Leptospirosis

Leptospirosis is the commonest zoonosis worldwide — a spirochaetal infection acquired from water or soil contaminated by the urine of carrier animals (chiefly rodents). It ranges from a mild, self-limiting "flu-like" anicteric illness to the fulminant, multi-organ Weil disease. For NEET PG, it is a favourite under "fever + AKI + jaundice + myalgia + history of water exposure (floods, sewer work, paddy fields)".

Definition & classification

Leptospirosis is an acute febrile illness caused by pathogenic spirochaetes of the genus Leptospira, classically Leptospira interrogans (now reclassified into multiple genomospecies). The organism is a thin, tightly coiled, motile spirochaete with characteristic hooked ends ("question-mark" / shepherd's-crook appearance) and axial flagella that drive its corkscrew motility — well-adapted to burrowing through tissue.

The disease is classically described as biphasic:

Phase	Timing	Pathophysiology	Key features
Leptospiraemic (septicaemic) phase	Days 1–7	Organism circulating in blood/CSF	Abrupt high fever, severe myalgia (calves), conjunctival suffusion, headache; organism cultivable from blood
Brief defervescence	~Day 7–8	Antibody appearance, organism cleared from blood	Transient drop in fever
Immune phase	After day 7–10	Immune-mediated; antibodies appear, organism shed in urine	Aseptic meningitis, uveitis, rash, AKI; antibodies (MAT) rise, organism in urine

High-yield: The two phases overlap and the biphasic pattern is best seen in anicteric disease; severe icteric (Weil) disease tends to be monophasic and progressive without a clear remission.

Clinically, it is divided into:

• Anicteric leptospirosis (~90%): self-limiting flu-like illness.
• Icteric leptospirosis / Weil disease (~5–10%): triad of jaundice, acute kidney injury (AKI) and bleeding, with high mortality.

Etiology & epidemiology

• Causative organism: Leptospira interrogans (pathogenic complex); >250 serovars grouped into serogroups. Important serovars: Icterohaemorrhagiae (classically Weil disease, rat reservoir), Canicola (dogs), Pomona (pigs/cattle), Grippotyphosa, Hardjo (cattle), Australis, Autumnalis (linked to outbreaks in India/Andamans).
• Reservoir hosts: rodents (especially the brown rat, Rattus norvegicus) are the principal reservoir; also dogs, cattle, pigs. They harbour leptospires in renal tubules and shed them in urine, usually asymptomatically.
• Transmission: contact of abraded skin or mucous membranes (conjunctiva, mouth) with water/soil/mud contaminated by infected animal urine. Direct ingestion or aerosol is rarer. Human-to-human spread is negligible.
• Risk groups / occupations: rice (paddy) field workers, sewer and sanitation workers, abattoir and farm workers, veterinarians, military personnel, miners, fishermen — and recreational water exposure (triathletes, white-water rafting). Classic exam scenario: post-flood / monsoon outbreaks, sugarcane and paddy cultivators.
• Geography: tropical, humid regions; in India, hyperendemic in Kerala, Tamil Nadu, Gujarat, Andaman & Nicobar, Maharashtra, peaking in the monsoon.

High-yield: Leptospira survives for weeks in warm, neutral-to-alkaline, fresh water — hence the strong link to floods and stagnant paddy water. Survival is poor in salt water and acidic conditions.

Pathophysiology

The leptospire penetrates intact mucosa or breached skin, disseminates haematogenously, and crosses tissue barriers (including the blood–brain and placental barriers) by virtue of its motility. The core lesion is a diffuse vasculitis / endothelial damage causing capillary leak, which underlies most organ manifestations:

• Kidney: interstitial nephritis and acute tubular injury → classically non-oliguric AKI with hypokalaemia (impaired sodium reabsorption and renal potassium wasting). This hypokalaemic, non-oliguric pattern is a distinguishing clue.
• Liver: hepatocellular dysfunction with cholestasis. Jaundice is largely conjugated hyperbilirubinaemia with only mildly raised transaminases — bilirubin out of proportion to AST/ALT. Hepatocyte necrosis is minimal, so liver failure is uncommon and recovery is usual.
• Lung: pulmonary haemorrhage from capillaritis — Severe Pulmonary Haemorrhage Syndrome (SPHS) is now a leading cause of death.
• Muscle: focal myositis → intense myalgia and raised creatine kinase (CK).
• Eye: later immune-mediated uveitis.
• Heart: myocarditis, arrhythmias.

High-yield: A raised serum bilirubin with disproportionately normal/mildly elevated transaminases, plus a markedly raised CK and hypokalaemic non-oliguric AKI, is a near-pathognomonic biochemical triad for leptospirosis.

Clinical features

Incubation period: typically 7–14 days (range 2–30).

Septicaemic phase:

• Abrupt onset high-grade fever with chills and intense headache (often retro-orbital).
• Severe myalgia, classically of the calf and lumbar muscles — a strong clinical pointer.
• Conjunctival suffusion (redness without purulent discharge or significant pus) appearing on days 3–4 — the single most useful clinical sign.
• Nausea, vomiting, abdominal pain; sometimes a transient rash.

Immune phase / severe disease:

• Aseptic meningitis (most common manifestation of the immune phase).
• Anterior or panuveitis, iridocyclitis (may appear weeks–months later).
• Weil disease — see below.

Weil disease (icteric leptospirosis)

The severe form, classically due to serogroup Icterohaemorrhagiae. Defined by the triad:

1. Jaundice (deep, "orange/saffron" — flavin jaundice from combined hepatic + haemolytic + capillary leak effects),
2. Acute kidney injury (often hypokalaemic, non-oliguric initially),
3. Bleeding diathesis (epistaxis, GI bleed, pulmonary haemorrhage, subconjunctival haemorrhage).

Plus features of vascular collapse, myocarditis and altered sensorium. Mortality 5–40%.

High-yield: Conjunctival suffusion + calf tenderness + jaundice with AKI after water exposure = think leptospirosis until proven otherwise. Conjunctival suffusion is the most specific clinical sign and is frequently the answer in image-based questions.

Diagnosis & investigation of choice

Diagnosis hinges on phase-appropriate testing, because the organism is in blood early and antibodies appear later.

Test	Best window	Use
Blood / CSF culture (EMJH medium)	First week (leptospiraemic)	Definitive but slow (weeks), low sensitivity
Urine culture / PCR	After ~1st week	Organism shed in urine in immune phase
Blood PCR	First 5–7 days	Early confirmation before antibodies rise
IgM ELISA	From ~day 5–7	Practical screening, becomes positive early in immune phase
MAT (Microscopic Agglutination Test)	Paired sera, acute + convalescent	Reference/gold standard, serogroup-specific

• Microscopic Agglutination Test (MAT) is the gold standard / reference serological test. A four-fold rise in titre between acute and convalescent sera, or a single high titre (≥1:800 in endemic, ≥1:200 with symptoms) is diagnostic. It is serovar-specific and useful epidemiologically, but needs live antigen panels and a reference lab.
• IgM ELISA is the most widely used practical bedside-to-lab confirmatory test; sensitive from the end of the first week.
• Darkfield microscopy of blood/urine is insensitive and unreliable (artefacts mimic spirochaetes) — not recommended for routine diagnosis.
• Culture on EMJH (Ellinghausen–McCullough–Johnson–Harris) or Fletcher/Korthof media; grows slowly at 28–30°C, low yield.

Supportive labs: neutrophilic leukocytosis (helps distinguish from viral fevers/dengue which cause leukopenia), thrombocytopenia, raised ESR/CRP, raised bilirubin (conjugated) with mildly raised transaminases, raised CK, raised urea/creatinine, hypokalaemia, and active urinary sediment (proteinuria, pyuria, haematuria).

High-yield: MAT = gold standard (paired sera, four-fold rise). IgM ELISA = best early practical test. PCR = best in the first week before antibodies. Memorise these three by timing.

Diagnostic approach (flow): Suspicious history (water/flood exposure) + fever, myalgia, conjunctival suffusion → check CBC, LFT, RFT, CK, urinalysis → if within 1st week, send blood PCR ± culture; if after 1st week, send IgM ELISA → confirm/serogroup with paired MAT → start empirical therapy without waiting for confirmation in a clinically compatible case.

The modified Faine's criteria (Parts A clinical, B epidemiological, C laboratory) are used in resource-limited settings to make a presumptive diagnosis.

Management / drug of choice

Antibiotics should be started early — do not wait for serology. Efficacy is greatest in the first few days.

Setting	Drug of choice	Alternative
Mild / outpatient (anicteric)	Doxycycline 100 mg BD × 7 days	Azithromycin, amoxicillin
Severe / hospitalised (Weil, organ involvement)	IV Penicillin G (1.5 MU 6-hourly)	IV Ceftriaxone 1 g OD (equally effective), cefotaxime, IV doxycycline
Pregnancy / children (where doxycycline avoided)	Amoxicillin / azithromycin / ceftriaxone	—

• Ceftriaxone is as effective as penicillin G in severe disease and is widely used.
• Jarisch–Herxheimer reaction (fever, rigors, hypotension from spirochaete lysis) may follow the first antibiotic dose — anticipate and manage supportively; it is not an allergy and is not a reason to stop the drug.
• Supportive care is decisive in severe disease: aggressive fluid/electrolyte management, early dialysis for AKI (markedly improves survival), ventilatory support and careful transfusion for pulmonary haemorrhage, vasopressors for shock. Severe pulmonary haemorrhage may need lung-protective ventilation ± consideration of immunomodulation.

High-yield: Doxycycline for mild/outpatient and IV penicillin G (or ceftriaxone) for severe disease. Mnemonic: "DoxyPenCef" — Doxy mild, Pen/Cef severe.

Chemoprophylaxis

• Doxycycline 200 mg once weekly for high-risk exposed individuals (e.g., soldiers, flood relief and sanitation workers in endemic areas) during the exposure period.
• General measures: rodent control, protective footwear/gloves, avoiding wading in flood water, covering wounds, vaccination of livestock/dogs. A human vaccine is used in some countries (e.g., Cuba, France) but is serovar-specific and not widely available in India.

High-yield: Prophylaxis = doxycycline 200 mg ONCE WEEKLY. (Contrast with scrub typhus prophylaxis, also doxycycline weekly — a common exam mix-up; both are weekly.)

Complications

• Weil disease — jaundice, AKI, haemorrhage (the defining severe syndrome).
• Severe Pulmonary Haemorrhage Syndrome (SPHS) — alveolar haemorrhage, ARDS; a leading cause of death, mortality can exceed 50%.
• Acute kidney injury — interstitial nephritis/ATN; usually reversible with dialysis support.
• Myocarditis & arrhythmias, hypotension/shock.
• Aseptic meningitis (immune phase, usually self-limiting).
• Uveitis / iridocyclitis — may present weeks to months after recovery; an important late sequela.
• Hepatic dysfunction — recovers fully in survivors (no chronic liver disease).
• In pregnancy: fetal loss, abortion, congenital infection.

Key differentials

Leptospirosis mimics the acute undifferentiated febrile illness (AUFI) of the tropics. In a monsoon/flood setting it must be separated from:

Condition	Distinguishing pointers
Dengue / viral haemorrhagic fever	Leukopenia + thrombocytopenia, retro-orbital pain, no conjunctival suffusion or calf tenderness; leptospirosis usually causes leukocytosis
Malaria	Periodic fever, smear/RDT positive, splenomegaly, no conjunctival suffusion
Scrub typhus	Eschar, lymphadenopathy; also tropical AUFI with AKI — responds to doxycycline
Viral hepatitis	Very high transaminases with mild bilirubin (opposite ratio to lepto); no myalgia/conjunctival suffusion or marked CK rise
Hantavirus / enteric fever / influenza	Epidemiology, relative bradycardia (typhoid), serology

High-yield: Leukocytosis (vs leukopenia in dengue) and bilirubin-out-of-proportion-to-transaminases (vs viral hepatitis) are the two laboratory clues that swing the diagnosis toward leptospirosis. Empirical doxycycline covers both leptospirosis and scrub typhus, which is why it is the pragmatic first choice in undifferentiated tropical fever.

Recently asked / exam angle

• Conjunctival suffusion as the most characteristic clinical sign — frequently tested with clinical images and single-best-answer stems.
• MAT = gold standard; IgM ELISA = best early practical confirmatory test; PCR in the first week. Match-the-test-to-the-phase questions are common.
• Doxycycline 200 mg weekly for prophylaxis; doxycycline for mild disease and penicillin G / ceftriaxone for severe disease — drug-of-choice MCQs.
• Weil disease triad (jaundice + AKI + bleeding) and its association with serogroup Icterohaemorrhagiae / Rattus norvegicus.
• Hypokalaemic, non-oliguric AKI as a distinctive renal pattern.
• Jarisch–Herxheimer reaction after the first antibiotic dose.
• Brown rat as the principal reservoir; transmission via urine-contaminated water; monsoon/flood/paddy-field epidemiology.
• Distinguishing leptospirosis (leukocytosis) from dengue (leukopenia) in a flood-related fever outbreak.
• Faine's criteria for presumptive diagnosis in resource-limited settings.

Rapid revision

1. Organism: Leptospira interrogans — spirochaete with hooked ends, corkscrew motility.
2. Reservoir: rodents (brown rat); transmission via skin/mucosa contact with urine-contaminated fresh water — floods, paddy fields, sewers.
3. Biphasic illness: leptospiraemic (blood culture +) then immune phase (urine, antibodies, meningitis/uveitis); severe icteric disease is monophasic.
4. Hallmark sign: conjunctival suffusion + severe calf myalgia.
5. Weil disease triad: jaundice + AKI + bleeding (serogroup Icterohaemorrhagiae).
6. Renal pattern: hypokalaemic, non-oliguric AKI.
7. Hepatic clue: bilirubin high, transaminases only mildly raised (opposite of viral hepatitis); CK markedly raised.
8. Blood picture: leukocytosis + thrombocytopenia (distinguishes from leukopenic dengue).
9. Gold-standard test: MAT (four-fold titre rise on paired sera); IgM ELISA best early practical test; PCR in first week.
10. Treatment: doxycycline (mild) / IV penicillin G or ceftriaxone (severe) + early dialysis for AKI.
11. Prophylaxis: doxycycline 200 mg ONCE WEEKLY in high-risk exposure.
12. Watch for: Jarisch–Herxheimer reaction, pulmonary haemorrhage (SPHS) as leading cause of death, and late uveitis.