Leptospirosis is a potentially life-threatening zoonosis with protean manifestations and a leading
cause of acute febrile illness (AFI) in the tropics. The acute phase of leptospirosis can trigger a
systemic inflammatory response, leading to multiorgan failure, including liver failure, acute
kidney injury (AKI), and pulmonary hemorrhage, significantly increasing mortality, and
potentially resulting in long-term complications. Early prediction of severe disease progression
and long-term consequences is of utmost importance. The proposed studies will involve
collaborations between the Principal Investigator and renowned researchers in the field of
leptospirosis. We have outlined two related but independent aims. Aim 1 focuses on
characterizing the host response and identifying novel biomarkers predictive of severe acute
leptospirosis using a multi-omics approach. We will analyze blood specimens and clinical data
from our existing biorepository and prospective patient recruitment, employing established and
novel machine learning analytical methods to refine proteomic, cytokine-based, and host gene
expression severity classifiers, accurately identifying patients at risk of severe disease. Our
existing biorepository contains samples collected at baseline from 218 patients with confirmed
leptospirosis, including 73 severe cases and 145 non-severe cases. Longitudinal follow-up
clinical data and blood specimens per patient are also available, enabling us to study the
temporal dynamics of the host response and disease progression. Aim 2 focuses on identifying
risk factors and novel biomarkers for leptospiral CKD and its progression. We have been
concurrently conducting a prospective multicenter cohort study and a clinical trial titled
"Leptospirosis Care Bundle Study" across several hospitals in endemic areas. We have, and will
continue to collect long-term follow-up data on adverse outcomes, including major kidney
adverse events (MAKEs), such as all-cause mortality, dialysis, and new-onset CKD in patients
with leptospirosis at baseline. Combining data from these two ongoing projects, totaling 160
patients, will provide us with a better understanding of the mechanisms and risk factors
associated with leptospiral CKD.
