Leptospirosis

 Question 7 from the second paper of 2014 asks for a substantial amount of detail regarding leptospirosis, including clinical features, diagnostic criteria, natural course of the disease, and specific treatment.

It is one of the tropical diseases listed in Sivakumar and Pelly's chapter of Oh's Manual (Ch. 73, p.743). Literally two paragraphs are spent on it; but the detailed model answer gives one the impression that the college expects a much more indepth knowledge of these tropical pathogens than a mere familiarity with the limited content of the Manual.

As such, the question favours infectious diseases specialists and people working in Queensland. For the rest of us, indepth knowledge must come from journal articles and textbook chapters.

Of specific interest:

Clinical features of leptospirosis

The 2003 WHO document on leptospirosis gives an exhaustingly long list of non-specific signs and symptoms, as well as a similarly long list of differential diagnoses.

The clinical features of leptospirosis are also presented in a good 2011 article, which asserts a certain order of importance over the protean manifestations of this disease. For the time-poor exam candidate, one can condense this wisdom in the following manner:

Leptospirosis in general:

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

Weil's disease in particular:

  • Jaundice
  • Bleeding diathesis
  • Hepatosplenomegaly
  • Renal failure
  • Pulmonary haemorrhage

Laboratory diagnosis of leptospirosis

Natural course of the disease

People describe a "biphasic" course.

  • 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 syndrome usually occurs at the beginning of this phase, and is characterised by some mixture of horrible inflammatory complications and organ system failures, including
      • Hepatic necrosis
      • Renal failure
      • Pulmonary haemorrhage
      • Aseptic meningitis
      • Uveitis
      • Cholecystitis
      • Pancreatitis
      • Myocarditis
      • Rhabodomyolysis

Once the spirochetes generate a vigorous antibody response, their numbers in the bloodstream dwindle (that usually takes about a week). Thereafter, they remain adherent to the renal tubular epithelium, and are shed into the urine.

Management of leptospirosis

The Sanford Guide recommends benzylpenicillin.

Alternatives include ceftriaxone or doxycycline.

The course is for 7 days, is not without risk, and may be without benefit. A 2012 Cochrane review could not demonstrate any difference between antibiotic regimens, nor indeed any benefit from antibiotics in general. On the other hand, it is known that the sudden wholesale death of millions of spirochetes in one's bloodstream may give rise to the Jarisch-Herxheimer reaction, which is horrible inflammatory state featuring rigors, shock, a temperature up to 42°C, and possibly DIC.

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.