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Temporal strain structure and response to interventions in a high endemicity region of Plasmodium falciparum

Award Number: R01AI149779
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/19/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Temporal strain structure and response to interventions in a high endemicity region of Plasmodium falciparum - Malaria control and elimination in areas of high transmission in sub-Saharan Africa present a significant challenge to global health. A large fraction of the population across all ages in these areas harbor Plasmodium falciparum without clinical manifestations, providing a vast reservoir of infection for transmission. This asymptomatic reservoir is sustained by the enormous antigenic diversity of the parasite. Thus, the challenge for hyperendemic regions requires that the malaria field comes to terms with such diversity, studying it as a complex adaptive system. This study addresses the two-way interaction between epidemiology and P. falciparum diversity from the perspective of the multigene and highly recombinant family known as var, which encodes for the major antigen of the blood stage of infection. This project combines theory with field and laboratory work lo generate new understanding of the diverse transmission reservoir of P. falciparum and its resilience to elimination. The first aim is the longitudinal deep sampling of this reservoir in the Bongo District, Ghana following two control interventions (i.e. indoor residual spraying and seasonal malaria chemoprevention). On the basis of age-stratified serial cross-sectional data, this study will assess how informative the var system is to monitor this reservoir under conditions of the control interventions, compared to traditional malariometric indices and neutral molecular markers. The second aim develops strain theory based on a stochastic agent-based model that tracks the history of infection of each host and the evolutionary change of the parasite. Pathogen population structure over time and responses of the var system to intervention are investigated in ways that inform both molecular data analyses and control efforts. The third aim develops a transmission model of intermediate complexity that can be fitted to routine epidemiological data but still incorporates the major effects of parasite diversity on epidemiology. In particular, the existence of a threshold in transmission intensity that impacts parasite antigenic diversity will be investigated. Contributions include computational models at the interface of epidemiology and evolution, and network analyses of population genetic structure applicable to other multigene families of P. falciparum, as well as to other pathogens whose immune escape relies on highly-recombinant gene families.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$60 )
2026	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Allergy and Infectious Diseases Research	000	6	12/10/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$60
														Subtotal = -$60

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	5	1/16/2025	NON-COMPETING CONTINUATION	-$1
2025	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Allergy and Infectious Diseases Research	002	6	1/16/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$252,425
2025	2022	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	4	1/16/2025	NON-COMPETING CONTINUATION	-$252,424
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $9,025 )
2024	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Allergy and Infectious Diseases Research	001	6	3/25/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$519,224
2024	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Allergy and Infectious Diseases Research	002	6	5/2/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	5	3/25/2024	NON-COMPETING CONTINUATION	-$510,199
														Subtotal = $9,025

Issue Date FY: 2023 ( Subtotal = $510,200 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	5	7/11/2023	NON-COMPETING CONTINUATION	$510,200
														Subtotal = $510,200

Issue Date FY: 2022 ( Subtotal = $574,059 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	4	6/30/2022	NON-COMPETING CONTINUATION	$574,059
														Subtotal = $574,059

Issue Date FY: 2021 ( Subtotal = $603,968 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	3	6/30/2021	NON-COMPETING CONTINUATION	$603,968
														Subtotal = $603,968

Issue Date FY: 2020 ( Subtotal = $612,795 )
2020	2020	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	2	7/1/2020	NON-COMPETING CONTINUATION	$612,795
														Subtotal = $612,795

Issue Date FY: 2019 ( Subtotal = $662,598 )
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	000	1	7/18/2019	NEW	$662,598
2019	2019	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Allergy and Infectious Diseases Research	001	1	7/25/2019	NEW	$0
														Subtotal = $662,598

Grand Total All Awards = $2,972,585

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Temporal strain structure and response to interventions in a high endemicity region of Plasmodium falciparum

Award Number: R01AI149779

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/19/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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