Leptospirosis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Leptospirosis is a zoonotic spirochaetal infection maintained in renal tubules of reservoir animals. Urinary shedding contaminates water and soil, where organisms can survive long enough to enter human skin or mucosa. Exposure may occur in the UK or abroad; a travel history is helpful but not required.

After haematogenous dissemination, organisms injure vascular endothelium and localise in kidney, liver, lung, meninges and myocardium. Most infections are mild or subclinical. Severe disease reflects capillary injury, immune activation and organ dysfunction rather than a simple bacterial load, so physiological review cannot wait for a diagnostic label.

The illness is sometimes biphasic: a leptospiraemic febrile phase may be followed by an immune phase with meningism, uveitis or renewed fever. In practice phases overlap. The most useful diagnostic question is how many days have elapsed, because blood PCR, urine PCR and serology have different windows.

The returning-traveller pathway remains active in parallel. Malaria, dengue, viral haemorrhagic fever and rickettsial infection can resemble leptospirosis, while ordinary bacterial sepsis can coexist. Exposure plus conjunctival suffusion, calf myalgia, renal urinary abnormalities and disproportionate bilirubin raise suspicion but do not prove the diagnosis.

Key points

Pathogenic Leptospira are shed in urine from rats, mice, cattle, pigs, dogs and other animals, contaminating freshwater, mud, soil and occupational environments.
Organisms enter through cuts, softened skin or conjunctival and oral mucosa; kayaking, open-water swimming, flooding, sewage work, farming and animal-tissue contact are typical risks.
Acute leptospirosis causes fever, severe headache, prominent calf or lower-back myalgia, nausea and conjunctival suffusion without purulent discharge.
Severe Weil disease combines jaundice, acute kidney injury and haemorrhagic features; pulmonary haemorrhage, aseptic meningitis, myocarditis and shock can occur with or without marked jaundice.
First-line assessment includes FBC, renal and liver profiles, CK, urinalysis, coagulation, ECG and chest imaging when indicated, plus blood cultures and malaria tests after travel.
Send blood and urine with exact illness and exposure dates to UKHSA RIPL; blood PCR performs best early, while urine often remains PCR-positive later.
IgM supports recent infection after antibodies emerge, but cross-reaction and persistence limit specificity; paired serology or microscopic agglutination testing can resolve uncertainty.
For suitable non-severe adult disease, doxycycline 100 mg orally twice daily for five to seven days is a commonly used early regimen.
For severe adult disease, intravenous benzylpenicillin 1.2 g every six hours for five to seven days is an established option; ceftriaxone is a specialist-selected alternative.
Leptospira interrogans is laboratory-notifiable in England; report clusters or other significant hazards to health protection without confusing laboratory duty with the clinician disease list.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Animal urinary shedding

Reservoir mammals carry pathogenic Leptospira in renal tubules and contaminate water, mud, soil, tissue and workplaces with urine.

Recreational freshwater

Swimming, kayaking, fishing and adventure races expose softened skin or mucosa to organisms, particularly after heavy rain or flooding.

Occupational contact

Farmers, veterinarians, abattoir workers, sewer workers, fish handlers and military personnel encounter infected animals or contaminated environments.

Mucocutaneous entry

Spirochaetes cross abrasions, cuts, water-softened intact skin or conjunctival, nasal and oral mucous membranes; person-to-person spread is very rare.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Leptospiraemic dissemination
Motile spirochaetes enter blood and rapidly seed kidneys, liver, lungs, meninges, myocardium and skeletal muscle during early illness.
2
Endothelial injury
Bacterial and host inflammatory effects damage small vessels, producing capillary leak, hypotension, thrombocytopenia and haemorrhage across organs.
3
Tubulointerstitial nephritis
Renal invasion and inflammation impair tubular transport and filtration, causing proteinuria, haematuria, potassium abnormalities and acute kidney injury.
4
Cholestatic liver dysfunction
Disrupted hepatocyte junctions and systemic inflammation impair bilirubin handling, causing striking jaundice without the massive necrosis of acute viral hepatitis.
5
Immune phase
Antibody emergence clears bloodstream organisms but can coincide with meningitis, uveitis and inflammatory symptoms while urinary shedding persists.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Acute febrile syndrome

Abrupt fever, rigors, severe frontal headache, nausea, vomiting and intense calf or lumbar muscle tenderness follows a variable incubation after exposure.

Conjunctival suffusion

Bilateral red conjunctivae without purulent exudate is a useful clue when combined with fever, myalgia and an animal or water history.

Weil triadRed flag

Jaundice, acute kidney injury and haemorrhagic tendency identify severe multisystem disease rather than uncomplicated viral-like illness.

Pulmonary haemorrhageRed flag

Cough, dyspnoea, haemoptysis, falling haemoglobin and diffuse infiltrates indicate alveolar capillary bleeding with high mortality.

Aseptic meningitisRed flag

Headache, photophobia, neck stiffness and lymphocytic cerebrospinal-fluid inflammation can arise during the immune phase.

Renal patternRed flag

Proteinuria, microscopic haematuria, pyuria, potassium disturbance and non-oliguric or oliguric acute kidney injury reflect tubulointerstitial injury.

Cardiac involvementRed flag

Myocarditis may present with chest discomfort, hypotension, conduction disturbance, atrial or ventricular arrhythmia and heart failure.

Red flags requiring action

Jaundice with oliguria or rising creatinine is classic severe Weil disease and requires admission even when aminotransferase elevation is modest.
Haemoptysis, falling haemoglobin, new hypoxaemia or bilateral infiltrates may be diffuse pulmonary haemorrhage and can progress to respiratory failure rapidly.
Shock, arrhythmia, chest pain or disproportionate tachycardia may indicate myocarditis, vasoplegia or major haemorrhage.
Severe headache, photophobia, neck stiffness, confusion or focal signs requires a meningitis and encephalitis pathway alongside leptospiral testing.
Pregnancy after a compatible exposure needs urgent obstetric and infection review because maternal infection can cause fetal loss and preterm birth.
Treatment should not wait for PCR or seroconversion when the exposure and severe syndrome are convincing; direct detection is time sensitive.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line organ severity panelFirst stepFirst line
Why
Identify kidney, liver, muscle, haematological and coagulation injury at presentation.
Interpretation and limitations
Request FBC, urea, creatinine, electrolytes, bilirubin, ALT, AST, ALP, CK, CRP, coagulation, glucose and urinalysis; severe bilirubin elevation may exceed transaminase rise.
02
Blood and urine Leptospira PCR
Why
Directly confirm active infection using specimens matched to illness timing.
Interpretation and limitations
Send both to RIPL with onset and exposure dates; blood is more useful early, whereas urine becomes positive after renal colonisation and can remain useful later.
03
Leptospira IgM serology
Why
Support recent infection after the antibody response develops.
Interpretation and limitations
Early samples can be negative and isolated positives can cross-react or persist; pair acute and convalescent sera or use reference confirmation when the result and syndrome disagree.
04
Microscopic agglutination test
Why
Provide specialist serological confirmation and epidemiological information when required.
Interpretation and limitations
A rising titre across paired sera is stronger evidence than a single result; the reference method is labour intensive and does not guide immediate treatment.
05
Blood cultures and sepsis sampling
Why
Detect ordinary bacterial sepsis and co-infection before antibiotics where this causes no delay.
Interpretation and limitations
Routine culture is insensitive and slow for Leptospira but identifies alternative pathogens; send malaria films and other imported-fever tests according to exposure.
06
Chest imaging and blood gases
Why
Assess pulmonary haemorrhage, oedema, acute respiratory distress and oxygenation.
Interpretation and limitations
Bilateral alveolar shadowing with falling haemoglobin supports haemorrhage but overlaps with pneumonia and oedema; escalating oxygen need drives critical-care review.
07
ECG, troponin and echocardiography
Why
Identify myocardial inflammation and rhythm complications.
Interpretation and limitations
ECG abnormalities or troponin rise are non-specific; echocardiography evaluates ventricular function and competing shock mechanisms when cardiac involvement is suspected.
08
Lumbar puncture when safe
Why
Distinguish leptospiral aseptic meningitis from treatable bacterial, viral or other central nervous system infection.
Interpretation and limitations
CSF often shows lymphocytic pleocytosis with moderately raised protein; take neuroimaging first if focal signs, seizures, papilloedema or reduced consciousness create a contraindication.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Malaria

Fever, jaundice, thrombocytopenia and renal injury overlap after tropical travel; urgent thick and thin films remain mandatory.

Dengue

Fever, myalgia, thrombocytopenia and bleeding overlap, while capillary-leak timing and arboviral direct tests help distinguish dengue.

Viral hepatitis

Jaundice and systemic illness suggest hepatitis, usually with a more hepatocellular enzyme pattern and exposure-specific viral markers.

Hantavirus disease

Rodent exposure, fever, thrombocytopenia, renal or pulmonary syndrome can resemble leptospirosis and requires reference molecular testing.

Bacterial sepsis

Pyelonephritis, cholangitis, meningococcal disease and other bloodstream infections cause shock and organ dysfunction and may coexist with zoonotic exposure.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01SUSPECTLink exposure to syndromeFirst stepAcute fever follows freshwater, floodwater, sewage, rodent, livestock or animal-tissue exposure.

1Record exposure date, skin breaks, immersion, occupation, country, animal species and protective equipment, then ask about calf pain, red eyes, urine, jaundice, bleeding and breathing.
2Perform ABCDE and an organ-focused examination, obtaining bedside glucose, urine output, blood tests, urinalysis, ECG and chest assessment before classifying severity.
3AlternativeSend blood and urine to RIPL with exact onset date, plus cultures, malaria films and alternative infection tests selected from the wider epidemiology.
4Start antibiotics when clinical suspicion is significant, particularly early or severe illness, rather than awaiting serology or reference confirmation.

02MILDTreat stable early diseaseA suitable adult has a compatible mild syndrome, reliable oral intake and no renal, hepatic, pulmonary, neurological, cardiac or obstetric red flag.

1Give doxycycline 100 mg orally twice daily for five to seven days after checking pregnancy, age, allergy, interactions and ability to take it correctly.
2AlternativeUse a locally approved alternative after infection or microbiology advice when doxycycline is unsuitable, particularly during pregnancy.
3Provide oral hydration and paracetamol within safe limits, but avoid nephrotoxic self-medication when renal involvement remains possible.
4Arrange early reassessment of symptoms, urine output, renal and liver function, with immediate return for jaundice, breathlessness, bleeding, reduced urine, confusion or persistent vomiting.

03SEVEREManage organ-threatening diseaseWeil disease, pulmonary haemorrhage, meningitis, myocarditis, shock or inability to absorb oral therapy is present.

1Admit, involve infection, renal, respiratory and critical-care teams as indicated, and obtain microbiology samples without postponing intravenous treatment.
2AlternativeGive benzylpenicillin 1.2 g intravenously every six hours for five to seven days under local antimicrobial governance, or use a suitable cephalosporin alternative after specialist advice.
3Provide cautious haemodynamic support, oxygen or ventilation, renal replacement, correction of electrolytes and blood-product support according to physiology rather than diagnosis alone.
4Monitor for a Jarisch–Herxheimer reaction soon after antibiotics, distinguishing transient inflammatory worsening from sepsis progression, allergy or pulmonary haemorrhage.

04PUBLIC HEALTHAddress source and notificationLeptospirosis is confirmed, occupationally acquired or linked to a cluster or shared environmental exposure.

1Ensure reference testing and laboratory notification proceed, and contact health protection when a cluster, unusual UK source or significant hazard may require investigation.
2Identify shared water, workplace, animal or flooding exposure and advise similarly exposed symptomatic people to seek prompt clinical assessment.
3Engage occupational health for farming, abattoir, veterinary, sewage or water-work risks, including gloves, boots, wound covering and hygiene review.
4Do not impose routine contact isolation or prophylaxis on household members because person-to-person transmission is exceptionally rare.

05PREVENTReduce urine-contaminated exposureA person undertakes water, animal or occupational activity associated with leptospirosis.

1Cover cuts with waterproof dressings, wear gloves, boots and protective clothing, and wash promptly after contact with animals, soil, mud or potentially contaminated water.
2Avoid swallowing untreated river, canal or lake water and reconsider recreational immersion after flooding or when local public-health warnings identify contamination.
3Control rodents and store food and waste securely; use workplace risk assessment for livestock birthing products, animal carcasses and sewage tasks.
4Do not offer routine human vaccination in the UK; pre-exposure doxycycline is not a substitute for exposure control and requires exceptional specialist justification.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Common early oral regimen for stable disease without organ failure or impaired gastrointestinal absorption.

Doxycycline

Give 100 mg orally twice daily for five to seven days for suitable non-severe adult leptospirosis, beginning promptly when clinical suspicion is strong.

Avoid routinely in pregnancy and children under 12 years, counsel on photosensitivity and oesophagitis, separate from cations and escalate immediately if jaundice, oliguria or respiratory signs emerge.

Established parenteral treatment for Weil disease or other severe manifestations while reference confirmation is pending.

Intravenous benzylpenicillin

Give 1.2 g intravenously every six hours for five to seven days for severe adult leptospirosis, adjusting the plan to renal function and local specialist advice.

Check immediate beta-lactam allergy, renal function and sodium or potassium formulation; observe for Jarisch–Herxheimer inflammation and do not mislabel it automatically as anaphylaxis.

Practical parenteral alternative that also covers several competing bacterial causes of severe febrile illness.

Intravenous ceftriaxone

Use a local infection-specialist regimen, commonly 1 to 2 g intravenously once daily for approximately seven days, when a cephalosporin is selected for severe disease.

Review severe beta-lactam allergy, biliary disease, interactions and renal-hepatic failure; broaden empiric cover when meningitis or another septic focus requires it.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Weil disease

Severe jaundice, acute renal failure, bleeding, electrolyte disturbance and shock form the classic multisystem syndrome with substantial mortality.

Pulmonary haemorrhage

Alveolar capillary injury causes diffuse bleeding, rapidly progressive hypoxaemia, acute respiratory distress and sometimes fatal respiratory failure.

Aseptic meningitis

Immune-phase meningeal inflammation produces severe headache, neck stiffness and CSF pleocytosis, while encephalitis is less common.

Myocarditis and arrhythmia

Myocardial inflammation and electrolyte disturbance cause conduction defects, atrial or ventricular arrhythmias, ventricular failure and sudden deterioration.

Pregnancy complications

Maternal leptospiraemia can cause miscarriage, fetal death, placental infection, congenital disease, growth restriction or preterm delivery.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

In severe disease, chart urine output, fluid balance, oxygen requirement, haemoglobin, platelets, coagulation, creatinine, potassium, bilirubin and acid-base state at least daily and often more frequently.
Reassess after every fluid intervention because renal salt loss, vasodilatation, capillary leak and pulmonary haemorrhage create competing risks.
Use continuous cardiac monitoring for shock, myocarditis, electrolyte disturbance or an abnormal ECG, and repeat echocardiography if haemodynamics change.
After discharge, repeat renal and liver profiles until recovery and ask about persistent fatigue, eye pain or visual change because uveitis can occur later.
Review reference PCR and paired serology, communicating confirmed occupational or cluster information to the relevant laboratory and health-protection routes.
Give explicit advice on future protective equipment, wound care and contaminated-water avoidance, tailored to the actual source rather than generic travel advice.
In pregnancy, coordinate maternal biochemical recovery with fetal surveillance and document exposure timing for obstetric and neonatal teams.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Red eyes are a clue

Conjunctival suffusion without purulent discharge is not universal, but its combination with calf tenderness and exposure is highly useful.

Bilirubin can dominate

Severe jaundice may coexist with only moderate aminotransferase elevation because cholestasis and systemic vascular injury exceed hepatocyte necrosis.

Urine outlasts blood

Leptospira move from early bloodstream dissemination to renal shedding, so urine PCR can remain useful after blood PCR loses sensitivity.

Pulmonary disease kills quickly

Diffuse alveolar haemorrhage can occur without the full jaundice-renal triad and should be considered when haemoglobin and oxygenation fall together.

Notification duties differ

The organism is laboratory-notifiable in England, while clinicians should report clusters or significant hazards rather than assuming every syndrome has identical statutory wording.

Scope boundary

Leptospira diagnosis and organ support are developed here; a separate returning-fever process still excludes malaria, arboviruses and high-consequence infections.

11Common pitfallsFrequent interpretation and management errors.

01
Do not require overseas travel; UK freshwater, rodents, livestock, sewage and occupational exposures can all transmit leptospirosis.
02
Do not wait for jaundice before considering severe disease; pulmonary haemorrhage, meningitis or myocarditis may dominate.
03
Do not send only serum without illness dates; paired blood and urine with precise timing lets RIPL choose and interpret direct tests appropriately.
04
Do not treat a negative early IgM as exclusion, because antibodies may not yet have developed.
05
Do not delay antibacterial treatment in a severely ill compatible case while waiting for a microscopic agglutination titre.
06
Do not assume post-antibiotic deterioration is harmless Jarisch–Herxheimer inflammation; reassess for anaphylaxis, shock and pulmonary bleeding.
07
Do not conflate laboratory organism notification with registered medical-practitioner disease notification; follow the current jurisdictional list and health-protection advice.