Translational studies of hookworm infection in ghana

Active Project Grant Awarded Last action

Award ID
R01AI162826
Recipient
Awarding agency
Obligated
$9,033,100

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 95% complete
Place of performance
New Haven, CT 06511, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Hookworm infection is a leading cause of malnutrition and growth delay in poor countries, especially in sub- saharan africa where millions of people are infected with necator americanus. Data from human studies suggest chronic hookworm infection also impairs routine vaccine efficacy and exacerbates other globally important, CO-endemic infectious diseases. Current strategies to control hookworm rely primarily on mass drug administration of standard anthelminthic drugs, although recent evidence calls into question the long-term effectiveness of this approach to control and eliminate hookworm in endemic populations. Since 2007, yale university and the noguchi memorial institute for medical research at the university of ghana have collaborated to characterize the epidemiology of hookworm infection in endemic communities. The longitudinal field study proposed in aim 1 will further probe the epidemiology of hookworm by defining risk factors for infection, response to deworming, and reinfection following treatment in the bono east region, ghana. Experiments outlined in aim 2 will be focused on characterizing changes in the frequency of resistance associated mutations in the N. Americanus SS-tubulin gene using next generation sequencing methods, as well as the impact of drug pressure on genetic diversity and the population genetics of human hookworms in beposo. Critical to the detailed study of hookworm pathogenesis is the availability of a facile animal model that is both reproducible and accurately reflects the major clinical features of human disease. Little is known about N. Americanus strains originating from populations in africa, resulting in a significant GAP in our understanding of hookworm biology, genomics and evolution. Building on experience in maintaining the laboratory model of ancylostoma ceylanicum hookworms, field isolates of N. Americanus cultured from study subjects in ghana in 2019 have been used to establish patent infections in hamsters. In the experimental studies outlined in aim 3, clinical parameters and the kinetics of primary infection with the ghana strain of N. Americanus will be fully characterized in the hamster model. Cellular, humoral and mucosal antibody responses to primary infection, reinfection and vaccination with hookworm proteins will be defined. In addition, novel proteomic methods will be applied to define human antibody profiles that correlate with infection status, intensity and risk of reinfection. The overarching goals of the research outlined in this proposal are (1) to identify factors associated with hookworm infection among people living in beposo, ghana, (2) to characterize the impact of deworming pressure on drug resistance markers and genetic diversity of hookworms in ghana and (3) to characterize the first laboratory adapted african strain of N. Americanus and optimize its utility for the study of human hookworm epidemiology, pathogenesis and vaccine development. Results from these innovative studies will enhance our understanding of hookworm pathogenesis in africa and inform future development of public health tools to reduce the global burden of this neglected tropical disease.

Transactions

Action Obligated Date
Amendment $84,829
Amendment $695,579
Amendment $780,408
Amendment $74,420
Amendment $74,420
Amendment $669,783
Amendment $669,783
Amendment $669,783
Amendment $0
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Amendment $744,203
Amendment $744,203
Amendment $744,203
Amendment $744,203
Amendment $744,203
Amendment $796,540
Original award $796,540
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Subawards

Subrecipient Amount Awarded
Noguchi Memorial Institute For Medical Research "Hookworms, soil transmitted helminths (STHs) that infect nearly one billion people worldwide, represent a leading cause of anemia and malnutrition in… $84,829
Board Of Regents Of The University Of Nebraska The sub-award PI (J. Fauver) will participate in experiments and analysis described in Specific Aim 2 of this proposal. The objective of this Aim is to apply… $137,200
Noguchi Memorial Institute For Medical Research Hookworms, soil transmitted helminths (STHs) that infect nearly one billion people worldwide, represent a leading cause of anemia and malnutrition in resource… $487,915

Quick answers

Who received award R01AI162826?

R01AI162826 was awarded to Yale Univ by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 22, 2022.

How much is award R01AI162826 worth?

$9,033,100 has been obligated on R01AI162826.

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