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.