Grants

U.S. National Science Foundation

Applied Mathematics

NIAID - National Institute of Allergy and Infectious Diseases

ABSTRACT Relapsing malaria species, such as Plasmodium vivax (Pv), remain major challenges to malaria elimination due to their propensity to form hypnozoites that cause chronic latent infection in the liver and give rise to frequent relapses. Pv relapses cause significant morbidity and mortality worldwide. Despite advances, genotyping to distinguish relapses from re-infections remains fraught, limiting the evaluation of anti-relapse interventions like primaquine and tafenoquine. This study applies novel genomic and bioinformatic tools to clinical trial data in Southeast Asia and introduces innovative approaches to parse Pv relapse outcomes. Our approach leverages molecular inversion probes (MIPs) to deeply sequence Pv infections, capturing the diversity across the vivax genome and complexity within infected individuals. We will use Tapestry, a new bioinformatics tool, to enable haplotype reconstruction and identity-by-descent (IBD) analysis within and across multiclonal infections. Finally, Bayesian statistical models will refine relapse predictions by integrating genetic complexity, IBD relatedness, and clinical factors. Aim 1 investigates primaquine failures observed in a Thai Pv relapse trial (NCT04228315). Suspected relapses occurred in four individuals despite chloroquine and primaquine treatment; host CYP2D6 polymorphisms were ruled out. We hypothesize that high initial hypnozoite burden drove these relapses. We will generate evidence for this via genomic analyses that enhance detection of circulating parasite variants and assess infection complexity as a proxy for liver-stage hypnozoite burden. Aim 2 evaluates malaria elimination interventions in a Cambodian military cohort. Aim 2A tests whether rebound infections after cessation of monthly prophylaxis (MMP with dihydroartemisinin - piperaquine and weekly primaquine) represent relapses due to high hypnozoite burden, as reflected by genetic complexity. Aim 2B classifies Pv recurrences in soldiers wearing permethrin-treated uniforms to estimate vector-prevention efficacy. Results will differentiate relapse from reinfection and recalibrate protective efficacy estimates. In summary, this proposal seeks to address a fundamental gap in our ability to use genotyping to evaluate anti-relapse and other interventions that are needed to decrease the global burden of Plasmodium vivax. Expected outcomes include refined relapse classification, improved understanding of hypnozoite dynamics, and insights into anti-vivax interventions across diverse settings. Future directions include scaling our approach to larger cohort studies across diverse settings to improve classification of relapse outcomes.

Klamath Community College

Apprenticeship and Industrial Trades Center

Wildlife Conservation Society

Local

Economic Development Initiatives 16-17

Aquasol Working Capital

Groundwork Yonkers

Development of an interpretive trail system and related educational programs along the Croton Aqueduct.

NYC Department of Cultural Affairs

Arab-American Family Support Center Inc.

Arbor Heights Elementary PTA

The Arbor Heights Parent Teacher Association, Family Engagement Action Team, and our school social worker are teaming up to present a Unity Night. This year's theme is 'Hate Has No Home Here'. The event will bring together the community and local artists to celebrate one another through food, poetry, music, dance, and art. The event will take place May 5th from 6:30-9:30 p.m. at Arbor Heights Elementary School located at 3701 SW 104th Street.

City of Gainesville

Arbor House

Multnomah County

Arbor Lodge Shelter Brownfields Cleanup Project

County Commissioners of Washington County

ARC Building Improvments

Carroll County

ARC Building Renovations

Reuter Walton Development

New Construction

Arch Cape Domestic Water Supply District

Arch Cape Forest Watershed Plan

Arch Cape Sanitary District

Arch Cape Wastewater Facilities Plan Update

U.S. National Science Foundation

Archaeology Program Senior Research Awards

U.S. National Science Foundation

Archaeometry

NYC Department of Cultural Affairs

Archipelago Books, Inc.

Rockland Center For The Arts

Architect Fees for Design of Facilities Expansion

Playwrights Horizons Inc.

Architect's Fee for New 42nd Street Home

Eckenhoff Saunders Architects, Inc.

Management and Business Professionals and Administrative Services

NYC Department of Cultural Affairs

Architectural League of New York

FGM Architects Inc.

Engineering and Research and Technology Based Services

EPSTEIN

Management and Business Professionals and Administrative Services