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Background: Leptospirosis has a mortality rate of 5-20%. Poor prognostic factors are older age; oliguria; elevated potassium, creatinine and/or bilirubin levels; and altered mental status. We conducted this retrospective study to analyse the predictors of mortality among Indian patients with leptospirosis., Methods: Clinical, biochemical, demographic and treatment related data (time between onset of symptoms and commencement of leptospira specific antibiotics) of 101 leptospirosis patients were reviewed. Predictors identified by univariate analysis were analysed by multivariable Cox regression for survival analysis., Results: Prominent clinical features were: fever (101/101, 100%), jaundice (62, 62.4%), vomiting (42, 41.6%), oliguria (35, 34.7%), cough (18, 17.8%) and dyspnoea (10, 10.0%). Common complications were acute kidney injury (22, 21.8%), cardiovascular collapse (13, 12.9%), haemorrhages (10, 10.0%), meningitis (7, 6.9%), acute respiratory distress syndrome and pancreatitis (5, 5.0% each). Seventeen patients died (16.8%). Univariate predictors of mortality were older age, delayed antibiotic therapy, higher bilirubin, aspartate aminotransferase, alkaline phosphatase, leucocyte count and aspartate/alanine aminotransferase ratio (AAR). Only AAR (HR 1.208, 95% CI 1.051-1.388) and number of days the patient was symptomatic before access to specific antibiotic therapy (HR 1.304, 95% CI 1.081-1.574) remained significant predictors after Cox regression., Conclusions: Multivariate analysis showed high AAR and delayed antibiotic therapy might be associated with fatality., (© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with leptospirosis are commonly treated with antibiotics. Jarisch-Herxheimer reaction caused by toxic bacterial substances massively released as a result of the antibiotic mediated-bacterial lysis occurs in some patients which may aggravate the existing severe clinical manifestations. In this study, a humanized-murine single-chain monoclonal antibody (HuScFv) was produced and tested as an alternative of antibiotics for treatment of leptospirosis. Complementary DNA was prepared from total RNA of a murine hybridoma clone secreting monoclonal antibody (MAb) specific to LipL32 of pathogenic Leptospira spp. The MAb had therapeutic efficacy in Leptospira challenged hamsters. The VH and VL coding sequences were amplified using the cDNA as a template. The sequences were linked to form a single-chain variable murine DNA fragment (muscFv). CDR sequences of the muscFv were grafted onto the best matching human VH and VL immunoglobulin frameworks. After cloning of the humanized murine DNA sequences (huscFv) into a phagemid vector and the vector was introduced into competent Escherichia coli, the HuScFv was produced. On the same weight basis, the HuScFv possessed equal neutralizing activities to the murine ScFv counterpart against heterologous Leptospira-mediated hemolysis in vitro and rescued hamsters from a heterologous Leptospira lethal challenge. The HuScFv antibody has high therapeutic potential as an alternative to antibiotics for human leptospirosis, especially for drug hypersensitive patients.

Leptospirosis is an emerging zoonosis. In the Andaman Islands during the early twentieth century, it occurred in the penal settlements of the British India Administration, mostly as Weil's disease, an acute febrile illness with hepato-renal complications. It was caused by leptospires belonging to groups Akiamy A and Andamans A. After the 1930s nothing further is known regarding the disease until the late 1980s, when Andaman haemorrhagic fever (AHF), a mysterious illness with the majority of cases presenting pulmonary involvement, appeared. AHF was later identified as leptospirosis and severe pulmonary haemorrhage was shown for the first time as a complication of leptospirosis from India. Leptospirosis continues to occur in the Islands annually. It generally presents as two separate clinical syndromes: the hepato-renal form, and the pulmonary form, which is associated with high case fatality rates ranging from 10 to 15%. Infections are due to a variety of serovars, Valbuzzi being the commonest. Leptospira interrogans sensu stricto has been the predominant infecting species. Doxycycline has been shown to confer a beneficial effect in reducing the clinical illness and mortality during outbreaks. The history of leptospirosis in the Islands, its epidemiology, clinical spectrum, characteristics of the isolates and control are reviewed and discussed in this article.

Background: Although the majority of patients with reported leptospirosis are male, several seroepidemiologic studies demonstrated that leptospirosis seroprevalences are at least identical between both sexes. To study the effect of sex on the severity--and possibly, recognition--of leptospirosis, we conducted a sex-specific analysis of the clinical manifestations of the disease among patients with reported leptospirosis in Germany during 1997-2005., Methods: Data on demographic characteristics, symptoms, place of infection and place of residence when infection occurred, possible exposure risks, infecting serovars, and mortality were evaluated for patients with laboratory-confirmed leptospirosis reported in Germany during 1997-2005. Mantel-Haenszel odds ratios (OR(MH)), adjusted for age, were used to determine the association between sex and the frequency of reported symptoms., Results: Among 338 patients with leptospirosis (263 male patients and 75 female patients) reported in Germany during 1997-2005, male patients were more likely than female patients to be hospitalized (OR, 2.6; P<.01) and to exhibit symptoms of severe leptospirosis with jaundice (OR(MH), 3.7; P<.01), renal impairment (OR(MH), 3.4; P<.01), and hemorrhage (OR(MH), 7.8; P<.05). These sex-related differences were not associated with differences in exposure risks, presumptive infecting serogroups, or health-seeking behavior., Conclusions: Our results indicate that male sex is associated with a higher severity of clinical leptospirosis. Reports on male predominance in leptospirosis may thus reflect sex-related variability in the incidence of severe disease, rather than different infection rates. In clinical practice, sex differences in the manifestation of leptospirosis may cause systematic underinvestigation and undertreatment of the disease in female patients.

Leptospirosis is a re-emerging infectious disease, affecting both animals and humans worldwide. Multiple organ involvement may be encountered in leptospirosis, and early renal involvement is very common, characterized by tubulo-interstitial nephritis and tubular dysfunction. All 12 patients diagnosed in Chang Gung Memorial Hospital (Taiwan) between 1997 and 1999 had acute renal failure, with five patients requiring dialysis. Leptospira shermani is the main serovar encountered in Taiwan, and penicillin may dramatically rescue patients from multiple organ failure provided it is given early. To understand the mechanism behind tubular injuries by leptospira infection, outer membrane proteins (OMPs) extracted from pathogenic leptospira were given to tubular cells in culture. Our in vitro experiment showed that OMPs of pathogenic leptospira activate nuclear NFkappaB binding and stimulate downstream inducible nitric oxide (iNOS), monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) expression. These results indicate that leptospiral infection may induce tubulo-interstitial nephritis through a toxic component in the outer membrane followed by expression of inflammatory genes.