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Preparing for a world with artemisinin resistance: using individual-based epidemiological modeling to minimize the long-term detrimental effects of antimalarial drug resistance

Award Number: R01AI153355
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: 08/10/2020
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Preparing for a world with artemisinin resistance: using individual-based epidemiological modeling to minimize the long-term detrimental effects of antimalarial drug resistance - Project Summary/Abstract Plasmodium falciparum is the deadliest of the five species of malaria parasites that infect humans. Annually, there are over 200 million symptomatic cases of falciparum malaria and over 400,000 deaths – the majority of which occur in African children under the age of five. The two major interventions that have had an effect on reducing malaria prevalence over the past twenty years are mosquito control and use of antimalarial drugs. The most important class of drugs in this effort has been the artemisinin derivatives, which since 2005 have been deployed as artemisinin combination therapies (ACTs) only, in order to reduce the probability of emergence and spread of artemisinin-resistant genotypes. Despite these efforts, artemisinin resistance did emerge, and we are now facing the dangerous prospect that these drug-resistant genotypes may spread to Africa, where most of the world’s malaria cases occur. In this proposal, we will introduce and evaluate a number of drug-resistance management strategies that are intended to prevent, delay, and slow down the spread of drug-resistant genotypes of P. falciparum. First, we will make a number of technical advances in our existing individual-based (agent-based) simulation that we already use to model the evolution and epidemiology of P. falciparum in human populations. We will add explicit grid- based spatial structure to make the model more realistic. Additionally, we will add a genotype-phenotype map and clinically-parameterized pharmacodynamic/pharmacokinetic sub-models to make the model’s drug- resistance component as realistic as current data allow. Second, we will evaluate strategies for how best to manage the population-level introduction of novel antimalarial therapies that will become available in the 2020s. The strategies will be aimed at minimizing the long-term risk of drug resistance to both the novel therapies and to currently used ACTs, in order to minimize the number of treatment failures in the long run. Finally, we will parameterize country scenarios for Cambodia, Zambia, and Burkina Faso to provide specific country-level advice in low, medium, and high transmission malaria settings on how best to preëmpt drug resistance or minimize its current spread. As Cambodia is the epicenter of the current wave of artemisinin resistance, the Cambodia- specific model will be used to provide advice on how to contain and eliminate currently circulating artemisinin- resistant genotypes of P. falciparum.


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 = $0 )
2026	2024	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	000	6	1/29/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	4	1/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $418,044 )
2024	2024	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	002	6	7/29/2024	NON-COMPETING CONTINUATION	$392,281
2024	2023	THE PENNSYLVANIA STATE UNIVERSITY	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	4	5/30/2024	NON-COMPETING CONTINUATION	-$104,956
2024	2023	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Allergy and Infectious Diseases Research	001	5	5/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$130,719
														Subtotal = $418,044

Issue Date FY: 2023 ( Subtotal = $387,379 )
2023	2023	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	4	7/14/2023	NON-COMPETING CONTINUATION	$387,379
														Subtotal = $387,379

Issue Date FY: 2022 ( Subtotal = $343,903 )
2022	2022	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	3	7/18/2022	NON-COMPETING CONTINUATION	$343,903
														Subtotal = $343,903

Issue Date FY: 2021 ( Subtotal = $339,988 )
2021	2021	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	2	7/26/2021	NON-COMPETING CONTINUATION	$339,988
														Subtotal = $339,988

Issue Date FY: 2020 ( Subtotal = $338,940 )
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	001	1	8/31/2020	NEW	$4,614
2020	2020	PENNSYLVANIA STATE UNIVERSITY, THE	201 OLD MAIN	UNIVERSITY PARK	PA	16802	CENTRE	USA	Allergy and Infectious Diseases Research	000	1	8/6/2020	NEW	$334,326
														Subtotal = $338,940

Grand Total All Awards = $1,828,254

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Preparing for a world with artemisinin resistance: using individual-based epidemiological modeling to minimize the long-term detrimental effects of antimalarial drug resistance

Award Number: R01AI153355

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: 08/10/2020

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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