ABSTRACT
Leptospira are motile, very thin, tightly coiled spirochetes with a typical gram-negative cell wall. Recently (2019) the taxonomy of the Genus Leptospira (leptospires) underwent a major review. This latest study used whole-genome sequencing (WGS) and other techniques and identified 30 new Leptospira species giving a total of 64 named species. The taxonomy generated by this study identified two major clades (saprophytic and pathogenic) and four sub-clades P1, P2, S1, and S2. A number of animal species act as a reservoir of infection, the common ones being rodents, but dogs and livestock can also act as reservoirs. Infected animals excrete the bacterium in their urine thus contaminating water sources and soil. Infection is acquired by contact with water or contaminated soil and entry is via skin lesions, or lesions in the mucosae of the respiratory tract, digestive tract or conjunctivae. Globally, Leptospira is the commonest zoonosis. The organism is spread around the body by the blood, entering all organs and thus giving rise to a wide spectrum of clinical presentations. Leptospirosis is a global disease, primarily a disease of tropical and subtropical regions and relatively uncommon in temperate climates. It is endemic in many countries, but outbreaks are also associated with adverse weather. The host response is through recognition of MAMPS of leptospires through pattern-recognition receptors especially TLR2 and NOD1 and 2. These lead to production of pro-inflammatory cytokines that recruit macrophages, neutrophils and DC to the site of infection. Complement and IgM and IgG antibodies are also involved in clearance of the organism. Leptospires, especially those that are pathogenic, use several ways of evading the host response.
Most infections with leptospires are asymptomatic (although seropositive) and self-limiting. The incubation period is about 10 days but can range from 5–30 days. Symptomatic disease may present as a biphasic illness with an initial nonspecific phase (leptospiremic phase) lasting about 7 days. After the temperature falls, more severe specific system-based symptoms may develop within a few days. The commonest presentation is anicteric, e.g. aseptic meningitis (80–90%) compared to icteric with renal failure (Weil’s Disease10–20%).
The laboratory diagnosis is made with: Dark-ground microscopy; Culture; Serology and Genomics. Leptospires can be detected in the blood, cerebrospinal fluid (CSF) or urine by dark-ground microscopy. The organism can be cultured on a variety of specialist media after incubation at 30°C for 6–8 weeks. Serologically, the disease can be diagnosed by the macroscopic agglutination test (MALT) or the IgM ELISA. Various genomic assays exist: PCR, RT-PCR real-time PCR, LAMP WGS. The differential diagnosis includes Dengue viral meningitis, viral hepatitis, malaria, hantavirus and Legionnaires disease.
Patients with mild disease are treated with doxycycline or azithromycin. Hospitalized patients with severe cases are given IV penicillin, and oral doxycycline for up to 7 days. A Jarisch-Herxheimer reaction may occur following antimicrobial therapy and is characterized clinically by fever, rigors, and hypotension. Prevention is by identifying risks, antimicrobial prophylaxis for individuals at high risk and animal immunization (although shown to have variable levels of protection).
Vaccines pose a major challenge because of the many different serovars. There are many new approaches, helped by WGS, and include live vaccines against some OMP, DNA vaccines and the use of NOD-1 and 2 agonists.
