More than ten genetic types ofLeptospira cause disease in humans.[13] Both wild and domestic animals can spread the disease, most commonly rodents.[8] The bacteria are spread to humans throughanimal urine orfeces, or water or soil contaminated with animal urine and feces, coming into contact with the eyes, mouth, nose or breaks in the skin.[8] In developing countries, the disease occurs most commonly in pest control, farmers and low-income people who live in areas with poor sanitation.[5] In developed countries, it occurs during heavy downpours and is a risk to pest controllers,sewage workers[14] and those involved in outdoor activities in warm and wet areas.[5] Diagnosis is typically by testing forantibodies against the bacteria or finding bacterialDNA in the blood.[5]
Efforts to prevent the disease include protective equipment to block contact when working with potentially infected animals, washing after contact, and reducing rodents in areas where people live and work.[7] The antibioticdoxycycline is effective in preventing leptospirosis infection.[7] Human vaccines are of limited usefulness;[15] vaccines for other animals are more widely available.[16] Treatment when infected is with antibiotics such as doxycycline,penicillin, orceftriaxone.[8] The overall risk of death is 5–10%.[10] However, when the lungs are involved, the risk of death increases to the range of 50–70%.[8]
It is estimated that one million severe cases of leptospirosis in humans occur every year, causing about 58,900 deaths.[11] The disease is most common intropical areas of the world but may occur anywhere.[7]Outbreaks may arise after heavy rainfall.[7] The disease was first described by physicianAdolf Weil in 1886 in Germany.[17][18] Infected animals may have no, mild or severe symptoms.[19] These may vary by the type of animal.[16][19] In some animalsLeptospira live in the reproductive tract, leading to transmission during mating.[16]
Global incidence and mortality: Leptospirosis is a widespread zoonotic disease, causing approximately 1 million cases and 60,000 deaths annually. PMC
High-risk regions: Countries like Sri Lanka report significant incidence rates, with over 700 deaths per year and an estimated annual hospitalization rate of 52.1 per 100,000 population.[20]
Schematic depiction of the symptoms and signs of leptospirosis[21]Conjunctival suffusion (redconjunctiva) together with jaundice is a specific feature of leptospirosis.[21]
The symptoms of leptospirosis usually appear one to two weeks after infection,[7] but theincubation period can be as long as a month.[22] The illness isbiphasic in a majority of symptomatic cases. Symptoms of the first phase (acute or leptospiremic phase) last five to seven days. In the second phase (immune phase), the symptoms resolve as antibodies against the bacteria are produced.[8] Additional symptoms develop in the second phase.[23] The phases of illness may not be distinct, especially in patients with severe illness.[24] 90% of those infected experience mild symptoms while 10% experience severe leptospirosis.[25]
Leptospiral infection in humans causes a range ofsymptoms, though some infected persons may have none. The disease begins suddenly with fever accompanied by chills, intense headache, severemuscle aches and abdominal pain.[5][22] A headache brought on by leptospirosis causes throbbing pain and is characteristically located at the head's bilateraltemporal orfrontal regions. The person could also have pain behind the eyes and asensitivity to light. Muscle pain usually involves thecalf muscle and the lower back. The most characteristic feature of leptospirosis is theconjunctival suffusion (conjunctivitis withoutexudate) which is rarely found in otherfebrile illnesses. Other characteristic findings on the eye includesubconjunctival bleeding andjaundice. A rash is rarely found in leptospirosis. When one is found alternative diagnoses such asdengue fever andchikungunya fever should be considered. Dry cough is observed in 20–57% of people with leptospirosis. Thus, this clinical feature can mislead a doctor to diagnose the disease as a respiratory illness. Additionally,gastrointestinal symptoms such asnausea, vomiting, abdominal pain, and diarrhoea frequently occur. Vomiting and diarrhea may contribute todehydration. The abdominal pain can be due toacalculous cholecystitis orinflammation of the pancreas.[22] Rarely, thelymph nodes,liver, andspleen may be enlarged and palpable.[8]
There will be a resolution of symptoms for one to three days.[7] The immune phase starts after this and can last from four to 30 days and can be anything from brain to kidney complications.[26] The hallmark of the second phase isinflammation of the membranes covering the brain.[7] Signs and symptoms of meningitis include severe headache and neck stiffness.[7] Kidney involvement is associated with reduced or absent urine output.[7]
A total of 66 species ofLeptospira has been identified. Based on their genomic sequence, they are divided into twoclades and four subclades: P1, P2, S1, and S2.[28] The 19 members of the P1 subclade include the 8 species that can cause severe disease in humans:L. alexanderi,L. borgpetersenii,L. interrogans,L. kirschneri,L. mayottensis,L. noguchii,L. santarosai, andL. weilii.[13][28] The P2 clade comprises 21 species that may cause mild disease in humans. The remaining 26 species comprise the S1 and S2 subclades, which include "saprophytes" known to consume decaying matter (saprotrophic nutrition).[28] PathogenicLeptospira do not multiply in the environment.Leptospira require high humidity for survival but can remain alive in environments such as stagnant water or contaminated soil. The bacterium can be killed by temperatures of 50 °C (122 °F) and can be inactivated by 70% ethanol, 1% sodium hypochlorite,formaldehyde, detergents and acids.[29]
Leptospira are also classified based on theirserovar. The diverse sugar composition of the lipopolysaccharide on the surface of the bacteria is responsible for the antigenic difference between serovars.[13] About 300 pathogenic serovars ofLeptospira are recognised. Antigenically related serovars (belonging to the same serogroup) may belong to different species because ofhorizontal gene transfer ofLPS biosynthetic genes between different species. Currently, the crossagglutination absorption test and DNA-DNA hybridisation are used to classifyLeptospira species but are time-consuming. Therefore, total genomic sequencing could potentially replace these two methods as the new gold standard of classifyingLeptospira species.[13]
Working in a paddy field barefoot is a risk factor for leptospirosis.[21]
The bacteria can be found in ponds, rivers, puddles, sewers, agricultural fields, and moist soil.[7] PathogenicLeptospira have been found in the form of aquaticbiofilms, which may aid survival in the environment.[30]
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.[7] The risk of contracting leptospirosis depends upon the risk of disease carriage in the community and the frequency of exposure.[22] In rural areas, farming and animal husbandry are the major risk factors for contracting leptospirosis.[5] Poor housing and inadequate sanitation also increase the risk of infection.[22] In tropical and semi-tropical areas, the disease often becomeswidespread after heavy rains or after flooding.[7]
Leptospira are found mostly in mammals.[5] However, reptiles andcold-blooded animals such as frogs, snakes, turtles, and toads have been shown to have the infection.[16] Whether there are reservoirs of human infection is unknown.[22][16] Rats, mice, and moles are importantprimary hosts, but other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, swine, raccoons, opossums, and skunks can also carry the disease.[16] In Africa, a number of wildlife hosts have been identified as carriers, including thebanded mongoose,Egyptian fox,Rusa deer, andshrews.[31] There are various mechanisms whereby animals can infect each other. Dogs may lick the urine of an infected animal off the grass orsoil, or drink from an infected puddle. House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house.[32] Leptospirosis can also be transmitted via the semen of infected animals.[16] The duration of bacteria being consistently present in animal urine may persist for years.[16]
Humans are theaccidental host ofLeptospira.[5] Humans become infected through contact with water or moist soil that contains urine & feces from infected animals.[7] The bacteria enter through cuts, abrasions,[7] ingestion of contaminated food, or contact withmucous membrane of the body (e.g. mouth, nose, and eyes).[33] Occupations at risk of contracting leptospirosis include farmers, fishermen, garbage collectors, and sewage workers.[5] The disease is also related toadventure tourism and recreational activities.[5] It is common among water-sports enthusiasts in specific areas, includingtriathlons, waterrafting,canoeing and swimming, as prolonged immersion in water promotes the entry of the bacteria.[5] However,Leptospira are unlikely to penetrate intact skin.[8] The disease is not known to spread between humans, and bacterial dissemination inrecovery period is extremely rare in humans.[8] Once humans are infected, bacterial shedding from the kidneys usually persists for up to 60 days.[29]
Rarely, leptospirosis can be transmitted through an organ transplant.[34] Infection through theplacenta during pregnancy is also possible.[35][36][37] It can causemiscarriage and infection ininfants.[38] Leptospirosis transmission through eating raw meat of wildlife animals have also been reported (e.g. psychiatric patients with allotriophagy).[39]
Occupational exposure: Individuals engaged in agriculture, such as rice paddy workers, and those in professions like livestock farming, sewer work, and wildlife research are at increased risk.[40]
Recreational activities: Participation in water-based activities like kayaking, canoeing, and adventure racing has been linked to leptospirosis outbreaks.[41]
Environmental conditions: The survival of Leptospira bacteria is influenced by environmental factors, with transmission dynamics affected by climate change, extreme weather events, urbanization, and interactions between human and animal populations.[42]
Environmental conditions play a major role in the transmission of leptospirosis. Leptospira species can remain viable in freshwater or moist soil environments for up to six weeks, provided temperatures remain above 22°C (72°F) and pH stays within a neutral to slightly alkaline range (6.5–8.0).[43] 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.[44] Flooding, inadequate drainage, and poor waste management facilitate the spread of Leptospira by increasing the likelihood of contact between humans and contaminated water or soil.[45]
Anthropogenic factors and changing transmission dynamics
Global climate change has expanded the geographic reach of climates conducive to leptospirosis. Rising temperatures are shifting tropical and subtropical zones poleward by approximately 0.3–0.5° latitude per decade, enlarging the areas with warm, humid environments that favor Leptospira survival. Warmer regions that historically saw few cases are reporting increased leptospirosis incidence as their climates become more subtropical. For example, climate projections for the Arctic indicate that previously inhospitable high-latitude areas may become suitable for Leptospira transmission – a modeling study in Yakutia (Sakha Republic, Russia) predicted a significant expansion of leptospirosis risk by 2060 under warming scenarios.[46]
Temperature directly influences Leptospira persistence in the environment and thus disease dynamics. Pathogenic Leptospira bacteria survive and remain infectious longer in warm (≈23–30 °C), humid conditions, especially in soil or fresh water. By contrast, extreme heat (>40 °C) or freezing can reduce bacterial survival.[47] Warmer climates not only prolong environmental survival of Leptospira, but also facilitate greater human outdoor activity (e.g., in agriculture or recreation), increasing opportunities for exposure.[48] A recent study in Fiji found that minimum weekly temperatures were positively associated with leptospirosis incidence, supporting the link between elevated ambient temperature and transmission risk.[49]
Increasing climate variability, notably heavier rainfall and more frequent extreme weather, has a pronounced impact on leptospirosis outbreaks. Leptospirosis is well known to surge after intense rainfall, flooding, and storms. A 2019 meta-analysis of 14 studies quantified that contact with flood water more than doubled the odds of human leptospirosis infection compared to no flood exposure.[50] Floodwater facilitates transmission by washing Leptospira-laden animal urine into streets and homes and by forcing people to wade through contaminated water. During floods, soil absorption and evaporation of urine are limited, allowing the bacteria to spread widely in stagnant water. Outbreak investigations around the world have consistently found that periods of abnormally high rainfall and inundation act as triggers for leptospirosis epidemics, especially in tropical regions prone to cyclones and monsoons.[51]
Stronger storms and hurricanes linked to climate change have been implicated in recent leptospirosis outbreaks. In Puerto Rico, after Hurricane Fiona struck in September 2022, severe flooding led to a leptospirosis outbreak with the post-hurricane weekly case rate approximately 3.6 times higher than pre-storm levels.[52] Similarly, an unusual cluster of over 30 leptospirosis cases occurred in central Greece following the extensive flash floods of Storm Daniel in 2023, whereas such infections were previously sporadic in that region.[53]
Urbanization, infrastructure, and animal–human contact
Rapid urbanization and infrastructure deficits have created new niches for leptospirosis transmission, especially in low-income city settings. Crowded urban slums often lack adequate sanitation and pest control, leading to conditions that amplify Leptospira exposure. A study in Salvador, Brazil found that open sewers, accumulations of garbage, and poor drainage were significant risk factors for infection.[54]
Urban landscapes also create new interfaces for animal–human contact. Expanding cities bring humans, domestic pets, and wildlife into closer proximity. Rodents thrive in cities and are known maintenance hosts of Leptospira. Stray dogs can act as carriers. The rise of urban green spaces and dog recreation areas has introduced shared spaces where pets and wildlife may intermingle. Dog parks, for example, are popular and beneficial for pet socialization and exercise, but can also pose transmission risks if contaminated. In 2023, a dog park in Fremont, California was temporarily closed following several canine leptospirosis cases, possibly linked to environmental contamination.[55] Experts emphasized that the issue was not with the parks themselves but with inadequate rodent control and poor drainage. Preventive measures such as pet vaccination and regular sanitation were recommended to maintain park safety.
Infrastructure-related exposures persist even in high-income countries. A study analyzing U.S. veterinary data found that dogs living in census tracts without indoor plumbing were significantly more likely to contract leptospirosis.[56] Public health officials have warned that weakening water safety standards may increase these risks. In March 2025, the U.S. Environmental Protection Agency announced rollbacks of several Clean Water Act protections, including looser standards for runoff pollution and wastewater management.[57]
Leptospirosis exemplifies the One Health paradigm, wherein human, animal, and environmental health are interconnected. Humans are incidental hosts—most infections originate from animal urine contaminating soil or water. Rodents, livestock, and dogs act as asymptomatic carriers. Preventing human leptospirosis thus requires veterinary, environmental, and medical collaboration.
Vaccinating pets and livestock against Leptospira reduces bacterial shedding. Rodent control programs and improved drainage help limit environmental contamination. In Brazil, seroprevalence maps comparing humans and dogs showed overlapping infection hotspots after flooding, suggesting dogs can act as environmental sentinels.[58] During leptospirosis outbreaks in Australia (2018–2019), One Health coordination between local public health agencies, veterinarians, and wildlife experts was crucial to controlling spread.[59] Global health bodies increasingly emphasize that integrated approaches are essential for leptospirosis prevention in a world shaped by human-driven environmental change.
Ways ofLeptospira bacteria infecting human cells and blood stream[21]
When animals ingest the bacteria, they circulate in the bloodstream, then lodge themselves into the kidneys through theglomerular orperitubular capillaries. The bacteria then pass into thelumens of therenal tubules and colonise thebrush border andproximal convoluted tubule. This causes the continuous shedding of bacteria in the urine without the animal experiencing significant ill effects. This relationship between the animal and the bacteria is known as acommensal relationship, and the animal is known as areservoir host.[22]
Humans are theaccidental host ofLeptospira.[5] The pathogenesis of leptospirosis remains poorly understood despite research efforts.[7][33] 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 theendothelial cells of the blood vessels andextracellular 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 asfibroblasts,macrophages, endothelial cells, and kidney epithelial cells. They also bind to several human proteins such as complement proteins,thrombin,fibrinogen, andplasminogen using surface leptospiralimmunoglobulin-like (Lig) proteins such as LigB and LipL32, whose genes are found in all pathogenic species.[13][33]
Through theinnate immune system, endothelial cells of the capillaries in the human body are activated by the presence of these bacteria. The endothelial cells producecytokines andantimicrobial peptides against the bacteria. These products regulate thecoagulation cascade and movements of white blood cells.[13] Macrophages presented in humans are able toengulfLeptospira. However,Leptospira can reside and proliferate in thecytoplasmic matrix after being ingested by macrophages.[13] Those with severe leptospirosis can experience a high level of cytokines such asinterleukin 6,tumor necrosis factor alpha (TNF-α), andinterleukin 10. The high level of cytokines causessepsis-like symptoms which is life-threatening instead of helping to fight against the infection.[25] Those who have a high risk of sepsis during a leptospirosis infection are found to have theHLA-DQ6genotype, possibly due tosuperantigen activation, which damages bodily organs.[22]
Leptospira LPS only activatestoll-like receptor 2 (TLR2) inmonocytes in humans. The lipid A molecule of the bacteria is not recognised by humanTLR4 receptors. Therefore, the lack ofLeptospira recognition by TLR4 receptors probably contributes to the leptospirosis disease process in humans.[13]
Although there are various mechanisms in the human body to 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 becomeplasmin that breaks down extracellular matrix, degradesfibrin clots and complemental proteins (C3b andC5) to avoidopsonisation. It can also recruit complement regulators such asFactorH,C4b-binding protein, factor H-like binding protein, andvitronectin to prevent the activation ofmembrane attack complex on its surface. It also secretesproteases to degrade complement proteins such asC3. It can bind to thrombin, which decreases the fibrin formation. Reduced fibrin formation increases the risk of bleeding.[13]Leptospira also secretessphingomyelinase andhaemolysin that target red blood cells.[7]
Leptospira spreads rapidly to all organs through the bloodstream.[13] They mainly affect the liver. They invade spaces betweenhepatocytes, causing apoptosis. The damaged hepatocytes and hepatocyte intercellular junctions cause bile leakage into the bloodstream, causing elevated levels ofbilirubin, resulting in jaundice. Congestedliver sinusoids andperisinusoidal spaces have been reported. Meanwhile, in the lungs, petechiae or frankbleeding can be found at thealveolar septum and spaces between alveoli.[22]Leptospira secretes toxins that cause mild to severe kidney failure orinterstitial nephritis.[33] The kidney failure can recover completely or lead toatrophy andfibrosis.[22] Rarely, inflammation of the heart muscles, coronary arteries, andaorta are found.[26]
Kidney tissue, using asilver staining technique, revealing the presence ofLeptospira bacteria[21] Diffuse lungs bleeding due to leptospirosis infection[21]
The kidneys are commonly involved in leptospirosis. Bloodurea andcreatinine levels will be elevated. Leptospirosis increases potassium excretion in urine, which leads to alow potassium level[22] and alow sodium level in the blood.[8][22] Urinalysis may reveal thepresence of protein,white blood cells, and microscopichaematuria.[8] Because the bacteria settle in the kidneys, urine cultures will be positive for leptospirosis starting after the second week of illness until 30 days of infection.[8]
For those with severe headaches who show signs of meningitis, alumbar puncture can be attempted. If infected,cerebrospinal fluid (CSF) examination showslymphocytic predominance with a cell count of about 500/mm3, protein between 50 and 100 mg/mL and normal glucose levels. These findings are consistent withaseptic meningitis.[22]
Rapid detection ofLeptospira can be done by quantifying the IgM antibodies using anenzyme-linked immunosorbent assay (ELISA). Typically,L. biflexa antigen is used to detect the IgM antibodies. This test can quickly determine the diagnosis and help in early treatment. However, the test specificity depends upon the type of antigen used and the presence of antibodies from previous infections. The presence of other diseases such asEpstein–Barr virus infection, viralhepatitis, andcytomegalovirus infection can cause false-positive results.[22] Other rapid screening tests have been developed such as dipsticks,latex, and slide agglutination tests.[8]
The microscopic agglutination test (MAT) is the reference test for the diagnosis of leptospirosis.[22] MAT is a test where serial dilutions of patient sera are mixed with different serovars ofLeptospira. The mixture is then examined under adark field microscope to look foragglutination. The highest dilution where 50% agglutination occurs is the result.[22] MATtitres of 1:100 to 1:800 are diagnostic of leptospirosis.[8] A fourfold or greater rise in titre of two sera taken at symptoms' onset and three to 10 days of disease onset confirms the diagnosis. During the acute phase of the disease, MAT is not specific in detecting a serotype ofLeptospira because of cross-reactivity between the serovars.[22] In theconvalescent phase, MAT is more specific in detecting the serovar types.[22] MAT requires a panel of live antigens and requires laborious work.[26]
Leptospiral DNA can be amplified by usingpolymerase chain reaction (PCR) from serum, urine,aqueous humour, CSF, and autopsy specimens.[22] It detects the presence of bacteria faster than MAT during the first few days of infection without waiting for the appearance of antibodies.[26] As PCR detects the presence of leptospiral DNA in the blood it is useful even when the bacteria is killed by antibiotics.[60]
In 1982, theWorld Health Organization (WHO) proposed the Faine's criteria for the diagnosis of leptospirosis. It consists of three parts: A (clinical findings), B (epidemiological factors), and C (lab findings and bacteriological data). Since the original Faine's criteria only included culture and MAT in part C, which is difficult and complex to perform, the modified Faine's criteria were proposed in 2004 to include ELISA and slide agglutination tests which are easier to perform. In 2012, modified Faine's criteria (with amendment) was proposed to includeshortness of breath and coughing up blood in the diagnosis. In 2013, India recommended modifying Faine's criteria in the diagnosis of leptospirosis.[61]
A notice board by a lakeside inSarawak, Malaysia, that warns against swimming in the lake as it has tested positive for pathogenicLeptospira[21] Blood samples being taken from a group of residents inBoyolali Regency, Indonesia, for leptospirosis screening tests[21]
Rates of leptospirosis can be reduced by improving housing, infrastructure, and sanitation standards. Rodent abatement efforts and flood mitigation projects can also help to prevent it.[22] Proper use ofpersonal protective equipment (PPE) by people who have a high risk of occupational exposure can prevent leptospirosis infections in most cases.[22]
There is no human vaccine suitable for worldwide use.[15] Only a few countries such as Cuba, Japan, France, and China have approved inactivated vaccines with limited protective effects.[15][62] Side effects such as nausea,injection site redness and swelling have been reported after the vaccine was injected. Since the immunity induced by oneLeptospiraserovar is only protective against that specific one,trivalent vaccines have been developed.[22] They do not confer long-lasting immunity to humans or animals.[13] Vaccines for other animals are more widely available.[16]
Doxycycline is given once a week as aprophylaxis and is effective in reducing the rate of leptospirosis infections amongst high-risk individuals in flood-prone areas.[63] 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 inendemic areas.[22]
The prevention of leptospirosis from environmental sources like contaminated waterways, soil, sewers, and agricultural fields, is disinfection used byeffective microorganisms, which is mixed withbokashi mudballs for the infected waterways & sewers.
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.[22]
For mild leptospirosis, antibiotic recommendations such as doxycycline,azithromycin,ampicillin, andamoxicillin were based solely onin vitro testing.[8] In 2001, the WHO recommended oral doxycycline (2 mg/kg up to 100 mg every 12 hours) for five to seven days for those with mild leptospirosis.Tetracycline, ampicillin, and amoxicillin can also be used in such cases.[64] However, in areas where bothrickettsia and leptospirosis are endemic, azithromycin and doxycycline are the drugs of choice.[8] Doxycycline is not used in cases where the patient suffers from liver damage as it has been linked to hepatotoxicity.[65]
Based on a 1988 study,intravenous (IV)benzylpenicillin (also known as penicillin G) is recommended for the treatment of severe leptospirosis.[8] Intravenous benzylpenicillin (30 mg/kg up to 1.2 g every six hours) is used for five to seven days. Amoxicillin, ampicillin, and erythromycin may also be used for severe cases.[64]Ceftriaxone (1 g IV every 24 hours for seven days) is also effective for severe leptospirosis.[22][8][66]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).[8][67] Therefore, there is no evidence on differences in death reduction when benzylpenicillin is compared with ceftriaxone or cefotaxime.[8] Another study conducted in 2007 also showed no difference in efficacy between doxycycline (200 mg initially followed by 100 mg orally every 12 hours for seven days) or azithromycin (2 g on day one followed by 1 g daily for two more days) for suspected leptospirosis. There was no difference in the resolution of fever and azithromycin is better tolerated than doxycycline.[68][69][70]
Outpatients are given doxycycline or azithromycin. Doxycycline can shorten the duration of leptospirosis by two days, improve symptoms, and prevent the shedding of organisms in their urine. Azithromycin and amoxicillin are given to pregnant women and children.[22] Rarely, aJarisch–Herxheimer reaction can develop in the first few hours after antibiotic administration.[8] However, according to ameta-analysis done in 2012, the benefit of antibiotics in the treatment of leptospirosis was unclear although the use of antibiotics may reduce the duration of illness by two to four days.[8][69] Another meta-analysis done in 2013 reached a similar conclusion.[8][70]
For those with severe leptospirosis, including potassium wasting with high kidney output dysfunction, intravenous hydration, and potassium supplements can prevent dehydration andhypokalemia. Whenacute kidney failure occurs, early initiation ofhaemodialysis orperitoneal dialysis can help to improve survival. For those with respiratory failure,tracheal intubation with lowtidal volume improves survival rates.[22]
Corticosteroids have been proposed to suppress inflammation in leptospirosis becauseLeptospira infection can induce the release ofchemical signals which promoteinflammation of blood vessels in the lungs. However, there is insufficient evidence to determine whether the use of corticosteroids is beneficial.[8][71]
Prevention of leptospirosis involves a multifaceted approach that aligns with the One Health framework, integrating human, animal, and environmental health strategies. In endemic areas, rodent control programs and improved sanitation systems play a critical role in reducing transmission.[72]
Vaccination of livestock and domestic animals, particularly dogs and cattle, is an effective measure in preventing both animal illness and zoonotic transmission to humans.[73]
For high-risk populations, such as agricultural workers, sewer workers, and people exposed to floodwaters, the use of protective clothing and prophylactic doxycycline may be recommended.[74]
Public health interventions focused on community education, clean water access, and disease surveillance have shown effectiveness in reducing disease incidence, especially during seasonal outbreaks.
The overall risk of death for leptospirosis is 5–10%.[10] For those with jaundice, the case fatality can increase up to 15%.[29] For those infected who present with confusion and neurological signs, there is a high risk of death.[22] Other factors that increase the risk of death include reduced urine output, age more than 36 years, and respiratory failure.[22] With proper care, most of those infected will recover completely. Those with acute kidney failure may develop persistent mild kidney impairment after they recover.[22] In those with severe lung involvement, the risk of death is 50–70%.[8] Thirty percent of people with acute leptospirosis complained of long-lasting symptoms characterised by weakness, muscle pain, and headaches.[22]
Eye problems can occur in 10% of those who recovered from leptospirosis[29] in the range from two weeks to a few years post-infection. Most commonly, eye complications can occur at six months after the infection. This is due to theimmune privilege of the eye which protects it from immunological damage during the initial phase of leptospiral infection.[75] These complications can range from mildanterior uveitis to severe panuveitis (which involves all three vascular layers of the eye).[29] The uveitis more commonly happens in young to middle-aged males and those working in agricultural farming.[75] In up to 80% of those infected,Leptospira DNA can be found in the aqueous humour of the eye.[22] Eye problems usually have a good prognosis following treatment or they are self-limiting.[29] In anterior uveitis, only topical steroids andmydriatics (an agent that causes dilation of the pupil) are needed while in panuveitis, it requires periocular corticosteroids.[75] Leptospiraluveitis is characterised byhypopyon, rapidly maturingcataract, free floating vitreous membranes, dischyperemia and retinalvasculitis.[75][76][77]
It is estimated that one million severe cases of leptospirosis occur annually, with 58,900 deaths. Severe cases account for 5–15% of all leptospirosis cases.[11] Leptospirosis is found in both urban and rural areas intropical,subtropical, andtemperate regions.[10] The global health burden for leptospirosis can be measured bydisability-adjusted life year (DALY). The score is 42 per 100,000 people per year, which is more than other diseases such asrabies andfilariasis.[7]
Leptospirosis is estimated to cause more than one million cases and nearly 60,000 deaths annually worldwide, with the highest disease burden occurring in tropical and subtropical regions, particularly in South and Southeast Asia, Latin America, and parts of Africa.[78]
Urban poor populations in densely populated cities are at particularly high risk due to limited access to sanitation and exposure to contaminated floodwaters.[79] 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.[80]
The disease is observed persistently in parts of Asia, Oceania, the Caribbean, Latin America and Africa.[29]Antarctica is the only place not affected by leptospirosis.[29] In the United States, there were 100 to 150 leptospirosis cases annually.[81] 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.[82] 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.[81] Research on epidemiology of leptospirosis in high-risk groups and risk factors is limited in India.[83]
The global rates of leptospirosis have been underestimated because most affected countries lack notification or notification is not mandatory.[22] Distinguishing clinical signs of leptospirosis from other diseases and lack of laboratory diagnostic services are other problems.[84] The socioeconomic status of many of the world's population is closely tied to malnutrition; subsequent lack ofmicronutrients may lead to increased risk of infection and death due to leptospirosis infection.[85] Micronutrients such asiron,calcium, andmagnesium represent important areas for future research.[85]
The disease was first described byAdolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice, andnephritis."[18] Before Weil's description, the disease was known as "rice fieldjaundice" in ancient Chinese text, "autumn fever", "seven-day fever",[86] and "nanukayami fever"[87] 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).[86] It has been known historically as "black jaundice",[88] or "dairy farm fever" in New Zealand.[89] Leptospirosis was postulated as the cause of an epidemic amongNative Americans along the coast of what is nowNew England during 1616–1619. The disease was most likely brought to theNew World by Europeans.[90]
Leptospira was first observed in 1907 in apost mortem kidney tissue slice by Arthur Stimson usingsilver deposition staining technique. He called the organismSpirocheta interrogans because the bacteria resembled a question mark.[86][91] In 1908, a Japanese research group led byRyukichi Inada and Yutaka Ito first identified this bacterium as the causative agent of leptospirosis[92] and noted its presence in rats in 1916.[93] Japanese coal mine workers frequently contracted leptospirosis. In Japan, the organism was namedSpirocheta icterohaemorrhagiae. The Japanese group also experimented with the first leptospiral immunisation studies in guinea pigs. They demonstrated that by injecting the infectedguinea 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.[86] Unaware of the Japanese group's work, two German groups independently and almost simultaneously published their first demonstration of transmitting leptospiral infection in guinea pigs in October 1915. They named the organismSpirochaeta nodosa andSpirochaeta Icterogenes respectively.[86]
Leptospirosis was subsequently recognised as a disease of all mammalian species. In 1933, Dutch workers reported the isolation ofLeptospira canicola which specifically infects dogs. In 1940, the strain that specifically infects cattle was first reported in Russia.[86] In 1942, soldiers atFort Bragg,North Carolina, were recorded to have an infectious disease which caused a rash over theirshinbones. This disease was later known to be caused by leptospirosis.[22] By the 1950s, the number of serovars that infected various mammals had expanded significantly. In the 1980s, leptospirosis was recognised as a veterinary disease of major economic importance.[86]
In 1982, there were about 200 serovars ofLeptospira available for classification. TheInternational Committee on Systematic Bacteriology's subcommittee on taxonomy ofLeptospira proposed classifying these serovars into two big groups:L. interrogans containing pathogenic serovars andL. biflexa containing saprophytic serovars.[86] In 1979, the leptospiral family ofLeptospiraceae was proposed. In the same year,Leptospira illini was reclassified as the new genusLeptonema.[86] In 2002, "Lepthangamushi syndrome" was coined to describe a series of overlapping symptoms of leptospirosis withHantavirus hemorrhagic fever with renal syndrome, andscrub typhus caused byOrientia tsutsugamushi.[94][95] In 2005,Leptospira parva was classified asTurneriella.[86] WithDNA-DNA hybridisation technology,L. interrogans was divided into seven species. MoreLeptospira species have been discovered since then.[86] 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.[22]
Liver of an unknown animal with multiple blackishnecrotic patches secondary to leptospirosis infection[21] Lungs of a canine with multiple bleeding spots due to leptospirosis[21]
Infected animals can have no, mild, or severe symptoms;[19] the presenting symptoms may vary by the type of animal.[16][19] In some animals, the bacteria live in the reproductive tract, leading to transmission during mating.[16]
Animals also present with similar clinical features when compared to humans. Clinical signs can appear in 5–15 days in dogs. The incubation period can be prolonged in cats. Leptospirosis can cause abortions after 2–12 weeks in cattle, and 1–4 weeks of infection in pigs. The illness tends to be milder in reservoir hosts. The most commonly affected organs are the kidneys, liver, and reproductive system, but other organs can be affected.[29] In dogs, the acute clinical signs include fever,loss of appetite, shivering, muscle pain, weakness, and urinary symptoms. Vomiting, diarrhea, and abdominal pain may also present. Petechiae and ecchymoses may be seen on mucous membranes. Bleeding from the lungs may also be seen in dogs. In chronic presentations, the affected dog may have no symptoms. In animals that have died of leptospirosis, their kidneys may be swollen with grey and white spots,mottling, or scarring. Their liver may be enlarged with areas ofcell death. Petechiae and ecchymoses may be found in various organs.[29][96]Inflammation of the blood vessels, inflammation of the heart, meningeal layers covering the brain and spinal cord, anduveitis are also possible.[16]Equine recurrent uveitis (ERU) is the most common disease associated withLeptospira infection in horses in North America and may lead to blindness.[97][98] ERU is an autoimmune disease involving antibodies againstLeptospira proteins LruA and LruB cross-reacting with eye proteins.[97] LiveLeptospira can be recovered from the aqueous or vitreous fluid of many horses withLeptospira-associated ERU.[98] 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.[29]
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 usingimmunofluorescence orimmunohistochemical or polymerase chain reaction techniques. Silver staining or immunogold silver staining is used to detectLeptospira in tissue sections. The organisms stain poorly withGram stain. Dark-field microscopy can be used to detectLeptospira 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.[29]
Various antibiotics such as doxycycline, penicillins,dihydrostreptomycin, andstreptomycin 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.[29][16]
Leptospirosis vaccines are available for animals such as pigs, dogs, cattle, sheep, and goats. Vaccines for cattle usually containLeptospira 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.[16] Isolation of infected animals and prophylactic antibiotics are also effective in preventing leptospirosis transmission between animals. Environmental control and sanitation also reduce transmission rates.[29][16]
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