Leptospirosis


– Leptospirosis is a zoonosis that affects many domestic and wild animals, mainly rodents (particularly rats) but also dogs and cattle, etc.
– It is transmitted to humans by contact through skin lesions or mucous membranes (e.g. eyes, mouth) with:
• freshwater or moist soil contaminated with urine of an infected animal (indirect contact);
• urine, blood and other body fluids or tissues of an infected animal (direct contact).
– It is caused by bacteria of the genus Leptospira.
– Leptospirosis occurs worldwide, particularly in tropical and subtropical regions. There are often outbreaks after heavy rainfall or flooding.

Clinical features

Approximately 90% of cases are a moderate form of the disease with a favourable outcome. 5 to 15% of cases present a severe form with multiple organ dysfunction and a high mortality rate.

Moderate form 
– Acute phase (septicaemic) 
• Sudden onset of high fever with chills, headache, muscle pain (especially calf pain), photophobia, ocular pain, bilateral conjunctival haemorrhage very frequent.
• May be associated with: gastrointestinal symptoms (anorexia, abdominal pain, nausea, vomiting), non-productive cough, adenopathies, hepatomegaly.
– Immune phase: the signs of the acute phase regress after 5 to 7 days then reappear for a few days usually in a milder form (milder fever, less severe myalgia) then disappear.

Severe or ictero-haemorrhagic form 
The onset is the same but a few days later the symptoms worsen: renal disorders (oliguria or polyuria), hepatic disorder (jaundice), widespread haemorrhages (purpura, ecchymoses, epistaxis, haemoptysis, etc.), pulmonary signs (chest pain) or cardiac signs (myocarditis, pericarditis).

Diagnosis is difficult because of the broad spectrum of clinical manifestations. Patients that present the following should be considered as suspected cases of leptospirosis:
• fever + 2 of the following signs: myalgia, calf pain, conjunctival haemorrhage, chills, abdominal pain, headache, jaundice or oliguria
and
• one or more risk factors for infection: contact with potentially contaminated surface freshwater (e.g. swimming, fishing, rice fields, flooding) or occupations at risk (e.g. crop and livestock farmers, veterinarians, butchers, slaughterhouse workers, miners).

Laboratory

In all cases, rule out malaria in endemic regions (rapid test).

Diagnosis
Laboratory diagnosis is difficult to obtain; it is only performed in the event of strongly suspected leptospirosis (on a blood sample):
– Serology:
• between 0 and 7 days: real-time PCR (early diagnosis);
• after 7 days: microscopic agglutination test (MAT); IgM ELISA test provides presumptive diagnosis
• after 10 days: MAT and IgM ELISA tests only.
– Culture: limited use (bacteria grow slowly, specific culture medium).

Other investigations (if available)
– Complete blood count: possible polymorphonuclear leukocytosis, thrombocytopenia or anaemia.
– Urine: proteinuria, leukocyturia, possible microscopic haematuria.

Treatment

According to the WHO recommendations, do not wait for diagnostic test results before starting antibiotherapy based on clinical and epidemiological suspicions1,2.

Moderate form (outpatient treatment)

– Rest and treatment of fever: paracetamol PO (Chapter 1).
– Acetylsalicylic acid (aspirin) is contra-indicated (risk of haemorrhage).
– Antibiotherapy:
doxycycline PO (except pregnant or breast-feeding women and children under 8 years) for 7 days 
Children over 8 years: 1 to 2 mg/kg 2 times daily
Adults: 100 mg 2 times daily
or
azithromycin PO for 3 days
Children: 10 mg/kg on D1 (max. 500 mg) then 5 mg/kg once daily on D2 and D3 (max. 250 mg daily)
Adults: 1 g on D1 then 500 mg once daily on D2 and D3 
or, if not available,
amoxicillin PO for 7 days
Children: 25 mg/kg 2 times daily 
Adults: 1 g 2 times daily

image2018-9-27_13-15-17.png Antibiotherapy can trigger a Jarisch-Herxheimer reaction (high fever, chills, fall in blood pressure and sometimes shock). It is recommended to monitor the patient for 2 hours after the first dose of antibiotic for occurrence and management of severe Jarisch-Herxheimer reaction (symptomatic treatment of shock).

Severe form (inpatient treatment)

– Specific management according to organs affected.
– Antibiotherapy: 
ceftriaxone IV for 7 days1
Children: 80 to 100 mg/kg once daily (max. 2 g daily)
Adults: 2 g once daily

Prevention

– Avoid bathing in endemic areas.
– Disinfect laundry and objects soiled by urine. 
– Vaccination and protection clothing (only for professionals at risk of exposure).



Footnotes
Ref Notes
1 For IV administration of ceftriaxone, dilute with water for injection only.


References

  1. World Health Organization‎. Human leptospirosis : guidance for diagnosis, surveillance and control. Geneva, 2003. 
    http://apps.who.int/iris/bitstream/handle/10665/42667/WHO_CDS_CSR_EPH_2002.23.pdf?sequence=1&isAllowed=y [consulté le 2 octobre 2018]

  2. Cyrille Goarant. Leptospirosis: risk factors and management challenges in developing countries. Research and Reports in Tropical Medicine 2016:7 49–62. 
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028063/pdf/rrtm-7-049.pdf [consulté le 2 octobre 2018]