# Measuring the transmissibility of recurrent parasitemias that arise following artemisinin-based combination therapy

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $231,613

## Abstract

ABSTRACT
Artemisinin-based combination therapies (ACT) have been the bedrock of malaria treatment in Africa for more
than a decade, spurring remarkable gains in malaria control, even as parasites tolerant to commonly used ACT
partner drugs continue to circulate. In East Africa, parasites harboring mutations associated with resistance to
the partner drug lumefantrine are selected through treatment and responsible for the majority of recurrent
infections that arise starting 3-4 weeks following ACT. These post-treatment parasitemias likely contribute to
the onward transmission of drug-resistant parasites to mosquitoes and further spread of antimalarial
resistance. Now, parasites with partial artemisinin resistance that have emerged in Rwanda are spilling over
into northwest Tanzania, a high malaria burden country, where 4% of the world’s malaria deaths occur.
Mitigating the spread of ACT-resistant parasites across sub-Saharan Africa will require a better understanding
of the transmission reservoir (who is transmitting drug-resistant parasites to mosquitoes) and ways to intervene
to interrupt this transmission. While ACT and single low dose primaquine effectively clear those presenting with
gametocytes, the parasite stages essential for transmission to mosquitoes, no current strategies target
gametocytes that arise in the weeks following treatment. We hypothesize that gametocytes associated with
post-ACT parasitemia are transmissible to mosquitoes and contribute to the spread of antimalarial resistance,
even as most go undetected. This R21 proposal will determine the risk of transmission from PCR-positive
individuals one month following ACT (Aim 1) and find whether drug resistant alleles that are selected during
treatment are maintained through transmission (Aim 2). To accomplish these aims, we will leverage the
capacity we have built over the last 5 years to characterize the infectious reservoir in Bagamoyo, Tanzania,
where we have performed >600 mosquito feeding assays in asymptomatic parasite carriers, most with
subpatent infection only detectable by PCR. Our team will screen >300 persons participating in a large triple
ACT trial for recurrent parasitemia during weeks 3-8 of follow-up and conduct mosquito membrane feeding
assays to measure their transmissibility to Anopheles gambiae and A. funestus, the primary malaria vectors in
East Africa. We will sequence transmitted parasites that survive to the salivary gland sporozoite stage within
mosquitoes and compare the frequency of key drug resistance alleles in these mosquitoes to blood collected
from persons pre and post-treatment. We expect that the post-treatment period, 4-8 weeks after first-line ACT
therapy, is indeed a vulnerable time for gametocytemia to arise without symptoms, and lead to transmission of
P. falciparum parasites bearing kelch 13 and mdr1 mutations selected through treatment. However, we also
expect that triple ACT therapies that reduce the rate of post-treatment parasitemia wi...

## Key facts

- **NIH application ID:** 10790561
- **Project number:** 1R21AI180675-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jessica Lin
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,613
- **Award type:** 1
- **Project period:** 2024-01-17 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10790561

## Citation

> US National Institutes of Health, RePORTER application 10790561, Measuring the transmissibility of recurrent parasitemias that arise following artemisinin-based combination therapy (1R21AI180675-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10790561. Licensed CC0.

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