APPENDICES

Appendix 1: Case Definitions

CDC: Case Classification.

Probable: A clinically compatible case with at least one of the following:
Involvement in an exposure event (e.g., adventure race, triathlon, flooding) with known
associated cases, or Presumptive laboratory findings, but without confirmatory laboratory
evidence of Leptospira infection.

Confirmed: A case with confirmatory laboratory results, as listed above.

Clinical Criteria: An illness characterized by fever, headache, and myalgia, and less frequently by
conjunctival suffusion, meningitis, rash, jaundice, or renal insufficiency. Symptoms may be
biphasic.
Clinical presentation: History of fever within the past two weeks and at least two of the following
clinical findings: myalgia, headache, jaundice, conjunctival suffusion without purulent discharge,
or rash (i.e. maculopapular or petechial); OR at least one of the following clinical findings:
Aseptic meningitis, GI symptoms (e.g., abdominal pain, nausea, vomiting, diarrhea), Pulmonary
complications (e.g., cough, breathlessness, hemoptysis), Cardiac arrhythmias, ECG abnormalities,
Renal insufficiency (e.g., anuria, oliguria), Hemorrhage (e.g., intestinal, pulmonary, hematuria,
hematemesis), or Jaundice with acute renal failure.

Laboratory Criteria for Diagnosis:

Diagnostic testing should be requested for patients in whom there is a high index of suspicion for
leptospirosis, based either on signs and symptoms, or on occupational, recreational or vocational
exposure to animals or environments contaminated with animal urine.

Supportive:
• Leptospira agglutination titer of ≥ 200 but < 800 by Microscopic Agglutination Test
(MAT) in one or more serum specimens, or
• Demonstration of anti-Leptospira antibodies in a clinical specimen by indirect
immunofluorescence, or
• Demonstration of Leptospira in a clinical specimen by darkfield microscopy, or
• Detection of IgM antibodies against Leptospira in an in acute phase serum specimen.
Confirmed:
• Isolation of Leptospira from a clinical specimen, or
• Fourfold or greater increase in Leptospira agglutination titer between acute- and
convalescent-phase serum specimens studied at the same laboratory, or
• Demonstration of Leptospira in tissue by direct immunofluorescence, or
• Leptospira agglutination titer of ≥ 800 by Microscopic Agglutination Test (MAT) in one
or more serum specimens, or
• Detection of pathogenic Leptospira DNA (e.g., by PCR) from a clinical specimen.

WHO: Case classification (humans)

Suspected: A case that is compatible with the clinical description and a presumptive laboratory
diagnosis.
Confirmed: A suspect case with a confirmatory laboratory diagnosis.

Clinical description: The usual presentation is an acute febrile illness with headache, myalgia
(particularly calf muscle) and prostration associated with any of the following symptoms/signs:
Conjunctival suffusion, Anuria or oliguria, Jaundice, Cough, hemoptysis and breathlessness,
Hemorrhages (from the intestines; lung bleeding is notorious in some areas), Meningeal irritation,
Cardiac arrhythmia or failure and Skin rash.
Note. Other common symptoms include nausea, vomiting, abdominal pain, diarrhea, arthralgia.

Laboratory criteria:
Presumptive diagnosis: A positive result of a rapid screening test such as IgM ELISA, latex
agglutination test, lateral flow, dipstick etc.
Confirmatory diagnosis:
• Isolation from blood or other clinical materials through culture of pathogenic leptospires.
• A positive PCR result using a validated method (primarily for blood and serum in the
early stages of infection).
• Fourfold or greater rise in titer or seroconversion in microscopic agglutination test
(MAT) on paired samples obtained at least 2 weeks apart.
• A battery of Leptospira reference strains representative of local strains to be used as
antigens in MAT.
Appendix 2: PICOS

P Participant Any children or adults who live in urban area.

I/ E Intervention/ Exposure Non-recreational leptospirosis

C Comparator Infection from recreational, water activity or

leptospirosis infection in rural.
O Outcome Primary: Confirmed leptospirosis infection in human.
Secondary: Leptospira serovars in urban environment.
S Study Observational studies
Appendix 3: Keywords

Participant Exposure Comparator Outcome

Urban Exposure* Recreation* Leptospirosis
Cit* Risk* Sport* Leptospiroses
Metropolitan Activit* Leisure* Weil disease
Downtown Job* Rural Weil’s disease
Urbanites Work* Agricultur* Leptospira
Urban population Occupation* Farm*
Environment*
PUBMED search strategy

1 Title/abstract Urban
2 MeSH Terms Urban
3 Title/abstract Metropolitan
4 MeSH Terms Metropolitan
5 Title/abstract Downtown
6 MeSH Terms Downtown
7 Title/abstract Urbanites
8 MeSH Terms Urbanites
9 Title/abstract “Urban population”
10 MeSH Terms “Urban population”
11 All #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10
12 Title/abstract Exposure*
13 MeSH Terms Exposure*
14 Title/abstract Risk*
15 MeSH Terms Risk*
16 Title/abstract Activit*
17 MeSH Terms Activit*
18 Title/abstract Job*
19 MeSH Terms Job*
20 Title/abstract Work*
21 MeSH Terms Work*
22 Title/abstract Occupation*
23 MeSH Terms Occupation*
24 Title/abstract Environment*
25 MeSH Terms Environment*
#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20
26 All OR #21 OR #22 OR #23 OR #24 OR #25
25 Title/abstract Leptospirosis
26 MeSH Terms Leptospirosis
27 Title/abstract Leptospiroses
28 MeSH Terms Leptospiroses
29 Title/abstract “Weil disease”
30 MeSH Terms “Weil disease”
31 Title/abstract “Weil’s disease”
32 MeSH Terms “Weil’s disease”
33 Title/abstract Leptospira
34 MeSH Terms Leptospira
#25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33
35 All OR #34
36 All #11 AND #26 AND #35
37 Title/abstract Recreation*
38 MeSH Terms Recreation*
39 Title/abstract Rural
40 MeSH Terms Rural
41 Title/abstract Agricultur*
42 MeSH Terms Agricultur*
43 Title/abstract Farm*
44 MeSH Terms Farm*
45 All #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44
46 All #36 NOT #45