Background
Methods
Study population
Reference laboratory evaluation for leptospirosis
Case definition of leptospirosis
Statistical analysis
Results
Epidemiology
Laboratory diagnostic tests
Clinical presentations
Clinical Diagnosis at Site | |||||||
---|---|---|---|---|---|---|---|
Dengue (n = 11) | Typhoid fever (n = 4) | UTI (n = 5) | CAP (n = 3) | Othera (n = 6) | Leptospirosis (n = 22) | Total (n = 51) | |
Demography | |||||||
Gender (male: female) | 10:1 | 1:3 | 2:3 | 2:1 | 3:3 | 16:6 | 34:17 |
Adult: Pediatricb | 9:2 | 4:0 | 4:1 | 3:0 | 4:2 | 22:0 | 46:5 |
Age, median (range) | 29 (5.3–58.1) | 42.3 (19.2–60.4) | 27 (10–61.4) | 62.5 (59.7–64.4) | 47 (13–85) | 41.7 (20.8–62.1) | 41.2 (5.3–85) |
Signs & Symptoms, N (%) | |||||||
Anorexia | 3 (27.3) | 2 (50) | 0 | 1 (33.3) | 3 (50) | 7 (31.8) | 16 (31.4) |
Chills | 4 (36.4) | 2 (50) | 3 (60) | 2 (66.7) | 1 (16.7) | 9 (40.9) | 21 (41.2) |
Lethargy | 2 (18.2) | 1 (25) | 1 (20) | 0 | 1 (16.7) | 10 (45.5) | 15 (29.4) |
Icterus | 2 (18.2) | 0 | 0 | 0 | 1 (16.7) | 6 (27.3) | 9 (17.6) |
Decrease of consciousness | 0 | 0 | 0 | 0 | 1 (16.7) | 0 | 1 (1.9) |
Headache | 5 (45.5) | 3 (75) | 3 (60) | 1 (33.3) | 3 (50) | 13 (59.1) | 28 (54.9) |
Dizziness | 2 (18.2) | 1 (25) | 3 (60) | 2 (66.7) | 2 (33.3) | 6 (27.3) | 16 (31.4) |
Cough | 2 (18.2) | 0 | 1 (20) | 1 (33.3) | 2 (33.3) | 9 (40.9) | 15 (29.4) |
Shortness of breath | 0 | 0 | 0 | 0 | 0 | 4 (18.2) | 4 (7.8) |
Epigastric pain | 0 | 2 (50) | 2 (40) | 1 (33.3) | 1 (16.7) | 8 (36.4) | 14 (27.5) |
Abdominal pain | 2 (18.2) | 0 | 0 | 0 | 1 (16.7) | 5 (22.7) | 8 (15.7) |
Nausea | 8 (72.7) | 4 (100) | 4 (80) | 3 | 4 (66.7) | 17 (77.3) | 40 (78.4) |
Vomiting | 7 (63.6) | 3 (75) | 3 (60) | 2 (66.7) | 5 (83.3) | 12 (54.5) | 32 (62.7) |
Constipation | 2 (18.2) | 2 (50) | 0 | 0 | 1 (16.7) | 0 | 5 (9.8) |
Diarrhea | 5 (45.5) | 0 | 2 (40) | 2 (66.7) | 3 (50) | 9 (40.9) | 21 (41.2) |
Arthralgia | 2 (18.2) | 0 | 4 (80) | 2 (66.7) | 0 | 12 (54.5) | 20 (39.2) |
Myalgia | 1 (9.1) | 1 (25) | 3 (60) | 1 (33.3) | 1 (16.7) | 15 (68.2) | 22 (43.1) |
Skin rash | 0 | 0 | 0 | 1 (33.3) | 0 | 1 (4.5) | 2 (3.9) |
Conjunctival suffusion | 2 (18.2) | 0 | 0 | 0 | 1 (16.7) | 11 (50) | 14 (27.5) |
Rhonchi | 0 | 0 | 0 | 2 (66.7) | 0 | 4 (18.2) | 6 (11.8) |
Pruritus | 0 | 1 (25) | 0 | 0 | 0 | 0 | 1 (1.9) |
Gastrocnemius pain | 1 (9.1) | 0 | 0 | 0 | 1 (16.7) | 6 (27.3) | 8 (15.7) |
Oliguria | 1 (9.1) | 0 | 0 | 0 | 0 | 3 (13.6) | 4 (7.8) |
Brown-coloured urine | 0 | 0 | 0 | 0 | 0 | 7 (31.8) | 7 (13.7) |
Haematology & Chemistry Results, N (%) / N/tested (%) | |||||||
Leukopenia | 0 | 0 | 1 (20) | 0 | 1 (16.7) | 0 | 2 (3.9) |
Normal leucocyte count | 10 (90.9) | 3 (75) | 2 (40) | 2 (66.7) | 0 | 6 (27.3) | 23 (45.1) |
Leukocytosis | 1 (9.1) | 1 (25) | 2 (40) | 1 (33.3) | 5 (83.3) | 16 (72.7) | 26 (50.9) |
Platelet ≤150,000/mm3 | 8 (72.7) | 2 (50) | 1 (20) | 2 (66.7) | 1 (16.7) | 16 (72.7) | 30 (58.8) |
Granulocytosis > 80% | 8/10 (80) | 2/3 (66.7) | 1/4 (25) | 2/2 (100) | 3/5 (60) | 10/12 (83.3) | 26/36 (72.2) |
Lymphopenia < 20% | 9/10 (90) | 4/4 (100) | 2/4 (50) | 2/2 (100) | 5/5 (100) | 13/13 (100) | 35/38 (92.1) |
Total bilirubin > 1 mg/dL | 3/11 (27.3) | 1/3 (33.3) | 0/4 | 1/3 (33.3) | 0/5 | 15/22 (68.2) | 20/48 (41.7) |
Bilirubin direct > 0.65 mg/dL | 2/11 (18.2) | 1/3 (33.3) | 0/4 | 0/3 | 0/5 | 16/22 (72.7) | 19/48 (39.6) |
ASTc > 100 | 1/11 (9.1) | 0/3 | 0/4 | 0/3 | 0/6 | 7/20 (35) | 8/47 (17) |
ALTd > 100 | 0/11 | 0/3 | 0/4 | 0/3 | 0/6 | 3/22 (13.6) | 3/47 (6.4) |
Creatinine > 1.4 mg/dL | 3/11 (27.3) | 0/3 | 2/4 (50) | 2/3 (66.7) | 0/5 | 15/22 (68.2) | 22/48 (45.8) |
Diagnostic tests at sites, N/ tested (%) | |||||||
Dengue IgM positive | 2/6 (33.3) | 2/4 (50) | 0/1 | 0/1 | 0/1 | 0/5 | 4/18 (22.2) |
Tubex TF®e | 2/5 (40) | 4/4 (100) | 1/2 (50) | 0/1 | 1/3 (33.3) | 2/5 (40) | 10/20 (50) |
Leptospira IgM positive | 0/1 | 0/4 | 0/1 | 0/1 | 0/1 | 18/22 (81.8) | 18/25 (72) |
Reference Laboratory tests, N (%) | |||||||
Dengue & S. typhi | 1 (9.1) | 0 | 0 | 0 | 0 | 0 | 1 (1.9) |
Leptospira PCR & Serology | 6 (54.5) | 2 (50) | 2 (40) | 3 (100) | 3 (50) | 12 (54.5) | 28 (54.9) |
Leptospira PCR only | 2 (18.2) | 0 | 0 | 0 | 1 (16.7) | 2 (9.1) | 5 (9.8) |
Leptospira serology only | 3 (27.3) | 2 (50) | 3 (60) | 0 | 2 (33.3) | 8 (36.4) | 18 (35.3) |
Outcome, N (%) | |||||||
Death | 1 (9.1) | 1 (25) | 0 | 0 | 0 | 0 | 2 (4) |
No | Leptospira symptoms | Other symptomsa | Leptospira Standard of Care Results at sites | Leptospira Reference Lab | Final pathogen identified & Lab results | |
---|---|---|---|---|---|---|
1 | Icterus | 2,5,6,9,13,14,17,18, 19,20,21, 22 | Rapid IgM (neg) | PCR negative IgM ELISA negative | UNK | |
2 | Icterus, suffusion, brown-colored urine | 2,4,5,6,7,10,13,14,16,17,18,19,20 | IgM ELISA, low titer (Conv) | PCR negative IgM ELISA negative | R. typhi | PCR Positive IgM (0.9–4.7) IgG (2.8–15.2) IFA Pos |
3 | 1,5,10,12 | Not done | PCR negative IgM ELISA negative | UNK | ||
4 | Gastrocnemius pain, Icterus | 2,5,10,13,16,19,20, 22 | Rapid IgM negative | PCR negative IgM ELISA negative | UNK | |
5 | Flank pain | 2,13,14 | Rapid IgM positive, MAT negative | PCR negative IgM ELISA negative | R. typhi | PCR Negative IgM (1.3–12.8) IgG (0.4–3.2) IFA Pos |
6 | 2,5,6,9,13,19 | Rapid IgM positive | PCR negative IgM ELISA negative | UNK | ||
7 | 3,4,6,12,13,14,17,18,20 | Rapid IgM positive | PCR negative IgM ELISA negative | R. typhi | PCR Positive IgM (2.3–8.9) IgG (1.5–10.1) IFA Pos | |
8 | Icteric, suffusion | 1,4,11,13,19 | Rapid IgM positive, MAT negative | PCR negative IgM ELISA negative | S. aureus | Blood culture |
9 | 2,3,4,13,16,17,19,20,22 | Rapid IgM negative | PCR negative IgM ELISA titer 1:100 convalescent sera | Chikungunya | PCR Negative IgM (6.4–3.3) IgG (0.2–3.0) | |
10 | Suffusion | 3,5,8,10,13.14.20 | Rapid IgM positive | PCR negative IgM ELISA negative | UNK | |
11 | Gastrocnemius pain, brown-colored urine, suffusion | 2,5,9, 16,17,18,19 | Rapid IgM positive, MAT negative | PCR negative IgM ELISA borderline | UNK | |
12 | Brown-colored urine, suffusion | 2,3,4,5,10,13,14,18,20 | Rapid IgM positive, MAT negative | PCR negative IgM ELISA negative | R. typhi | PCR Negative IgM (0.4–1) IgG (2.7–13.4) IFA Pos |
13 | 6,13,20 | Rapid IgM positive | PCR negative IgM ELISA borderline | Dengue | PCR Positive DENV-3 NS1 positive IgM (6.335–3.819) IgG (12.371–12.931) | |
14 | Suffusion | 3,16,23,19,20 | Rapid IgM positive, MAT inconclusive | PCR negative IgM ELISA negative | UNK | |
15 | Gastrocnemius pain | 13,14,15 | Rapid IgM positive | PCR negative IgM ELISA titer 1:100 in acute and convalescent sera | UNK |
Patient 1 (Surabaya) | Patient 2 (Makassar) | |
---|---|---|
Gender, age range (years) | Male, 45–50 | Female, 60–65 |
Comorbidities | No comorbidities | Diabetes mellitus |
Signs/Symptoms | Fever (3 days), nausea, vomiting, diarrhea | Fever (3 days), chills, headache, dizzy, nausea, vomiting |
Hematology profiles | ||
Hb (mg/dL) | 11.5 | 13 |
Hematocrit (%) | 32.9 | 38.7 |
Leukocyte count (/mm3) | 9600 | 9500 |
Granulocytes (%) | 92% | Not available |
Lymphocytes (%) | 3.8% | 6.9% |
Platelet (/mm3) | 45,000 | 118,000 |
Chemistries | ||
Bilirubin total, direct, indirect (mg/dL) | 0.9; 0.6; 0.3 | |
ASTa (IU/mL) | 139 | 93 |
ALTb (IU/mL) | 33 | 64 |
Creatinine (mg/dL) | 4.1 | 1.1 |
Diagnostic tests at the hospital | ||
Dengue test | Not tested | Negative IgM/IgG |
Salmonella typhi | Not tested | Tubex TF® test positive [6] |
Diagnosis at the hospital | Dengue hemorrhagic fever grade I | Typhoid fever |
Antibiotics | Ceftriaxone | Cefotaxime, intra-venous |
Cause of death, hospitalization day | Respiratory failure, 2 days | Respiratory failure, 2 days |
Diagnostic test at the reference laboratory (only acute specimen available) | ||
Dengue virus | RT-PCR, NS1, IgM negative, IgG positive | RT-PCR, NS1, IgM negative, IgG positive |
Salmonella typhi | Blood culture, PCR, ELISA IgM, IgG negative | Blood culture, PCR, ELISA IgM and IgG negative |
Leptospira spp | PCR positive (ct value = 30) | PCR positive (ct value = 19) |
ELISA IgM, IgG negative | ELISA IgM, IgG negative |