Rural infections series: Leptospirosis

The diagnosis of leptospirosis is usually clinical, with specific laboratory testing used to retrospectively confirm the diagnosis for Notification purposes (see: “Leptospirosis is a Notifiable disease”).

Clinical presentation and patient history

The incubation period of leptospirosis varies from 2 – 30 days (mean ten days).⁶ The eventual symptomatic illness can range from mild to severe.⁸ Approximately 90% of people will have an acute, self-limiting, febrile illness.⁸ The remaining 10% will develop a more severe, potentially life-threatening condition.⁸ Signs and symptoms of leptospirosis are classically biphasic, although in many severe cases the distinction between the two phases is not apparent.

The initial phase of leptospirosis is an acute-onset febrile illness lasting three to nine days.⁸ The most common symptoms are chills or rigors, myalgia, headache and conjunctival suffusion.⁴ Conjunctival suffusion is relatively specific to leptospirosis, and typically appears on the third or fourth day of the illness.⁸ It presents as bilateral redness (hyperaemia) and oedema (chemosis) of the conjunctiva, without an inflammatory exudate. An erythematous macular rash, nausea, vomiting and fatigue may also be present, but are less typical features of leptospirosis.⁸

The initial phase is usually (but not always) followed by an asymptomatic period lasting two to three days, before the second (immune) phase begins.^{1, 3, 8}

The immune phase occurs as serum IgM antibodies increase and the spirochetes disappear from the blood and cerebrospinal fluid. The response to the antibodies ranges from a more severe form of the initial phase (as above), including aseptic meningitis, to Weil’s disease, characterised by jaundice, renal failure, pulmonary symptoms (dyspnoea, chest pain and haemoptysis), myocarditis, cardiac arrhythmias and haemorrhagic diathesis (spontaneous bleeding).⁴ In severe infection, multiple organ failure can cause a wide range of symptoms.

Examination

Findings on examination may differ widely among patients. Signs will vary depending on the stage and severity of the illness and the organ systems involved.

A general examination should be performed and will indicate features typical of an infection, such as fever (up to 40°C), tachycardia and muscle tenderness.⁸ Localised tenderness in the calf muscles and, in particular, in the paraspinal muscles, is an important, relatively specific finding.⁴ Hypotension may be found in patients with severe infection.

A brief eye examination is important for both diagnosis and identification of complications. Photophobia, jaundice and bilateral conjunctival suffusion are often present.⁴ Optic neuritis (inflammation of the optic nerve) and uveitis (inflammation of the uvea, including the iris, ciliary body and choroid) can develop as secondary complications.⁸

Palpation of the abdomen may indicate abdominal tenderness and hepatosplenomegaly.⁴

Auscultation of the patient’s chest may indicate crackles and wheeze associated with pulmonary oedema. Signs of consolidation, such as bronchial breath sounds, dullness to percussion and reduced chest movement, may be present in severe cases due to pulmonary haemorrhage.

A brief neurological examination should be conducted in patients with suspected leptospirosis with severe signs and symptoms. Aseptic meningitis is suggested by vomiting, headache and meningeal irritation (neck stiffness and photophobia). Immediate referral to hospital is required for anyone presenting with signs and symptoms of suspected meningitis.

Differential diagnosis

The symptoms and signs associated with leptospirosis are non-specific, therefore there are a wide range of other conditions that should be considered in the differential diagnosis, including:⁸

• Influenza
• Other causes of meningitis and meningococcal disease
• Viral hepatitis
• Septicaemia
• HIV seroconversion illness
• Toxoplasmosis
• Other rural infections, e.g. rickettsial infections such as murine typhus
• Tropical diseases, such as yellow fever and malaria; consider in people returning from overseas travel

Investigations

Specific testing for leptospirosis should be used to confirm a suspected diagnosis. However, as the results will not be immediately available (results may take up to three days, or more, depending on the testing laboratory), treatment can be commenced based on the clinical diagnosis.

Serology should be requested first-line for a patient with suspected leptospirosis.⁹ Polymerase chain reaction (PCR) testing for DNA should be added if the patient’s symptoms are severe or if infection is thought to be acquired through occupational exposure.

N.B. Patients who have laboratory-confirmed leptospirosis due to an occupational exposure are eligible for ACC cover.

Serology is used to retrospectively confirm leptospirosis,⁴ and should be requested whenever there is a reasonable suspicion of the infection.² Antibodies begin to appear five to seven days after the onset of symptoms,¹⁰ and can remain raised for several months.⁷ Two serology samples are required: referred to as the acute and convalescent samples. The first sample should be taken at the initial presentation, with the approximate date of the start of the illness recorded on the form. The second sample should be taken a minimum of 10 – 14 days after the first and ideally at 21 days after the onset of symptoms. A four-fold increase between titre levels in the first and second samples is considered diagnostic of leptospirosis.¹⁰ In some patients, seroconversion is delayed (>30 days), therefore if both samples are negative but there is still a suspicion of leptospirosis, a third serum sample should be requested. Patients with a previous exposure to leptospirosis will often have a positive first sample, but this does not necessarily indicate current infection. An increase in titre levels in the second sample would suggest active infection.

The serology test is specific to the Leptospira genus, but does not differentiate between serovars, i.e. different “strains” of leptospirosis. Positive serology samples are forwarded to Environmental Science & Research (ESR) for microscopic agglutination titres (MAT) which test for antibodies to specific serovars. This information is of limited use for the management of leptospirosis, but is important for epidemiological monitoring.

PCR testing for Leptospira DNA should be requested in addition to serology if the infection is severe, or for confirmation of an occupationally acquired infection, as the results will be available more rapidly than those from paired serology. The type of sample for PCR depends on the duration of the illness: during the first week of signs and symptoms a blood sample should be collected (approximately 5 mL in an EDTA tube; usually purple top). After the first week, a urine sample (at least 20 mL) is used, as leptospires will no longer be reliably detectable in the blood. Due to the intermittent excretion of leptospires in urine, a negative result does not exclude leptospirosis, and a repeat sample may be necessary if there is still a strong clinical suspicion of the infection.

If the patient develops meningitis, a cerebrospinal fluid sample obtained in a secondary care setting can also be used for PCR testing in the first ten days of infection.¹⁰

Leptospirosis culture is available from some New Zealand laboratories, however, the results usually take a significant time, making it impractical for clinical use.

Other laboratory investigations

Additional laboratory investigations are not necessary for the diagnosis of leptospirosis. However, some tests may be useful to add evidence to a suspected diagnosis of leptospirosis while waiting for results of leptospirosis-specific testing. Most findings will, however, be non-specific. The following tests may be considered:

• Full blood count – lymphocytopaenia is common in people with leptospirosis.⁹ Leukocytes may be low, normal or high, but are commonly associated with a left shift.⁸ Thrombocytopaenia is also present in up to 50% of people with leptospirosis.⁶
• LFTs – increases in transaminases, alkaline phosphatase and bilirubin may be seen on liver function tests.⁶
• Serum creatinine – levels may be elevated due to tubular damage and dehydration.⁸
• Urinalysis – proteinuria, pyuria and microscopic haematuria may be present, with granular casts on microscopy.⁶

It is not necessary to wait for the results from laboratory testing for leptospirosis before starting treatment if there is a strong clinical suspicion of the infection.¹ Discussion with an Infectious Diseases Physician is encouraged in addition to notification to the Medical Officer of Health.

Doxycycline 100 mg, twice daily, for five to seven days is the first-line treatment for leptospirosis in the community setting. Amoxicillin 500 mg, three times daily, for five to seven days is an alternative.^{1, 11} Treatment is most effective if antibiotics are initiated within five days of symptom onset, after which the efficacy of antibiotic treatment is less certain.^{1, 12} In practice, however, treatment is usually initiated in patients with severe illness regardless of the date of onset.¹

As with other spirochete infections, e.g. syphilis, antibiotic treatment can be associated with the development of a septicaemia-like reaction in the first few hours after starting treatment, due to the sudden release of endotoxins as the bacteria die.⁴ This is referred to as a Jarisch–Herxheimer reaction. This reaction is assumed to be rare, although the exact prevalence in patients with leptospirosis treated with antibiotics is unknown.¹³ Patients should be instructed to seek immediate medical attention if they become acutely unwell after starting the course of antibiotics.

When should a patient with leptospirosis be referred?

All patients with severe infection or signs of meningitis should be referred to hospital immediately.¹ Treatment with intravenous antibiotics, e.g. benzylpenicillin 1200 mg IV, every four to six hours, for five to seven days is usually required.¹¹ Intensive supportive care with particular attention to fluid and electrolyte balance is also often necessary.¹ Further treatment is dependent on complications, e.g. patients who develop acute renal failure may require haemodialysis.¹

All women who are pregnant and are suspected of having leptospirosis of any severity should be referred to hospital. Leptospiral infection in either early or late pregnancy results in miscarriage or premature delivery in more than 50% of cases.⁴

Consideration should be given to referral to an Infectious Diseases Physician for people with risk factors for developing severe illness. Risk factors include age less than five years or over 65 years and the presence of co-morbidities, such as liver disease or an immunocompromised status.⁴

Preventing future infections

Primary prevention of leptospirosis focuses on educating people to avoid high-risk exposure, such as immersion in fresh water that could be infected, contact with stagnant water and contact with animal urine. However, for many people who are occupationally exposed, avoidance will not be possible. Minimising exposure to animal urine through the use of protective clothing (e.g. gloves, goggles or face shields, gumboots) and good hygiene is recommended. Preventive measures are now widespread in certain industries, such as dairy and meat processing.⁵

Advise patients who have a high level of unavoidable occupational risk to be aware of leptospirosis and its prevention and to present to primary care if they develop flu-like symptoms.