized as transfusion-acquired infection Lack of resources for investigation Hypothetical reasons preventive measures for SoHO not specified in EU legislation individual EU Ms are developing their own criteria according to provision on the deferral in particular epidemiological situation

21 Number of cases Cases/ Malaria-Number and rate of reported cases , , , , Year Type of SoHO Transmission Reported cases Confirmed cases Conf.case rate Cells & Tissues + (bone marrow) Overall case rate (2012): 0.88/ Source: Country reports (19) from Austria, Cyprus, Czech Republic, Estonia, Finland, Germany, Greece, Hungary, Ireland, Malta, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden and United Kingdom Organs + Blood & blood comp. +

22 Crude rate per population Malaria Age and gender distribution 2012, Seasonality 2,50 Male Female 2,00 1,50 1, , , Age Groups Min-Max ( ) Mean January February March April May June July August September October November December Month Includes: AT CY CZ DE EE ES FI GR HU IE MT NL NO PL PT SE SI SK UK

23 Locally acquired cases of malaria in Greece Year Region Regional subunit Municipality Villages * Peloponnese Lakonia Evrotas Skala Agios Georgios Leimonas Elos Agioi Taxiarches Glikovrisi Attiki East Attiki Marathon Nea Makri Avra Kato Souli Marathon Saronikos Kalivia Thorikou Markopoulo Markopoulo Central Greece Viotia Thiva Orchomenos Orchomenos Lake Paralimni Lake Paralimni Evia Chalkideon Faros Avlidas Fylla Thessaly Larisa Agia Omolio Karditsa Sofades Filia East Macedonia Xanthi Avdira Selino TOTAL *up to 26/10/2012

24 Number of cases Cases / Hantavirus infection Number and rate of reported cases , , , , , ,65 0,65 0, Year Reported cases Confirmed cases Conf.case rate Overall case rate (2012): 1.03/ Source: Country reports from Austria, Belgium, Bulgaria, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Romania, Slovakia, Slovenia, Spain, Sweden and United Kingdom 0 Type of SoHO Transmission Cells & Tissues - Organs - Blood & blood comp. -

25 Crude rate per population Hantavirus infection Age and gender distribution 2012 Seasonality 2,50 Male Female 2,00 1,50 1,00 0,50 0, Age Group For Hantavirus infection, is the most commonly reported disease with potential haemorrhagic features in the EU and EEA region.

26 Number of cases Chikungunya Number and rate of reported cases Cases / ,2 0,18 0,16 0, ,12 0, , ,04 0, ,01 0, ,08 0,06 0,04 0, Year 0 Type of SoHO Transmission Reported cases Confirmed cases Conf.case rate Overall case rate (2012): 0.01/ Source: Country reports (18) from Austria, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Lithuania, Luxembourg, Latvia, Malta, Poland, Romania, Slovakia, Slovenia and United Kingdom Cells & Tissues - Organs - Blood & blood comp. -

27 Chikungunya Age and gender distribution 2012 Seasonality Crude rate per population 0,04 Male Female 0,03 0,02 0,01 0, Age Group Cases of locally acquired CHIKV fever in EU : Italy 2010 Var, France Languedoc-Roussillon, France

28 Chikungunya outbreak in the Caribbean

29 Number of cases Cases / Q fever Number and rate of reported cases ,8 1, ,4 1, , ,15 0,51 0, ,19 0,15 0,16 0,8 0,6 0,4 0, Year Reported cases Confirmed cases Conf.case rate Overall case rate (2012): 0.15/ Type of SoHO Transmission Cells & Tissues - Organs + Source: Country reports from Cyprus, Estonia, Finland, Germany, Greece, Hungary, Ireland, Lithuania, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia and Sweden Blood & blood comp. likely

30 Crude rate per population Q fever Age and gender distribution 2012, Seasonality 0,40 0,35 0,30 Male Female 0,25 0,20 0,15 0,10 0,05 0, Age Groups The Netherlands - sharp drop in case numbers (2007 till 2010, with more than 4000 cases and 24 deaths). The outbreak is considered to be over. A reduction in case numbers -in most countries. Small outbreaks still occur in Europe where areas with infected sheep and goat herds are considered at risk.

31 Hepatitis E virus Family: Hepeviridae; Genus: Hepevirus, Non-enveloped, icosahedral nucleocapsid symmetry, spherical particles,30-34 nm diameter. Nucleic acid: Linear, positive-sense, single-stranded RNA, ~7.2 kb; One serotype and 5 genotypes : humans (1 and 2), humans and swine (3 and 4), and avian (5) (7 subtypes) Physicochemical properties: Less stable to heat than HAV; most strains totally inactivated at 60 C although a Mexican strain was moderately more resistant; stable to multiple cycles of freezing and thawing

32 Presence in the human population of EU Country Seroprevalence anti-hev General Population Blood Donors RNA HEV blood donors Germany 16.8 % 29 % 1 : (0.022%) Netherlands - 27 % 1 : Sweden 9.8 % - 1 : (0.012%) Belgium 14 % - - United Kingdom 13.5 % 16 % 1 : (0.014%) France % -

33 HEV infection prevalence and transmission study in southeast England 9382 minipools, ( donations) > 79 donations containing HEV RNA 1 : 2848 donations (0 04%)/ 56 (71%) donors were seronegative (anti-hev IgM and anti-hev IgG). Component Number Recalled/ discarded Transfused Followed up Evidence of infection Total (42%) Red cells (25%) Platelet pool (40%) Apheresis platelet (50%) FFP (100%) Cryoprecipitate n/a Granulocytes (100%) Transmission rate : 42% Hewitt et al. The Lancet, 2014

34 Transmission of HEV Recipient immunosuppression delayed or prevented seroconversion and extended the duration of viraemia. Three recipients cleared longstanding infection after intervention with ribavirin or alteration in immunosuppressive therapy. Ten recipients developed prolonged or persistent infection. Transaminitis was common, but short-term morbidity was rare; Only one recipient developed apparent but clinically mild posttransfusion hepatitis.

35 USUTU virus Discovered in South Africa in 1959 & named after a river in Swaziland Reported in several African countries In 2001 identified for the first time outside of Africa, namely in Europe (Austria,Italy,Germany, Hungary, UK, Czech republic, Poland) Vector: mosquitoes various sp. Blackbird, Great gray owl, Blue tit, House sparrow, Great tit, Nuthatch, Robin and Song thrush

36 USUTU virus Small, spherical, enveloped virus with a diameter of nm Family Flaviviridae, genus Flavivirus, Japanese encephalitis sero-complex positive-sense, single stranded RNA genome one open-reading frame encoding polyprotein, Subsequently cleaved into three structural (core, membrane, and envelope) and eight non-structural proteins. History: 2001: Austria, deaths in bird species 2009: Italy, two neuroinvasive human 2010: mosquitoes positive in Germany 2011: dead blackbirds in Germany 2012: detection in blood donations (Germany) Circulation demonstrated in several EU countries

37 Human cases in EU Italy, summer immuno-compromised patients - neurological disorders = first human cases of USUV neuroinvasive illness described worldwide. both patients received transfusions transmission not confirmed common clinical symptoms : persistent fever of 39.5 C, headache and neurological disease (impaired neurological functions). One patient developed a fulminant hepatitis, a pathology that had been described previously in rare cases of WNV infection A blood donor was found to be positive for presence of antibodies to Usutu virus for the first time in Germany when 4200 blood samples were assayed. The blood donor did not have any symptoms of illness.

38 USUTU virus potentially emerging infectious disease Virus is present in vectors in EU countries Transmission to human has been documented Infected individuals can be without symptoms Transmission through SoHO possible Usutu is a potentially emerging infectious disease that may be under-recognised in some areas in Europe.

39 39 Zika virus Zika is a mosquito-borne viral disease caused by Zika virus (ZIKAV), a flavivirus from the Flaviviridae family Zika is described as a mild, self-limiting febrile illness of 4-7 days without severe complications, no fatalities and a low hospitalization rate. Overlapping symptoms dengue and CHIKV Zika outbreak on Yap Island in the Federated States of Micronesia is so far the only well documented and investigated large outbreak. October 2013 in French Polynesia cases January 2014: first autochthonous Zika cases in New Caledonia Two cases imported to Japan from French Polynesia and a Zika case in a Canadian traveller returning from Thailand. Norway reported one case returning from Tahiti

40 Zika virus outbreak in the Pacific 40 ZIKAV infection is considered an emerging infectious disease with the potential to spread to new areas where the Aedes mosquito vector is present. There is a risk for sporadic imported cases in Europe from endemic areas. Vigilance must be enhanced towards imported cases of ZIKAV infection in the EU Member States and EU overseas countries and territories and outermost regions, in particular where effective vectors are present. Early detection of cases is essential to reduce the risk of autochthonous transmission. Clinicians and travel medicine clinics should be aware of the situation in the Pacific islands and include ZIKAV infection in their differential diagnosis. There is no available vaccine against ZIKAV infection. Travellers can protect themselves by preventing mosquito bites.

41 Conclusion Arthropod-borne diseases remain a significant burden for Member States, partly through infected travellers returning from countries where some of these diseases are endemic. Endemicity of WNV infection appears to be established in some countries. There is also an apparently increasing risk in some EU countries of locally acquiring these diseases previously only considered to be imported. Q fever case rates continue to decline. Because of its non-specific clinical features, Q fever is an underdiagnosed disease. Hantavirus infections remain the most commonly reported of the viral haemorrhagic fevers, with the highest rates reported from Finland. Coordinated and enhanced human, veterinary, entomological and environmental surveillance is needed in all Member States at risk of these diseases, together with the development of effective countermeasures.