1 INTRODUCTION

Leptospirosis is prevalent in underdeveloped regions in tropical and subtropical areas.¹ The transmission of the leptospirosis commonly occurs through contact with contaminated urine, water, or soil.² Leptospirosis infection are presented with complex and diverse symptoms. Therefore, leptospirosis infection is commonly misdiagnosed, leading to high mortality rate.³ With the rapid urbanization, leptospirosis infection in Chinese cities is extremely uncommon.⁴ Consequently, leptospirosis is not typically considered as the primary diagnosis. However, there are potential risk of leptospirosis infection after typhoon events.^5-7 In this report, we present a case of a patient who developed leptospirosis infection presented with acalculous cholecystitis and septic shock in a non-epidemic region following typhoon events.

2 CASE PRESENTATION

2.2 Method (differential diagnosis, investigations, and treatment)

The laboratory findings revealed a white blood cell count of 6.8 × 10⁹/L, platelet count of 138 × 10⁹/L, neutrophil percentage of 94.8%, hemoglobin level of 112 g/L, C-reactive protein concentration of 124.5 mg/L, procalcitonin level of 2.791 ng/mL, and interleukin-6 concentration exceeding 5000 pg/mL. The biochemical analysis results indicated a creatinine level of 78.9umol/L, total bilirubin level of 8.8 μmol/L, alanine aminotransferase level of 17 U/L, and aspartate aminotransferase level of 32 U/L. The chest computed tomography (CT) indicated no abnormalities was detected. The abdominal CT indicated the presence of acalculous cholecystitis (Figure 1). The blood cultures conducted to detect microorganisms, as well as the tests performed to identify viral hepatitis, HIV, syphilis, clonorchis sinensis, influenza viruses, and COVID-19 were negative. Further investigations were conducted to explore the underlying cause of the patient's infection. Hence, peripheral blood metagenomic next-generation sequencing (mNGS) testing was conducted. The mNGS detected the presence of Leptospira interrogans (sequence number 4174). After conducting a thorough patient history, the leptospirosis infection was considered due to the patient's report of significant rainfall and extensive water accumulation around his residence following typhoons. And he engaged in recreational activities on the beach after the typhoons.

3 DISCUSSION

Leptospirosis is a zoonotic disease. Leptospirosis infection has been overlooked or given insufficient attention in the cities of China.⁸ However, leptospirosis infection are commonly reported following typhoons or severe flooding in many regions.^{5, 6, 9} The transmission of the leptospirosis commonly occurs through contact with contaminated urine, water, or soil.² In this case, significant rainfall and extensive water accumulation around the residence of the patient following typhoons and he engaged in recreational activities on the beach after the typhoons, which likely caused infection of Leptospira.

Leptospirosis typically presented with fever, muscle pain, and headache in a majority of patients. Conjunctival suffusion, characterized by prominent redness of the conjunctiva, is observed in approximately 50% of cases and is considered a distinctive feature of the leptospirosis infection.^{5, 9} Weil's syndrome, characterized by the presence of three key symptoms: conjunctival injection, jaundice, and acute kidney injury, is a well-known clinical manifestation in the severe cases of leptospirosis infection.¹⁰ This patient initially presented with a high fever and abdominal pain. The abdominal CT revealed the presence of cholecystitis. These symptoms can be easily overlooked by clinicians and often poses challenges in early diagnosis.

To the best of our knowledge, there are limited literatures regarding leptospirosis infection presented with cholecystitis as the initial manifestation.^{11, 12} A proposed mechanism is an immune-mediated response to leptospira, which subsequently leads to endothelial damage and submucosal edema of the gallbladder.¹²

There are various diagnostic methods for the detection of leptospirosis. The Leptospira culture is a diagnostic test and is widely regarded as the definitive method for identifying the causative agent of leptospirosis. However, the detection of Leptospira through Leptospira culture can be time-consuming, usually about 13 weeks, and require specific types of growth media. The role of culture in clinical diagnosis is limited.^{13, 14} An enzyme-linked immunosorbent assay has been developed to detect specific antibodies in leptospirosis, usually after 1 week, including IgM and IgG. However, this method do not facilitate the early diagnosis of the infection and has a tendency to false-positive results.¹⁵ In addition to traditional techniques, patients may benefit from metagenomic next-generation sequencing (mNGS). The mNGS technique is a fast and efficient method that enables the comprehensive analysis of nucleotide sequences in a given sample. In recent years, mNGS has emerged as a valuable tool in the microbiology examinations.^{16, 17} The mNGS holds great potential as a highly sensitive approach for the identification of specific microorganisms and the early detection of uncertain, infrequent, or newly emerging microorganisms. The mNGS can accurately and effectively identify leptospira DNA during the infection. In this case, the test of mNGS on the patient's blood sample successfully identified the leptospires infection. This timely and accurate detection played a crucial role in preventing misdiagnosis.

4 CONCLUSION

Medical professionals should be aware of the potential Leptospirosis infection in patients presented with acalculous cholecystitis and septic shock after typhoon events. Furthermore, mNGS is a valuable diagnostic tool in the timely identification of leptospirosis infections, particularly in patients who presented with the non-specific symptoms.

AUTHOR CONTRIBUTIONS

Xueying Han: Writing – review and editing. Bihan Huang: Writing – original draft. Lilei Yang: Writing – review and editing. Jinglan Wu: Writing – review and editing. Haigang Zhang: Writing – original draft.

FUNDING INFORMATION

This study was supported by the Health Science and Technology Program of Nanshan District (grant number NS2024023).

CONFLICT OF INTEREST STATEMENT

The authors declare no competing interests.

ETHICS STATEMENT

Not applicable.

CONSENT

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.