A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was conducted from July 2000 through December 2001 to compare the clinical efficacies of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis. A total of 173 patients with severe leptospirosis were randomly assigned to be treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86). The primary outcome was time to fever resolution. Survival analysis demonstrated that the median duration of fever was 3 days for both groups. Ten patients (5 in each group) died of leptospirosis infection. There were no statistically significant differences in the duration of organ dysfunction. Ceftriaxone and sodium penicillin G were equally effective for the treatment of severe leptospirosis. Once-daily administration and the extended spectrum of ceftriaxone against bacteria provide additional benefits over intravenous penicillin.

The presence of oliguria, hyperkalemia, pulmonary rales, or hypotension on admission in patients with leptospirosis indicated high risk of death. Intensive care and early intervention should be provided for patients who present with these risk factors.

Hybridomas secreting specific monoclonal antibodies (MAb) to all members of the genus Leptospira (clone LF9) and those that are specific only to the pathogenic species (clones LD5 and LE1) were produced. MAb LF9, which was immunoglobulin G1 (IgG1), reacted to a 38-kDa component of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated whole-cell lysates of all Leptospira spp., while MAb LD5 and MAb LE1, which were IgG1 and IgG2a, respectively, reacted to the 35-to 36-kDa components of all serogroups of the pathogenic species of Leptospira. The MAb LD5 was used in a dot blot-enzyme-linked immunosorbent assay (dot-ELISA) for detecting Leptospira antigen in urine samples serially collected from two groups of patients diagnosed with leptospirosis, i.e., 36 clinically diagnosed patients and 25 Leptospira culture confirmed patients. Their serum samples were tested serologically by IgM Dipstick assay, indirect immunofluorescence assay (IFA), and/or microscopic agglutination test (MAT). Urine samples of 26 patients diagnosed with other illnesses and 120 healthy individuals served as controls. For the first group of patients, who had been ill for an average of 3.4 days before hospitalization, the IgM Dipstick test, IFA, and MAT were positive for 69.4, 70.0, and 85.7% of patients, while the Leptospira antigenuria tested by the MAb-based dot-ELISA was positive for 75.0, 88.9, 97.2, 97.2, and 100% of patients on days 1, 2, 3, 7, and 14 of hospitalization, respectively. All but 1 of 11 patients whose serum samples collected on the first day of hospitalization were IgM seronegative, were positive by urine antigen test on day 1. This is strong evidence that detection of antigen in urine can provide diagnostic information that could be useful in directing early therapeutic intervention. The MAT was positive in 10 of 12 patients (83.3%) of the 25 culture-positive Leptospira patients who had been ill for an average of 5.04 days before hospitalization, and the Leptospira antigen was found in 64.0, 84.0, 96.0, 100, 100, 100, and 100% of the patients' urine samples collected on days 1, 2, 3, 4, 5, 6, and 7 of hospitalization, respectively. Leptospira antigenuria was found in 3 of the 26 patients diagnosed with other illnesses and 1 of the 120 healthy controls. The reasons for this positivity are discussed. The detection of antigen in urine by the monoclonal antibody-based dot-ELISA has high potential for rapid, sensitive, and specific diagnosis of leptospirosis at a low cost.