Commission Implementing Decision (EU) 2018/945 of 22 June 2018 on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitionsText with EEA relevance.

Commission Implementing Decision (EU) 2018/945 of 22 June 2018 on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions (Text with EEA relevance) THE EUROPEAN COMMISSION, Having regard to the Treaty on the Functioning of the European Union, Having regard to Decision No 1082/2013/EU of the European Parliament and of the Council of 22 October 2013 on serious cross-border threats to health and repealing Decision No 2119/98/EC OJ L 293, 5.11.2013, p. 1. , and in particular Article 6(5)(a) and (b) thereof, Whereas: (1) Pursuant to Decision No 2119/98/EC of the European Parliament and of the Council Decision No 2119/98/EC of the European Parliament and of the Council of 24 September 1998 setting up a network for the epidemiological surveillance and control of communicable diseases in the Community (OJ L 268, 3.10.1998, p. 1). , Commission Decision 2000/96/EC Commission Decision 2000/96/EC of 22 December 1999 on the communicable diseases to be progressively covered by the Community network under Decision No 2119/98/EC of the European Parliament and of the Council (OJ L 28, 3.2.2000, p. 50). established a list of communicable diseases and special health issues to be covered by epidemiological surveillance in the Community network. (2) Commission Decision 2002/253/EC Commission Decision 2002/253/EC of 19 March 2002 laying down case definitions for reporting communicable diseases to the Community network under Decision No 2119/98/EC of the European Parliament and of the Council (OJ L 86, 3.4.2002, p. 44). laid down case definitions for reporting communicable diseases listed in Decision 2000/96/EC to the Community network. (3) The Annex to Decision No 1082/2013/EU sets out the criteria for selecting the communicable diseases and related special health issues to be covered by epidemiological surveillance within the network. (4) The list of diseases and related special health issues established by Decision 2000/96/EC should be updated to reflect changes in disease incidence and prevalence, the needs of the European Union and its Member States, as well as to ensure compliance with the criteria provided in the Annex to Decision No 1082/2013/EU. (5) The list of case definitions should be updated in the light of new scientific information and evolving laboratory diagnostic criteria and practices. (6) Both the list of diseases and the list of case definitions are brought into line with the World Health Organisation nomenclature according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10). (7) The updated list of diseases should cover the following communicable diseases threatening public health that have emerged or re-emerged more recently in accordance with the criteria provided in the Annex to Decision No 1082/2013/EU for selection of communicable diseases and related special health issues to be covered by epidemiological surveillance:

Chikungunya: In view of autochthonous outbreaks of chikungunya virus infections in Italy (2007) and France (2010 and 2014), the widespread presence of competent vectors (Aedes albopictus) in the Mediterranean basin, and the return of travellers from endemic areas, systematic surveillance is necessary to prevent the spread of chikungunya virus in the Union, Dengue: The large dengue outbreak in Madeira in 2012 and the presence of competent vectors (Aedes mosquitos), in particular in Mediterranean Member States, highlight the need for additional surveillance to help prevent the spread of the dengue virus in the Union, Zika: The infection of pregnant women with the Zika virus can lead to the birth of children with severe neurological defects. Early detection and surveillance of people returning from affected areas are crucial. Surveillance data is needed to inform public health measures to prevent the introduction and spread of the Zika virus to the Union, Lyme neuroborreliosis: The transmission of Lyme neuroborreliosis, a complication of Lyme disease which is caused by the bacterium Borrelia burgdorferi and transmitted to humans through the bite of infected ticks, is a concern for the Union. Systematic surveillance is needed to monitor its epidemiology in order to support measures to prevent and control the disease and its complications. (8) Pursuant to Article 9 of Regulation (EC) No 851/2004 of the European Parliament and of the Council Regulation (EC) No 851/2004 of the European Parliament and of the Council of 21 April 2004 establishing a European Centre for disease prevention and control (OJ L 142, 30.4.2004, p. 1). , the European Centre for Disease Prevention and Control (ECDC) has, at the Commission's request, provided scientific assistance on the establishment of case definitions for Chikungunya, Dengue, Lyme neuroborreliosis and Zika infections on the revision of case definitions for a number of other diseases Botulism, brucellosis, campylobacter enteritis, giardiasis, gonococcal infection, listeriosis, rubella, salmonella enteritis, shiga toxin/verocytotoxin-producing E. coli infection, shigellosis, syphilis and congenital syphilis, tetanus, tuberculosis, typhoid and paratyphoid fevers, pertussis, enteritis due to Yersinia enterocolitica or Yersinia pseudotuberculosis and healthcare-associated infections. , as well as on the revision of case definitions related to certain healthcare associated infections and to antimicrobial resistance In general and, more specifically, campylobacter enteritis, gonococcal infection, salmonella enteritis, shigellosis, tuberculosis and bloodstream infections due to specific pathogens, in particular Staphylococcus aureus (susceptibility to meticillin and other anti-staphylococcal beta-lactams), Enterococcus faecium and Enterococcus faecalis (susceptibility to glycopeptides), Klebsiella pneumoniae and Escherichia coli (susceptibility to carbapenems and to colistin in carbapenem-resistant isolates), and Pseudomonas aeruginosa and Acinetobacter species (susceptibility to carbapenems).

. The case definitions should therefore be amended accordingly. (9) The measures provided for in this Decision are in accordance with the opinion of the Committee on serious cross-border threats to health established under Article 18 of Decision No 1082/2013/EU. (10) Accordingly, Decisions 2000/96/EC and 2002/253/EC should be replaced by this Decision, HAS ADOPTED THIS DECISION:

Article 1

The communicable diseases and related special health issues to be covered by the epidemiological surveillance network are listed in Annex I.

Article 2

For the purposes of submitting data for the epidemiological surveillance of the communicable diseases and related special health issues listed in Annex I, Member States shall apply the case definitions specified in Annex II.

Article 3

Decisions 2000/96/EC and 2002/253/EC are hereby repealed. References to those Decisions shall be construed as references to this Decision.

Article 4

This Decision shall enter into force on the 20th day following that of its publication in the Official Journal of the European Union. Done at Brussels, 22 June 2018. For the Commission The President Jean-Claude Juncker

Annex

ANNEX I Communicable diseases and related special health issues to be covered by the epidemiological surveillance network

1. DISEASES Anthrax Botulism Brucellosis Campylobacter enteritis Chikungunya virus disease Chlamydial infection, including Chlamydial lymphogranuloma (venereum) (LGV) Cholera Creutzfeldt-Jakob disease Cryptosporidiosis Dengue Diphtheria Echinococcosis Giardiasis (lambliasis) Gonococcal infection Haemophilus influenzae infection, invasive disease Acute hepatitis A Hepatitis B Hepatitis C Human immunodeficiency virus (HIV) infection and Acquired immunodeficiency syndrome (AIDS) Influenza Influenza A/H5N1 Legionnaires' disease Leptospirosis Listeriosis Lyme neuroborreliosis Malaria Measles Meningococcal infection, invasive disease Mumps Pertussis Plague Streptococcus pneumoniae infection, invasive disease Acute poliomyelitis Q fever Rabies Rubella Congenital rubella syndrome Salmonella enteritis Severe acute respiratory syndrome (SARS) Shiga toxin/verocytotoxin-producing E. coli infection (STEC/VTEC), including Haemolytic-uraemic syndrome (HUS) Shigellosis Smallpox Syphilis Congenital syphilis Tetanus Tick-borne viral encephalitis Congenital toxoplasmosis Trichinellosis Tuberculosis Tularaemia Typhoid and paratyphoid fevers Viral haemorrhagic fevers (VHF) West Nile virus infection Yellow fever Enteritis due to Yersinia enterocolitica or Yersinia pseudotuberculosis Zika virus disease Congenital Zika virus disease
2. SPECIAL HEALTH ISSUES 2.1. Nosocomial infections 2.2. Antimicrobial resistance

Annex

ANNEX II

1. EXPLANATION OF THE SECTIONS USED IN THE DEFINITION AND CLASSIFICATION OF CASES CLINICAL CRITERIA Clinical criteria include common and relevant signs and symptoms of the disease which either individually or in combination constitutes a clear or indicative clinical picture of the disease. They give the general outline of the disease and do not necessarily indicate all the features needed for individual clinical diagnosis.

LABORATORY CRITERIA Laboratory criteria are a list of laboratory methods that are used to confirm a case. Usually only one of the listed tests will be enough to confirm the case. If a combination of methods is needed to meet the laboratory confirmation, this is specified. The type of specimen to be collected for the laboratory tests is only specified when only certain specimen types are considered relevant for the confirmation of a diagnosis. Laboratory criteria for a probable case are included for some agreed exceptional cases. Those laboratory criteria consist of a list of laboratory methods which can be used to support the diagnosis of a case but which are not confirmatory. EPIDEMIOLOGICAL CRITERIA AND EPIDEMIOLOGICAL LINK Epidemiological criteria are deemed to have been met when an epidemiological link can be established. Epidemiological link, during the incubation period, means one of the following six: —Human to human transmissionthe fact that a person has had contact with a laboratory confirmed human case in such a way as to have had the opportunity to acquire the infection;—Animal to human transmissionthe fact that a person has had contact with an animal with a laboratory confirmed infection/colonization in such a way as to have had the opportunity to acquire the infection;—Exposure to a common sourcethe fact that a person has been exposed to the same common source or vehicle of infection, as a confirmed human case;—Exposure to contaminated food/drinking waterthe fact that a person has consumed food or drinking water with a laboratory confirmed contamination or has consumed potentially contaminated products from an animal with a laboratory confirmed infection/colonization;—Environmental exposurethe fact that a person has bathed in water or has had contact with a contaminated environmental source that has been laboratory confirmed;—Laboratory exposurethe fact that a person has worked in a laboratory where there is a potential for exposure. A person may be considered epidemiologically linked to a confirmed case if at least one case in the chain of transmission is laboratory confirmed. In case of an outbreak of faeco-oral or airborne transmitted infections, the chain of transmission does not necessarily need to be established to consider a case epidemiologically linked. Transmission may occur by one or more of the following routes: Airborne: by projection of aerosol from an infected person onto the mucous membranes while coughing, spitting, singing or talking, or when microbial aerosols dispersed into the atmosphere are inhaled by others; Contact: direct contact with an infected person (faecal-oral, respiratory droplets, skin or sexual exposure) or animal (for example, biting, touching) or indirect contact to infected materials or objects (infected fomites, body fluids, blood); Vertical: from mother to child, often in utero, or as a result of the incidental exchange of body fluids usually during the perinatal period; Vector transmission: transmission by infected mosquitoes, ticks, mites, flies and other insects which transmit disease to humans through their bites;

Food or water: consumption of potentially contaminated food or drinking water. CASE CLASSIFICATION Cases are classified as possible, probable and confirmed. The incubation periods for diseases are given in the additional information to facilitate the assessment of the epidemiological link. POSSIBLE CASE A possible case means a case classified as possible for reporting purposes. It is usually a case meeting the clinical criteria as described in the case definition without epidemiological or laboratory evidence of the disease in question. The definition of a case as possible has high sensitivity and low specificity. It allows for detection of most cases but some false positives cases will be included into this category. PROBABLE CASE A probable case means a case classified as probable for reporting purposes. It is usually a case with clinical criteria and an epidemiological link as described in the case definition. Laboratory tests for probable cases are specified only for some diseases. CONFIRMED CASE A confirmed case means a case classified as confirmed for reporting purposes. Confirmed cases are laboratory confirmed and may or may not fulfil the clinical criteria as described in the case definition. The definition of a case as confirmed is highly specific and less sensitive; therefore most of the collected cases will be true cases although some will be missed. The clinical criteria of some diseases do not allude to the fact that many acute cases are asymptomatic (for example, hepatitis A, B and C, campylobacteriosis, salmonellosis) although these cases may still be important from a public health perspective on national level. Confirmed cases fall in one of the three subcategories listed below. They will be assigned to one of those subcategories during the analysis of data using the variables collected within the context of the case information. LABORATORY-CONFIRMED CASE WITH CLINICAL CRITERIA The case meets the laboratory criteria for case confirmation and the clinical criteria included in the case definition. LABORATORY-CONFIRMED CASE WITH UNKNOWN CLINICAL CRITERIA The case meets the laboratory criteria for case confirmation but there is no information available regarding the clinical criteria (for example,only laboratory report). LABORATORY-CONFIRMED CASE WITHOUT CLINICAL CRITERIA The case meets the laboratory criteria for case confirmation but doesn't meet the clinical criteria in the case definition or is asymptomatic. Note: For some of the conditions under surveillance the structure of the case definitions does not follow the typical structure of the case definition such as in the cases of Creutzfeldt-Jakob disease (CJD), healthcare associated infections and antimicrobial resistance. 2. ABBREVIATION LIST 1.AFPacute flaccid paralysis2.AIDSacquired immune deficiency syndrome3.AMRantimicrobial resistance4.Anti-HBchepatitis B core antibody5.anti-HCVhepatitis C virus specific antibody6.ARIacute respiratory infection7.BALbroncho-alveolar lavage8.BCGBacille de Calmette et Guérin9.BJbone and joint infection

10.BJ-BONEosteomyelitis11.BJ-DISCdisc space infection12.BJ-JNTjoint or bursa infection13.BoNTbotulinum neurotoxin14.BSIbloodstream infection15.C-CVCcatheter-related — central venous catheter16.CDADClostridium difficile associated diarrhoea17.CFUcolony-forming unit18.CJDCreutzfeldt-Jakob disease19.CMVcytomegalovirus20.CNRLEU Community Network of Reference Laboratories for human influenza21.CNScentral nervous system22.CNS-ICcentral nervous system infection — intracranial infection23.CNS-MENcentral nervous system infection — meningitis or ventriculitis24.CNS-SAcentral nervous system infection — spinal abscess without meningitis25.C-PVCcatheter-related — peripheral venous catheter26.CRIcatheter-related infection27.CRSCongenital rubella syndrome28.CRTcapillary refilling time29.CSFCerebrospinal fluid30.CT scancomputed tomography scan31.CVScardiovascular system infection32.CVS-CARDcardiovascular system infection — myocarditis or pericarditis33.CVS-ENDOcardiovascular system infection — endocarditis34.CVS-MEDcardiovascular system infection — mediastinitis35.CVS-VASCcardiovascular system infection — arterial or venous infection36.DFAdirect fluorescent antibody37.DFA-TPdirect fluorescent antibody test for Treponema pallidum38.DNAdeoxyribonucleic acid39.DPAdistal protected aspirate40.EARS-NetEuropean Antimicrobial Resistance Surveillance Network41.ECDCEuropean Centre for Disease Prevention and Control42.ECOFFsepidemiological cut-off values43.EEGelectroencephalography44.EENTeye, ear, nose, throat, or mouth infection45.EENT-CONJeye, ear, nose, throat, or mouth infection — conjunctivitis46.EENT-EAReye, ear, nose, throat, or mouth infection — ear mastoid47.EENT-EYEeye, ear, nose, throat, or mouth infection — eye, other than conjunctivitis 48.EENT-ORALeye, ear, nose, throat, or mouth infection — oral cavity (mouth, tongue, or gums)49.EENT-SINUeye, ear, nose, throat, or mouth infection — sinusitis50.EENT-UReye, ear, nose, throat, or mouth infection — upper respiratory tract, pharyngitis, laryngitis, epiglottitis51.EFNSEuropean Federation of Neurological Societies52.EIAenzyme immunoassay53.ELISAenzyme-linked immunosorbent assay54.EMelectron microscopy55.EUCASTEuropean Committee on Antimicrobial Susceptibility Testing56.FAMAfluorescent antibody to membrane antigen57.FTA-absfluorescent treponemal antibody absorption58.FUOfever of unknown origin59.GIgastrointestinal system infection60.GI-CDIgastrointestinal system infection — Clostridium difficile infection61.GI-GEgastrointestinal system infection — gastroenteritis (excl. CDI)62.GI-GITgastrointestinal system infection — gastrointestinal tract (esophagus, stomach, small and large bowel, and rectum) excluding gastroenteritis and appendicitis63.GI-HEPgastrointestinal system infection — hepatitis64.GI-IABgastrointestinal system infection — intraabdominal, not specified elsewhere including gallbladder, bile ducts, liver (excluding viral hepatitis), spleen, pancreas, peritoneum, subphrenic or subdiaphragmatic space, or other intraabdominal tissue or area not specified elsewhere65.HAIhealthcare-associated infections66.HbeAghepatitis B e antigen67.HbsAghepatitis B surface antigen68.HBV-DNAhepatitis B nucleic acid69.HCV-corehepatitis C virus core antigen70.HCV-RNAhepatitis C virus nucleic acid71.HIVhuman immunodeficiency virus72.HUShaemolytic-uraemic syndrome73.IAPintubation-associated pneumonia74.IFAindirect fluorescent antibody75.IgGimmunoglobulin G76.IgMimmunoglobulin M77.ILIinfluenza-like illness78.LGVlymphogranuloma (venereum)79.LPSlipopolysaccharides80.LRIlower respiratory tract infection, other than pneumonia81.LRI-BRONlower respiratory tract infection — bronchitis, tracheobronchitis, bronchiolitis, tracheitis, without evidence of pneumonia82.TBETick-borne encephalitis

1. CASE DEFINITIONS OF COMMUNICABLE DISEASES 3.1. ANTHRAX Clinical Criteria Any person with at least one of the following clinical forms: Cutaneous anthrax At least one the following two: Papular or vesicular lesion; Depressed black eschar with surrounding oedema. Gastrointestinal anthrax Fever or feverishness; AND at least one of the following two: Severe abdominal pain; Diarrhoea. Inhalational anthrax Fever or feverishness; AND at least one of the following two: Acute respiratory distress; Radiological evidence of mediastinal widening. Meningeal/meningoencephalitic anthrax Fever; AND at least one of the following three: Convulsions; Loss of consciousness; Meningeal signs. Anthrax septicaemia Laboratory Criteria At least one of the following two: Isolation of Bacillus anthracis from a clinical specimen Detection of Bacillus anthracis nucleic acid in a clinical specimen Positive nasal swab without clinical symptoms does not contribute to a confirmed diagnosis of a case. Epidemiological Criteria At least one of the following three epidemiological links: Animal to human transmission; Exposure to a common source; Exposure to contaminated food/drinking water. Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.2. BOTULISM Clinical Criteria Any person with at least one of the following clinical forms: Food-borne and wound botulism At least one of the following two: Bilateral cranial nerve impairment (for example, diplopia, blurred vision, dysphagia, bulbar weakness); Peripheral symmetric paralysis. Infant botulism Any infant with at least one of the following six: Constipation; Lethargy; Difficulty in sucking or feeding; Ptosis; Dysphagia; General muscle weakness. The type of botulism usually encountered in infants (< 12 months of age) can affect children also over 12 months of age and occasionally adults, with altered gastrointestinal anatomy and microflora Laboratory Criteria At least one of the following three: Isolation of BoNT-producing clostridia (for example, Clostridium botulinum, C. baratii, C. butyricum) for infant botulism (stool) or wound botulism (wound); Detection of botulinum neurotoxins in a clinical specimen; Detection of genes encoding for botulinum neurotoxins in a clinical specimen. Epidemiological Criteria At least one of the following two epidemiological links: Exposure to a common source (for example, food, sharing of needles or other devices); Exposure to contaminated food/drinking water Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.3. BRUCELLOSIS Clinical Criteria Any person with fever

And at least one of the following seven: Sweating (profuse, malodorous, specially nocturnal); Chills; Arthralgia; Weakness; Depression; Headache; Anorexia. Laboratory Criteria At least one of the following three: Isolation of human pathogenic Brucella spp. from a clinical specimen; Human pathogenic Brucella specific antibody response (Standard Agglutination Test, Complement Fixation, ELISA); Detection of human pathogenic Brucella spp. nucleic acid in a clinical specimen. Epidemiological Criteria At least one of the following five epidemiological links: Exposure to contaminated food/drinking water; Exposure to products from a contaminated animal (milk or milk products); Animal to human transmission (contaminated secretions or organs for example, vaginal discharge, placenta); Exposure to a common source; Laboratory exposure. Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.4. CAMPYLOBACTER ENTERITIS Clinical Criteria Any person with at least one of the following three: Diarrhoea; Abdominal pain; Fever. Laboratory Criteria At least one of the following two: Isolation of human pathogenic Campylobacter spp. from a clinical specimen; Detection of Campylobacter spp. nucleic acid in a clinical specimen. Note: Antimicrobial susceptibility testing of Campylobacter spp. should be performed on a representative subset of isolates Epidemiological Criteria At least one of the following five epidemiological links: Animal to human transmission; Human to human transmission; Exposure to a common source; Exposure to contaminated food/drinking water; Environmental exposure. Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. Antimicrobial resistance The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified in the EU protocol for harmonised monitoring of antimicrobial resistance in human Salmonella and Campylobacter isolates The EU protocols, including future updates, can be found at the following ECDC webpage: https://ecdc.europa.eu/en/publications-data/eu-protocol-harmonised-monitoring-antimicrobial-resistance-human-salmonella-and-0 . 3.5. CHIKUNGUNYA VIRUS DISEASE Clinical Criteria Clinical criteria should be interpreted by taking into account the presence of an alternative diagnosis that can fully explain the illness. Fever Laboratory Criteria Serological results should be interpreted according to previous exposure to other alphaviral infections.

A. Probable case Detection of chikungunya specific IgM antibodies in a single serum sample. B. Confirmed case At least one of the following four: Isolation of chikungunya virus from a clinical specimen; Detection of chikungunya viral nucleic acid from a clinical specimen; Detection of chikungunya specific IgM antibodies in a single serum sample AND confirmation by neutralisation; Seroconversion or four-fold antibody titre increase of chikungunya specific antibodies in paired serum samples. Epidemiological Criteria History of travel to, or residence in an area with documented on-going transmission of chikungunya, within the two-week period prior to the onset of symptoms Case Classification A. Possible case NA B. Probable case Any person meeting the clinical and the epidemiological criteria, and the laboratory criteria for a probable case C. Confirmed case Any person meeting the laboratory criteria for a confirmed case Note: Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. 3.6. CHLAMYDIAL INFECTION, INCLUDING CHLAMYDIAL LYMPHOGRANULOMA (VENEREUM) (LGV) Clinical Criteria Any person with at least one of the following clinical forms: Chlamydial infection non-LGV At least one of the following six: Urethritis; Epididymitis; Acute salpingitis; Acute endometritis; Cervicitis; Proctitis. In newborn children at least one of the following two: Conjunctivitis; Pneumonia. LGV At least one of the following five: Urethritis; Genital ulcer; Inguinal lymphadenopathy; Cervicitis; Proctitis. Laboratory Criteria Chlamydial infection non-LGV At least one of the following three: Isolation of Chlamydia trachomatis from a specimen of the ano-genital tract or from the conjunctiva; Demonstration of Chlamydia trachomatis by DFA test in a clinical specimen; Detection of Chlamydia trachomatis nucleic acid in a clinical specimen. LGV At least one of the following two: Isolation of Chlamydia trachomatis from a specimen of the ano-genital tract or from the conjunctiva; Detection of Chlamydia trachomatis nucleic acid in a clinical specimen. AND Identification of serovar (genovar) L1, L2 or L3 Epidemiological Criteria An epidemiological link by human to human transmission (sexual contact or vertical transmission) Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria 3.7. CHOLERA Clinical Criteria Any person with at least one of the following two: Diarrhoea; Vomiting. Laboratory Criteria Isolation of Vibrio cholerae from a clinical specimen AND Demonstration of O1 or O139 antigen in the isolate AND Demonstration of cholera-enterotoxin or the cholera-enterotoxin gene in the isolate Epidemiological Criteria At least one of the following four epidemiological links:

Exposure to a common source; Human to human transmission; Exposure to contaminated food/drinking water; Environmental exposure. Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria; Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.8. CREUTZFELDT-JAKOB DISEASE (CJD) Preconditions Any person with a progressive neuropsychiatric disorder with a duration of illness of at least 6 months Routine investigations do not suggest an alternative diagnosis No history of exposure to human pituitary hormones or human dura mater graft No evidence of a genetic form of transmissible spongiform encephalopathy Clinical Criteria Any person with at least four of the following five: Early psychiatric symptoms Depression, anxiety, apathy, withdrawal, delusions ; Persistent painful sensory symptoms This includes both frank pain and/or dysaesthesia ; Ataxia; Myoclonus or chorea or dystonia; Dementia. Diagnostic Criteria Diagnostic criteria for case confirmation: Neuropathological confirmation: spongiform change and extensive prion protein deposition with florid plaques throughout the cerebrum and cerebellum Diagnostic criteria for a probable or a possible case: EEG does not show the typical appearance The typical appearance of the EEG in sporadic CJD consists of generalised periodic complexes at approximately one per second. These may occasionally be seen in the late stages of vCJD of sporadic CJD The typical appearance of the EEG in sporadic CJD consists of generalised periodic complexes at approximately one per second. These may occasionally be seen in the late stages of vCJD in the early stages of the illness; Bilateral pulvinar high signal on MRI brain scan; A positive tonsil biopsy Tonsil biopsy is not recommended routinely nor in cases with EEG appearances typical of sporadic CJD, but may be useful in suspect cases in which the clinical features are compatible with vCJD and MRI does not show pulvinar high signal . Epidemiological Criteria An epidemiological link by human to human transmission (for example, blood transfusion) Case Classification A. Possible case Any person fulfilling the preconditions AND meeting the clinical criteria AND a negative EEG for sporadic CJD The typical appearance of the EEG in sporadic CJD consists of generalised periodic complexes at approximately one per second. These may occasionally be seen in the late stages of vCJD B. Probable case Any person fulfilling the preconditions AND meeting the clinical criteria AND a negative EEG for sporadic CJD The typical appearance of the EEG in sporadic CJD consists of generalised periodic complexes at approximately one per second. These may occasionally be seen in the late stages of vCJD AND a positive MRI brain scan OR Any person fulfilling the preconditions

AND a positive tonsil biopsy C. Confirmed case Any person fulfilling the preconditions AND meeting the diagnostic criteria for case confirmation 3.9. CRYPTOSPORIDIOSIS Clinical Criteria Any person with at least one of the following two: Diarrhoea; Abdominal pain. Laboratory Criteria At least one of the following four: Demonstration of Cryptosporidium oocysts in stool; Demonstration of Cryptosporidium in intestinal fluid or small-bowel biopsy specimens; Detection of Cryptosporidium nucleic acid in stool; Detection of Cryptosporidium antigen in stool. Epidemiological Criteria One of the following five epidemiological links: Human to human transmission Exposure to a common source Animal to human transmission Exposure to contaminated food/drinking water Environmental exposure Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.10. DENGUE Clinical Criteria Clinical criteria should be interpreted by taking into account the presence of an alternative diagnosis that can fully explain the illness. Fever Laboratory Criteria Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. A. Probable case Detection of dengue specific IgM antibodies in a single serum sample B. Confirmed case At least one of the following five: Isolation of a dengue virus from a clinical specimen; Detection of dengue viral nucleic acid from a clinical specimen; Detection of dengue viral antigen from a clinical specimen; Detection of dengue specific IgM antibodies in a single serum sample AND confirmation by neutralization; Seroconversion or four-fold antibody titre increase of dengue specific antibodies in paired serum samples Epidemiological Criteria History of travel to, or residence in an area with documented on-going transmission of dengue, within the two-week period prior to the onset of symptoms Case Classification A. Possible case NA B. Probable case Any person meeting the clinical and the epidemiological criteria, and the laboratory criteria for a probable case C. Confirmed case Any person meeting the laboratory criteria for a confirmed case. 3.11. DIPHTHERIA Clinical Criteria Any person with at least one of the following clinical forms: Classic Respiratory Diphtheria: An upper respiratory tract illness with laryngitis or nasopharyngitis or tonsillitis AND an adherent membrane/pseudomembrane Mild Respiratory Diphtheria: An upper respiratory tract illness with laryngitis or nasopharyngitis or tonsillitis WITHOUT an adherent membrane/pseudomembrane. Cutaneous Diphtheria: Skin lesion

Diphtheria of other sites: Lesion of conjunctiva or mucous membranes Laboratory Criteria Isolation of toxin-producing Corynebacterium diphtheriae, Corynebacterium ulcerans or Corynebacterium pseudotuberculosis from a clinical specimen. Epidemiological Criteria At least one of the following epidemiological links: Human to human transmission Animal to human transmission Case Classification A. Possible case Any person meeting the clinical criteria for classical respiratory diphtheria B. Probable case Any person meeting the clinical criteria for diphtheria (Classic Respiratory Diphtheria, Mild Respiratory Diphtheria, Cutaneous Diphtheria, Diphtheria of other sites) with an epidemiological link to a human confirmed case or with an epidemiological link to animal to human transmission C. Confirmed case Any person meeting the laboratory criteria AND at least one of the clinical forms 3.12. ECHINOCOCCOSIS Clinical Criteria Not relevant for surveillance purposes Diagnostic Criteria At least one of the following five: Histopathology or parasitology compatible with Echinococcus multilocularis or granulosus (for example, direct visualization of the protoscolex in cyst fluid) Detection of Echinoccocus granulosus pathognomonic macroscopic morphology of cyst(s) in surgical specimens Typical organ lesions detected by imaging techniques (for example, computerized tomography, sonography, MRI) AND confirmed by a serological test Echinococcus spp. specific serum antibodies by high-sensitivity serological test AND confirmed by a high specificity serological test Detection of Echinococcus multilocularis or granulosus nucleic acid in a clinical specimen Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the diagnostic criteria 3.13. GIARDIASIS (LAMBLIASIS) Clinical Criteria Any person with at least one of the following four: Diarrhoea Abdominal pain Bloating Signs of malabsorption (for example, steatorrhoea, weight loss) Laboratory Criteria At least one of the following three: Demonstration of Giardia lamblia cysts or trophozoites in stool, duodenal fluid or small-bowel biopsy Demonstration of Giardia lamblia antigen in stool, duodenal fluid or small-bowel biopsy Detection of Giardia lamblia nucleic acid in stool, duodenal fluid or small-bowel biopsy Epidemiological Criteria At least one of the following four epidemiological links: Exposure to contaminated food/drinking water Human to human transmission Exposure to a common source Environmental exposure Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.14. GONOCOCCAL INFECTION Clinical Criteria Any person with at least one of the following eight:

Urethritis Acute salpingitis Pelvic inflammatory disease Cervicitis Epididymitis Proctitis Pharyngitis Arthritis OR Any newborn child with conjunctivitis Laboratory Criteria At least one of the following four: Isolation of Neisseria gonorrhoeae from a clinical specimen Detection of Neisseria gonorrhoeae nucleic acid in a clinical specimen Demonstration of Neisseria gonorrhoeae by a non-amplified nucleic acid probe test in a clinical specimen Microscopic detection of intracellular Gram-negative diploccocci in an urethral male specimen Epidemiological Criteria An epidemiological link by human to human transmission (sexual contact or vertical transmission) Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria Antimicrobial resistance For cases ascertained by culture, the results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified in the ECDC standard protocol for gonococcal antimicrobial resistance surveillance The ECDC standard protocol for gonococcal antimicrobial resistance surveillance is published yearly as part of the annexes of the annual report on Gonococcal antimicrobial susceptibility surveillance in Europe. See: European Centre for Disease Prevention and Control. Gonococcal antimicrobial susceptibility surveillance in Europe, www.ecdc.europa.eu . 3.15. HAEMOPHILUS INFLUENZAE INFECTION, INVASIVE DISEASE Clinical Criteria Not relevant for surveillance purposes Laboratory Criteria At least one of the following two: Isolation of Haemophilus influenzae from a normally sterile site Detection of Haemophilus influenzae nucleic acid from a normally sterile site Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the laboratory criteria 3.16. ACUTE HEPATITIS A Clinical Criteria Any person with a discrete onset of symptoms (for example, fatigue, abdominal pain, loss of appetite, intermittent nausea and vomiting) AND At least one of the following three: Fever Jaundice Elevated serum aminotransferase levels Laboratory Criteria At least one of the following three: Detection of hepatitis A virus nucleic acid in serum or stool Hepatitis A virus specific antibody response Detection of hepatitis A virus antigen in stool Epidemiological Criteria At least one of the following four: Human to human transmission Exposure to a common source Exposure to contaminated food/drinking water Environmental exposure Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.17. HEPATITIS B

When reporting cases of Hepatitis B, the Member States should distinguish between acute and chronic disease, according to ECDC requirements. Clinical Criteria Not relevant for surveillance purposes Laboratory Criteria Positive results of at least one or more of the following tests or combination of tests: IgM hepatitis B core antibody (anti-HBc IgM) Hepatitis B surface antigen (HBsAg) Hepatitis B e antigen (HBeAg) Hepatitis B nucleic acid (HBV-DNA) Epidemiological Criteria Not relevant for surveillance purposes Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the laboratory criteria 3.18. HEPATITIS C When reporting cases of Hepatitis C, the Member States should distinguish between acute and chronic disease, according to ECDC requirements. Clinical Criteria Not relevant for surveillance purposes Laboratory Criteria At least one of the following three: Detection of hepatitis C virus nucleic acid (HCV RNA) Detection of hepatitis C virus core antigen (HCV-core) Hepatitis C virus specific antibody (anti-HCV) response confirmed by a confirmatory (for example, immunoblot) antibody test in persons older than 18 months without evidence of resolved infection) Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the laboratory criteria 3.19. HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION AND ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Clinical Criteria (AIDS) Any person who has any of the clinical conditions as defined in the European AIDS case definition for: Adults and adolescents ≥ 15 years Children < 15 years of age Laboratory Criteria (HIV) Adults, adolescents and children aged ≥ 18 months At least one of the following three: Positive result of a HIV screening antibody test or a combined screening test (HIV antibody and HIV p24 antigen) confirmed by a more specific antibody test (for example, Western blot); Positive result of 2 EIA antibody test confirmed by a positive result of a further EIA test; Positive results on two separate specimens from at least one of the following three: Detection of HIV nucleic acid (HIV-RNA, HIV-DNA); Demonstration of HIV by HIV p24 antigen test, including neutralisation assay; Isolation of HIV. Children aged < 18 months Positive results on two separate specimens (excluding cord blood) from at least one of the following three: Isolation of HIV; Detection of HIV nucleic acid (HIV-RNA, HIV-DNA); Demonstration of HIV by HIV p24 antigen test, including neutralisation assay in a child ≥ 1 month of age. Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case HIV infection: Any person meeting the laboratory criteria for HIV infection. AIDS: Any person meeting the clinical criteria for AIDS and the laboratory criteria for HIV infection. 3.20. INFLUENZA Clinical Criteria Any person with at least one of the following clinical forms: Influenza-like illness (ILI) Sudden onset of symptoms

AND at least one of the following four systemic symptoms: Fever or feverishness Malaise Headache Myalgia AND At least one of the following three respiratory symptoms: Cough Sore throat Shortness of breath Acute respiratory infection (ARI) Sudden onset of symptoms AND At least one of the following four respiratory symptoms: Cough Sore throat Shortness of breath Coryza AND A clinician's judgement that the illness is due to an infection Laboratory Criteria At least one the following four: Isolation of influenza virus from a clinical specimen Detection of influenza virus nucleic acid in a clinical specimen Identification of influenza virus antigen by DFA test in a clinical specimen Influenza specific antibody response Sub typing of the influenza isolate should be performed, if possible Epidemiological Criteria An epidemiological link by human to human transmission Case Classification A. Possible case Any person meeting the clinical criteria (ILI or ARI) B. Probable case Any person meeting the clinical criteria (ILI or ARI) with an epidemiological link C. Confirmed case Any person meeting the clinical (ILI or ARI) and the laboratory criteria 3.21. INFLUENZA A/H5N1 Clinical Criteria Any person with one of the following two: Fever AND signs and symptoms of acute respiratory infection; Death from an unexplained acute respiratory illness. Laboratory Criteria At least one of the following three: Isolation of influenza A/H5N1 from a clinical specimen; Detection of influenza A/H5 nucleic acid in a clinical specimen; Influenza A/H5 specific antibody response (four-fold or greater rise or single high titre). Epidemiological Criteria At least one of the following four: Human to human transmission by having been in close contact (within 1 metre) to a person reported as probable or confirmed case; Laboratory exposure: where there is a potential exposure to influenza A/H5N1; Close contact (within 1 metre) with an animal with confirmed A/H5N1 infection other than poultry or wild birds (for example, cat or pig); Reside in or have visited an area where influenza A/H5N1 is currently suspected or confirmed AND at least one of the following two: Having been in close contact (within 1 metre) with sick or dead domestic poultry or wild birds in the affected area; Having been in a home or a farm where sick or dead domestic poultry have been reported in the previous month in the affected area. Case Classification A. Possible case Any person meeting the clinical and the epidemiological criteria B. Probable case Any person with a positive test for influenza A/H5 or A/H5N1 performed by a laboratory which is not a National Reference Laboratory participating in the EU Community Network of Reference Laboratories for human influenza (CNRL) C. Nationally confirmed case Any person with a positive test for influenza A/H5 or A/H5N1 performed by a National Reference Laboratory participating in the EU Community Network of Reference Laboratories for human influenza (CNRL) D. WHO confirmed case

Any person with a laboratory confirmation by a WHO Collaborating Centre for H5 3.22. LEGIONNAIRES' DISEASE Clinical Criteria Any person with pneumonia Laboratory Criteria Laboratory criteria for case confirmation At least one of the following three: Isolation of Legionella spp. from respiratory secretions or any normally sterile site Detection of Legionella pneumophila antigen in urine Significant rise in specific antibody level to Legionella pneumophila serogroup 1 in paired serum samples Laboratory criteria for a probable case At least one of the following four: Detection of Legionella pneumophila antigen in respiratory secretions or lung tissue for example, by DFA staining using monoclonal-antibody derived reagents Detection of Legionella spp. nucleic acid in respiratory secretions, lung tissue or any normally sterile site Significant rise in specific antibody level to Legionella pneumophila other than serogroup 1 or other Legionella spp. in paired serum samples Single high level of specific antibody to Legionella pneumophila serogroup 1 in serum Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criterion AND at least one laboratory criterion for a probable case C. Confirmed case Any person meeting the clinical criterion AND at least one laboratory criterion for a confirmed case 3.23. LEPTOSPIROSIS Clinical Criteria Any person with Fever OR At least two of the following eleven: Chills Headache Myalgia Conjunctival suffusion Haemorrhages into skin and mucous membranes Rash Jaundice Myocarditis Meningitis Renal impairment Respiratory symptoms such as haemoptysis Laboratory Criteria At least one of the following four: Isolation of Leptospira interrogans or any other pathogenic Leptospira spp. from a clinical specimen Detection of Leptospira interrogans or any other pathogenic Leptospira spp. nucleic acid in a clinical specimen Demonstration of Leptospira interrogans or any other pathogenic Leptospira spp. by immunofluorescence in a clinical specimen Leptospira interrogans or any other pathogenic Leptospira spp. specific antibody response Epidemiological Criteria At least one of the following three epidemiological links: Animal to human transmission Environmental exposure Exposure to a common source Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.24. LISTERIOSIS Clinical Criteria Any person with at least one of the following five: Fever Meningitis, meningoencephalitis, or encephalitis Influenza-like symptoms Septicaemia Localized infections such as arthritis, endocarditis, endophthalmitis, and abscesses Listeriosis in pregnancy: Pregnancy-related consequences of Listeria infection defined as: miscarriage, stillbirth or premature birth during the pregnancy

Listeriosis of newborns defined as one of the following Stillbirth (fetal death after 20 weeks of gestation) Premature birth (before 37 gestational weeks) OR At least one of the following five in the first month of life (neonatal listeriosis): Meningitis or meningoencephalitis Septicaemia Dyspnoea Granulomatosis infantiseptica Lesions on skin, mucosal membranes or conjunctivae Laboratory Criteria At least one of the following two: Isolation of Listeria monocytogenes or detection of nucleic acid of Listeria monocytogenes from a normally sterile site In a pregnancy-associated case also: Isolation of Listeria monocytogenes or detection of nucleic acid from Listeria monocytogenes in a normally non-sterile site (for example, placental tissue, amniotic fluid, meconium, vaginal swab) or from a foetus, stillborn, newborn or the mother Epidemiological Criteria At least one of the following four epidemiological links: Exposure to a common source Human to human transmission (vertical transmission) Exposure to contaminated food Animal to human transmission Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria for a normal sterile site OR In a pregnancy-associated case (mother or newborn in the first month of life) meeting the laboratory criteria, only the mother is to be reported as a case. Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.25. LYME NEUROBORRELIOSIS Clinical Criteria Neurological symptoms according to European Federation of Neurological Societies (EFNS) suggested case definition EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis, European Journal of Neurology 17, 8-16: doi:10.1111/j.1468-1331.2009.02862.x , without other obvious reasons Laboratory Criteria A. Confirmed case Pleocytosis in cerebrospinal fluid, AND Evidence of intrathecal production of Lyme borreliosis antibodies, OR Borrelia burdgorferi s.l. isolation, OR nucleic acid detection in cerebrospinal fluid OR Detection of IgG Lyme borreliosis antibodies in blood specimen only for children (age under 18) with facial palsy or other cranial neuritis and a recent (< 2 months) history of erythema migrans B. Probable case Pleocytosis in cerebrospinal fluid AND positive Lyme borreliosis serology in cerebrospinal fluid OR Specific intrathecal Lyme borreliosis antibody production Epidemiological Criteria Not applicable Case Classification A. Possible case Not applicable B. Probable case Any person meeting the clinical criteria and at least one of the laboratory criteria for probable cases C. Confirmed case Any person meeting the clinical criteria and at least one of the laboratory criteria for confirmed cases 3.26. MALARIA Clinical Criteria Any person with fever OR a history of fever Laboratory Criteria At least one of the following three:

Demonstration of malaria parasites by light microscopy in blood films Detection of Plasmodium nucleic acid in blood Detection of Plasmodium antigen Differentiation of Plasmodium spp. should be performed if possible Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.27. MEASLES Clinical Criteria Any person with fever AND Maculo-papular rash AND at least one of the following three: Cough Coryza Conjunctivitis Laboratory Criteria At least one of the following four: Isolation of measles virus from a clinical specimen Detection of measles virus nucleic acid in a clinical specimen Measles virus specific antibody response characteristic for acute infection in serum or saliva Detection of measles virus antigen by DFA in a clinical specimen using measles specific monoclonal antibodies Laboratory results need to be interpreted according to the vaccination status. If recently vaccinated, investigate for wild virus Epidemiological criteria An epidemiological link by human to human transmission Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person not recently vaccinated and meeting the clinical and the laboratory criteria 3.28. MENINGOCOCCAL INFECTION, INVASIVE DISEASE Clinical Criteria Any person with at least one of the following symptoms: Meningeal signs Haemorrhagic rash Septic shock Septic arthritis Laboratory Criteria At least one of the following four: Isolation of Neisseria meningitidis from a normally sterile site, or from purpuric skin lesions Detection of Neisseria meningitidis nucleic acid from a normally sterile site, or from purpuric skin lesions Detection of Neisseria meningitidis antigen in CSF Detection of Gram-negative stained diplococcus in CSF Epidemiological Criteria An epidemiological link by human to human transmission Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria 3.29. MUMPS Clinical Criteria Any person with Fever AND At least one of the following three: Sudden onset of unilateral or bilateral tender swelling of the parotid or other salivary glands without other apparent cause Orchitis Meningitis Laboratory Criteria At least one of the following three: Isolation of mumps virus from a clinical specimen Detection of mumps virus nucleic acid Mumps virus specific antibody response characteristic for acute infection in serum or Saliva Laboratory results need to be interpreted according to the vaccination status Epidemiological Criteria An epidemiological link by human to human transmission

Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person not recently vaccinated and meeting the laboratory criteria In case of recent vaccination: any person with detection of wild-type mumps virus strain 3.30. PERTUSSIS Clinical Criteria Any person with a cough lasting at least two weeks AND at least one of the following three: Paroxysms of coughing Inspiratory whooping Post-tussive vomiting OR Any person diagnosed as pertussis by a physician OR Apnoeic episodes in infants Notes: All individuals including adults, adolescents or vaccinated children can present with atypical symptoms. Characteristics of cough should be investigated, particularly whether the cough is paroxysmal in nature, increases during the night and occurs in the absence of fever. Laboratory Criteria At least one of the following three: (i) Isolation of Bordetella pertussis from a clinical specimen (ii) Detection of Bordetella pertussis nucleic acid in a clinical specimen (iii) Bordetella pertussis specific antibody response Direct diagnosis (i)-(ii): Bordetella pertussis and its nucleic acid are best isolated/detected from nasopharyngeal samples. Indirect diagnosis (iii): if possible ELISA should be performed using highly purified Pertussis Toxin and WHO reference sera as a standard. Results need to interpreted according to pertussis vaccination status. If vaccinated within the last few years before specimen collection, the titre of specific antibodies against Bordetella pertussis toxin may be a consequence of, or modified by, previous vaccination. Epidemiological Criteria An epidemiological link by human to human transmission Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.31. PLAGUE Clinical Criteria Any person with at least one of the following clinical forms: Bubonic plague: Fever AND Sudden onset of painful lymphadenitis Septicaemic plague: Fever Pneumonic plague: Fever AND At least one of the following three: Cough Chest pain Haemoptysis Laboratory Criteria At least one of the following three: Isolation of Yersinia pestis from a clinical specimen Detection of Yersinia pestis nucleic acid from a clinical specimen Yersinia pestis anti-F1 antigen specific antibody response Epidemiological Criteria At least one of the following four epidemiological links: Human to human transmission Animal to human transmission Laboratory exposure (where there is a potential exposure to plague) Exposure to a common source Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria 3.32. STREPTOCOCCUS PNEUMONIAE INFECTION, INVASIVE DISEASE Clinical Criteria

Not relevant for surveillance purposes Laboratory Criteria At least one of the following three: Isolation of Streptococcus pneumoniae from a normally sterile site Detection of Streptococcus pneumoniae nucleic acid from a normally sterile site Detection of Streptococcus pneumoniae antigen from a normally sterile site Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any person meeting the laboratory criteria Antimicrobial resistance: The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified by ECDC's European Antimicrobial Resistance Surveillance Network (EARS-Net) The criteria for reporting are published each year as part of the Antimicrobial resistance (AMR) reporting protocol. See: The European Surveillance system. Antimicrobial resistance (AMR) reporting protocol. European Antimicrobial Resistance Surveillance Network (EARS-Net). www.ecdc.europa.eu . 3.33. ACUTE POLIOMYELITIS Clinical Criteria Any person < 15 years of age with Acute flaccid paralysis (AFP) OR Any person in whom polio is suspected by a physician Laboratory Criteria At least one of the following three: Isolation of a polio virus and intratypic differentiation — Wild polio virus (WPV) Vaccine derived poliovirus (VDPV) (for the VDPV at least 85 % similarity with vaccine virus in the nucleotide sequences in the VP1 section) Sabin-like poliovirus: intratypic differentiation performed by a WHO-accredited polio laboratory (for the VDPV a > 1 % up to 15 % VP1 sequence difference compared with vaccine virus of the same serotype) Epidemiological Criteria At least one of the following two epidemiological links: Human to human transmission An history of travel to a polio-endemic area or an area with suspected or confirmed circulation of poliovirus Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.34. Q FEVER Clinical Criteria Any person with at least one of the following three: Fever Pneumonia Hepatitis Laboratory Criteria At least one of the following three: Isolation of Coxiella burnetii from a clinical specimen Detection of Coxiella burnetii nucleic acid in a clinical specimen Coxiella burnetii specific antibody response (IgG or IgM phase II) Epidemiological Criteria At least one of the following two epidemiological links: Exposure to a common source Animal to human transmission Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.35. RABIES Clinical Criteria Any person with an acute encephalomyelitis AND At least two of the following seven: Sensory changes referred to the site of a preceding animal bite

Paresis or paralysis Spasms of swallowing muscles Hydrophobia Delirium Convulsions Anxiety Laboratory Criteria At least one of the following four: Isolation of Lyssa virus from a clinical specimen Detection of Lyssa virus nucleic acid in a clinical specimen (for example, saliva or brain tissue) Detection of viral antigens by a DFA in a clinical specimen Lyssa virus specific antibody response by virus neutralization assay in serum or CSF Laboratory results need to be interpreted according to the vaccination or immunization status Epidemiological Criteria At least one of the following three epidemiological links: Animal to human transmission (animal with suspected or confirmed infection) Exposure to a common source (same animal) Human to human transmission (for example, transplantation of organs) Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.36. RUBELLA Clinical Criteria Any person with sudden onset of generalised maculo-papular rash AND At least one of the following five: Cervical adenopathy Sub-occipital adenopathy Post-auricular adenopathy Arthralgia Arthritis Laboratory Criteria At least one of the following four: Isolation of rubella virus from a clinical specimen Detection of rubella virus nucleic acid in a clinical specimen Rubella IgM antibody detection In elimination settings, additional testing may be considered in certain situations to exclude false-positive IgM results (WHO Manual for the Laboratory Surveillance of Measles and Rubella Viruses, 2017). Rubella IgG seroconversion or significant rise in rubella IgG antibody titre in paired specimens tested in parallel. Laboratory results need to be interpreted according to the vaccination status (possible persistence of IgM antibodies upon vaccination). Epidemiological Criteria An epidemiological link to a confirmed case Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria who has not been recently vaccinated. In case of recent vaccination, a person meeting the clinical criteria with detection of wild-type rubella virus strain is considered as a confirmed case. Note: When rubella in pregnancy is suspected, further confirmation of a positive rubella IgM results is required for case management (for example, a rubella specific IgG avidity test, rubella IgM and comparison of rubella IgG levels on paired sera conducted in a reference laboratory). 3.37. CONGENITAL RUBELLA SYNDROME Clinical Criteria Congenital rubella infection (CRI) No clinical criteria can be defined for CRI Congenital rubella syndrome (CRS) Any infant < 1 year of age or any stillborn with: At least two of the conditions listed in (A) OR One in category (A) and one in category (B)

(A) Cataract(s) Congenital glaucoma Congenital heart disease Loss of hearing Pigmentary retinopathy (B) Purpura Splenomegaly Microcephaly Developmental delay Meningo-encephalitis Radiolucent bone disease Jaundice that begins within 24 hours after birth Laboratory Criteria At least one of the following four: Isolation of rubella virus from a clinical specimen Detection of Rubella virus nucleic acid Rubella virus specific antibody response (IgM) Persistence of rubella IgG between 6 and 12 months of age (at least two samples with similar concentration of rubella IgG) Laboratory results need to be interpreted according to the vaccination status Epidemiological Criteria Any infant or any stillborn born to a woman with a laboratory confirmed rubella infection during pregnancy by human to human transmission vertical transmission) Case Classification Congenital Rubella A. Possible case NA B. Probable case Any stillborn or infant either not tested OR with negative laboratory results with at least one of the following two: An epidemiological link AND at least one of the conditions listed in the category A CRS clinical criteria Meeting the clinical criteria for CRS C. Confirmed case Any stillborn meeting the laboratory criteria OR Any infant meeting the laboratory criteria AND at least one of the following two: An epidemiological link At least one of the conditions listed in the category A CRS clinical criteria 3.38. SALMONELLA ENTERITIS Clinical Criteria Any person with at least one of the following four: Diarrhoea Fever Abdominal pain Vomiting Laboratory Criteria At least one of the following two: Isolation of Salmonella (other than S. Typhi or S. Paratyphi) in a clinical specimen Detection of nucleic acid from Salmonella (other than S. Typhi or S. Paratyphi) in a clinical specimen Note: Antimicrobial susceptibility testing of Salmonella enterica should be performed on a representative subset of isolates Epidemiological Criteria At least one of the following five epidemiological links: Human to human transmission Exposure to a common source Animal to human transmission Exposure to contaminated food/drinking water Environmental exposure Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. Antimicrobial resistance The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified in the EU protocol for harmonised monitoring of antimicrobial resistance in human Salmonella and Campylobacter isolates The EU protocols, including future updates, can be found at the following ECDC webpage: https://ecdc.europa.eu/en/publications-data/eu-protocol-harmonised-monitoring-antimicrobial-resistance-human-salmonella-and-0

. 3.39. SEVERE ACUTE RESPIRATORY SYNDROME (SARS) Clinical Criteria Any person with fever or a history of fever AND At least one of the following three: Cough Difficulty in breathing Shortness of breath AND At least one of the following four: Radiographic evidence of pneumonia Radiographic evidence of acute respiratory distress syndrome Autopsy findings of pneumonia Autopsy findings of acute respiratory distress syndrome AND No alternative diagnosis which can fully explain the illness Laboratory Criteria Laboratory criteria for case confirmation At least one of the following three: Isolation of virus in cell culture from any clinical specimen and identification of SARS-CoV using method such as RT-PCR Detection SARS-CoV nucleic acid in at least one of the following three: At least two different clinical specimens (for example, nasopharyngeal swab and stool) The same clinical specimen collected on two or more occasions during the course of the illness (for example, sequential nasopharyngeal aspirates) Two different assays or repeat RT-PCR using a new RNA extract from the original clinical sample on each occasion of testing SARS-CoV specific antibody response by one of the following two: Seroconversion by ELISA or IFA in acute and convalescent phase serum tested in parallel Four-fold or greater rise in antibody titre between acute and convalescent phase sera tested in parallel Laboratory criteria for a probable case At least one of the following two: A single positive antibody test for SARS-CoV A positive PCR result for SARS-CoV on a single clinical specimen and assay Epidemiological Criteria At least one of the following three: Any person with at least one of the following three: Employed in an occupation associated with an increased risk of SARS-CoV exposure (for example, staff in a laboratory working with live SARS-CoV/SARS-CoV-like viruses or storing clinical specimens infected with SARS-CoV; persons with exposure to wildlife or other animals considered a reservoir of SARS-CoV, their excretions or secretions, etc.) Close contact A close contact is a person who has cared for, lived with, or having had direct contact with the respiratory secretions, body fluids and/or excretions (e.g. faeces) of cases of SARS. of one or more persons with confirmed SARS or under investigation for SARS History of travel to, or residence in, an area experiencing an outbreak of SARS Two or more health-care workers In this context the term health-care worker includes all hospital staff. The definition of the health care unit in which the cluster occurs will depend on the local situation. Unit size may range from an entire health care facility if small, to a single department or ward of a large tertiary hospital. with clinical evidence of SARS in the same health-care unit with onset of illness in the same 10-day period Three or more persons (health-care workers and/or patients and/or visitors) with clinical evidence of SARS with onset of illness in the same 10-day period and epidemiologically linked to a healthcare facility

Case Classification for the inter-epidemic period Also applies during an outbreak in a non-affected country or area A. Possible case Any person meeting the clinical criteria with an epidemiological link B. Probable case Any person meeting the clinical criteria with an epidemiological link and meeting the laboratory criteria for a probable case C. Nationally confirmed case Any person meeting the clinical and the laboratory criteria for case confirmation where the testing has been performed at a national reference laboratory D. Confirmed case Any person meeting the clinical and the laboratory criteria for case confirmation where the testing has been performed at a WHO SARS verification and reference laboratory Case Classification during an outbreak Applies during an outbreak in a country/area where at least one person has been laboratory confirmed by a WHO SARS verification and reference laboratory A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria with an epidemiological link to a nationally confirmed or a confirmed case C. Nationally confirmed case Any person meeting the clinical and the laboratory criteria for case confirmation where the testing has been performed at a national reference laboratory D. Confirmed case One of the following three: Any person meeting the clinical and the laboratory criteria for case confirmation where the testing has been performed at a WHO SARS verification and reference laboratory Any nationally confirmed case with an epidemiological link to a chain of transmission where at least one case has been independently verified by a WHO SARS Reference and Verification Laboratory Any person meeting the clinical criteria and with laboratory criteria for probable case with an epidemiological link to a chain of transmission where at least one case has been independently verified by a WHO SARS Reference and Verification Laboratory 3.40. SHIGA TOXIN/VEROCYTOTOXIN-PRODUCING E. COLI INFECTION (STEC/VTEC), INCLUDING HAEMOLYTIC-URAEMIC SYNDROME (HUS) Clinical Criteria STEC/VTEC diarrhoea Any person with at least one of the following two: Diarrhoea Abdominal pain HUS Any person with acute renal failure and at least one of the following two: Microangiopatic haemolytic anaemia Thrombocytopenia Laboratory Criteria At least one of the following four: Isolation/cultivation of Escherichia coli that produces Shiga toxin/verocytotoxin or harbours stx1/vtx1 or stx2/vtx2 gene(s) Isolation of non-sorbitol-fermenting (NSF) Escherichia coli O157 (without testing for the toxin or toxin-producing genes) Direct detection of stx1/vtx1 or stx2/vtx2 gene(s) nucleic acid Direct detection of free Shiga toxin/verocytotoxin in faeces Only for HUS the following can be used as a laboratory criterion to confirm STEC/VTEC: Escherichia coli serogroup-specific (LPS) antibody response Epidemiological Criteria At least one of the following five epidemiological links: Human to human transmission Exposure to a common source

Animal to human transmission Exposure to contaminated food/drinking water Environmental exposure Case Classification A. Possible case of STEC-associated HUS Any person meeting the clinical criteria for HUS B. Probable case of STEC/VTEC Any person meeting the clinical criteria with an epidemiological link C. Confirmed case of STEC/VTEC Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.41. SHIGELLOSIS Clinical Criteria Any person with at least one of the following four: Diarrhoea Fever Vomiting Abdominal pain Laboratory Criteria For a confirmed case: Isolation of Shigella spp. from a clinical specimen For a probable case: Detection of Shigella spp. nucleic acid in a clinical specimen Note: Antimicrobial susceptibility testing of Shigella should be performed, if possible Epidemiological Criteria At least one of the following four epidemiological links: Human to human transmission Exposure to a common source Exposure to contaminated food/drinking water Environmental exposure Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link OR Any person meeting the clinical criteria and laboratory criteria for a probable case C. Confirmed case Any person meeting the clinical and the laboratory criteria for a confirmed case Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. Antimicrobial resistance The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States. 3.42. SMALLPOX Clinical Criteria Any person with at least one of the following two: Fever AND Vesicles or firm pustules rash at the same stage of development with a centrifugal distribution Atypical presentations defined as at least one of the following four: Haemorrhagic lesions Flat velvety lesions not progressing to vesicles Variola sine eruptione Milder type Laboratory Criteria Laboratory criteria for case confirmation At least one of the following two laboratory tests: Isolation of smallpox (Variola virus) from a clinical specimen followed by sequencing (designated P4 laboratories only) Detection of Variola virus nucleic acid in a clinical specimen followed by sequencing Laboratory results need to be interpreted according to the vaccination status Laboratory criteria for a probable case Identification of orthopox virus particles by EM Epidemiological Criteria At least one of the following two epidemiological links: Human to human transmission Laboratory exposure (where there is a potential exposure to Variola virus) Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria and with at least one of the following two:

An epidemiological link to a confirmed human case by human to human transmission Meeting the laboratory criteria for a probable case C. Confirmed case Any person meeting the laboratory criteria for case confirmation During an outbreak: any person meeting the clinical criteria with an epidemiological link 3.43. SYPHILIS Clinical Criteria Primary syphilis Any person with one or several (usually painless) chancres in the genital, perineal, anal area or mouth or pharyngeal mucosa or elsewhere extragenitally Secondary syphilis Any person with at least one of the following five: Diffuse maculo-papular rash often involving palms and soles Generalized lymphadenopathy Condyloma lata Enanthema Diffuse alopecia Early latent syphilis (< 1 year) No symptoms and a history of symptoms compatible with those of the earlier stages of syphilis within the previous 12 months Note that ocular and neurological manifestations may occur at any stage of syphilis. Note that cases of late latent syphilis (> 1 year) are not under EU/EEA surveillance. Laboratory Criteria At least one of the following: Demonstration of Treponema pallidum in lesion exudates or tissues by dark-field microscopic examination Demonstration of Treponema pallidum in lesion exudates or tissues by DFA test Demonstration of Treponema in lesion exudates or tissues by nuclear acid amplification techniques (NAAT) Detection of Treponema pallidum antibodies by screening test (TPHA, TPPA or EIA) AND additionally detection of either TP-IgM antibodies (for example, IgM-ELISA or immunoblot or 19S-IgM-FTA-abs) OR non-TP antibodies (for example, RPR, VDRL). Epidemiological Criteria Primary/secondary syphilis An epidemiological link by human to human (sexual contact) Early latent syphilis An epidemiological link by human to human (sexual contact) within the 12 previous months Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the laboratory criteria for case confirmation 3.44. CONGENITAL SYPHILIS Clinical Criteria Any infant < 2 years of age with at least one of the following ten: Hepatospenomegaly Mucocutaneous lesions Condyloma lata Persistent rhinitis Jaundice Pseudoparalysis (due to periostitis and osteochondritis) Central nervous involvement Anaemia Nephrotic syndrome Malnutrition Laboratory Criteria Laboratory criteria for case confirmation At least one of the following three: Demonstration of Treponema pallidum by dark field microscopy in the umbilical cord, the placenta, a nasal discharge or skin lesion material Demonstration of Treponema pallidum by DFA-TP in the umbilical cord, the placenta, a nasal discharge or skin lesion material Detection of Treponema pallidum-specific IgM (FTA-abs, EIA) AND a reactive non-treponemal test (VDRL, RPR) in the child's serum Laboratory criteria for a probable case At least one of the following three: Reactive VDRL-CSF test result Reactive non-treponemal and treponemal serologic tests in the mother's serum

Infant's non-treponemal antibody titre is four-fold or greater than the antibody titre in the mother's serum Epidemiological Criteria Any infant with an epidemiological link by human to human transmission (vertical transmission) Case Classification A. Possible case NA B. Probable case Any infant or child meeting the clinical criteria and with at least one of the following two: An epidemiological link Meeting the laboratory criteria for a probable case C. Confirmed case Any infant meeting the laboratory criteria for case confirmation 3.45. TETANUS Clinical Criteria Any person with acute onset of at least two of the following three: Painful muscular contractions primarily of the masseter and neck muscles leading to facial spasms known as trismus and risus sardonicus Painful muscular contractions of trunk muscles Generalized spasms, frequently position of opisthotonus Laboratory Criteria NA Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria in the absense of a more likely diagnosis C. Confirmed case NA 3.46. TICK-BORNE VIRAL ENCEPHALITIS Clinical Criteria Any person with symptoms of inflammation of the CNS (for example, meningitis, meningo-encephalitis, encephalomyelitis, encephaloradiculitis) Laboratory Criteria Serological results should be interpreted according to the vaccination status and previous exposure to other flaviviral infections. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. Laboratory criteria for case confirmation: At least one of the following five: TBE specific IgM AND IgG antibodies in blood TBE specific IgM antibodies in CSF Seroconversion or four-fold increase of TBE-specific antibodies in paired serum samples Detection of TBE viral nucleic acid in a clinical specimen, Isolation of TBE virus from clinical specimen Laboratory criteria for a probable case: Detection of TBE-specific IgM-antibodies in a unique serum sample Epidemiological Criteria Exposure to a common source (unpasteurised dairy products) Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria and the laboratory criteria for a probable case, OR Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and laboratory criteria for case confirmation Note: Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. 3.47. CONGENITAL TOXOPLASMOSIS Clinical Criteria Not relevant for surveillance purposes Laboratory Criteria At least one of the following four: Demonstration of Toxoplasma gondii in body tissues or fluids Detection of Toxoplasma gondii nucleic acid in a clinical specimen Toxoplasma gondii specific antibody response (IgM, IgG, IgA) in a newborn

Persistently stable IgG Toxoplasma gondii titres in an infant (< 12 months of age) Epidemiological Criteria NA Case Classification A. Possible case NA B. Probable case NA C. Confirmed case Any infant meeting the laboratory criteria 3.48. TRICHINELLOSIS Clinical Criteria Any person with at least three of the following six: Fever Muscle soreness and pain Diarrhoea Facial oedema Eosinophilia Subconjunctival, subungual and retinal haemorrhages Laboratory Criteria At least one of the following two: Demonstration of Trichinella larvae in tissue obtained by muscle biopsy Trichinella specific antibody response (IFA test, ELISA or Western Blot) Epidemiological Criteria At least one of the following two epidemiological links: Exposure to contaminated food (meat) Exposure to a common source Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical criteria and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.49. TUBERCULOSIS Clinical Criteria Any person with the following two: Signs, symptoms and/or radiological findings consistent with active tuberculosis in any site AND A clinician's decision to treat the person with a full course of anti-tuberculosis therapy OR A case discovered post-mortem with pathological findings consistent with active tuberculosis that would have indicated anti-tuberculosis antibiotic treatment had the patient been diagnosed before dying Laboratory Criteria Laboratory criteria for case confirmation At least one of the following two: Isolation of Mycobacterium tuberculosis complex (excluding Mycobacterium bovis-BCG) from a clinical specimen Detection of Mycobacterium tuberculosis complex nucleic acid in a clinical specimen AND positive microscopy for acid-fast bacilli or equivalent fluorescent staining bacilli on light microscopy Laboratory criteria for a probable case At least one of the following three: Microscopy for acid-fast bacilli or equivalent fluorescent staining bacilli on light microscopy Detection of Mycobacterium tuberculosis complex nucleic acid in a clinical specimen Histological appearance of granulomata Epidemiological Criteria NA Case Classification A. Possible case Any person meeting the clinical criteria B. Probable case Any person meeting the clinical criteria and the laboratory criteria for a probable case C. Confirmed case Any person meeting the clinical and the laboratory criteria for case confirmation Antimicrobial resistance The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified by the European Reference Laboratory Network for Tuberculosis and the European Tuberculosis Surveillance Network The criteria for reporting are included each year in the European Centre for Disease Prevention and Control/WHO Regional Office for Europe report on Tuberculosis surveillance and monitoring in Europe. www.ecdc.europa.eu.

. 3.50. TULARAEMIA Clinical Criteria Any person with at least one of the following clinical forms: Ulceroglandular tularaemia Cutaneous ulcer AND Regional lymphadenopathy Glandular tularaemia Enlarged and painful lymph nodes without apparent ulcer Oculoglandular tularaemia Conjunctivitis AND Regional lymphadenopathy Oropharyngeal tularaemia Cervical lymphadenopathy AND at least one of the following three: Stomatitis Pharyngitis Tonsillitis Intestinal tularaemia At least one of the following three: Abdominal pain Vomiting Diarrhoea Pneumonic tularaemia Pneumonia Typhoidal tularaemia At least one of the following two: Fever without early localising signs and symptoms Septicaemia Laboratory Criteria At least one of the following three: Isolation of Francisella tularensis from a clinical specimen Detection of Francisella tularensis nucleic acid in a clinical specimen Francisella tularensis specific antibody response Epidemiological Criteria At least one of the following three epidemiological links: Exposure to a common source Animal to human transmission Exposure to contaminated food/drinking water Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.51. TYPHOID AND PARATYPHOID FEVERS Clinical Criteria Any person with at least one of the following two: Onset of sustained fever OR At least two of the following four: Headache Relative bradycardia Non-productive cough Diarrhoea, constipation, malaise or abdominal pain Laboratory Criteria At least one of the following two: Isolation of Salmonella Typhi or Paratyphi from a clinical specimen Detection of Salmonella Typhi or Paratyphi nucleic acid in a clinical specimen Epidemiological Criteria At least one of the following three epidemiological links: Exposure to a common source Human to human transmission Exposure to contaminated food/drinking water Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.52. VIRAL HAEMORRHAGIC FEVERS (VHF) Clinical Criteria Any person with at least one of the following two: Fever Haemorrhagic manifestations in various forms that may lead to multi-organ failure Laboratory Criteria At least one of the following two: Isolation of specific virus from a clinical specimen Detection of specific virus nucleic acid in a clinical specimen and genotyping Epidemiological Criteria At least one of the following: Travel in the last 21 days to a region where VHF cases are known or believed to have occurred Exposure within the last 21 days to a probable or confirmed case of a VHF whose onset of illness was within the last 6 months Case Classification

A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria 3.53. WEST NILE VIRUS INFECTION (WNV) Clinical Criteria At least one of the following three: Any person with fever Encephalitis Meningitis Laboratory Criteria Laboratory test for case confirmation At least one of the following four: Isolation of WNV from blood or CSF Detection of WNV nucleic acid in blood or CSF WNV specific antibody response (IgM) in CSF WNV IgM high titre AND detection of WNV IgG, AND confirmation by neutralisation Laboratory test for a probable case WNV specific antibody response in serum Laboratory results need to be interpreted according to flavivirus vaccination status Epidemiological Criteria At least one of the following two epidemiological links: Animal to human transmission (residing, having visited or having been exposed to mosquito bites in an area where WNV is endemic in horses or birds) Human to human transmission (vertical transmission, blood transfusion, transplants) Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria AND with at least one of the following two: an epidemiological link a laboratory test for a probable case C. Confirmed case Any person meeting the laboratory criteria for case confirmation Note: Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. 3.54. YELLOW FEVER Clinical Criteria Any person with fever AND At least one of the following two: Jaundice Generalised haemorrhage Laboratory Criteria At least one of the following five: Isolation of yellow fever virus from a clinical specimen Detection of yellow fever virus nucleic acid Detection of yellow fever antigen Yellow fever specific antibody response Demonstration of typical lesions in post mortem liver histopathology Epidemiological Criteria Travel in the last 1 week to a region where yellow fever cases are known or believed to have occurred Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person not recently vaccinated meeting the clinical and the laboratory criteria In case of recent vaccination, a person with detection of wild-type yellow fever virus strain Note: Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. 3.55. ENTERITIS DUE TO YERSINIA ENTEROCOLITICA OR YERSINIA PSEUDOTUBERCULOSIS Clinical Criteria Any person with at least one of the following five: Fever Diarrhoea Vomiting Abdominal pain (pseudoappendicitis) Rectal tenesmus

Laboratory Criteria At least one of the following two: Isolation of human pathogenic Yersinia enterocolitica or Yersinia pseudotuberculosis from a clinical specimen Detection of Y. enterocolitica or Y. pseudotuberculosis virulence genes in a clinical specimen Epidemiological Criteria At least one of the following four epidemiological links: Human to human transmission Exposure to a common source Animal to human transmission Exposure to contaminated food Case Classification A. Possible case NA B. Probable case Any person meeting the clinical criteria with an epidemiological link C. Confirmed case Any person meeting the clinical and the laboratory criteria Note: If the national surveillance system is not capturing clinical symptoms, all laboratory-confirmed individuals should be reported as confirmed cases. 3.56. ZIKA VIRUS DISEASE Clinical Criteria A person presenting with a rash Laboratory Criteria A. Confirmed case At least one of the following: Detection of Zika virus nucleic acid in a clinical specimen; Detection of Zika virus antigen in a clinical specimen; Isolation of Zika virus from a clinical specimen; Detection of Zika virus specific IgM antibodies in serum sample(s) AND confirmation by neutralization test; Seroconversion or four-fold increase in the titre of Zika specific antibodies in paired serum samples. B. Probable case Detection of Zika specific IgM antibodies in a serum sample. Epidemiological Criteria History of travel to, or residence in an area with documented on-going transmission of Zika virus, within the two-week period prior to the onset of symptoms OR Sexual contact with a person recently exposed to or confirmed with Zika virus infection Case Classification A. Possible case NA B. Probable case A person meeting the clinical and the epidemiological criteria, and the laboratory criteria for a probable case. C. Confirmed case A person meeting the laboratory criteria for a confirmed case. Note: Serological results should be interpreted according to previous exposure to other flaviviral infections and the flavivirus vaccination status. Confirmed cases in such situations should be validated by serum neutralization assay or other equivalent assays. 3.57. CONGENITAL ZIKA VIRUS DISEASE Clinical Criteria An infant or foetus with microcephaly or intracranial calcifications or other central nervous system abnormalities. Laboratory Criteria A. Confirmed case Detection of Zika virus nucleic acid in a clinical specimen; Detection of Zika virus antigen in a clinical specimen; Isolation of Zika virus from a clinical specimen; Detection of Zika specific IgM antibodies in serum, cerebrospinal fluid (CSF) or amniotic fluid. Epidemiological Criteria Mother having had confirmed Zika virus infection during pregnancy. Case Classification A. Probable case An infant or foetus that meets the clinical criteria with an epidemiological link. B. Confirmed case An infant or foetus that meets the clinical criteria and the laboratory criteria. 4. CASE DEFINITIONS OF SPECIAL HEALTH ISSUES

4.1. GENERAL CASE DEFINITION OF NOSOCOMIAL INFECTION (OR HEALTHCARE-ASSOCIATED INFECTION (HAI)) A nosocomial infection associated to the current hospital stay is defined as infection that matches one of the case definitions AND the onset of symptoms was on day 3 or later (day of admission = day 1) of the current hospital admission OR the patient underwent surgery on day 1 or day 2 and develops symptoms of a Surgical Site Infection before day 3 OR an invasive device was placed on day 1 or day 2 resulting in an HAI before day 3 A nosocomial infection associated to a previous hospital stay is defined as an infection that matches one of the case definitions AND the patient presents with an infection but has been readmitted less than 48 hours after a previous admission to an acute care hospital OR the patient has been admitted with an infection that meets the case definition of a Surgical Site Infection i.e. the SSI occurred within 30 days of the operation (or in the case of surgery involving an implant was a deep or organ/space SSI that developed within 90 days of the operation) and the patient either has symptoms that meet the case definition and/or is on antimicrobial treatment for that infection OR the patient has been admitted (or develops symptoms within 2 days) with Clostridium difficile infection less than 28 days from a previous discharge from an acute care hospital. Note: For the purpose of point prevalence surveys, an active nosocomial infection present on the day of the survey is defined as an infection for which signs and symptoms of the infection are present on the survey date or signs and symptoms were present in the past and the patient is (still) receiving treatment for that infection on the survey date. The presence of symptoms and signs should be verified until the start of the treatment in order to determine whether the treated infection matches one of the case definitions of nosocomial infection 4.1.1. BJ: Bone and joint infection BJ-BONE: Osteomyelitis Osteomyelitis must meet at least one of the following criteria: Patient has organisms cultured from bone Patient has evidence of osteomyelitis on direct examination of the bone during a surgical operation or histopathologic examination Patient has at least 2 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), localized swelling, tenderness, heat, or drainage at suspected site of bone infection AND at least 1 of the following: organisms cultured from blood positive blood antigen test (for example, Haemophilus influenzae, Streptococcus pneumoniae) radiographic evidence of infection (for example, abnormal findings on X-ray, CT scan, MRI, radiolabel scan (gallium, technetium, etc.)). Note reporting instruction Report mediastinitis following cardiac surgery that is accompanied by osteomyelitis as surgical site infection-organ/space (SSI-O). BJ-JNT: Joint or bursa Joint or bursa infections must meet at least one of the following criteria: Patient has organisms cultured from joint fluid or synovial biopsy

Patient has evidence of joint or bursa infection seen during a surgical operation or histopathologic examination Patient has at least two of the following signs or symptoms with no other recognized cause: joint pain, swelling, tenderness, heat, evidence of effusion or limitation of motion AND at least one of the following: organisms and white blood cells seen on Gram's stain of joint fluid positive antigen test on blood, urine, or joint fluid cellular profile and chemistries of joint fluid compatible with infection and not explained by an underlying rheumatologic disorder radiographic evidence of infection (for example, abnormal findings on X-ray, CT scan, MRI, radiolabel scan (gallium, technetium, etc.)) BJ-DISC: Disc space infection Vertebral disc space infection must meet at least one of the following criteria: Patient has organisms cultured from vertebral disc space tissue obtained during a surgical operation or needle aspiration Patient has evidence of vertebral disc space infection seen during a surgical operation or histopathologic examination Patient has fever (> 38 °C) with no other recognized cause or pain at the involved vertebral disc space AND radiographic evidence of infection (for example, abnormal findings on X-ray, CT scan, MRI, radiolabel scan (gallium, technetium, etc.)). Patient has fever (> 38 °C) with no other recognized cause and pain at the involved vertebral disc space AND positive antigen test on blood or urine (for example, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, or Group B Streptococcus). 4.1.2. BSI: Bloodstream infection BSI: Laboratory-confirmed bloodstream infection One positive blood culture for a recognised pathogen OR Patient has at least one of the following signs or symptoms: fever (> 38 °C), chills, or hypotension AND Two positive blood cultures for a common skin contaminant (from 2 separate blood samples, usually within 48 hours) Skin contaminants = coagulase-negative staphylococci, Micrococcus spp., Propionibacterium acnes, Bacillus spp., Corynebacterium spp. Source of bloodstream infection: Catheter-related: the same micro-organism was cultured from the catheter or symptoms improve within 48 hours after removal of the catheter (C-PVC: peripheral catheter, C-CVC: central venous catheter (Note: report C-CVC or C-PVC BSI as CRI3-CVC or CRI3-PVC respectively if microbiologically confirmed, see CRI3 definition)). Secondary to another infection: the same micro-organism was isolated from another infection site or strong clinical evidence exists that bloodstream infection was secondary to another infection site, invasive diagnostic procedure or foreign body Pulmonary (S-PUL) Urinary tract infection (S-UTI) Digestive tract infection (S-DIG) SSI (S-SSI): surgical site infection Skin and soft tissue (S-SST) Other (S-OTH) Unknown origin (UO): None of the above, bloodstream infection of unknown origin (verified during survey and no source found) Unknown (UNK): No information available about the source of the bloodstream infection or information missing

4.1.3. CNS: Central nervous system infection CNS-IC: Intracranial infection (brain abscess, subdural or epidural infection, encephalitis) Intracranial infection must meet at least one of the following criteria: Patient has organisms cultured from brain tissue or dura Patient has an abscess or evidence of intracranial infection seen during a surgical operation or histopathologic examination Patient has at least 2 of the following signs or symptoms with no other recognized cause: headache, dizziness, fever (> 38 °C), localizing neurologic signs, changing level of consciousness, or confusion AND at least 1 of the following: organisms seen on microscopic examination of brain or abscess tissue obtained by needle aspiration or by biopsy during a surgical operation or autopsy positive antigen test on blood or urine radiographic evidence of infection (for example, abnormal findings on ultrasound, CT scan, MRI, radionuclide brain scan, or arteriogram) diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy. Note reporting instruction If meningitis and a brain abscess are present together, report the infection as IC CNS-MEN: Meningitis or ventriculitis Meningitis or ventriculitis must meet at least one of the following criteria: Patient has organisms cultured from cerebrospinal fluid (CSF) Patient has at least 1 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), headache, stiff neck, meningeal signs, cranial nerve signs, or irritability AND at least one of the following: increased white cells, elevated protein, and/or decreased glucose in CSF organisms seen on Gram's stain of CSF organisms cultured from blood positive antigen test of CSF, blood, or urine diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy. Note reporting instructions Report CSF shunt infection as SSI if it occurs <=90 days of placement; if > 90 days or after manipulation/access of the shunt, report as CNS-MEN if the infection meets the general case definition of HAI Report meningoencephalitis as MEN Report spinal abscess with meningitis as MEN CNS-SA: Spinal abscess without meningitis An abscess of the spinal epidural or subdural space, without involvement of the cerebrospinal fluid or adjacent bone structures, must meet at least one of the following criteria: Patient has organisms cultured from abscess in the spinal epidural or subdural space Patient has an abscess in the spinal epidural or subdural space seen during a surgical operation or at autopsy or evidence of an abscess seen during a histopathologic examination Patient has at least 1 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), back pain, focal tenderness, radiculitis, paraparesis, or paraplegia AND at least 1 of the following:

organisms cultured from blood radiographic evidence of a spinal abscess (for example, abnormal findings on myelography, ultrasound, CT scan, MRI, or other scans (gallium, technetium, etc.)) AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy Note reporting instruction Report spinal abscess with meningitis as meningitis (CNS-MEN) 4.1.4. CRI: Catheter-related infection CVC = central vascular catheter, PVC = peripheral vascular catheter. Central vascular catheter colonisation should not be reported. A CRI3 (-CVC or -PVC) is also a bloodstream infection with source C-CVC or C-PVC respectively; however when a CRI3 is reported, the BSI should not be reported in the point prevalence survey; microbiologically confirmed catheter-related BSI should be reported as CRI3 CRI1-CVC: Local CVC-related infection (no positive blood culture) quantitative CVC culture ≥ 103 CFU/ml or semi-quantitative CVC culture > 15 CFU AND pus/inflammation at the insertion site or tunnel CRI1-PVC: Local PVC-related infection (no positive blood culture) quantitative PVC culture ≥ 103 CFU/ml or semi-quantitative PVC culture > 15 CFU AND pus/inflammation at the insertion site or tunnel CRI2-CVC: General CVC-related infection (no positive blood culture) quantitative CVC culture ≥ 103 CFU/ml or semi-quantitative CVC culture > 15 CFU AND clinical signs improve within 48 hours after catheter removal CRI2-PVC: General PVC-related infection (no positive blood culture) quantitative PVC culture ≥ 103 CFU/ml or semi-quantitative PVC culture > 15 CFU AND clinical signs improve within 48 hours after catheter removal CRI3-CVC: microbiologically confirmed CVC-related bloodstream infection BSI occurring 48 hours before or after catheter removal (if any) AND positive culture with the same micro-organism of either: quantitative CVC culture ≥ 103 CFU/ml or semi-quantitative CVC culture > 15 CFU quantitative blood culture ratio CVC blood sample/peripheral blood sample > 5 differential delay of positive blood cultures: CVC blood sample culture positive 2 hours or more before peripheral blood culture (blood samples drawn at the same time) positive culture with the same micro-organism from pus from insertion site CRI3-PVC: microbiologically confirmed PVC-related bloodstream infection BSI occurring 48 hours before or after catheter removal (if any) AND positive culture with the same micro-organism of either: quantitative PVC culture ≥ 103 CFU/ml or semi-quantitative PVC culture > 15 CFU positive culture with the same micro-organism from pus from insertion site 4.1.5. CVS: Cardiovascular system infection CVS-VASC: Arterial or venous infection Arterial or venous infection must meet at least one of the following criteria: Patient has organisms cultured from arteries or veins removed during a surgical operation AND blood culture not done or no organisms cultured from blood Patient has evidence of arterial or venous infection seen during a surgical operation or histopathologic examination

Patient has at least 1 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), pain, erythema, or heat at involved vascular site AND more than 15 colonies cultured from intravascular cannula tip using semiquantitative culture method AND blood culture not done or no organisms cultured from blood Patient has purulent drainage at involved vascular site AND blood culture not done or no organisms cultured from blood Note reporting instructions Report infections of an arteriovenous graft, shunt, or fistula or intravascular cannulation site without organisms cultured from blood as CVS-VASC. Report CVS-VASC matching the third criterion as CRI1 or CRI2, as appropriate. CVS-ENDO: Endocarditis Endocarditis of a natural or prosthetic heart valve must meet at least one of the following criteria: Patient has organisms cultured from valve or vegetation Patient has two or more of the following signs or symptoms with no other recognized cause: fever (> 38 °C), new or changing murmur, embolic phenomena, skin manifestations (for example, petechiae, splinter hemorrhages, painful subcutaneous nodules), congestive heart failure, or cardiac conduction abnormality AND at least one of the following: organisms cultured from two or more blood cultures organisms seen on Gram's stain of valve when culture is negative or not done valvular vegetation seen during a surgical operation or autopsy positive antigen test on blood or urine (for example, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, or Group B Streptococcus) evidence of new vegetation seen on echocardiogram AND if diagnosis is made antemortem, physician institutes appropriate antimicrobial therapy CVS-CARD: Myocarditis or pericarditis Myocarditis or pericarditis must meet at least one of the following criteria: Patient has organisms cultured from pericardial tissue or fluid obtained by needle aspiration or during a surgical operation Patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C), chest pain, paradoxical pulse, or increased heart size AND at least one of the following: abnormal EKG consistent with myocarditis or pericarditis positive antigen test on blood (for example, Haemophilus influenzae, Streptococcus pneumoniae) evidence of myocarditis or pericarditis on histologic examination of heart tissue 4-fold rise in type-specific antibody with or without isolation of virus from pharynx or feces pericardial effusion identified by echocardiogram, CT scan, MRI, or angiography CVS-MED: Mediastinitis Mediastinitis must meet at least one of the following criteria: Patient has organisms cultured from mediastinal tissue or fluid obtained during a surgical operation or needle aspiration Patient has evidence of mediastinitis seen during a surgical operation or histopathologic examination Patient has at least one of the following signs or symptoms with no other recognized cause: fever (> 38 °C), chest pain, or sternal instability

AND at least 1 of the following: purulent discharge from mediastinal area organisms cultured from blood or discharge from mediastinal area mediastinal widening on X-ray Note reporting instruction Report mediastinitis following cardiac surgery that is accompanied by osteomyelitis as SSI-O 4.1.6. EENT: Eye, ear, nose, throat, or mouth infection EENT-CONJ: Conjunctivitis Conjunctivitis must meet at least one of the following criteria: Patient has pathogens cultured from purulent exudate obtained from the conjunctiva or contiguous tissues, such as eyelid, cornea, meibomian glands, or lacrimal glands Patient has pain or redness of conjunctiva or around eye AND at least 1 of the following: WBCs and organisms seen on Gram's stain of exudates purulent exudates positive antigen test (for example, ELISA or IF for Chlamydia trachomatis, herpes simplex virus, adenovirus) on exudate or conjunctival scraping multinucleated giant cells seen on microscopic examination of conjunctival exudate or scrapings positive viral culture diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen Note reporting instructions Report other infections of the eye as EYE Do not report chemical conjunctivitis caused by silver nitrate (AgNO3) as a health care-associated infection Do not report conjunctivitis that occurs as a part of a more widely disseminated viral illness (such as measles, chickenpox, or a URI) EENT-EYE: Eye, other than conjunctivitis An infection of the eye, other than conjunctivitis, must meet at least one of the following criteria: Patient has organisms cultured from anterior or posterior chamber or vitreous fluid Patient has at least 2 of the following signs or symptoms with no other recognized cause: eye pain, visual disturbance, or hypopyon AND at least 1 of the following: physician diagnosis of an eye infection positive antigen test on blood (for example, Haemophilus influenzae, Streptococcus pneumoniae) organisms cultured from blood EENT-EAR: Ear mastoid Ear and mastoid infections must meet at least one of the following criteria: Otitis externa must meet at least one of the following criteria: Patient has pathogens cultured from purulent drainage from ear canal Patient has at least one of the following signs or symptoms with no other recognized cause: fever (> 38 °C), pain, redness, or drainage from ear canal and organisms seen on Gram's stain of purulent drainage Otitis media must meet at least one of the following criteria: Patient has organisms cultured from fluid from middle ear obtained by tympanocentesis or at surgical operation Patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C), pain in the eardrum, inflammation, retraction or decreased mobility of eardrum, or fluid behind eardrum Otitis interna must meet at least one of the following criteria: Patient has organisms cultured from fluid from inner ear obtained at surgical operation Patient has a physician diagnosis of inner ear infection

Mastoiditis must meet at least one of the following criteria: Patient has organisms cultured from purulent drainage from mastoid Patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C), pain, tenderness, erythema, headache, or facial paralysis AND at least 1 of the following: organisms seen on Gram's stain of purulent material from mastoid positive antigen test on blood EENT-ORAL: Oral cavity (mouth, tongue, or gums) Oral cavity infections must meet at least one of the following criteria: Patient has organisms cultured from purulent material from tissues of oral cavity Patient has an abscess or other evidence of oral cavity infection seen on direct examination, during a surgical operation, or during a histopathologic examination Patient has at least 1 of the following signs or symptoms with no other recognized cause: abscess, ulceration, or raised white patches on inflamed mucosa, or plaques on oral mucosa AND at least one of the following: organisms seen on Gram's stain positive KOH (potassium hydroxide) stain multinucleated giant cells seen on microscopic examination of mucosal scrapings positive antigen test on oral secretions diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen physician diagnosis of infection and treatment with topical or oral antifungal therapy Note reporting instruction Report health care-associated primary herpes simplex infections of the oral cavity as ORAL; recurrent herpes infections are not healthcare-associated EENT-SINU: Sinusitis Sinusitis must meet at least 1 of the following criteria: Patient has organisms cultured from purulent material obtained from sinus cavity Patient has at least 1 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), pain or tenderness over the involved sinus, headache, purulent exudate, or nasal obstruction AND at least 1 of the following: positive transillumination positive radiographic examination (including CT scan) EENT-UR: Upper respiratory tract, pharyngitis, laryngitis, epiglottitis Upper respiratory tract infections must meet at least 1 of the following criteria: Patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C), erythema of pharynx, sore throat, cough, hoarseness, or purulent exudate in throat AND at least 1 of the following: organisms cultured from the specific site organisms cultured from blood positive antigen test on blood or respiratory secretions diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen physician diagnosis of an upper respiratory infection Patient has an abscess seen on direct examination, during a surgical operation, or during a histopathologic examination 4.1.7. GI: Gastrointestinal system infection GI-CDI: Clostridium difficile infection A Clostridium difficile infection (previously also referred to as Clostridium difficile associated diarrhoea or CDAD) must meet at least one of the following criteria:

Diarrhoeal stools or toxic megacolon, AND a positive laboratory assay for Clostridium difficile toxin A and/or B in stools or a toxin-producing C. difficile organism detected in stool via culture or other means for example, a positive PCR result; Pseudomembranous colitis revealed by lower gastro-intestinal endoscopy Colonic histopathology characteristic of Clostridium difficile infection (with or without diarrhoea) on a specimen obtained during endoscopy, colectomy or autopsy GI-GE: Gastroenteritis (excl. CDI) Gastroenteritis must meet at least one of the following criteria: Patient has an acute onset of diarrhea (liquid stools for more than 12 hours) with or without vomiting or fever (> 38 °C) and no likely noninfectious cause (for example, diagnostic tests, therapeutic regimen other than antimicrobial agents, acute exacerbation of a chronic condition, or psychologic stress) Patient has at least 2 of the following signs or symptoms with no other recognized cause: nausea, vomiting, abdominal pain, fever (> 38 °C), or headache AND at least 1 of the following: an enteric pathogen is cultured from stool or rectal swab an enteric pathogen is detected by routine or electron microscopy an enteric pathogen is detected by antigen or antibody assay on blood or feces evidence of an enteric pathogen is detected by cytopathic changes in tissue culture (toxin assay) diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen GI-GIT: Gastrointestinal tract (esophagus, stomach, small and large bowel, and rectum) excluding gastroenteritis and appendicitis Gastrointestinal tract infections, excluding gastroenteritis and appendicitis, must meet at least 1 of the following criteria: Patient has an abscess or other evidence of infection seen during a surgical operation or histopathologic examination Patient has at least 2 of the following signs or symptoms with no other recognized cause and compatible with infection of the organ or tissue involved: fever (> 38 °C), nausea, vomiting, abdominal pain, or tenderness AND at least 1 of the following: organisms cultured from drainage or tissue obtained during a surgical operation or endoscopy or from a surgically placed drain organisms seen on Gram's or KOH stain or multinucleated giant cells seen on microscopic examination of drainage or tissue obtained during a surgical operation or endoscopy or from a surgically placed drain organisms cultured from blood evidence of pathologic findings on radiographic examination evidence of pathologic findings on endoscopic examination (for example, Candida spp. esophagitis or proctitis) GI-HEP: Hepatitis Hepatitis must meet the following criterion: Patient has at least 2 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), anorexia, nausea, vomiting, abdominal pain, jaundice, or history of transfusion within the previous 3 months AND at least 1 of the following: positive antigen or antibody test for hepatitis A, hepatitis B, hepatitis C, or delta hepatitis

abnormal liver function tests (for example, elevated ALT/AST, bilirubin) cytomegalovirus (CMV) detected in urine or oropharyngeal secretions Note reporting instructions Do not report hepatitis or jaundice of non-infectious origin (alpha-1 antitrypsin deficiency, etc.) Do not report hepatitis or jaundice that results from exposure to hepatotoxins (alcoholic or acetaminophen-induced hepatitis, etc.) Do not report hepatitis or jaundice that results from biliary obstruction (cholecystitis) GI-IAB: Intraabdominal, not specified elsewhere including gallbladder, bile ducts, liver (excluding viral hepatitis), spleen, pancreas, peritoneum, subphrenic or subdiaphragmatic space, or other intraabdominal tissue or area not specified elsewhere Intraabdominal infections must meet at least one of the following criteria: Patient has organisms cultured from purulent material from intraabdominal space obtained during a surgical operation or needle aspiration Patient has abscess or other evidence of intraabdominal infection seen during a surgical operation or histopathologic examination Patient has at leasttwo of the following signs or symptoms with no other recognized cause: fever (> 38 °C), nausea, vomiting, abdominal pain, or jaundice AND at least one of the following: organisms cultured from drainage from surgically placed drain (for example, closed suction drainage system, open drain, T-tube drain) organisms seen on Gram's stain of drainage or tissue obtained during surgical operation or needle aspiration organisms cultured from blood and radiographic evidence of infection (for example, abnormal findings on ultrasound, CT scan, MRI, or radiolabel scans (gallium, technetium, etc.) or on abdominal X-ray) Note reporting instruction Do not report pancreatitis (an inflammatory syndrome characterized by abdominal pain, nausea, and vomiting associated with high serum levels of pancreatic enzymes) unless it is determined to be infectious in origin 4.1.8. LRI: Lower respiratory tract infection, other than pneumonia LRI-BRON: Bronchitis, tracheobronchitis, bronchiolitis, tracheitis, without evidence of pneumonia Patient has no clinical or radiographic evidence of pneumonia AND patient has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C), cough, new or increased sputum production, rhonchi, wheezing AND at least one of the following: positive culture obtained by deep tracheal aspirate or bronchoscopy positive antigen test on respiratory secretions Note reporting instruction Do not report chronic bronchitis in a patient with chronic lung disease as an infection unless there is evidence of an acute secondary infection, manifested by change in organism LRI-LUNG: Other infections of the lower respiratory tract Other infections of the lower respiratory tract must meet at least one of the following criteria: Patient has organisms seen on smear or cultured from lung tissue or fluid, including pleural fluid Patient has a lung abscess or empyema seen during a surgical operation or histopathologic examination

Patient has an abscess cavity seen on radiographic examination of lung Note reporting instruction Report lung abscess or empyema without pneumonia as LUNG 4.1.9. NEO: Specific neonatal case definitions NEO-CSEP: Clinical Sepsis ALL of the three following criteria: Supervising physician started appropriate antimicrobial therapy for sepsis for at least 5 days No detection of pathogens in blood culture or not tested No obvious infection at another site AND 2 of the following criteria (without other apparent cause): Fever (> 38 °C) or temperature instability (frequent post-set of the incubator) or hypothermia (< 36,5 °C) Tachycardia (> 200/min) or new/increased bradycardia (< 80/min) Capillary refilling time (CRT) > 2s New or increased apnoea (s) (> 20s) Unexplained metabolic acidosis New-onset hyperglycemia (> 140 mg/dl) Another sign of sepsis (skin colour (only if the CRT is not used), laboratory signs (CRP, interleukin), increased oxygen requirement (intubation), unstable general condition of the patient, apathy) NEO-LCBI: Laboratory-confirmed BSI at least two of: temperature > 38 °C or < 36,5 °C or temperature instability, tachycardia or bradycardia, apnoea, extended capillary refilling time (CRT), metabolic acidosis, hyperglycaemia, other sign of BSI such as apathy AND a recognised pathogen other than coagulase-negative staphylococci cultured from blood or cerebrospinal fluid (CSF; this is included because meningitis in this age group is usually haematogenous, so positive CSF can be regarded as evidence of BSI even if blood cultures are negative or were not taken) Note reporting instructions in order to be consistent with BSI reporting in adults (including secondary BSI), the criterion the organism is not related to an infection at another site was removed from the Neo-KISS definition for the purposes of the EU PPS report the origin of the neonatal BSI in the field BSI origin if both the case definitions for NEO-LCBI and NEO-CNSB are matched, report NEO-LCBI NEO-CNSB: Laboratory-confirmed BSI with coagulase-negative staphylococci at least two of: temperature > 38 °C or < 36,5 °C or temperature instability, tachycardia or bradycardia, apnoea, extended recapillarisation time, metabolic acidosis, hyperglycaemia, other sign of BSI such as apathy AND coagulase-negative staphylococci is cultured from blood or catheter tip AND patient has one of: C-reactive protein > 2,0 mg/dL, immature/total neutrophil ratio (I/T ratio) > 0,2, leukocytes < 5/nL, platelets < 100/nL Note reporting instructions in order to be consistent with BSI reporting in adults (including secondary BSI), the criterion the organism is not related to an infection at another site was removed from the Neo-KISS definition for the purposes of the EU PPS report the origin of the neonatal BSI in the field BSI origin if both the case definitions for NEO-LCBI and NEO-CNSB are matched, report NEO-LCBI NEO-PNEU: Pneumonia respiratory compromise AND new infiltrate, consolidation or pleural effusion on chest X ray

AND at least four of: temperature > 38 °C or < 36,5 °C or temperature instability, tachycardia or bradycardia, tachypnoea or apnoea, dyspnoea, increased respiratory secretions, new onset of purulent sputum, isolation of a pathogen from respiratory secretions, C-reactive protein > 2,0 mg/dL, I/T ratio > 0,2 NEO-NEC: Necrotising enterocolitis Histopathological evidence of necrotising enterocolitis OR at least one characteristic radiographic abnormality (pneumoperitoneum, pneumatosis intestinalis, unchanging rigid loops of small bowel) plus at least two of the following without other explanation: vomiting, abdominal distention, prefeeding residuals, persistent microscopic or gross blood in stools 4.1.10. PN: Pneumonia Two or more serial chest X-rays or CT-scans with a suggestive image of pneumonia for patients with underlying cardiac or pulmonary disease. In patients without underlying cardiac or pulmonary disease one definitive chest X-ray or CT-scan is sufficient AND at least one of the following symptoms Fever > 38 °C with no other cause Leukopenia (< 4000 WBC/mm3) or leucocytosis (≥ 12000 WBC/mm3) AND at least one of the following (or at least two if clinical pneumonia only = PN 4 and PN 5) New onset of purulent sputum, or change in character of sputum (colour, odour, quantity, consistency) Cough or dyspnea or tachypnea Suggestive auscultation (rales or bronchial breath sounds), ronchi, wheezing Worsening gas exchange (for example, O2 desaturation or increased oxygen requirements or increased ventilation demand) and according to the used diagnostic method (a) Bacteriologic diagnostic performed by: Positive quantitative culture from minimally contaminated LRT LRT = Lower Respiratory Tract specimen (PN 1) Broncho-alveolar lavage (BAL) with a threshold of ≥ 104 CFU CFU = Colony Forming Units /ml or ≥ 5 % of BAL obtained cells contains intracellular bacteria on direct microscopic exam (classified on the diagnostic category BAL) Protected brush (PB Wimberley) with a threshold of ≥ 103 CFU/ml Distal protected aspirate (DPA) with a threshold of ≥ 103 CFU/ml Positive quantitative culture from possibly contaminated LRT specimen (PN 2) Quantitative culture of LRT specimen (for example, endotracheal aspirate) with a threshold of 106 CFU/ml (b) Alternative microbiology methods (PN 3) Positive blood culture not related to another source of infection Positive growth in culture of pleural fluid Pleural or pulmonary abscess with positive needle aspiration Histologic pulmonary exam shows evidence of pneumonia Positive exams for pneumonia with virus or particular germs (for example, Legionella, Aspergillus, mycobacteria, mycoplasma, Pneumocystis jirovecii): Positive detection of viral antigen or antibody from respiratory secretions (for example, EIA, FAMA, shell vial assay, PCR) Positive direct exam or positive culture from bronchial secretions or tissue Seroconversion (for example, influenza viruses, Legionella, Chlamydia) Detection of antigens in urine (Legionella)

(c) Others Positive sputum culture or non-quantitative LRT specimen culture (PN 4) No positive microbiology (PN 5) Notes: One definitive chest X-ray or CT-scan for the current pneumonia episode may be sufficient in patients with underlying cardiac or pulmonary disease if comparison with previous X-rays is possible. PN 1 and PN 2 criteria were validated without previous antimicrobial therapy. However, this does not exclude the diagnosis of PN 1 or PN 2 in case of previous antimicrobial use. Intubation-associated pneumonia (IAP) A pneumonia is defined as intubation-associated (IAP) if an invasive respiratory device was present (even intermittently) in the 48 hours preceding the onset of infection Note: Pneumonia for which intubation was started on the day of onset without additional information on the sequence of the events is not considered as IAP 4.1.11. REPR: Reproductive tract infection REPR-EMET: Endometritis Endometritis must meet at least 1 of the following criteria: Patient has organisms cultured from fluid or tissue from endometrium obtained during surgical operation, by needle aspiration, or by brush biopsy Patient has at least 2 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), abdominal pain, uterine tenderness, or purulent drainage from uterus Note reporting instruction Report postpartum endometritis as a health care-associated infection unless the amniotic fluid is infected at the time of admission or the patient was admitted 48 hours after rupture of the membrane REPR-EPIS: Episiotomy Episiotomy infections must meet at least 1 of the following criteria: Postvaginal delivery patient has purulent drainage from the episiotomy Postvaginal delivery patient has an episiotomy abscess REPR-VCUF: Vaginal cuff Vaginal cuff infections must meet at least 1 of the following criteria: Posthysterectomy patient has purulent drainage from the vaginal cuff Posthysterectomy patient has an abscess at the vaginal cuff Posthysterectomy patient has pathogens cultured from fluid or tissue obtained from the vaginal cuff Note reporting instruction Report vaginal cuff infections as SSI-O if other SSI criteria are met (within 30 days following hysterectomy). REPR-OREP: Other infections of the male or female reproductive tract (epididymis, testes, prostate, vagina, ovaries, uterus, or other deep pelvic tissues, excluding endometritis or vaginal cuff infections) Other infections of the male or female reproductive tract must meet at least 1 of the following criteria: Patient has organisms cultured from tissue or fluid from affected site Patient has an abscess or other evidence of infection of affected site seen during a surgical operation or histopathologic examination Patient has 2 of the following signs or symptoms with no other recognized cause: fever (> 38 °C), nausea, vomiting, pain, tenderness, or dysuria AND at least 1 of the following: organisms cultured from blood physician diagnosis Note reporting instructions Report endometritis as EMET

Report vaginal cuff infections as VCUF 4.1.12. SSI: Surgical site infection Note: All definitions are to be assumed to be confirmed for the purposes of surveillance reporting. Superficial incisional (SSI-S) Infection occurs within 30 days after the operation AND infection involves only skin and subcutaneous tissue of the incision AND at least one of the following: Purulent drainage with or without laboratory confirmation, from the superficial incision Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat AND superficial incision is deliberately opened by surgeon, unless incision is culture-negative Diagnosis of superficial incisional SSI made by a surgeon or attending physician Deep incisional (SSI-D) Infection occurs within 30 days after the operation if no implant is left in place or within 90 days if implant is in place AND the infection appears to be related to the operation AND infection involves deep soft tissue (for example, fascia, muscle) of the incision AND at least one of the following: Purulent drainage from the deep incision but not from the organ/space component of the surgical site A deep incision spontaneously dehisces or is deliberately opened by a surgeon when the patient has at least one of the following signs or symptoms: fever (> 38 °C), localized pain or tenderness, unless incision is culture-negative An abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination Diagnosis of deep incisional SSI made by a surgeon or attending physician Organ/Space (SSI-O) Infection occurs within 30 days after the operation if no implant is left in place or within 90 days if implant is in place AND the infection appears to be related to the operation AND infection involves any part of the anatomy (for example, organs and spaces) other than the incision which was opened or manipulated during an operation AND at least one of the following: Purulent drainage from a drain that is placed through a stab wound into the organ/space Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space An abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination Diagnosis of organ/space SSI made by a surgeon or attending physician 4.1.13. SST: Skin and soft tissue infection SST-SKIN: Skin infection Skin infections must meet at least one of the following criteria: Patient has purulent drainage, pustules, vesicles, or boils Patient has at least two of the following signs or symptoms with no other recognized cause: pain or tenderness, localized swelling, redness, or heat AND at least one of the following: organisms cultured from aspirate or drainage from affected site; if organisms are normal skin flora (for example, diphtheroids (Corynebacterium spp.), Bacillus (not B. anthracis) spp., Propionibacterium spp., coagulase-negative staphylococci (including Staphylococcus epidermidis), viridans group streptococci, Aerococcus spp., Micrococcus spp.), they must be a pure culture

organisms cultured from blood positive antigen test performed on infected tissue or blood multinucleated giant cells seen on microscopic examination of affected tissue diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen Note reporting instructions Report infected decubitus ulcers as DECU Report infected burns as BURN Report breast abscesses or mastitis as BRST SST-ST: Soft tissue (necrotizing fascitis, infectious gangrene, necrotizing cellulitis, infectious myositis, lymphadenitis, or lymphangitis) Soft tissue infections must meet at least 1 of the following criteria: Patient has organisms cultured from tissue or drainage from affected site Patient has purulent drainage at affected site Patient has an abscess or other evidence of infection seen during a surgical operation or histopathologic examination Patient has at least 2 of the following signs or symptoms at the affected site with no other recognized cause: localized pain or tenderness, redness, swelling, or heat AND at least 1 of the following: organisms cultured from blood positive antigen test performed on blood or urine (for example, Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, Group B Streptococcus, Candida spp.) diagnostic single antibody titre (IgM) or 4-fold increase in paired sera (IgG) for pathogen Note reporting instructions Report infected decubitus ulcers as DECU Report infection of deep pelvic tissues as OREP SST-DECU: Decubitus ulcer, including both superficial and deep infections Decubitus ulcer infections must meet the following criterion: Patient has at least 2 of the following signs or symptoms with no other recognized cause: redness, tenderness, or swelling of decubitus wound edges AND at least one of the following: organisms cultured from properly collected fluid or tissue organisms cultured from blood SST-BURN: Burn Burn infections must meet at least 1 of the following criteria: Patient has a change in burn wound appearance or character, such as rapid eschar separation, or dark brown, black, or violaceous discoloration of the eschar, or edema at wound margin and histologic examination of burn biopsy shows invasion of organisms into adjacent viable tissue Patient has a change in burn wound appearance or character, such as rapid eschar separation, or dark brown, black, or violaceous discoloration of the eschar, or edema at wound margin AND at least one of the following: organisms cultured from blood in the absence of other identifiable infection isolation of herpes simplex virus, histologic identification of inclusions by light or electron microscopy, or visualization of viral particles by electron microscopy in biopsies or lesion scrapings Patient with a burn has at least two of the following signs or symptoms with no other recognized cause: fever (> 38 °C) or hypothermia (< 36 °C), hypotension, oliguria (< 20 cc/hr), hyperglycemia at previously tolerated level of dietary carbohydrate, or mental confusion

AND at least one of the following: histologic examination of burn biopsy shows invasion of organisms into adjacent viable tissue organisms cultured from blood isolation of herpes simplex virus, histologic identification of inclusions by light or electron microscopy, or visualization of viral particles by electron microscopy in biopsies or lesion scrapings SST-BRST: Breast abscess or mastitis A breast abscess or mastitis must meet at least one of the following criteria: Patient has a positive culture of affected breast tissue or fluid obtained by incision and drainage or needle aspiration Patient has a breast abscess or other evidence of infection seen during a surgical operation or histopathologic examination Patient has fever (> 38 °C) and local inflammation of the breast AND physician diagnosis of breast abscess 4.1.14. SYS: Systemic infection SYS-DI: Disseminated infection Disseminated infection is infection involving multiple organs or systems, without an apparent single site of infection, usually of viral origin, and with signs or symptoms with no other recognized cause and compatible with infectious involvement of multiple organs or systems Note reporting instructions Use this code for viral infections involving multiple organ systems (for example, measles, mumps, rubella, varicella, erythema infectiosum). These infections often can be identified by clinical criteria alone. Do not use this code for healthcare-associated infections with multiple metastatic sites, such as with bacterial endocarditis; only the primary site of these infections should be reported Do not report fever of unknown origin (FUO) as DI Report viral exanthems or rash illness as DI SYS-CSEP: treated unidentified severe infection Patient has at least one of the following clinical signs or symptoms with no other recognized cause fever (> 38 °C) hypotension (systolic pressure < 90 mm/Hg) or oliguria (20 cm3 (ml)/hr) And blood culture not done or no organisms or antigen detected in blood And no apparent infection at another site And physician institutes treatment for sepsis Note reporting instructions Do not use this code unless absolutely needed For CSEP in neonates, use NEO-CSEP case definition (see below) 4.1.15. UTI: Urinary tract infection UTI-A: microbiologically confirmed symptomatic UTI Patient has at least one of the following signs or symptoms with no other recognized cause: fever (> 38 °C), urgency, frequency, dysuria, or suprapubic tenderness AND patient has a positive urine culture, that is, ≥ 105 microorganisms per ml of urine with no more than two species of microorganisms. UTI-B: not microbiologically confirmed symptomatic UTI Patient has at least two of the following with no other recognized cause: fever (> 38 °C), urgency, frequency, dysuria, or suprapubic tenderness AND at least one of the following: Positive dipstick for leukocyte esterase and/or nitrate Pyuria urine specimen with ≥ 104 WBC/ml or ≥ 3 WBC/high-power field of unspun urine Organisms seen on Gram stain of unspun urine

At least two urine cultures with repeated isolation of the same uropathogen (Gram-negative bacteria or Staphylococcus saprophyticus) with ≥ 102 colonies/ml urine in nonvoided specimens ≤ 105 colonies/ml of a single uropathogen (Gram-negative bacteria or Staphylococcus saprophyticus) in a patient being treated with effective antimicrobial agent for a urinary infection Physician diagnosis of a urinary tract infection Physician institutes appropriate therapy for a urinary infection Asymptomatic bacteriuria should not be reported, but bloodstream infections secondary to asymptomatic bacteriuria are reported as BSI with source (origin) S-UTI A urinary tract infection is defined as catheter-associated if an indwelling urinary catheter was present (even intermittently) in the 7 days preceding the onset of infection 4.2. GENERAL CASE DEFINITION OF BLOOD STREAM INFECTION DUE TO SPECIFIC PATHOGENS Clinical criteria Not relevant for surveillance purposes Laboratory criteria At least one blood culture positive for Staphylococcus aureus or Klebsiella pneumoniae or Escherichia coli or Enterococcus faecium or Enterococcus faecalis or Pseudomonas aeruginosa or Acinetobacter species or Streptococcus pneumoniae. Epidemiological criteria Not relevant for surveillance purposes Case classification A. Possible case NA B. Probable case NA C. Confirmed case Antimicrobial resistance The results of antimicrobial susceptibility tests must be reported according to the methods and criteria agreed between ECDC and Member States as specified by ECDC's European Antimicrobial Resistance Surveillance Network (EARS-Net) The criteria for reporting are published each year as part of the Antimicrobial resistance (AMR) reporting protocol. See: Antimicrobial resistance (AMR) reporting protocol. European Antimicrobial Resistance Surveillance Network (EARS-Net). www.ecdc.europa.eu , and in particular: for Staphylococcus aureus: susceptibility to meticillin and other anti-staphylococcal beta-lactams; for Enterococcus faecium and Enterococcus faecalis: susceptibility to glycopeptides; for Klebsiella pneumoniae and Escherichia coli: susceptibility to carbapenems, and susceptibility to colistin in carbapenem-resistant isolates; for Pseudomonas aeruginosa and Acinetobacter species: susceptibility to carbapenems. 4.3. GENERIC CASE DEFINITION AND CLASSIFICATION OF ANTIMICROBIAL REISTANCE TO ANTIMICROBIAL AGENTS Clinical resistance to antimicrobial agents Definition A micro-organism is classified as clinically susceptible, clinically intermediate, or clinically resistant to an antimicrobial agent by applying the appropriate EUCAST clinical breakpoints in a standardized methodology (or a methodology calibrated to a standardized methodology) http://www.eucast.org/clinical_breakpoints/. Equivalent quantitative antimicrobial susceptibility testing (AST) methods may be used instead of MIC or disk diffusion if endorsed by EUCAST. , i.e. clinical minimum inhibitory concentration (MIC) breakpoints and their inhibition zone diameter correlates. Breakpoints may be altered with legitimate changes in circumstances.

Classification Clinically Susceptible (S) a micro-organism is defined as susceptible (S) by a level of antimicrobial exposure associated with a high likelihood of therapeutic success. Clinically Intermediate (I) a micro-organism is defined as intermediate (I) by a level of antimicrobial agent activity associated with uncertain therapeutic effect. It implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physically concentrated or when a dosage regimen of drug producing higher exposure can be used; it also indicates a buffer zone that should prevent small, uncontrolled, technical factors from causing major discrepancies in interpretations. Clinically Resistant (R) a micro-organism is defined as resistant (R) by a level of antimicrobial exposure associated with a high likelihood of therapeutic failure. Clinical breakpoints http://www.eucast.org/clinical_breakpoints/. Equivalent quantitative antimicrobial susceptibility testing (AST) methods may be used instead of MIC or disk diffusion if endorsed by EUCAST. are presented as: S: MIC ≤ x mg/L; disk diffusion zone diameter ≥ σ mm I: MIC > x, ≤ y mg/L; disk diffusion zone diameter ≥ ρ mm, < σ mm R: MIC > y mg/L; disk diffusion zone diameter < ρ mm Pandrug-resistant (PDR) for Staphylococcus aureus, Enterococcus species, Enterobacteriaceae including Klebsiella pneumoniae and Escherichia coli, Pseudomonas aeruginosa and Acinetobacter species, an isolate is defined as pandrug-resistant (PDR) based on the fact that it is resistant to all antimicrobial agents, as in the international expert proposal for interim standard definitions for acquired resistance Magiorakos AP, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar;18(3):268-81. http://www.sciencedirect.com/science/article/pii/S1198743X14616323 an isolate is defined as confirmed PDR when it is non-susceptible (i.e. intermediate — I, or resistant — R) to all agents in all antimicrobial categories, confirmed by a reference or other clinical microbiology laboratory testing a supplemental panel of antimicrobial agents beyond those routinely tested, in accordance with the definitions by microorganism in the international expert proposal for interim standard definitions for acquired resistance Magiorakos AP, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar;18(3):268-81. http://www.sciencedirect.com/science/article/pii/S1198743X14616323 an isolate is defined as possibly PDR when it is non-susceptible (i.e. intermediate — I, or resistant — R) to all the antimicrobial agents tested in the laboratory an isolate is defined as not PDR when it is susceptible to at least one of the tested antimicrobial agents

Microbiological resistance to antimicrobial agents Phenotypic definition A microorganism is classified as having a wild-type phenotype or a non-wild-type phenotype for a species according to the EUCAST epidemiological cut-off concentrations (ECOFFs) in a standardized methodology (or a methodology calibrated to a standardized methodology) http://www.eucast.org/ast_of_bacteria/ http://www.eucast.org/mic_distributions_and_ecoffs/ based on species-specific MIC distributions and their inhibition zone diameter correlates. Phenotypic classification Wild-type (WT) phenotype a micro-organism is defined as wild-type (WT) for a species or species complex when it is devoid of phenotypically-detectable acquired resistance mechanism Non-wild-type (NWT) phenotype a micro-organism is defined as non-wild-type (NWT) for a species when it expresses at least one phenotypically-detectable acquired resistance mechanism ECOFFs are presented as http://www.eucast.org/mic_distributions_and_ecoffs/ WT: ECOFF ≤ x mg/L; disk diffusion zone diameter ≥ σ mm NWT: ECOFF > x mg/L; disk diffusion diameter < σ mm Identification of an acquired antimicrobial resistance mechanism (for example, drug inactivating enzyme, modification of drug target protein type, efflux pump) Expression of an acquired antimicrobial resistance mechanism by a micro-organism can be determined in vitro and the type of mechanism identified using standardized methodology according to the EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_v1.0_20131211.pdf Genotypic definition A microorganism is classified as harbouring or lacking a genetic determinant or combination of determinants conferring to it a non-wild type susceptibility phenotype in relation to antimicrobial agent (transferable gene or core gene mutation). The presence of a genetic determinant or combination of determinants conferring to it a non-wild type susceptibility phenotype in relation to one or several antimicrobial agents can be shown by detecting and identifying the corresponding nucleic acid sequence(s) in a bacterial genome. Genotypic classification Genotypes are reported as: Positive: presence of [name of resistance gene or core gene mutation] Negative: absence of [name of resistance gene] or wild-type core gene sequence