Severe leptospirosis with rhabdomyolysis in a traveller visiting Thailand

Case description

A 32-year-old German male, residing in Bangkok for 1.5 years, presented at Fever Clinic, Hospital for Tropical Diseases with a 2-day history of fever, accompanied by headache, myalgia and loss of appetite, without any organ-specific symptoms. He had recently spent 3 days camping with his girlfriend in Khao Yai National Park (located 3 hours from Bangkok) 2 weeks prior to the onset of symptoms. He has no underlying medical problems and is not currently taking any medication. He has not experienced any recent injuries or extreme physical exertion before the onset of symptoms. Physical examination was unremarkable, and the basic laboratory results, including dengue NS1 antigen test, returned negative. Consequently, he was treated supportively as an outpatient.

Two days later, on the follow-up (Day 4 of fever), his symptoms worsened, with the addition of severe calf pain and prostration. Upon further inquiry, it was disclosed that he engages in activities such as waterfall swimming and kayaking, in addition to camping. On the physical examination, his body temperature was 40.2°C, and he exhibited slight tachycardia (110 beats/minute) with a blood pressure of 144/64 mmHg. No jaundice or conjunctival suffusion was observed. Markedly tender on both calves. The initial blood exam results are displayed in Table 1.

He was hospitalized, and empirical intravenous ceftriaxone (2 g/day) and oral doxycycline (initial dose of 200 mg, followed by 100 mg twice daily) were initiated on the next day (Day 5 of fever) to cover common tropical infections. One day later, his fever subsided, but kidney function declined, with creatinine at 7.4 mg/dL, and creatinine phosphokinase (CPK) drastically rose to 2381 U/L. Despite the extremely high serum creatinine, polyuria was observed. Urinalysis revealed abnormalities with signs of myoglobinuria/haemoglobinuria, Blood 3+, Protein 2+, RBC 3-5/HPF, WBC 10-20/HPF and granular cast 5-10/LPF suggesting acute kidney injury (AKI) with rhabdomyolysis.

A blood sample collected on the 4th day of fever was sent to an in-house multiplex Real-Time Polymerase Chain Reaction (RT-PCR) targeting for Leptospira species (16S rDNA), Rickettsia species (gltA gene), Orientia tsutsugamushi (16S rDNA) and Eubacteria (16S rDNA). The targeted PCR for the 16S rDNA from the blood sample confirmed the presence of Leptospira spp. infection. Serologic testing using Bioline^TMLeptospira IgG/IgM on that day yielded negative results. The microscopic agglutination test was still negative on Day 10 of fever. He was diagnosed with leptospirosis with AKI and rhabdomyolysis.

All other diagnostic tests returned negative results, including multiplex RT-PCR for scrub typhus, the Indirect Immunofluorescent Assay for both scrub typhus and murine typhus, a repeated second dengue serology test alongside chikungunya serology, and malaria thick and thin films. Notably, urine and blood cultures remained sterile.

The treatment with ceftriaxone and doxycycline lasted for 7 days, during which adequate hydration and renal function monitoring were maintained. He was hospitalized for 7 days and discharged with improved creatinine at 1.66 mg/dL and decreased CPK. Subsequent follow-ups indicated further improvement in kidney function, with creatinine 1.12 mg/dL. (The chronologically laboratory findings demonstrated in Table 1)

Discussion

Leptospirosis is a significant public health concern in Thailand, with an incidence rate of 5.07 cases per 100 000 population reported from January to October 2023.¹ Leptospirosis is uncommon among travellers, with less than 1.2% of febrile travellers returning from tropical areas being diagnosed with the disease.^2,3 The disease is increasingly reported in travellers engaging in high-risk activities, such as freshwater bathing and other leisure activities such as canoeing, kayaking and rafting in endemic areas, especially during the rainy season or times of flooding, often in the setting of pre-existing non-intact skin.³

The spirochete bacteria Leptospira spp. primarily spreads through direct or indirect contact with freshwater contaminated by animal urine, with an incubation period ranging from 2 to 30 days.^4,5 While the initial symptoms are non-specific and may overlap with other common tropical diseases, specific manifestations such as calf and lower back muscle pain, and conjunctival suffusion, can assist in differential diagnosis.⁴

Approximately 10% of patients develop manifestations of severe leptospirosis, especially AKI, characterized by non-oliguric potassium-wasting nephropathy, as demonstrated in our patient. Rhabdomyolysis can occur in up to 62% of cases in some literatures.⁴ However, on the day of admission, there was no change in urine colour, and diuresis remained normal; a subsequent decrease in the frequency of urination was noted. Consequently, the decision was made to closely monitor kidney function, assess CPK levels and ensure adequate hydration, which successfully prevented the need for renal replacement therapy.

Although the gold standard for diagnosing leptospirosis is the microscopic agglutination test, it may not yield positive results in the early stages.⁴ Molecular diagnosis targeting Leptospira DNA can be particular helpful, especially when the patient presents early, just a few days after the onset of fever. This allows for early diagnosis and treatment, helping to prevent the severe complications.⁵

In summary, this case underscores the important of considering travel history, high-risk exposures and clinical clues for the early suspicion of leptospirosis. Utilizing molecular diagnosis for early identification is crucial in avoiding delays in antibiotic treatment, thereby preventing severe complications.

Funding

None

Author contributions

A.P. and W.M. conceptualized the idea. A.P, R.C. and N.T. developed the initial manuscript draft. W.M., S.C. and J.T. critically revised and edited the manuscript draft. All authors reviewed and approved the final manuscript.

Conflict of interest: The authors declare they have no conflict of interest.

Ethical statement

Written consent for publication was obtained from the patient.

References