Leptospirosis - A Complete Review

Leptospirosis is a rare but neglected bacterial infection that affects people and animals. It is caused by bacteria of the genus Leptospira. The disease was reported as early as 1886 by Adolf Weil. Leptospirosis may cause kidney damage, meningitis, liver failure, respiratory distress, and even death when it is not treated. Occupations at risk include surfers, slaughterhouse workers, farmers, sewer workers and, people working on derelict buildings. Amjad Islam et al. had reported that among Asian countries, its highest prevalence is found in India. In 2015, Federico Costa et al. estimated that leptospirosis causes 1.03 million cases worldwide each year. The pooled mortality rate is 25%. WHO has estimated that 0.1 to 1 per 100 000 people living in temperate climates are affected each year, with the number increasing to 10 or more per 100 000 people living in tropical climates. It is reported in all continents except Antarctica. Lesser availability of treatment resources is detrimental, and unfortunately, it is commonly reported in lower-middle-income group countries.

The current treatment modalities for milder cases of leptospirosis rely on antibiotic administration viz penicillin, ampicillin, cefmetazole, oxalactam, ceftizoxime, and cefotaxime.

Whereas, in severe cases, intravenous penicillin G has long been the drug of choice; the patients treated with penicillin for the management of this disease are to be monitored throughout the treatment to prevent the severe threat of potential Jarisch-Herxheimer reactions. In particular, this immune-mediated hypersensitivity reaction may occur within 4-5 h after administration of penicillins. Various kinds of human leptospirosis vaccines have been developed, including inactivated whole-cell, outer-envelope, and recombinant vaccines. Of these, only a multivalent inactivated leptospirosis vaccine (killed vaccine) is available in China, Japan, and Vietnam. However, human vaccines for leptospirosis are serovar-specific and require yearly boosters. So there is a need for the development of novel compounds which have leptospirocidal activity. Notably, drugs for treating leptospirosis are minimum; the present research for the development of novel lead compounds for this pathogen is very limited.

This review aims to summarize the most recent literature on synthetic lead molecules, natural products for its treatment, drug targets, etc., and provide recommendations to researchers who may encounter difficulties in finding details on the subject.

Keywords: Drug targets, Leptospirosis, Natural products, Synthetic analogs.