Prevalence of Asymptomatic Urinary Leptospira Carriage Among Young Adults at Risk of Mesoamerican Nephropathy

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Background: Leptospirosis is a bacterial zoonosis with a range of clinical manifestations including acute kidney injury. Chronic carriage of leptospira is well-described in several species, but it remains unclear whether this occurs in humans. Furthermore, chronic experimental infection with leptospira is associated with progressive kidney injury in small animal models and asymptomatic carriage of leptospira has been proposed as a cause of CKD of unknown aetiology, one form of which is Mesoamerican Nephropathy (MeN). Determining the burden of asymptomatic leptospiral infection is challenging as serological assays may not be sensitive to antibodies against all serovars and immunity may wane over time. We therefore explored the evidence for asymptomatic carriage of urinary leptospira in a young adult population at risk of MeN. Methods: Samples were analysed at multiple timepoints per individual from a community-based, longitudinal study of apparently healthy young adults (mean age = 24.2, mean baseline eGFR = 110.5 ml/min/1.73m2, % male = 83.2) from rural north-west Nicaragua followed-up annually for 7 years. Serum anti-leptospira IgG antibodies were measured in 346 participants using a commercial ELISA kit and an established nested 16S PCR method was used to screen for leptospiral DNA in urine in 94 participants. Sanger sequencing was used to confirm leptospiral species in a subset of 16S PCR positive samples. Results: None of the participants had recent symptoms of acute leptospiral illness. 55 (59%) participants were 16S PCR positive at ≥1 timepoint and 18% were positive at 2 timepoints. Sequencing of a subset demonstrated 29% of 16S PCR positive samples were consistent with leptospiral DNA, suggesting an overall prevalence of asymptomatic carriage of 17%. Overall, 8.7% (30/346) of participants tested IgG positive for leptospira in at least one timepoint of whom 12 seroreverted at follow-up testing. Rates of seropositivity were similar between 16S PCR positive and negative groups. Conclusions: Asymptomatic urinary shedding of leptospires is common in a young population at risk of MeN which appears to be persistent or recurrent in some cases. Serological assays do not reliably identify individuals shedding urinary leptospiral DNA.

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