Leptospirosis

Leptospirosis is a known One Health issue because its transmission involves complex interactions among humans, animals, and the environment. Transmission commonly occurs through water when it is contaminated with urine from infected animals like rodents and livestock. Environmental factors such as heavy rainfall, flooding, and poor sanitation significantly increased the risk of leptospirosis transmission by allowing the spread of contaminated water. Additionally, urbanization and inadequate waste management promote the growth of rodent populations, which act as primary reservoirs for the bacteria. Climate change is associated with a higher incidence of leptospirosis because extreme weather events create a suitable environment for outbreaks. The One Health approach highlights the significance of coordinated efforts among human health, veterinary health, and environmental health, and environmental management sectors to prevent and control the disease. Leptospirosis disproportionately affects populations in environments where exposure is unavoidable, particularly in regions with inadequate drainage, poor sanitation, and frequent flooding. In these environments, individuals are routinely exposed to contaminated soil and water, which increases infection risk. These patterns underscore the role of environmental conditions and structural inequalities in shaping disease distribution. Beyond direct transmission from animal reservoirs, growing evidence indicates that Leptospira can persist in environmental reservoirs such as soil and freshwater systems, thereby extending the window of exposure beyond intermediate contamination events. Studies show that the organism survives for prolonged periods in moist environments, with factors such as temperature, pH, and nutrient availability affecting its viability. This persistence complicates traditional transmission models by enabling indirect exposure pathways that do not require recent animal contact. Public health interventions and One Health implementation Effective control of leptospirosis requires coordinated interventions across human, animal, and environmental health sectors. Public health strategies include surveillance systems to monitor outbreaks, particularly in regions prone to flooding and poor sanitation. Early diagnosis and improved laboratory capacity are essential for timely case identification and response. Animal health interventions include vaccination of livestock and domestic animals, as well as rodent control programs aimed at reducing reservoir populations. In agricultural and occupational settings, the use of protective equipment can reduce exposure risk among workers. Environmental interventions focus on improving sanitation infrastructure, ensuring safe water management, and implementing waste control measures to limit contamination of soil and water. Urban planning and drainage improvements are also important in reducing standing water that facilitates bacterial survival. The One Health framework emphasizes interdisciplinary collaboration among healthcare providers, veterinarians, environmental scientists, and policymakers to improve prevention and outbreak response. An estimated one million severe cases of leptospirosis in humans occur every year, causing about 58,900 deaths. The disease is most common in tropical areas of the world, but may occur anywhere. Infected animals may have no, mild, or severe symptoms. These may vary by the type of animal. In some animals, Leptospira live in the reproductive tract, leading to transmission during mating. ==Signs and symptoms==

(red conjunctiva) together with jaundice is a specific feature of leptospirosis. The phases of illness may not be distinct, especially in patients with severe illness. About 90% of those infected experience mild symptoms, while 10% experience severe leptospirosis. Leptospiral infection in humans causes a range of symptoms, though some infected persons may have none. The disease begins suddenly with fever accompanied by chills, intense headache, severe muscle aches, and abdominal pain. The hallmark of the second phase is inflammation of the membranes covering the brain. Signs and symptoms of meningitis include severe headache and neck stiffness. Kidney involvement is associated with reduced or absent urine output. The classic form of severe leptospirosis, known as Weil's disease, is characterised by liver damage (causing jaundice), kidney failure, and bleeding, which happens in 5–10% of those infected. Lung and brain damage can also occur. For those with signs of inflammation of membranes covering the brain and the brain itself, altered level of consciousness can happen. A variety of neurological problems such as paralysis of half of the body, complete inflammation of a whole horizontal section of spinal cord, and Guillain-Barré syndrome are the complications. Signs of bleeding such as petechiae, ecchymoses, nose bleeding, blackish stools due to bleeding in the stomach, vomiting blood, and bleeding from the lungs can also be found. Prolongation of prothrombin time in coagulation testing is associated with severe bleeding manifestations. However, low platelet count is not associated with severe bleeding. Pulmonary haemorrhage is alveolar haemorrhage (bleeding into the alveoli of the lungs) leading to massive coughing up of blood, and causing acute respiratory distress syndrome, where the risk of death is more than 50%. Rarely, inflammation of the heart muscles, inflammation of membranes covering the heart, abnormalities in the heart's natural pacemaker and abnormal heart rhythms may occur. ==Cause==

Bacteria of a number of Leptospira sp. bacteria atop a 0.1 μm polycarbonate filter In addition, Leptospira bacteria have a flagellum located in the periplasm, associated with corkscrew-style movement. The 19 members of the P1 subclade include the eight species that can cause severe disease in humans: L. alexanderi, L. borgpetersenii, L. interrogans, L. kirschneri, L. mayottensis, L. noguchii, L. santarosai, and L. weilii. The bacteria thrive in warm and humid climates due to their preference for environments that maintain high moisture content and optimal temperatures for metabolic activity and motility. The bacteria can be found in ponds, rivers, puddles, sewers, agricultural fields, and moist soil. The number of cases of leptospirosis is directly related to the amount of rainfall, making the disease seasonal in temperate climates and year-round in tropical climates. Various mechanisms are known whereby animals can infect each other. Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle. House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house. Leptospirosis can also be transmitted by the semen of infected animals. Once humans are infected, bacterial shedding from the kidneys usually persists for up to 60 days. Infection through the placenta during pregnancy is also possible. It can cause miscarriage and infection in infants. Leptospirosis transmission through eating raw meat of wildlife animals has also been reported (e.g. psychiatric patients with allotriophagy). Transmission of Leptospirosis is via direct or indirect contact with urine from infected animals. These animals can include livestock, rodents, and pet animals. Humans serve as incidental hosts when infections come into contact with broken skin or mucous membranes, or with contaminated soil or water. Inadequate sanitation and hygiene during flooding events increase the transmission rate. Leptospirosis risk factors include exposures such as farming, swage management, and contact with infected animals. Along with environmental exposure to contaminated water. Leptospirosis outbreaks correlate with heavy rainfall and flooding events. Communities in tropical areas ad urban slums are primarily affected. ==Pathogenesis==

of Leptospira. The bacteria enter the human body through a breach in the skin or the mucous membrane, then into the bloodstream. The bacteria later attach to the endothelial cells of the blood vessels and extracellular matrix (a complex network of proteins and carbohydrates present between cells). The bacteria use their flagella to move between cell layers. They bind to cells such as fibroblasts, macrophages, endothelial cells, and kidney epithelial cells. They also bind to several human proteins such as complement proteins, thrombin, fibrinogen, and plasminogen using surface leptospiral immunoglobulin-like (Lig) proteins such as LigB and LipL32, whose genes are found in all pathogenic species. Through the innate immune system, endothelial cells of the capillaries in the human body are activated by the presence of these bacteria. The endothelial cells produce cytokines and antimicrobial peptides against the bacteria. These products regulate the coagulation cascade and movements of white blood cells. Macrophages presented in humans are able to engulf Leptospira. However, Leptospira can reside and proliferate in the cytoplasmic matrix after being ingested by macrophages. Those with severe leptospirosis can experience a high level of cytokines such as interleukin 6, tumor necrosis factor alpha (TNF-α), and interleukin 10. The high level of cytokines causes sepsis-like symptoms, which are life-threatening instead of helping to fight against the infection. Those who have a high risk of sepsis during a leptospirosis infection are found to have the HLA-DQ6 genotype, possibly due to superantigen activation, which damages bodily organs. Leptospira LPS only activates toll-like receptor 2 (TLR2) in monocytes in humans. The lipid A molecule of the bacteria is not recognised by human TLR4 receptors. Therefore, the lack of Leptospira recognition by TLR4 receptors probably contributes to the leptospirosis disease process in humans. Although various mechanisms in the human body fight against the bacteria, Leptospira is well adapted to such an inflammatory condition created by it. In the bloodstream, it can activate host plasminogen to become plasmin that breaks down extracellular matrix, degrades fibrin clots and complemental proteins (C3b and C5) to avoid opsonisation. It can also recruit complement regulators such as Factor H, C4b-binding protein, factor H-like binding protein, and vitronectin to prevent the activation of membrane attack complex on its surface. It also secretes proteases to degrade complement proteins such as C3. It can bind to thrombin, which decreases the fibrin formation. Reduced fibrin formation increases the risk of bleeding. Leptospira also secretes sphingomyelinase and haemolysin that target red blood cells. Leptospira spreads rapidly to all organs through the bloodstream. They mainly affect the liver. They invade spaces between hepatocytes, causing apoptosis. The damaged hepatocytes and hepatocyte intercellular junctions cause bile leakage into the bloodstream, causing elevated levels of bilirubin, resulting in jaundice. Congested liver sinusoids and perisinusoidal spaces have been reported. Meanwhile, in the lungs, petechiae or frank bleeding can be found at the alveolar septum and spaces between alveoli. Leptospira secretes toxins that cause mild to severe kidney failure or interstitial nephritis. The kidney failure can recover completely or lead to atrophy and fibrosis. Rarely, inflammation of the heart muscles, coronary arteries, and aorta are found. ==Diagnosis==

ing technique, revealing the presence of Leptospira bacteria Imaging In those who have lung involvement, a chest X-ray may demonstrate diffuse alveolar opacities. ==Prevention==

, Malaysia, that warns against swimming in the lake as it has tested positive for pathogenic Leptospira Only a few countries, such as Cuba, Japan, France, and China, have approved inactivated vaccines with limited protective effects. Side effects such as nausea, injection site redness and swelling have been reported after the vaccine was injected. Since the immunity induced by one Leptospiraserovar is only protective against that specific one, trivalent vaccines have been developed. Doxycycline is given once a week as a prophylaxis and is effective in reducing the rate of leptospirosis infections amongst high-risk individuals in flood-prone areas. In one study, it reduced the number of leptospirosis cases in military personnel undergoing exercises in the jungles. In another study, it reduced the number of symptomatic cases after exposure to leptospirosis under heavy rainfall in endemic areas. The prevention of leptospirosis from environmental sources like contaminated waterways, soil, sewers, and agricultural fields is disinfection used by effective microorganisms, which is mixed with bokashi mudballs for the infected waterways & sewers. ==Treatment==

Most leptospiral cases resolve spontaneously. Early initiation of antibiotics may prevent the progression to severe disease. Therefore, in resource-limited settings, antibiotics can be started once leptospirosis is suspected after history taking and examination. Based on a 1988 study, intravenous (IV) benzylpenicillin (also known as penicillin G) is recommended for the treatment of severe leptospirosis. Ceftriaxone (1 g IV every 24 hours for seven days) is also effective for severe leptospirosis. Cefotaxime (1 g IV every six hours for seven days) and doxycycline (200 mg initially followed by 100 mg IV every 12 hours for seven days) are equally effective as benzylpenicillin (1.5 million units IV every six hours for seven days). Therefore, there is no evidence on differences in death reduction when benzylpenicillin is compared with ceftriaxone or cefotaxime. Another meta-analysis done in 2013 reached a similar conclusion. For those with severe leptospirosis, including potassium wasting with high kidney output dysfunction, intravenous hydration and potassium supplements can prevent dehydration and hypokalemia. When acute kidney failure occurs, early initiation of haemodialysis or peritoneal dialysis can help to improve survival. For those with respiratory failure, tracheal intubation with low tidal volume improves survival rates. ==Prognosis==

The overall risk of death for leptospirosis is 5–10%. These complications can range from mild anterior uveitis to severe panuveitis (which involves all three vascular layers of the eye). ==Epidemiology==

(DALY) lost per 100,000 people per year The global health burden for leptospirosis can be measured by disability-adjusted life year (DALY). The score is 42 per 100,000 people per year, which is more than other diseases such as rabies and filariasis. Urban poor populations in densely populated cities are at particularly high risk due to limited access to sanitation and exposure to contaminated floodwaters. In countries such as Brazil, India, and the Philippines, outbreaks often follow heavy rainfall and flooding events. Leptospirosis is considered a neglected tropical disease (NTD), and its incidence may be significantly underreported due to diagnostic challenges and low awareness among healthcare providers. Leptospirosis is a worldwide zoonotic disease. Primarily found in the tropical and subtropical areas, in particularly those undergoing significant heavy rainfall and flooding. In a systematic review, it was found that 1 million cases and about 60,000 deaths occur annually worldwide due to Leptospirosis. The disease burden is higher among populations in low- and middle-income countries, where environmental factors and poor hygiene contribute to its spread and transmission. Animal reservoirs such as rodents, dogs, cattle, pigs, and wildlife contribute to environmental contamination through urinary shedding of Leptospira. Effective prevention therefore requires collaboration across public health, veterinary, and environmental sectors, including rodent control, animal vaccination, sanitation improvement, and reduction of exposure to contaminated water and soil. The disease is observed persistently in parts of Asia, Oceania, the Caribbean, Latin America and Africa. In the United States, there were 100 to 150 leptospirosis cases annually. In 1994, leptospirosis ceased to be a notifiable disease in the United States except in 36 states/territories where it is prevalent such as Hawaii, Texas, California, and Puerto Rico. About 50% of the reported cases occurred in Puerto Rico. In January 2013, leptospirosis was reinstated as a nationally notifiable disease in the United States. The global rates of leptospirosis have been underestimated because most affected countries lack notification, or notification is not mandatory. The socioeconomic status of many of the world's population is closely tied to malnutrition; subsequent lack of micronutrients may lead to increased risk of infection and death due to leptospirosis infection. Public health interventions Effective control of leptospirosis requires coordinated public health strategies that integrate human, animal, and environmental health approaches. Surveillance systems are essential for early detection of outbreaks, particularly in regions prone to flooding and extreme weather events. Integrated pest management, including rodent control programs and improved waste management, plays a critical role in reducing environmental contamination. Community-based interventions, such as health education and improved sanitation infrastructure, are also important in reducing exposure risk, especially in low-income urban settings. In addition, collaboration between veterinary and public health sectors enables vaccination of livestock and domestic animals, reducing transmission at the human-animal interface. These combined strategies reflect the application of the One Health approach in preventing and controlling leptospirosis. ==History==

The disease was first described by Adolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice, and nephritis." in Japan; in Europe and Australia, the disease was associated with certain occupations and given names such as "cane-cutter's disease", "swine-herd's disease", and "Schlammfieber" (mud fever). It has been known historically as "black jaundice", or "dairy farm fever" in New Zealand. Leptospirosis was postulated as the cause of an epidemic among Native Americans along the coast of what is now New England during 1616–1619. The disease was most likely brought to the New World by Europeans. Leptospira was first observed in 1907 in a post mortem kidney tissue slice by Arthur Stimson using silver deposition staining technique. He called the organism Spirocheta interrogans because the bacteria resembled a question mark. In 1908, a Japanese research group led by Ryukichi Inada and Yutaka Ito first identified this bacterium as the causative agent of leptospirosis and noted its presence in rats in 1916. Japanese coal mine workers frequently contracted leptospirosis. In Japan, the organism was named Spirocheta icterohaemorrhagiae. The Japanese group also experimented with the first leptospiral immunisation studies in guinea pigs. They demonstrated that by injecting the infected guinea pigs with sera from convalescent humans or goats, passive immunity could be provided to the guinea pigs. In 1917, the Japanese group discovered rats as the carriers of leptospirosis. Leptospirosis was subsequently recognised as a disease of all mammalian species. In 1933, Dutch workers reported the isolation of Leptospira canicola, which specifically infects dogs. In 1940, the strain that specifically infects cattle was first reported in Russia. In 2005, Leptospira parva was classified as Turneriella. With DNA–DNA hybridisation technology, L. interrogans was divided into seven species. More Leptospira species have been discovered since then. The WHO established the Leptospirosis Burden Epidemiology Reference Group (LERG) to review the latest disease epidemiological data of leptospirosis, formulate a disease transmission model, and identify gaps in knowledge and research. The first meeting was convened in 2009. In 2011, LERG estimated that the global yearly rate of leptospirosis is five to 14 cases per 100,000 population. ==Other animals==

secondary to leptospirosis infection Inflammation of the blood vessels, inflammation of the heart, meningeal layers covering the brain and spinal cord, and uveitis are also possible. ERU is an autoimmune disease involving antibodies against Leptospira proteins LruA and LruB cross-reacting with eye proteins. Live Leptospira can be recovered from the aqueous or vitreous fluid of many horses with Leptospira-associated ERU. Risk of death or disability in infected animals varies depending upon the species and age of the animals. In adult pigs and cattle, reproductive signs are the most common signs of leptospirosis. Up to 40% of cows may have a spontaneous abortion. Younger animals usually develop more severe disease. About 80% of dogs can survive with treatment, but the survival rate is reduced if the lungs are involved. ELISA and microscopic agglutination tests are most commonly used to diagnose leptospirosis in animals. The bacteria can be detected in blood, urine, and milk or liver, kidney, or other tissue samples by using immunofluorescence or immunohistochemical or polymerase chain reaction techniques. Silver staining or immunogold silver staining is used to detect Leptospira in tissue sections. The organisms stain poorly with Gram stain. Dark-field microscopy can be used to detect Leptospira in body fluids, but it is neither sensitive nor specific in detecting the organism. A positive culture for leptospirosis is definitive, but the availability is limited, and culture results can take 13–26 weeks for a result, limiting its utility. Paired acute and convalescent samples are preferred for serological diagnosis of leptospirosis in animals. A positive serological sample from an aborted fetus is also diagnostic of leptospirosis. Various antibiotics such as doxycycline, penicillins, dihydrostreptomycin, and streptomycin have been used to treat leptospirosis in animals. Fluid therapy, blood transfusion, and respiratory support may be required in severe disease. For horses with ERU, the primary treatment is with anti-inflammatory drugs. Leptospirosis vaccines are available for animals such as pigs, dogs, cattle, sheep, and goats. Vaccines for cattle usually contain Leptospira serovar Hardjo and Pomona, for dogs, the vaccines usually contain serovar Icterohaemorrhagiae and Canicola. Vaccines containing multiple serovars do not work for cattle as well as vaccines containing a single serovar, yet the multivalent vaccines continue to be sold. Isolation of infected animals and prophylactic antibiotics are also effective in preventing leptospirosis transmission between animals. Environmental control and sanitation also reduce transmission rates. ==References==