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Principal Investigator: Nattachai Srisawat
Organization: CHULALONGKORN UNIVERSITY
Fiscal Year: 2024
Award: $137,229
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <19S Gamma Globulin><Active Follow-up><Acute><Acute Renal Failure with Renal Papillary Necrosis><Adverse Experience><Adverse event><Age><Antibiotic Therapy><Antibiotic Treatment><Area><Assay><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Bioassay><Biological Assay><Biological Markers><Bleeding><Blood Plasma><Blood Sample><Blood specimen><CRISPR><CRISPR/Cas system><Caring><Characteristics><Chronic Kidney Failure><Chronic Renal Disease><Chronic Renal Failure><Clinical><Clinical Data><Clinical Trials><Clustered Regularly Interspaced Short Palindromic Repeats><Cohort Studies><Collaborations><Concurrent Studies><Data><Data Bases><Databases><Diagnosis><Diagnostic><Diagnostic tests><Dialysis><Dialysis procedure><Disease><Disease Progression><Disorder><Early Diagnosis><Enrollment><Epidemiology><Fever><Frequencies><Gene Expression><Goals><HPGF><Health><Hemorrhage><Hepatic Failure><Hepatocyte-Stimulating Factor><Hospitals><Human><Hybridoma Growth Factor><IFN-beta 2><IFNB2><IL-6><IL6 Protein><IgM><Immune response><Immunoglobulin M><Immunological response><Inpatients><Interleukin-6><Investigators><Kidney><Kidney Failure><Kidney Insufficiency><Kidney Urinary System><LCN2><LCN2 gene><Laboratories><Leptospirosis><Life><Lipocalin 2><Liver Dysfunction><Liver Failure><Long-term Follow-up><Longitudinal Studies><Longterm Follow-up><Low-resource area><Low-resource community><Low-resource environment><Low-resource region><Low-resource setting><Lung><Lung Respiratory System><MGI-2><MOF syndrome><Machine Learning><Magnesium><Mg element><Micro RNA><MicroRNAs><Modern Man><Molecular><Multiple Organ Dysfunction Syndrome><Multiple Organ Failure><Myeloid Differentiation-Inducing Protein><NGAL><Neutrophil Gelatinase-Associated Lipocalin><Oncogenic Lipocalin 24P3><Out-patients><Outcome><Outpatients><Patient Recruitments><Patients><Performance><Phase><Phosphates><Plasma><Plasma Serum><Plasmacytoma Growth Factor><Polymerase Chain Reaction><Population><Position><Positioning Attribute><Principal Investigator><Proteins><Proteomics><Province><Publishing><Pyrexia><Rapid diagnostics><Recovery><Renal Failure><Renal Insufficiency><Reporting><Research Personnel><Researchers><Resource-constrained area><Resource-constrained community><Resource-constrained environment><Resource-constrained region><Resource-constrained setting><Resource-limited area><Resource-limited community><Resource-limited environment><Resource-limited region><Resource-limited setting><Resource-poor area><Resource-poor community><Resource-poor environment><Resource-poor region><Resource-poor setting><Reticuloendothelial System, Serum, Plasma><Risk><Risk Factors><Sampling><Sepsis><Serology test><Severities><Severity of illness><Site><Survivors><Thailand><Time><Uterocalin><active followup><acute kidney injury><adverse consequence><adverse outcome><ages><analytical method><bacterial disease treatment><bacterial infectious disease treatment><bio-markers><biobank><biologic marker><biomarker><biomarker identification><biorepository><blood infection><blood loss><bloodstream infection><chronic kidney disease><clinical database><clinical predictors><co-morbid><co-morbidity><cohort><comorbidity><cytokine><data base><demographics><dialysis therapy><disease severity><early detection><enroll><epidemiologic><epidemiological><experience><febrile><febris><follow up><follow-up><followed up><followup><host response><identification of biomarkers><identification of new biomarkers><immune system response><immunoresponse><improved><improved outcome><innovate><innovation><innovative><inorganic phosphate><interferon beta 2><isothermal amplification><long-term followup><long-term sequelae><long-term study><longitudinal outcome studies><longterm followup><longterm study><machine based learning><marker identification><miRNA><miRNAs><mortality><multiomics><multiorgan failure><multiple omics><multiple organ system failure><nano-string><nanostring><new marker><novel><novel biomarker><novel marker><panomics><participant recruitment><point of care><predictive biomarkers><predictive marker><predictive molecular biomarker><progression risk><prospective><pulmonary><renal><serology assay><sex><systemic inflammation><systemic inflammatory response><wasting>