Table 1. Characteristics of included studies, arranged alphabetically by first author.
| Study Title (Reference) (Language if not English) | County, Year of Study | Study design | Untreated Patients and serovar | Median (Unless stated) age (range) | % Male | Median (Unless stated) Duration of Fever (Days) (Range) | Diagnostic test | Proportion of patients jaundiced (%) | Proportion of patients impaired renal function (%) | Mortality (%) (Deaths / Number of patients) | Patients excluded |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baermann G & Smits E. Zentralbl Bakteriol. 1928 [16] (German) | Sumatra, Indonesia 1923–1927 | Prospective case series | 196 (196/346) * | - | 100% (101/101) | - | (196/196) Blood culture or guinea pig inoculation | 17% (NA/196) | - | 1% (NA/196) | 150 patients excluded as no bacteriological confirmation of diagnosis |
| Berman SJ, et al. Ann Intern Med. 1973 [17] | Vietnam 1971–2 | Prospective case series | 101 (101/200) * | - | - | 8.8 (mean) | (200/200) Single high titre MAT (≥1:400). (27/200) Positive cultures | 1.5% (2/150) | 26% (22/84) urea>10.7mmol/L | 0% (0/101) | 49 treated patients and 50 patients with incomplete records excluded |
| Borg-Petersen C. P Roy Soc Med. 1949 [18] | Denmark 1934–48 | Danish reference laboratory. Retrospective case series | 254 (254/254) Icterohaemorrhagiae | - | 86% (218/254) | - | (254/254) Single high titre MAT (Titre not specified) | 65.4% (NA/254) | - | 14.6% (37/254) | No patients excluded |
| Denmark 1934–48 | Danish reference laboratory. Retrospective case series | 459 (459/459) Serjo & others | - | 68.4% (314/459) | - | (459/459) Single high titre MAT (Titre not specified) | 14.7% (NA/459) | - | 1.3% (6/459) | No patients excluded | |
| Denmark 1934–48 | Danish reference laboratory. Retrospective case series | 95 (95/95) Canicola | - | 57% (54/95) | - | (95/95) Single high titre MAT (Titre not specified) | 13% (NA/95) | - | 0% (0/95) | No patients excluded | |
| Broom JC & Alston JM. Lancet. 1948 [19] | UK 1940–46 | UK reference laboratory. Retrospective case series | 114 (114/195) Icterohaemorrhagiae | 34.4 (100/195) | 96.6% (181/189) | - | (114/114) Single high titre (≥1:300) | 89% (107/120) | - | 21.9% (25/114) | (81/195) patients with no information on mortality excluded |
| Broom JC. Brit Med J. 1951 [20] | UK 1947–50 | UK reference laboratory. Retrospective case series | 259 (259/465) Icterohaemorrhagiae | 36.7 (361/465) | 95% (439/465) | - | (259/259) Single high titre MAT (Titre not specified) | 74% (344/465) | - | 13.9% (36/259) | (206/465) Patients treated with penicillin excluded |
| UK 1947–50 | UK reference laboratory. Retrospective case series | 70 (70/70) Canicola | 36.7 (64/70) | 63% (44/70) | - | (70/70) Single high titre MAT (Titre not specified) | 17% (10/54) | - | 1.4% (1/70) | No patients excluded | |
| Btesh S. T Roy Soc Trop Med H. 1947 [21] | Palestine / Israel 1947 | Summary of case reports | 15 (15/17) Bovis | 41.25 (23–60) (16/17) | 100% (17/17) | 11 (9–45) (15/15) | (3/15) Autopsy. (12/15) Single high MAT (≥1:280) | 100% (17/17) | 88% (15/17) “urea raised” | 20% (3/15) | 2 treated patients excluded |
| Bulmer E. Brit Med J. 1945 [22] | Normandy, France 1944 | NRCT | 23 (23/39) * | - | 100% (23/23) | - | (NA/29) Single high titre MAT for majority (Titre not specified). (NA/29) Isolation from blood or urine | 95% (37/39) | - | 8.7% (2/23) | Penicillin treated patients excluded (16/39) |
| Cavigneaux, et al. Arch Mal Prof Med. Trav Soc Sec. 1948 [23] (French) | Paris, France 1948 | Retrospective case series | 32 (32/32) Icterohaemorrhagiae | 38.25 (17–61) (32/32) | 96.6% (28/29) | - | (21/32) “Definitive” Single high titre MAT. (7/32) “Borderline” Single High Titre MAT. (4/32) Autopsy | 84.4% (27/32) | - | 12.5% (4/32) | No patients excluded |
| Fairburn AC & Semple SJG. Lancet. 1956 [24] | Kuala Lumpur, Malaysia 1955 | RCT | 31 (31/83) * | 21(mean) (18–35) (31/31) | 100% (83/83) | 9.4 (Mean) (31/31) | (31/31) Paired serum MAT | 6% (2/31) | 33% (4/12) urea >14.2mmol/L | 0% (0/31) | (52/83) Penicillin and chloramphenicol treated patients excluded |
| Fletcher W. T Roy Soc Trop Med H.1927 [25] | Malaysia 1925–6 | Prospective case series | 32 (32/32) * | - | - | 8.5 (6–12) (26/32) | (13/20) guinea pig inoculation. (13/21) Positive urine microscopy. (18/21) Positive blood culture | 22.8% (7/32) | - | 3.1% (1/32) | No patients excluded |
| Gardner AD & Wylie JAH. Lancet. 1946 [26] | England, UK 1940–45 | Retrospective case series. Reference Laboratory | 182 (182/182) Icterohaemorrhagiae | - | 93.6% (147/157) | - | (182/182) Single high titre MAT (≥1:400) | - | - | 8.8% (16/182) | No patients excluded |
| Hall HE, et al. Ann Intern Med. 1951 [27] | Puerto Rico 1950 | NRCT | 12 (12/79) * | - | - | 8.6 (Mean) (12/12) | (9/12) Guinea pig inoculation. (3/12) paired MAT | 0% (0/12) | 0% (0/12) | 0% (0/12) | (67/79) Treated patients excluded |
| Hamilton Fairley N. Brit Med J. 1934 [28] | London, UK 1933–4 | Retrospective case series | 10 (10/10) * | 31 (22–60) (9/10) | 100% (10/10) | - | (8/10) Single high titre MAT. (≥1:300 for 7/8). (2/10) Autopsy | 100% (10/10) | - | 20% (2/10) | No patients excluded |
| Ido Y, et al. J Exp Med. 1918 [29] | Japan 1917 | Prospective, non-consecutive case series | 20 (20/23) hebdomidis | - | - | - | (20/23) Guinea pig inoculation | 0% (0/20) | - | 0% (0/20) | Three patients excluded as no confirmed diagnosis |
| Kocen RS. Brit Med J. 1962 [30] | Malaysia 1959–60 | NRCT | 33 (33/61) * | - | 100% (33/33) | 8.25 (mean) (33/33) | (NA/33) “Confirmed by blood culture or serology” | 15% (5/33) | - | 0% (0/33) | (28/61) Penicillin cohort excluded |
| Kouwenaar W. Trans Far-East Ass Trop Med. 1925 [31] | Sumatra, Indonesia 1920s | Prospective case series | 32 (32/32) * | - | - | - | (27/32) Direct identification of leptospires. (10/32) Demonstration of leptospires on autopsy | 100% (32/32) | 68% (15/22) “raised urea” | 18.8% (6/32) | No patients excluded |
| Sumatra, Indonesia 1920s | Prospective case series | 58 (58/58) * | - | - | - | (40/58) Direct visualisation in urine. (18/58) Blood culture | 0% (58/58) | 44.8% (13/29) “raised urea” | 1.7% (1/58) | No patients excluded | |
| Kristensen B. Ugeskrift Laeger. 1935 [32] (Danish) | Denmark 1933–5 | Retrospective case series | 19 (19/19) Icterohaemorrhagiae | 40 (13–65) (19/19) | 68% (13/19) | - | (19/19) Single High Titre (Titre not specified) | 100% (18/18) | - | 26.3% (5/19) | No patients excluded |
| McClain BL, et al. Ann Intern Med. 1984 [33] | Panama 1983 | RCT | 15 (15/69) * | - | 100% (15/15) | 7.7 (Mean) (S.D. 1.5) (15/15) | (28/69) Culture positive. (1/29) Serological conversion only | 0% (15/15) | - | 0% (0/15) | (54/69) Patients treated or with life threatening illness excluded |
| Minkenhof J. Lancet. 1947 [34] | Netherlands 1946 | Retrospective case series | 17 (17/49) * | - | - | (2–48) (17/17) | Positive agglutination ≥1:1000 (17/17), (3/17) direct identification of leptospires | 0% (0/17) | - | 0% (0/17) | (32/49) No laboratory diagnosis |
| Molner JG, et al. JAMA. 1948 [35] | USA, Detroit 1937–48 | Retrospective cases series | 78 (78/78) * | 40 (3–64) (78/78) | 93.6% (73/78) | - | (73/78) Single MAT (≥1:300). (5/78) by autopsy | 100% (78/78) | - | 39.7% (31/78) | No patients excluded |
| USA 1905–1941 | Summary of case reports | 178 (178/178) * | - | - | - | (178/178) “Confirmed diagnosis” | - | - | 24.8% (44/178) | No patients excluded | |
| Mulder J, et al. Geneesk Tijdschr Ned-indië. 1931 [36] [Dutch] | Borneo 1929–30 | Prospective case series | 50 (50/50) * | “20–50 years old” | - | - | (41/50) Positive guinea pig inoculation. (18/50) MAT Single titre (≥1:400) | 8% (4/50) | - | 4% (2/50) | No patients excluded |
| Patterson HM. JAMA. 1947 [37] | Hawaii, USA 1941–1946 | Retrospective case series | (44/61) Icterohaemorrhagiae | - | - | 15.3 (mean) (44/44) | (44/44) Single high titre MAT (≥1:300). (?/44) Paired and rising titre. | - | - | 0% (0/44) | (17/61) Patients received treatment with antibiotics or serum |
| Robinson CR & Kennedy HF. J R Army Med Corps. 1956 [38] | Malaysia 1953 | Retrospective case series | (29/31) * | - | 100% (29/29) | - (1–11) (29/29) | (20/23) Positive culture. (28/29) Single high titre MAT. (Titre not specified) | 0% (0/29) | 58.6% (17/29) >16mg/100 ml blood | 0% (0/29) | (2/31) Patients excluded as no laboratory diagnosis |
| Ross Russell RW. Lancet. 1958 [39] | Malaysia 1957–8 | RCT | 25 (25/52) * | 21 (mean) (18–36) (25/25) | 100% (25/25) | 9.4 (25/25) | (NA/25) “Culture or serology” | 20% (5/25) jaundice. 52% | (13/25) Urea>16mmol/L | 0% (0/25) | (27/52) Tetracycline treated patients excluded |
| Rugiero HR et al. Rev Med Cienc Af. 1948 [40] (Spanish) | Argentina 1948 | Retrospective case series | 12 (12/12) * | 14.5 (10–28) (12/12) | - | - | (12/12) Single high titre MAT (≥1:50) | 0% (0/12) jaundice- | 0% (0/12) | No patients excluded | |
| Schüffner W. Deut Med Wochenschr. 1941 [41] (German) | Netherlands 1924–39 | Retrospective case series. Dutch reference laboratory | 272 (272/272) * | - | - | - | (272/272) Single high titre MAT. (Titre not specified) | 100% (272/272) | 35.8% (38/106) “oliguria” | 19.1% (52/272) | No patients excluded |
| Netherlands 1924–39 | Retrospective case series. Dutch reference laboratory | 158 (158/158) * | - | - | - | (158/158) Single high titre MAT. (Titre not specified) | 0% (158/158) | 5.3% (5/95) “oliguria” | 0% (0/158) | No patients excluded | |
| Senekjie HA. JAMA. 1944 [42] | Louisiana, USA 1939–44 | Retrospective case series | 30 (30/30) * | - (14–68) | 96.7% (29/30) | 8–37 (30/30) | (24/30) single high titre MAT (≥1:300). (7/30) through direct identification of leptospires | 93% (28/30) | 100% (30/30) urea >17mmol/L | 16.7% (5/30) | No patients excluded |
| Slot G, Van der Walle N. Geneesk Tijdschr Ned-indië. 1932 [43] [Dutch] | Sumatra, Indonesia 1929–30 | Retrospective case series | 17 (17/17) * | - | - | (2–15) (17/17) | (3/17) Leptospirosis Culture. (7/17) Animal inoculation. (7/17) Positive agglutination (≥1:400) | 47.1% (8/17) | - | 0% (0/17) | No patients excluded |
| Smith J. Brit J Ind Med. 1949 [44] | Scotland, UK 1934–48 | Reference laboratory Scotland. Retrospective case series | 198 (198/214) * | 25.5 (214/214) | 52.8% (113/214) | - | (214/214) high titre (≥1:10). (93/187) Animal inoculation | 64% (137/214) | 59.5% (127/214) urea >14.3mmol/L | 7.6% (15/198) | Treated cohort excluded (16/214) |
| Swan WGA & McKeon JA. Newcastle M J. 1938 [45] | Newcastle, England 1933–7 | Retrospective case series | 18 (18/30) * | 36 (29/30) | 100% (30/30) | - | (8/30) Inoculation of Guinea Pig. (9/30) Diagnosed at autopsy. (23/30) Single high titre MAT. (≥1:100 (up to 3 years later)) | 96.7% (29/30) | 100% (16/16) urea >11mmol/L | 22.2% (4/18) | (12/30) Treated (serum) cohort excluded |
| Taylor J & Goyle AM. Indian J Med Res 1931 [46] | Andaman Islands, India 1929 | Prospective case series | 46 (46/64) * | - | 100% (46/46) | 7 days (2–16) | (36/64) Blood culture positive. (15/48) Positive urine microscopy. (3/19) Positive animal inoculation | 65.2% (30/46) | - | 19.6% (9/46) | (36/64) Cases excluded with no laboratory diagnosis |
| Van Riel J. Ann Soc Belg Med Tr. 1939 [47] (French) | Democratic Republic of the Congo 1937–8 | Retrospective case series | 32 (32/32) * | - | 100% (32/32) | 25 (mean) (10–63) (32/32) | (32/32) Single high titre MAT (Titre Not Specified) | 65.6% (21/32) | - | 9.4% (3/32) | No patients excluded |
| Vervoort H. Geneesk Tijdschr Ned-indië. 1923 [48] [Dutch] | Sumatra, Indonesia 1923 | Prospective case Series | 90 (90/90) * | - | - | - | (90/90) Blood culture positive | 8.9% (8/90) | - | 2.2% (2/90) | No patients excluded |
| Walch-Sorgdrager B. B World Health Organ. 1939 [49] | Netherlands 1924–39 | Retrospective case series | 12 (12/12) Canicola | - | - | - | (4/12) Positive urine culture. (12/12) Positive serology (>1:300) | 0% (0/12) | - | 0% (0/12) | No patients excluded |
| Wilmaers L & Renaux E. Arch Méd Belg. 1917 [50] [French] | Belgium 1916 | Retrospective case series | 22 (22/47) * | - | 22/22 (100%) | - (7–13) (22/22) | (22/22) Isolation of leptospira | 100% (22/22) | - | 0% (0/22) | (25/47) Cases excluded as no laboratory diagnosis |
When studies contained more than one patient series each series was displayed separately. All available data are included, but if data were not extractable it is indicated by a “-“. Percentage and (number/total number of patients) are quoted, but if no patient number was quoted then a “NA” is used. If no information on serovars is present a “*” is used.