A 28-year-old Australian aid worker, returns from the Philippines’ flood disaster and is subsequently admitted to your ICU. Twelve days following her return she developed fevers, headaches and severe myalgias. This continued for a week, and then improved. Despite feeling weak she remained well for three days before deteriorating again.

On clinical examination the following is evident:

She appears unwell, respiratory rate 24 breaths per minute; bibasal crackles on auscultation, heart rate 102 beats per minute, blood pressure 92/45 mmHg, cool peripheries, conjunctival suffusion, and mild meningism. She is confused but with no focal neurological signs.

Results of investigations are as follows:

Haemoglobin 86 g/L*

115 – 160

White blood cell 21 x 109/L with a left shift*

4.0 – 11.0

Platelets 95 x 109/L*

140 – 400

International Normalised Ratio (INR) 1.6*

0.8 – 1.2

Activated partial thromboplastin time (APTT) 39 seconds*

30 – 34

Creatine kinase (CK) 3000 U/L*

< 100

Urea 19.0 mmol/L*

2.1 – 7.1

Creatinine 350 µmol/L*

46 – 90

Alanine aminotransferase (ALT) 272 U/L*

< 34

Aspartate aminotransferase (AST) 240 U/L*

< 31

Gamma glutamyl transferase (GGT) 92 U/L*

< 38

Alkaline phosphatase (ALP) 300 U/L*

42 – 98

Bilirubin 87 µmol/L*

4.0 – 12.0

a) List the features on the history, examination and results of investigations, given above, that are in keeping with a diagnosis of leptospirosis in this patient.

b) Briefly describe the natural course of this disease.

c) Discuss the specific treatment of this patient for this condition.

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College Answer

a)
Contracted in a flooding tropical environment
1. Biphasic pattern of illness
2. Conjunctival suffusion
3. The combination of hepatitis and renal failure in the setting of a tropical febrile illness.

b)
The natural course of leptospirosis falls into 2 distinct phases:
A. Septicaemic - During this stage, which lasts about 4-7 days, the patient experiences fever,
chills, weakness, and myalgias. Other symptoms include sore throat, cough, chest pain,
haemoptysis, rash, frontal headache, photophobia, mental confusion, and other symptoms of
meningitis.
B. Immune - This stage occurs as a consequence of the body's immunologic response to
infection and lasts 0-30 days or more. Aseptic meningitis, renal failure, cardiomyopathy,
pulmonary manifestations, uveitis.

During a brief period of 1-3 days between the 2 phases, the patient shows some improvement.
Weil syndrome is the severe form of leptospirosis and primarily manifests as profound jaundice,
renal dysfunction, hepatic necrosis, pulmonary dysfunction, and hemorrhagic diathesis - occurs at the
end of the first stage and peaks in the second stage.

c)
Penicillin (1.5 million units IV every 6 hours) OR
Doxycycline (100 mg IV twice daily) OR
Ceftriaxone (1 to 2 g IV once daily), OR
Cefotaxime (1 g IV every 6 hours).
The duration of treatment in severe disease is usually seven days.
Initiation of antibiotic treatment may be associated with the Jarisch-Herxheimer reaction
(inflammatory reaction to endotoxins released by bacterial lysis)

Use of intravenous corticosteroid therapy has been proposed given the vasculitic nature of severe
leptospirosis, particularly in the setting of pulmonary involvement; however there is insufficient
evidence for routine use of corticosteroids.

Discussion

The college's model answer is both brief and comprehensive.

One can only add general remarks and references, fleshing the answer out somewhat to include the general clinical features and diagnosis. Of course, the candidate at the exam should answer the question they asked, rather than blabbering about microagglutination.

In brief:

Clinical features of Leptospirosis in general; particularly of Phase 1 (early disease)

  • History of travel to a tropical flood-prone area
  • Conjunctival suffusion
  • Headache, particularly retroorbital
  • Myalgia, particularly of the lower back and calf.

Clinical features of Weil's disease in particular (Phase 2)

  • Jaundice
  • Bleeding diathesis
  • Hepatosplenomegaly and hepatic necrosis
  • Renal failure
  • Pulmonary haemorrhage
  • Aseptic meningitis
  • Uveitis
  • Cholecystitis
  • Pancreatitis
  • Myocarditis
  • Rhabodomyolysis

Laboratory diagnosis

Natural course of the disease

  • Incubation period: 5-14 days.
  • Leptospiraemia (Phase 1) - 1 week. Oh's Manual calls it the "Septicaemic phase"
    • Characterised by fevers, myalgia, conjunctival effusion, etc.
  • A brief break in symptoms usually follows.
  • Leptospiruria (Phase 2) - up to 1 month. Oh's Manual calls it the "Immune phase"
    • Weil's disease usually appears around the beginning of Phase 2.

Antibiotic management

References

Oh's Manual: Chapter 73  (pp. 743) Tropical  diseases  by R. Sivakumar  and  M.  E.  Pelly

Smith, James KG, et al. "Leptospirosis following a major flood in Central Queensland, Australia." Epidemiology and infection 141.03 (2013): 585-590.

World Health Organization. "Human leptospirosis: guidance for diagnosis, surveillance and control." (2003).

Toyokawa, Takao, Makoto Ohnishi, and Nobuo Koizumi. "Diagnosis of acute leptospirosis." Expert Rev Anti Infect Ther. 2011 Jan;9(1):111-21.

Palaniappan, Raghavan UM, Subbupoongothai Ramanujam, and Yung-Fu Chang. "Leptospirosis: pathogenesis, immunity, and diagnosis." Current opinion in infectious diseases 20.3 (2007): 284-292.

Dolhnikoff, Marisa, et al. "Pathology and pathophysiology of pulmonary manifestations in leptospirosis." Brazilian Journal of Infectious Diseases 11.1 (2007): 142-148.

Kobayashi, Y. "Human leptospirosis: management and prognosis." Journal of postgraduate medicine 51.3 (2005): 201.

Ferreira, Ana Sofia, et al. "Direct Detection and Differentiation of Pathogenic Leptospira Species Using a Multi-Gene Targeted Real Time PCR Approach."PloS one 9.11 (2014): e112312.

Brett‐Major, David M., and Rodney Coldren. "Antibiotics for leptospirosis." The Cochrane Library (2012).

Bryceson, Anthony DM. "Clinical pathology of the Jarisch-Herxheimer reaction." Journal of infectious Diseases 133.6 (1976): 696-704.