# Resistance Project

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $139,312

## Abstract

Summary
 Among our best tools for the control of malaria are effective drugs and insecticides used for treatment and
prevention of the disease. However, the value of these tools is limited by drug resistance in malaria parasites
and insecticide resistance in anopheline mosquitoes. Alarmingly, partial resistance to artemisinins (ART-R), the
backbone of treatment regimens, has emerged in Uganda, as demonstrated by our group. Susceptibility to key
artemisinin partner drugs is also in jeopardy, threatening efficacy of artemisinin-based combination therapies to
treat malaria. ART-R also decreases activity against early gametocytes and is associated with increased
production of transmissible gametocytes. Resistance to multiple classes of insecticides similarly puts vector
control strategies at risk, and suboptimal performance of vector control interventions has been demonstrated in
Uganda. We already have an understanding of mediators of antimalarial and insecticide resistance. For
antimalarials, polymorphisms in drug transporters and folate enzymes are associated with resistance to key
components of treatment and chemoprevention regimens, and specific mutations in PfK13 are primary
mediators of ART-R. For insecticides, point mutations in insecticide target-sites and altered activity of
detoxification enzymes are associated with resistance to pyrethroid, carbamate, organophosphate, and
neonicotinoid insecticides. Markers for these polymorphisms are valuable tools for the longitudinal surveillance
of drug and insecticide resistance in Uganda. This project will leverage the large PRISM surveillance network
and utilize deep sequencing strategies to conduct broad surveys of the prevalence of known resistance
markers across Uganda. In addition, we will search for associations between resistance markers and both
utilization of specific control interventions and longitudinal measures of malaria metrics. Lastly, we will
characterize impacts of resistance on malaria transmission. We hypothesize that malaria treatment and control
in Uganda will be challenged by increasing resistance in malaria parasites and anopheline vectors, that the
rate of resistance development will vary depending on the extent of implementation of control measures and
level of malaria transmission, and that resistance will impact on both human malaria and ongoing transmission.
We will test these hypotheses with serial surveys for parasite and mosquito resistance mediators at sites with
varied malaria control interventions and transmission intensity and with specific studies of transmission to
mosquitoes. Our specific aims will be 1) to characterize antimalarial drug resistance by serial surveillance at
diverse sites with varied implementation of control measures across Uganda, 2) to characterize anopheline
insecticide resistance by serial surveillance at diverse sites with varied implementation of control measures
across Uganda, and 3) to characterize impacts of antimalarial drug resistanc...

## Key facts

- **NIH application ID:** 10836946
- **Project number:** 2U19AI089674-15
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SAM NSOBYA
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $139,312
- **Award type:** 2
- **Project period:** 2010-07-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10836946

## Citation

> US National Institutes of Health, RePORTER application 10836946, Resistance Project (2U19AI089674-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10836946. Licensed CC0.

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