Leptospirosis

In the Rapid Review series, I briefly review the key points of a clinical review paper. The topic this time: Leptospirosis

The paper: 

Haake DA, Levett PN. Leptospirosis in humans. Current topics in microbiology and immunology. 2015; 387:65-97. PMID: 25388133 [free full text]

What is leptospirosis?

Leptospirosis is a zoonotic infection caused by the bacteria Leptospira interrogans – a spirochete. (Many of the features of leptospirosis, such as the highly variable secondary phase presentations, remind me of syphilis – another spirochete). It is endemic in many tropical areas, and causes outbreaks after heavy rainfall or flooding. Leptospirosis can be carried by many small mammals, but the most important to human transmission is the rat. 

How common is it?

Most cases are mild and go unreported, and therefore the true incidence is unknown. It is estimated that there are about 500,000 cases of severe leptospirosis worldwide each year.  The rate varies dramatically depending on where you are, with less than 1 case in 100,000 people in Europe to almost 100 cases per 100,000 in Africa. Some estimates suggest more than 50,000 die of leptospirosis worldwide each year. (Costa 2015)

How is it transmitted?

Leptospirosis can be caught when infected urine comes into contact with mucous membranes or broken skin, either directly or through contaminated fresh water..

Who is at risk?

In Canada and the United States, the primary risk factor will be international travel. However, there have been a number of outbreaks in the United States as well. Poor sanitation is the biggest risk worldwide. 

It can occur after any exposure to fresh water, such as camping, hiking, swimming, after flooding, or while working in sewers or canals. Contaminated soil puts field workers at risk. It can also be contracted through direct contact with animals, and so cases have been seen in veterinarians, abattoir workers, and farmers.

The typical incubation phase is 7-12 days, but can be as short as 3 days and as long as a month.

What is the clinical presentation?

The typical presentation is that of a nonspecific febrile illness, with headache and myalgias. The presentation can be very similar to Dengue fever. Gastrointestinal symptoms are common, and a nonproductive cough is seen in up to half of patients. Conjunctival suffusion (dilation of the conjunctival vessels without exudate) is a classic sign of leptospirosis. Rash is rare, and suggests an alternative diagnosis such as Dengue or Chikunguna.

Leptospirosis is classically biphasic. The acute febrile illness will usually resolve after about 1 week. Patients then may go on to have a secondary more severe immune phase, with varying presentations depending on the tissues affected, including aseptic meningitis, hepatitis, uveitis, and renal failure.

What are the complications?

Severe leptospirosis is characterized by multiorgan failure. The kidneys and lungs are the most common organs affected, with significant renal failure and ARDS. Disordered bleeding is present in most severe leptospirosis, ranging from petechiae to life threatening GI hemorrhage. Neurologic adverse events include aseptic meningitis, transverse myelitis, and Guillain-Barre syndrome. It can also cause pancreatitis and acalculous cholecystitis. Cardiac complications, such as myocarditis, are also relatively common. Another classic complications is severe uveitis, often lasting months or even years after the initial infection. 

What is Weil’s syndrome?

Weil’s syndrome, also called icteric leptospirosis, is a severe form of the disease characterized by jaundice and renal failure. The reported mortality is between 5 and 15%. 

How is it diagnosed?

Serology is the diagnostic test of choice. However, IgM will not be consistently positive until 5-7 days after symptom onset.

How is it treated?

Most cases are mild and resolve without treatment. Early antibiotics may prevent severe disease. The suggested antibiotics for outpatient management are doxycycline 100mg twice daily or azithromycin 500 mg daily. For patients sick enough to require inpatient management, the treatment is generally with ceftriaxone, cefotaxime, ampicillin, or fluoroquinolones. (Considering how often I use those antibiotics for undifferentiated febrile illness with many of the above features, I wonder how many times I have just got lucky and treated leptospirosis despite never making the diagnosis)

Prognosis

With good supportive care, most patients, including those requiring dialysis, make a full recovery. 

Can it be prevented?

There is a vaccine for this condition, but its use has thus far has been limited to high risk occupations, and in response to floods and epidemics. The original vaccine was trialed in Paris sewer workers in 1979, and completely eliminated the incidence of leptospirosis over a 7 year follow up period. It isn’t clear to me why this vaccine isn’t more widely used, aside from the obvious answer that this condition is only endemic in low and middle income countries.

Prophylaxis with doxycycline is effective, and could be considered for short term, unavoidable risk. 

Worldwide, poverty is the largest contributor to this condition. Improvements in sanitation and rodent control strategies are essential in the management of leptospirosis.

Other References

Costa F, Hagan JE, Calcagno J, et al. Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoS neglected tropical diseases. 2015; 9(9):e0003898. [pubmed]

Levett PN. Leptospirosis Clinical Microbiology Reviews. 2001; 14(2):296-326.