Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fever (<15 days), without an obvious focus of infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of azithromycin. The cure rate, fever clearance time, and adverse drug events were compared between the two study groups. A total of 296 patients were enrolled in the study. The cause of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis; 57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11 patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse events occurred more frequently in the doxycycline group than in the azithromycin group (27.6% and 10.6%, respectively; P ‫؍‬ 0.02). In conclusion, doxycycline is an affordable and effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was better tolerated than doxycycline but is more expensive and less readily available.

Abstract. A prospective study in Thailand identified 106 patients with culture-proven leptospirosis. The accuracy of the microscopic agglutination test (MAT) in predicting the infecting serovar was evaluated in 78/106 (74%) patients with a diagnostic titer. MAT correctly determined the infecting serovar in 26 cases (33%), indicating that this assay is a poor predictor of infecting serovar in our setting.Leptospirosis is an acute febrile illness caused by pathogenic members of the genus Leptospira . This disease has a worldwide distribution but is most common in tropical regions, including Thailand. [1][2][3][4][5] In a prospective observational study of undifferentiated fever in 845 patients in rural Thailand, leptospirosis was reported to be responsible for 36.9% of cases.4 Leptospira isolation is the gold standard for confirmation of leptospirosis in humans. This provides definitive identification of the infecting serovar and is an important technique for the study of outbreaks and global epidemiology. It has a number of significant drawbacks, however, including low diagnostic sensitivity, prolonged culture period, and the associated expertise necessary for identification of the infecting serovar together with related costs.The microscopic agglutination test (MAT) is commonly used to reach a serologic diagnosis of leptospirosis and is performed by detecting agglutinating antibodies by mixing patient serum with a panel of Leptospira serovars that are considered to be representative of the endemic strains for a given region. 3A positive diagnostic result for the MAT is a 4-fold change in titer or a single pre-defined titer. MAT has also been used to provide an indication of the presumptive serovars causing leptospirosis in a given region. The ability of MAT to accurately determine the prevalent serovars was called into question by a retrospective study conducted in Barbados where disease in 151 individuals was caused by four serovars ( L. kirschneri serovar Bim, L. interrogans serovar Copenhageni, L. borgpetersenii serovar Arborea, and L. noguchii serovar Bajan); serologic analysis was found to have a low degree of accuracy for determining the infecting serovar in this setting. 6 The epidemiology of infecting isolates in Thailand differs markedly, with a recent study showing that the majority of human disease was caused by L. interrogans serovar Autumnalis. 7 The aim of this study was to determine whether MAT provides an accurate guide to the infecting serovars of Leptospira in Thailand.A prospective study was conducted in hospitals situated in six provinces in northeast Thailand (Udon Thani, Burirum, Loei, Nakhon Ratchasima, Maha Sarakham, and Yasothon) between October 2000 and December 2006 to identify patients with culture proven leptospirosis. The study protocol was approved by the Ethical Committee of the Ministry of Public Health, Royal Government of Thailand. Admitting physicians were asked to recruit patients of all ages who they suspected on clinical grounds to have leptospirosis. Clinical features cons...

Pulmonary involvement in leptospirosis is emerging as a common complication of severe leptospirosis. A prospective randomized controlled trial of desmopressin or high-dose (pulse) dexamethasone as adjunctive therapy in 68 patients with pulmonary involvement associated with severe leptospirosis was conducted between July 2003 and October 2006 at five hospitals in Thailand. There were 23 patients in the desmopressin group, 22 in the pulse dexamethasone group, and 23 in a control group who received standard critical care alone. The diagnosis of leptospirosis was confirmed in 52 patients (77%). There were 15 deaths (22%), of which eight patients received desmopressin, four patients received pulse dexamethasone, and three patients received critical care alone (p 0.19). Eight patients with confirmed leptospirosis died (five patients in the desmopressin group, one in the pulse dexamethasone group and two in the control group). The mortality was not significantly different in the desmopressin group or pulse dexamethasone group compared to the control group in both intention-to-treat patients, and in patients with confirmed leptospirosis. There were no serious events associated with desmopressin treatment, although pulse dexamethasone treatment was associated with a significant increase in nosocomial infection. The results of logistic regression analysis revealed that serum bilirubin level was the only significant risk factor associated with mortality (OR 0.759, 95% CI 0.598-0.965, p 0.024). The results obtained in the present study do not support the use of either pulse dexamethasone or desmopressin as adjunct therapy for pulmonary involvement associated with severe leptospirosis.