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 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 transmission: the 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 transmission: the 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 source: the 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 water: the 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 exposure: the fact that a person has bathed in water or has had contact with a contaminated environmental source that has been laboratory confirmed;

—   Laboratory exposure: the 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.   AFP: acute flaccid paralysis

2.   AIDS: acquired immune deficiency syndrome

3.   AMR: antimicrobial resistance

4.   Anti-HBc: hepatitis B core antibody

5.   anti-HCV: hepatitis C virus specific antibody

6.   ARI: acute respiratory infection

7.   BAL: broncho-alveolar lavage

8.   BCG: Bacille de Calmette et Guérin

9.   BJ: bone and joint infection

10.   BJ-BONE: osteomyelitis

11.   BJ-DISC: disc space infection

12.   BJ-JNT: joint or bursa infection

13.   BoNT: botulinum neurotoxin

14.   BSI: bloodstream infection

15.   C-CVC: catheter-related — central venous catheter

16.   CDAD: Clostridium difficile associated diarrhoea

17.   CFU: colony-forming unit

18.   CJD: Creutzfeldt-Jakob disease

19.   CMV: cytomegalovirus

20.   CNRL: EU Community Network of Reference Laboratories for human influenza

21.   CNS: central nervous system

22.   CNS-IC: central nervous system infection — intracranial infection

23.   CNS-MEN: central nervous system infection — meningitis or ventriculitis

24.   CNS-SA: central nervous system infection — spinal abscess without meningitis

25.   C-PVC: catheter-related — peripheral venous catheter

26.   CRI: catheter-related infection

27.   CRS: Congenital rubella syndrome

28.   CRT: capillary refilling time

29.   CSF: Cerebrospinal fluid

30.   CT scan: computed tomography scan

31.   CVS: cardiovascular system infection

32.   CVS-CARD: cardiovascular system infection — myocarditis or pericarditis

33.   CVS-ENDO: cardiovascular system infection — endocarditis

34.   CVS-MED: cardiovascular system infection — mediastinitis

35.   CVS-VASC: cardiovascular system infection — arterial or venous infection

36.   DFA: direct fluorescent antibody

37.   DFA-TP: direct fluorescent antibody test for Treponema pallidum

38.   DNA: deoxyribonucleic acid

39.   DPA: distal protected aspirate

40.   EARS-Net: European Antimicrobial Resistance Surveillance Network

41.   ECDC: European Centre for Disease Prevention and Control

42.   ECOFFs: epidemiological cut-off values

43.   EEG: electroencephalography

44.   EENT: eye, ear, nose, throat, or mouth infection

45.   EENT-CONJ: eye, ear, nose, throat, or mouth infection — conjunctivitis

46.   EENT-EAR: eye, ear, nose, throat, or mouth infection — ear mastoid

47.   EENT-EYE: eye, ear, nose, throat, or mouth infection — eye, other than conjunctivitis

48.   EENT-ORAL: eye, ear, nose, throat, or mouth infection — oral cavity (mouth, tongue, or gums)

49.   EENT-SINU: eye, ear, nose, throat, or mouth infection — sinusitis

50.   EENT-UR: eye, ear, nose, throat, or mouth infection — upper respiratory tract, pharyngitis, laryngitis, epiglottitis

51.   EFNS: European Federation of Neurological Societies

52.   EIA: enzyme immunoassay

53.   ELISA: enzyme-linked immunosorbent assay

54.   EM: electron microscopy

55.   EUCAST: European Committee on Antimicrobial Susceptibility Testing

56.   FAMA: fluorescent antibody to membrane antigen

57.   FTA-abs: fluorescent treponemal antibody absorption

58.   FUO: fever of unknown origin

59.   GI: gastrointestinal system infection

60.   GI-CDI: gastrointestinal system infection — Clostridium difficile infection

61.   GI-GE: gastrointestinal system infection — gastroenteritis (excl. CDI)

62.   GI-GIT: gastrointestinal system infection — gastrointestinal tract (esophagus, stomach, small and large bowel, and rectum) excluding gastroenteritis and appendicitis

63.   GI-HEP: gastrointestinal system infection — hepatitis

64.   GI-IAB: gastrointestinal 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 elsewhere

65.   HAI: healthcare-associated infections

66.   HbeAg: hepatitis B e antigen

67.   HbsAg: hepatitis B surface antigen

68.   HBV-DNA: hepatitis B nucleic acid

69.   HCV-core: hepatitis C virus core antigen

70.   HCV-RNA: hepatitis C virus nucleic acid

71.   HIV: human immunodeficiency virus

72.   HUS: haemolytic-uraemic syndrome

73.   IAP: intubation-associated pneumonia

74.   IFA: indirect fluorescent antibody

75.   IgG: immunoglobulin G

76.   IgM: immunoglobulin M

77.   ILI: influenza-like illness

78.   LGV: lymphogranuloma (venereum)

79.   LPS: lipopolysaccharides

80.   LRI: lower respiratory tract infection, other than pneumonia

81.   LRI-BRON: lower respiratory tract infection — bronchitis, tracheobronchitis, bronchiolitis, tracheitis, without evidence of pneumonia

82.   TBE: Tick-borne encephalitis

3.   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 (1).

3.5.   CHIKUNGUNYA VIRUS DISEASE

Clinical Criteria (2)

—

Fever

Laboratory Criteria (3)

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 (4);

—	Persistent painful sensory symptoms (5);

—

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 (6) of sporadic CJD (6) in the early stages of the illness;

—	Bilateral pulvinar high signal on MRI brain scan;

—	A positive tonsil biopsy (7).

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 (6)

B.	Probable case Any person fulfilling the preconditions AND — meeting the clinical criteria AND — a negative EEG for sporadic CJD (8) 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 (9)

—

Fever

Laboratory Criteria (10)

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 (11).

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 (12)

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 (13)

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 (14), 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) (15).

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 (*1)

—	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 (16).

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 (17) 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 (18) 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 (19)

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 (20).

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 (21)

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 (< 4 000 WBC/mm3) or leucocytosis (≥ 12 000 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 (22) specimen (PN 1) — Broncho-alveolar lavage (BAL) with a threshold of ≥ 104 CFU (23)/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) (24), 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) (25), 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 (25) 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 (26)

—

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 (27)

—	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) (28) (29) 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 (29)

—	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 (30)

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

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(1)  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

(2)  Clinical criteria should be interpreted by taking into account the presence of an alternative diagnosis that can fully explain the illness.

(3)  Serological results should be interpreted according to previous exposure to other alphaviral infections.

(4)  Depression, anxiety, apathy, withdrawal, delusions

(5)  This includes both frank pain and/or dysaesthesia

(6)  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

(7)  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

(8)  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

(9)  Clinical criteria should be interpreted by taking into account the presence of an alternative diagnosis that can fully explain the illness.

(10)  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.

(11)  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

(12)  When reporting cases of Hepatitis B, the Member States should distinguish between acute and chronic disease, according to ECDC requirements.

(13)  When reporting cases of Hepatitis C, the Member States should distinguish between acute and chronic disease, according to ECDC requirements.

(14)  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

(15)  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

(*1)  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).

(16)  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

(17)  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.

(18)  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.

(19)  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.

(20)  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.

(21)  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

(22)  LRT = Lower Respiratory Tract

(23)  CFU = Colony Forming Units

(24)  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

(25)  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.

(26)  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

(27)  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

(28)  http://www.eucast.org/ast_of_bacteria/

(29)  http://www.eucast.org/mic_distributions_and_ecoffs/

(30)  http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_v1.0_20131211.pdf