Lethal gram- negative spirochete Leptospira characterization and disease mechanism with infection of Leptospirosis spread in Sri Lanka.

Leptospirosis is a zoonotic disease caused by spirochetes of the genus Leptospira, affecting most mammals and rodents. It has a wide spectrum of clinical manifestations, ranging from mild illness to adverse diseases associated with multi-organ dysfunction. The global mortality and morbidity rate of leptospirosis is estimated at 58,900 deaths per year and 2.9 million disability-adjusted life years. In Sri Lanka, the annual incidence of leptospirosis is estimated at 300 (95%) per 100,000 people. Leptospirosis is a long, motile bacterium with over 300 servers, categorized into several semigroups. The most common servers in Sri Lanka are Australis, Banking, Batavia, Nicola, Annapurna, Hard, Icterohaemorrhagiae, Pyogenes, Pomona, Hebdomadis, and Cynopteri. The disease is associated with different animal hosts, such as cattle, pigs, sheep, and farm animals. The spirochete order of bacteria, Spirochaetaceae and Leptospiraceae, is divided into several species and subspecies, called servers. Leptospires are obligate aerobic and slow-growing organisms, ranging between 6-20 μm in length and 0.1 μm in diameter.Leptospira, a type of spirochete, have an outer membrane composed of lipopolysaccharides (LPS), which is functionally versatile due to its complex composition of proteinaceous components. These proteins, including lipoprotein L32, lipopolysaccharides (LPS), immunoglobulin-like proteins (Big), endostatin-like proteins (Len), and OMP A-like lipoprotein (Loa22), are highly virulent due to their virulence against host defense units. Leptospira interrogate consists of two flagella, an axial filament and endoflagella, and requires aerobic conditions with adequate nitrogen, phosphate, calcium, magnesium, and iron. Pathogenic species require unsaturated fatty acids, vitamins B1 and B12, and biotin. Leptospirosis is a zoonotic disease that transmits from carrier animals, mainly rats and mice, and can be transmitted through direct contact with infected animals or indirect contact with contaminated environmental media. Urban slums with inadequate sanitation and poor housing are at high risk of rat and mouse exposure and leptospirosis, which is expected to rise due to climate change and increased urban poor in tropical areas. Leptospirosis is a highly invasive disease that can be transmitted through various routes, including urination, breastfeeding, sexual intercourse, and livestock and pet-borne transmission. The disease enters the host through small abrasions, breaches of the surface internal system, conjunctiva, mucous membrane, and genital tract. The bacteria accumulate in the kidneys and can be shed in urine for weeks to months. After the number of leptospires in the blood and tissues reaches a critical level, lesions due to undefined leptospiral toxin or toxic cellular components and consequent symptoms appear. Leptospiral LPS preparations exhibit activity in biological assays for endotoxin similar to other Gram-negative bacteria. The humoral immune response appears in the first week of infection, activating the process of phagocytosis by neutrophils and macrophages. In humans, systemic infection can produce severe multi-organ manifestations, including chills, fever, headache, diarrhea, myalgic, malaise, prostration, retro-oral pain, conjunctival suffusion, muscle tenderness, and lung involvement. The pathophysiological mechanism of leptospirosis remains poorly understood, but it is theorized that the disease occurs due to the host immune response towards the organisms. As leptospires bind to host cells, cytokines (interleukin-6, interleukin-10, TNF alpha) and antimicrobial peptides (AMP’s) are released to limit invasive damages incurred by the bacteria. Acute kidney injury (AKA) in severe leptospirosis varies from 40% to 60%, with major histological findings being acute interstitial nephritis, acute tubular necrosis, and vasculitis. Pulmonary manifestations are an important and serious complication associated with poor outcomes. Pulmonary involvement is higher in urban populations and has a male preponderance and increased incidence in smokers. Recent studies using echocardiograms and ECG show that nearly 50% of patients have cardiac involvement, which tends to predict a poor outcome in leptospirosis. Leptospirosis is a rare and complex disease that can cause severe renal dysfunction, pericardial involvement, hepatic involvement, bleeding, and complications. The disease’s symptoms can be confusing and lead to false negative diagnoses. Early detection of the infection is crucial for preventing complications and identifying potential reservoir hosts and the likely source of infection. Diagnosis methods for leptospirosis include direct evidence, such as demonstration of leptospires or their DNA or isolation, and indirect evidence based on the detection of specific antibodies to leptospires. Blood and cerebrospinal fluid (CSF) should be obtained as soon as possible on presentation within the first week of the acute illness. Isolation of leptospires remains the gold standard test available in laboratories, but it is time-consuming and laborintensive.Polymerase chain reaction (PCR) has the advantage of diagnosing early disease, especially during the acute leptospiremic phase.