By Philip R. Fischer, MD, DTM&H
Synopsis: Leptospirosis continues to cause seasonal problems in some urban areas, especially those with large populations of rats and imperfect garbage handling. New diagnostic tests are being developed, and plasma exchange offers the potential of improved outcomes for patients with leptospirosis accompanied by severe pulmonary hemorrhage.
Background
A major city is overrun with an abundance of rats that swim in a major river and hang out at children’s playgrounds. The number of leptospirosis cases is rising rapidly. More sanitation workers have been hired, and safer processes for storage and removal of trash have been implemented.
What city is struggling with sanitation, rats, and leptospirosis? In spring 2025, this was a description of Sarajevo, the capital of Bosnia and Herzegovina, where there were 12 cases of leptospirosis reported in one hospital during one 24-hour period in May.1 However, the same description fit for New York City in spring 2024; New York City typically had about three cases of leptospirosis per year from 2001 to 2020 but then had about 15 cases per year from 2021 through 2023, then 24 in 2023, and six in the first 100 days of 2024 (with six deaths from 2001 through 2023).2 As large cities with seasonal moisture struggle with garbage removal, rats flourish, and leptospirosis becomes more common.
We know that leptospirosis is spread through water contaminated by the urine of rats and other animals, both wild and domesticated.3 Globally, there are more than 1 million cases of leptospirosis and about 60,000 deaths from it each year.3 Cases occur after flooding and hurricanes as well as in extreme athletes swimming or people walking in fresh water.4-6 Leptospirosis can be shared with household pets.7 Clinically, the infection can be asymptomatic or mild with fever, discomfort, and gastrointestinal symptoms.3 The diagnosis usually is made with immunoglobulin M (IgM)-specific serologic screening tests, which can be confirmed at a reference laboratory with a microscopic agglutination test.8 Without early treatment, some patients progress to respiratory, renal, and hepatic failure.3 Treatment is with doxycycline or azithromycin and, in severe cases, parenteral penicillin or ceftriaxone.3
Aware of recent urban outbreaks of leptospirosis, what new scientific advances will guide our future diagnosis and management of leptospirosis?
Diagnosis
Beyond serologic testing for leptospirosis infection, it also is possible to perform polymerase chain reaction (PCR) testing of whole blood during the first week of illness, urine after the first week of illness, and cerebrospinal fluid when there are signs of meningitis.8 Two new papers point to other emerging possibilities for diagnostic testing.
Current PCR tests for leptospirosis are not widely available, so investigators in Japan developed and evaluated a new microfluidic-based PCR test.9 Direct detection of the 16S rDNA Leptospira allowed rapid testing of whole blood without requiring DNA purification. Pathogens in spiked human blood samples could be detected at concentrations of less than 100 per microliter. Using hamster models of leptospirosis, these investigators found that their new test could ably detect pathogens in as little as a 1 microliter blood sample. Prior to commercialization of this new assay, further testing will be required using additional species of Leptospira in samples of infected humans.
The gold-standard serologic test for leptospirosis currently is the microscopic agglutination test, which requires incubation of a patient’s serum with live, cultured Leptospira of several serovars. This is a labor-intensive and potentially dangerous test. Investigators in Brazil studied a chimera containing two immunogenic lipoprotein antigens from pathogenic Leptospira (ErpY-LemA).10 Serum samples from hamsters artificially infected with 13 strains of Leptospira and serum samples from 80 humans who had undergone microscopic agglutination testing (60 with positive results) were mixed with Escherichia coli-produced ErpY-LemA chimera and observed for chimera-antibody binding. Compared to the microscopic agglutination test, the new chimeric test was 80% sensitive and 100% specific for immunoglobulin G (IgG) and 95% sensitive and specific for IgM. This assay holds good potential to replace the microscopic agglutination test, with improved ease and safety.
Management
Approximately 11% of patients with leptospirosis do not survive the infection, and having pulmonary symptoms is a strong risk for mortality.11 Leptospirosis continues to be a problem in Sri Lanka during the seasons when rice paddies are cultivated and harvested.12 Symptomatic dogs, cattle, and pigs can spread the infection to humans, as can asymptomatic rodents that carry Leptospira. Sri Lanka reports more than 100 deaths due to leptospirosis per year. The pathogenesis of severe pulmonary hemorrhage is not well understood, but it might relate to deposition of immune compounds that cause necrosis at the alveolar-capillary membrane and, thus, hemorrhage. Sometimes, therapeutic plasma exchange is provided for patients with severe pulmonary hemorrhage due to leptospirosis. Comparison was made between those who did and did not receive plasma exchange in two Sri Lankan hospitals.12 (This was an observational study and did not include randomization.) Of the 59 who received plasma exchange, 29% died; of the 19 who did not receive plasma exchange, 90% died.12 Controlled studies should follow.
Renal insufficiency is another risk factor for a fatal outcome with leptospirosis, and anecdotal evidence suggests that these patients might be more likely to survive if they start renal replacement therapy earlier than would otherwise be strictly indicated.11,13 A French study team on Reunion Island conducted an observational study of 295 adult patients hospitalized at one of two academic medical centers with leptospirosis and stage 3 acute kidney injury.13 They compared the 28% who started renal replacement therapy within the first 48 hours of hospitalization with those who did not (25% of whom eventually did receive renal replacement therapy). Early initiation of renal replacement therapy was associated with increased risk of death or progressing to chronic renal insufficiency.13 Early renal replacement therapy is not an option to pursue.
Philip R. Fischer, MD, DTM&H, is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
References
1. De Launey G. Rat-borne diseases cause crisis in Sarajevo. BBC. May 28, 2025. www.bbc.com/news/articles/cvgvk58enxpo
2. Quinn C. 2024 Health Advisory #10: Continued Increase in Leptospirosis Cases in New York City. New York City Department of Health and Mental Hygiene. April 12, 2024. www.nyc.gov/assets/doh/downloads/pdf/han/advisory/2024/han-advisory-10.pdf
3. Centers for Disease Control and Prevention. Clinical overview of leptospirosis. April 4, 2025. www.cdc.gov/leptospirosis/hcp/clinical-overview/index.html
4. Jones FK, Medina AG, Ryff KR, et al. Leptospirosis outbreak in aftermath of Hurricane Fiona — Puerto Rico, 2022. MMWR Morb Mortal Wkly Rep. 2024;73(35):763-768.
5. Delamare H, Septfons A, Alfandari S, Mailles A. Freshwater sports and infectious diseases: A narrative review. Infect Dis Now. 2024;54(4S):104883.
6. Gundacker ND, Rolfe RJ, Rodriguez JM. Infections associated with adventure travel: A systematic review. Travel Med Infect Dis. 2017;16:3-10.
7. Thielen BK, Holzbauer S, Templen B, et al. Case report: Locally acquired leptospirosis in a Minnesota boy and his dog. Am J Trop Med Hyg. 2023;110(1):123-126.
8. Centers for Disease Control and Prevention. Leptospirosis. April 23, 2025. www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/leptospirosis.html
9. Miyahara S, Yoneda T, Kimura S, et al. Development of a PCR method for rapid detection of Leptospira from one microliter of whole blood. Diagn Microbiol Infect Dis. 2025;113(1):116894.
10. Cardoso TL, Pereira IL, Wozeak DR, et al. ErpY-LemA: A breakthrough in human leptospirosis diagnosis. Diagn Microbiol Infect Dis. 2025;113(2):116883.
11. Chagas GCL, Aguiar GRF, Chagas RCL, et al. Epidemiology and risk factors for death in leptospirosis: A 20-year retrospective cohort study in Brazil. J Vector Borne Dis. 2025;May 15. doi: 10.4103/jvbd.jvbd_181_24. [Online ahead of print].
12. Wijenayake APH, Abeysinghe P, Suaris VM, Dharmarathna WBSM. The role of therapeutic plasma exchange in leptospirosis patients. Transfus Apher Sci. 2025;64(3):104147.
13. Julien M, Rafat C, Raffray L, et al. Immediate or delayed initiation of renal replacement therapy in patients with leptospirosis and acute kidney injury: A target trial emulation. Ann Intensive Care. 2025;15(1):65.
Leptospirosis continues to cause seasonal problems in some urban areas, especially those with large populations of rats and imperfect garbage handling. New diagnostic tests are being developed, and plasma exchange offers the potential of improved outcomes for patients with leptospirosis accompanied by severe pulmonary hemorrhage.
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