IDENTIFICATION OF PREDICTIVE BIOMARKERS FOR SEVERE ACUTE LEPTOSPIROSIS AND ITS LONG-TERM SEQUELAE - LEPTOSP…

Assistance award details

Assistance award identifier

ASST_NON_R01AI183353_075

FAIN

R01AI183353

Recipient

CHULALONGKORN UNIVERSITY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.855

Total obligated

$411,286

Period

Aug 9, 2024 – Jul 31, 2029

Fiscal year

2024

Place of performance state

—

Source file

FY2024_All_Assistance_Full_20261006.zip

Description

IDENTIFICATION OF PREDICTIVE BIOMARKERS FOR SEVERE ACUTE LEPTOSPIROSIS AND ITS LONG-TERM SEQUELAE - 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 A