EMmedonline

• Leptospirosis is one of the commonest zoonotic disease.

• Genus leptospira is divided into leptospira interrogans which comprises all pathogenic strains and leptospira biflexa, containing the saprohytic strain.

• Leptospires are tightly coiled , thread like organism about 5-7µm in length which are actively motile ; each end is bent into a hook . Leptospira interrogans is pathognomic for humans.

Pathogenesis

• Leptospirosis can enter their human hosts through intact skin or mucous membrane but entry is facilitated by cuts and abrasions.

• Source of transmission are rats, dogs, cattle and pigs.

• Humans gets infected from indirect contact with contaminated animal urine through surface waters, moist soil or other wet environments or direct contact with urine or excreta.

• The organism resist innate immune defenses, proliferate in blood stream or extracellularly within organs and then disseminate hematogenously to all organs.

• As antibodies develop they disappear from blood but persist in various organs like brain, liver, kidney, lung, liver.

• Life cycle is completed as leptospiroses transverse the interstitial spaces of the kidney, penetrate the basement membrane of the proximal renal tubules, cross through proximal renal tubuloepithelial cells and become adherent to proximal renal tubular brush border, whence they are excreted in urine.

• Chronic and persistent renal colonisation can last for weeks or years with unknown pathophysiologic consequences.

• Human to human transmission doesnot occur.

• Leptosirosis cause two phase

  • Septicemic or Leptospiremic phase : It lasts for 3 - 10 days during which the organism may be cultured from blood.

  • Immune phase : Here the host immune response, including immune complex deposition leads to endothelial injury. During this phase leptospires can be isolated from urine.

CLINICAL FEATURES

Bacteraemic Leptospirosis

Can be caused by any serotype. Comes to an end by one week or merges into other forms.

• High grade fever

• muscle pain & tenderness ( especially of the calf and back )

• Intense headache

• Weakness

• Photophobia

• Conjuntival suffusion

• Sometimes diarrhoea & vomiting.

• Macular or maculopapular rashes; eryhtmatous or purpuric rash.

Icteric Leptospirosis

• Weil's disease is a dramatic life threatening disease.

• It is characterised by combination of jaundice, acute kidney injury, hypotension and hemorrhage most commonly involving the lungs.

• In severe cases there may be epistaxsis, haematemsis and malena or bleeding into pleura, pericardial or sub arachnoid spaces.

• Jaundice is not associated with fulminant hepatic necrosis or hepatocellular damage.

• Liver may be enlarged and tender. Splenomegaly may be seen.

• Renal failure due to impaired renal perfusion and acute tubular necrosis manifest as Oliguria or anuria ; with presence of albumin, blood and cast in the urine. It can also cause non oliguric renal failure with hypokalemia and hypomagnesemia due to renal tubular dysfunction.

• Renal failure typically returns to normal in survivors of severe disease.

• Patient may have transient erythematous rash.

• Weil's disease is associated with myocarditis, encephalitis & aseptic meningitis.

Pulmonary Syndrome

• Patient may manifest with cough, chest pain and hemoptysis but without purulent sputum.

• Patchy lung infiltrate on chest X- ray

• Patient develop ARDS, Respiratory failure and MODS.

Aseptic Meningitis

• It is very difficult to differentiate from viral meningitis.

• CSF pleocytosis can range from a few cells to > 1000 cells/µL, with a polymorphonuclear cell predominance.

• Hypo or areflexia of legs may be seen.

• The conjuntivae may be congested but there are no other differentiating signs.

• Laboratory clues include a neutrophil leucocytosis , abnormal LFT's and the occasional presence of albumin and cast in the urine.

Investigations

• WBC: A polymorphonuclear leucocytosis, Thrombocytopenia.

• LFT : Elevated AST & ALT (mild)with mixed conjugated and unconjugated hyperbilirubinemia. prothrombin time may be a little prolonged.

• LDH elevated.

• Elevation of creatinine kinase indicates skeletal muscle injury.

• Urine Routine : Proteinuria, pyuria, hematuria and hyaline granular cast.

• CSF: Elevated protein level and normal glucose level.

• ECG : Non specific ST and T wave changes, RBBB

Definitive diagnosis

1. Isolation of organism

• Blood & CSF culture are most likely to be positive if taken before 10^th day of illness.

• Leptospires appear in urine during 2^nd week of illness. It can be detected by dark field microscopy.

2. Serological test

• IgM ELISA & Slide agglutination test (SAT) : It is simple diagnostic tool. It is positive as early as 2 days. It is 100% specific and 93% specific respectively.

• MAT (Microscopic agglutination Test ) : It is cubersome and not routinely done. A four fold increase in titre is diagnostic.

• DOT-ELISA and dipstick methods for detecting IgM antibodies are newer screening methods.

3. Detection of specific DNA

• Detection of leptospiral DNA by PCR is possible in blood in early symptomatic disease and in urine from the 8^th day of illness and for many months after that.

Modified FAINE'S DIAGNOSTIC CRITERIA

• A score 25 or more is diagnostic and score of 20 – 25 is suggestive of leptospirosis.

Management

Antibiotics

• Prompt initiation of antibiotics shortens the course of severe leptospirosis.

• Duration of treatment is 7 days.

• Studies on animals indicates that oral azithromycin is also likely to be useful in mild leptospirosis.

Chemoprophylaxsis

• Doxycycline 200mg PO once a week or Azithromycin 250 mg PO once or twice a week.

• Efficacy is not proven.

Prognosis

• The severity of illness in terms of pulmonary and renal dysfunction is the most important determinant of prognosis.

• Advanced age, clinically evident pulmonary involvement, elevated serum creatinine level, oliguria and thrombocytopenia are associated with poor prognosis.

• Chronic alcoholism is associated with severe disease.

• Mortality rates varies from <5% - >20%.

Updated on 26/12/2014

Reference

• Harrison; 18 th edition

• Davidson

• Leptospirosis – AN overview by TK dutta; JAPI