PROJECT SUMMARY
The overall goals of this Tropical Medicine Research Center (TMRC), proposed for the Research Institute of
Tropical Medicine (RITM) in the Philippines, are to a) execute the key scientific aims of this study, b) build
research capacity at RITM, and c) build research capacity and support the development of junior investigators
at all TMRCs in partnership with the TMRC coordinating center’s “opportunity funds” and other initiatives
Currently, preventative chemotherapy strategies with Praziquantel (PZQ) are the mainstay of treatment for
schistosomiasis, with “mass drug administration” (MDA) delivered annually or bi-annually. The primary cause
of severe morbidity and death due to intestinal schistosomiasis is portal fibrosis secondary to intra-hepatic egg
deposition with consequent portal hypertension and esophageal varices with high risk of hemorrhage.
Importantly, there are no current recommendations to identify and more aggressively treat individuals with
hepatic fibrosis in most regions, including The Philippines, leaving individuals to receive infrequent, if any,
treatment. Currently, little is known with respect to risk factors for progression to higher grade portal fibrosis,
including biomarkers to identify risk. This is a lost opportunity to mitigate this risk through more frequent
treatment, which has been shown to halt and even reverse fibrosis if identified early. Our groups have
developed a multiplexed “FibroPlex_v2” assay that now captures 38 key analytes involved in fibro-proliferation
or degradation. We will employ this to address the scientific goals of the study which are to:
1) Evaluate biomarkers that will identify individuals with S. japonicum associated hepatic fibrosis as diagnosed
by ultrasound (US) at baseline as well as biomarkers that identify risk of progression from mild-moderate to
higher grades as assessed by US annually for three years
2) To develop diagnostic tests to facilitate identification of high-risk individuals in the field who would ultimately
benefit from more frequent treatment with PZQ or other treatment approaches. We expect many analytes will
predict progression and these will be developed singly or in combination as lateral flow-based assays that can
ultimately be developed as POCTs for use with MDA.
The availability of potential treatment approaches to halt progression, the lack of approaches to reverse higher
grade periportal fibrosis once established, and sub-optimal interventions for addressing portal hypertension
and its high mortality rate once established, make this an ideal screening target. Biomarkers that longitudinally
predict risk of progression to less reversible grades are a crucial first step. The successful execution of these
aims will also build research capacity at RITM and provide outstanding opportunities for related studies through
TMRC “opportunity funds” as well as future grants to evaluate different treatment strategies for individuals at
risk for fibrosis progression with definitive randomized controlled trials.
