Integrated surveillance of vector borne diseases The example of WNV surveillance in Italy

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1 Preventing vector borne diseases around the Mediterranean and Black Sea regions Integrated surveillance of vector borne diseases The example of WNV surveillance in Italy MediLabSecure - Public Health Flavia Riccardo CNESPS/Istituto Superiore di Sanità -ISS (Italy) Round table: towards an improved surveillance of zoonotic vector-borne diseases, Tunis 10th February 2016

2 Outline The MediLabSecure project and the public health work package Integration of vector borne disease surveillance in the MediLabSecure framework A story of integration development in Italy Integration of surveillance in the MediLabSecure countries

MediLabSecure Aims to increase, through capacity building, the health security in the Mediterranean Area, South-East European and Black Sea region by enhancing and strengthening the preparedness to

3 MediLabSecure Aims to increase, through capacity building, the health security in the Mediterranean Area, South-East European and Black Sea region by enhancing and strengthening the preparedness to common health viral emergencies and biosafety management at national and regional levels by the creation of a network of laboratories for a better surveillance of infectious diseases in non-eu countries of the Mediterranean and Black Sea (48 months) European Union DEVCO / EuropeAid 19 non-eu countries covered by the EU Enlargement and European Neighbourhood policies

4 Public Health and MediLabSecure

WP5-Public Health General objective To facilitate the integration of surveillance, risk assessment and early case detection across the different

5 WP5-Public Health General objective To facilitate the integration of surveillance, risk assessment and early case detection across the different project s areas of activity: animal virology, human virology and medical entomology and the national surveillance system (NSS) for communicable diseases.

6 Levels of integration between human/animal/entomological surveillance for a specific exposure Level of integration Sublevels of integration Policy and institutional level Policy level Institutional level Data collection and analysis level Interoperability mechanisms at data collection level Interoperability mechanisms at data analysis level Dissemination level

7 WNV circulation in Italy Based on a presentation made by Caterina Rizzo (ISS-Rome) and Paolo Calistri (IZS- Teramo) at the MediLabSecure Mid Term Meeting in Paris on the 16th of December 2015

8 WNV circulation in Italy Lineage I

9 WNV circulation in Italy Lineage I

10 WNV circulation in Italy Lineage I

11 WNV circulation in Italy Lineage I

12 WNV circulation in Italy Lineage I and Lineage II

13 WNV circulation in Italy Lineage I and Lineage II

14 WNV circulation in Italy Lineage I and Lineage II

15 WNV circulation in Italy Lineage I and Lineage II

16 WNV circulation in Italy Lineage I and Lineage II Territories with constant and greater WNV circulation Round table: towards an improved surveillance of zoonotic vector-borne diseases, Tunis 10 th 16 February 2016

17 Trend of human cases of WNND by year/month of symptom onset. Italy,

18 Spatial distribution of human WNND cases, Italy

19 WNND annual mean incidence, Italy Incidence (per million) No cases > 4.00

20 A story of integration development: WNV surveillance in Italy

21 Human and Veterinary Public Health Organization in Italy LHU Prevention Dep.

22 WND in Tuscany (Padule di Fucecchio) First documented outbreak farms 14 horses (prevalence total case 2.8%) 6 dead horses No human cases (serological positivity in men working closely with horses)

23 National WND veterinary surveillance plan In selected risk areas Surveillance in horses Sentinel horses Surveillance in birds Sentinel chickens Screening on carcasses of birds found dead Entomological surveillance

24 Human surveillance recommendations in Italy as of 2002: a parallel system Human surveillance: Active: to identify cases and possible WNV seroconversion in close contacts of infected animals (employees of stables and Veterinarian or people living in the area). Passive: using mandatory surveillance system in all hospitalized aseptic meningitis and encephalitis with unknown etiology, fever with rash in the areas where veterinary cases where identified. ISS - CNESPS Epidemiology of Infectious Disease Unit

25 First human outbreak Presence of WNV in horses, 2008

26 The Emilia Romagna outbreak September 22 nd 2008: 12 horses with neurological symptoms (6 lab confirmed) belonging to 8 different stables (Ferrara and Bologna). Surveillance in wild birds from August 19 th to 14 th September detected six crows and seven magpies in the province of Ferrara. Human passive and active surveillance started immediately (neuroinvasive diseases surveillance and seroconversion of stables workers and close contacts of cases)

27 Human cases in Emilia Romagna At the beginning: Possible cases: 21 Lab confirmed: 4* Lab negative: 17 In total, 3 confirmed cases, from 2 provinces (Bologna and Ferrara) No deaths reported * 1 case initially classified from the regional reference Lab as IgM positive was not confirmed from the National Reference Lab at ISS.

28 The Veneto outbreak September 2008: 1 positive horse in a 20 horse sample (Rovigo) Human passive and active surveillance started immediately (neuroinvasive diseases surveillance and seroconversion of stables workers and close contact of cases): Confirmed cases: 2 Possible case: 1 No deaths reported ISS - CNESPS Epidemiology of Infectious Disease Unit

29 Regional Plans: Emilia Romagna, Veneto and Lombardia Regions, 2008 and 2009 Active surveillance: to identify cases and possible WNV seroconversion in close contacts of infected animals (employees of stables and veterinarians or people living in the area). Passive surveillance: using mandatory surveillance system in all hospitalized aseptic meningitis and encephalitis with unknown etiology fever with rash in the areas where veterinary cases where identified

30 The outbreak highlighted a gap The human and animal system (including entomological surveillance) were both working well but in parallel Generic triggering action was in place of animal human surveillance Further integration was needed.

31 Veterinary Surveillance The main aim of veterinary surveillance is to early detect the WNV circulation both in endemic and newly infected areas to provide useful information to Public Health authorities for the implementation of preventive measures. Surveillance Humans Horses Birds Mosquitoes Time

Veterinary Surveillance Passive surveillance all over the country

vectors activity period, develops: ataxia or sudden death or, at

maintain quadrupedal stance, paralysis/paresis of limbs, muscle

32 Veterinary Surveillance Passive surveillance all over the country Case definitions Clinical criteria An equidae which, during the vectors activity period, develops: ataxia or sudden death or, at least one of the following symptoms: circular movements, inability to maintain quadrupedal stance, paralysis/paresis of limbs, muscle twitching, proprioceptive deficits. Surveillance on birds mortality all over the country

Veterinary Surveillance Active surveillance in specific areas Since 2001.

33 Veterinary Surveillance Active surveillance in specific areas Since Annually reviewed 2015 SURVEILLANCE PLAN ENDEMIC AREAS: geographical areas affected by WNV circulation in the last 2 years -> early detection of virus circulation (based on mosquitoes and birds) REST OF THE COUNTRY -> WND monitoring (based on horses) Endemic areas

34 ENDEMIC AREAS: Veterinary Surveillance Active surveillance Surveillance on resident birds of target species (magpies, crows, etc.) or in rural poultry farms (animals less than 6 months of age, sentinel chickens) Entomological surveillance REST OF THE COUNTRY: Surveillance on equines: serological (IgM) random sampling

Veterinary Surveillance Active surveillance Case definitions

non-vaccinated animal, even in the absence of clinical symptoms.

RT-PCR sentinel chicken seroconverted to ELISA IgG and confirmed

positive to ELISA IgG and confirmed by serum-neutralization

35 Veterinary Surveillance Active surveillance Case definitions Laboratory criteria Suspected case: a seropositive result in a non-vaccinated animal, even in the absence of clinical symptoms. Confirmation: equidae positive to ELISA IgM and/ or virological RT-PCR sentinel chicken seroconverted to ELISA IgG and confirmed by serum-neutralization rural poultry (less than 6months of age) positive to ELISA IgG and confirmed by serum-neutralization birds positive to RT-PCR On vectors: mosquito pools positive to RT-PCR

36 Human surveillance WNND autochthonous case special surveillance The increasing number of confirmed human cases from 2008 to 2009 and the occurrence of the WNV in a larger geographical area in 2009 prompted the Ministry of Health to publish, in spring 2010, a national program for WNND human surveillance, integrating information from veterinary and vector surveillances. All possible autochthonous cases have to be notified by the Regional Heath Authorities using a standard form, through a specific web-based platform that is operating protected by password The system permits to the Regional Health Authorities to introduce possible cases directly in the web platform and then more information on diagnostic tests when they become available.

37 Italian MoH directive: Surveillance of WNV disease in Italy, 2010 Between June 15 and November 15. Integrated human and veterinary surveillance. Defining the risk: - affected area : province areas (secondary administrative unit) with positivity in the veterinary surveillance or autochthonous lab. confirmed animal/human cases. - surveillance area : regions (surrounding an affected area) with vector presence and with autochthonous animal/human cases within their provinces.

38 Italian MoH directive: Surveillance of WNV disease in Italy, 2011 It includes surveillance of Chikungunya e Dengue Between June 15 and November 15 for autochthonous cases and for the whole year for imported cases. Defining the risk: - affected area : area (Provinces) with positivity in the veterinary and enthomological surveillances or autochtonous animal cases or lab. confimed human cases - surveillance area : subnational area (Regions) with vector presence and with autochtonous laboratory confirmed animal/human cases within its Provinces

39 Italian MoH directive: Surveillance of WNV disease in Italy, 2012 Between June 15 and November 30 for autochthonous cases and all year for imported ones. Modified EC case definition (WNV fever not included): Clinical symptoms: Cases are classified as: possible: patients, with fever >= 38.5ºC and neurological symptoms: encephalitis, meningitis or Guillain-Barré syndrome or acute flaccid paralysis. probable: possible case + anti-wn IgM positive in blood and/or anti-wn IgG positive in blood confirmed: possible case and at least one of the following laboratory criteria: Viral isolation in blood or CSF or anti-wn IgM positive in CSF or PCR - test positive in blood, CSF or urine or seroconversion or 4 fold increase in anti-wn antibodies or confirmed presence of anti-wn antibodies in blood by neutralization test

40 Italian MoH directive: Surveillance of WNV disease in Italy, 2013 Modified EC case definition (WNV fever not included): Clinical symptoms: Cases are classified as: possible: patients, with fever >= 38.5ºC and neurological symptoms: encephalitis, meningitis or Guillain-Barré syndrome or acute flaccid paralysis. probable: possible case + anti-wn IgM positive in blood and/or anti-wn IgG positive in blood, PCR test positive in urine confirmed: possible case and at least one of the following laboratory criteria: Viral isolation in blood or CSF or anti-wn IgM positive in CSF or PCR test positive in blood, CSF or seroconversion or 4 fold increase in anti-wn antibodies or confirmed presence of anti-wn antibodies in blood by neutralization test

41 Italian MoH directive: Surveillance of WNV disease in Italy, 2014 It includes surveillance of Zika virus Italian MoH directive: Surveillance of WNV disease in Italy, 2015 Between June and October for autochthonous cases and for the whole year for imported cases Also fever sporadic cases and blood donors positive cases have to be reported.

42 Specific integrated surveillance triggers: Risk areas for human surveillance affected area area (Provinces, NUTS3) with autochthonous laboratory confirmed infections in the veterinary and entomological surveillances or autochthonous animal cases or lab. confirmed human cases surveillance area region (surrounding an affected area, NUTS2) with vector presence and with autochthonous lab confirmed animal/human cases within its Provinces

Joint data reporting: Human and equine cases in Italy 2008-2015 Year Total cases (neurological cases and diagnostic positivity) Horses

2010 128 11 3 3 2011 197 58 15 14 2012 63 15 45 28 2013 50 12 70 40 2014 27 6 24 21 2015 30 6 61 38 Totale 1281 177 244 170 70 60 50 40 30

43 Joint data reporting: Human and equine cases in Italy Year Total cases (neurological cases and diagnostic positivity) Horses Neurological cases Total cases (neurological cases and diagnostic positivity) Humans Neurological cases Totale Neurological cases in horses Neurological cases in humans

44 Joint data reporting: WNV circulation in humans, animals and vectors, Provinces with demonstrated WNV circulation in humans and in animals/vectors Provinces with demonstrated WNV circulation in humans Provinces with demonstrated WNV circulation in animal/vectors

45 West Nile Disease Seasonal distribution of humans and horse cases and comparison with entomological results

Each possible, probable and confirmed case filled in the webbased form is immediately available for: MoH, ISS-National

46 Data collection: human cases The access is limited (username and password). Regional health authorities notify possible human cases within 12 hours to MoH and National Institute of Health. Each possible, probable and confirmed case filled in the webbased form is immediately available for: MoH, ISS-National Institute of Health (National Centre for Epidemiology) National Transplant Centre National Blood Centre The WNV information system ISS - CNESPS Epidemiology of Infectious Disease Unit

47 WNND, weekly reporting

48 The WNV information system Data collection: animal cases Web portal directly accessible by Veterinary services Accessibility for smartphones Data inserted by local veterinary services

49 Dissemination of veterinary surveillance Bi-lingual (IT-EN) website National and European Bulletins Informative leaflets for horse owners and general public results

50 Intersectorial data exchange Data on animal cases Data on human cases Feed-back data on confirmed human cases Evidences of new virus circulations

51 Criteria met for integration in the Italian WNV surveillance system Level of integration Policy and institutional level Sublevels of The Italian example integration Policy level 1. Official national directives/plans referring to integration of findings to make decisions (eg in the definition of affected areas for surveillance) still in parallel between the 2 systems 2. Presence of regional plans addresing these aspects a sub-national level Institutional level Presence of coordination mechanisms (as yet mostly informal) Data collection and analysis level Dissemination level Interoperability mechanisms at data collection level Interoperability mechanisms at data analysis level Data sharing is in place. Veterinary and entomological surveillance act as triggers for human WNND surveillance Information from both surveillances is cross referenced through inter-institutional data exchange within the dissemination tools.

52 Is the model in Italy similar to what is happening in countries of the Mediterranean and Black Sea?

The MediLabSecure Survey WP5-Public health asked questions on integrated surveillance in the context of an

surveillance for each disease Existence of a coordination mechanisms among the institutions involved Data collection

facilitate joint analysis among sectors.

53 The MediLabSecure Survey WP5-Public health asked questions on integrated surveillance in the context of an inter-sectorial survey Policy and Institutional level Existence of a National policy addressing integrated surveillance for each disease Existence of a coordination mechanisms among the institutions involved Data collection and analysis level Existence of integrated data collection tools Presence of DB exchange/merging/other mechanisms to facilitate joint analysis among sectors. Performance of joint/integrated data analysis among the different surveillance sectors Dissemination level Existence of joint result dissemination mechanisms (e.g. bulletins, reports, papers, media reports, websites )

54 Results 19 countries of the Mediterranean and Black Sea, invited to participate in the survey (December 2014 and July 2015) 56 contact points from laboratories (animal virology, human virology and medical entomology) 19 contact points from Public Health Institutes (PHI)/Ministries of Health (MoH) (human epidemiology) Responses from 51 laboratories (51/56; 91%) and 12 PHI/MoH (12/19; 63%): Black Sea 14, North Africa & Middle East 26 and Balkans 23.

55 Levels of integration reported Level of integration Sublevels of integration Number of countries reporting integration (N 19) Number of respondents reporting integration (N 63) N Respondents reporting integration Balkans (N 23) Black Sea ( N 14) NA & ME ( N 26) Policy and institutional level Policy level 17 54% (34) 43% (10) 57% (8) 62% (16) Institutional level 16 49% (31) 39% (9) 57% (8) 54% (14) Data collection and analysis level % (18) 30% (7) 29% (4) 27% (7) Dissemination level % (34) 48% (11) 43% (6) 65% (17)

56 Levels of integration reported, by region and sector Balkans, N=23 Black Sea, N=14 N. Africa and Middle East, N=26

57 Conclusions Integration of surveillance is a process Contingencies can stimulate integration (e.g. outbreaks in the Italian experience) Data collection and analysis interoperation is the least common integration level met (probably the hardest) Levels of integration can be diversely met in a functioning integrated system

58 Acknowledgements MediLabSecure is a project funded by the European Union DEVCO/EuropeAid (Contract Number: IFS/2013/ ). The Project is led by The Institut Pasteur (Paris). The presentation of the West Nile surveillance system in Italy is based on a presentation made by Caterina Rizzo (ISS-Rome) and Paolo Calistri (IZS-Teramo) at the MediLabSecure Mid Term Meeting in Paris on the 16th of December 2015 The MedilabSecure WP5 survey was performed under the leadership of the WP5 leader Silvia Declich and the WP5 key expert Maria Grazia Dente.

59 For your attention Questions?

Establishment of networks of human and animal virology laboratories and medical entomology

Establishment of networks of human and animal virology laboratories and medical entomology Maria Grazia Dente, Flavia Riccardo and Silvia Declich CNESPS/Istituto Superiore di Sanità -ISS (Italy) Workshop