# Does treating low density malaria infections reduce malaria transmission?

> **NIH NIH R03** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $77,750

## Abstract

ABSTRACT
Evidence is now robust that asymptomatic carriers contribute to the bulk of malaria transmission in Sub-
Saharan Africa, where 95% of the global malaria burden resides. This is true in both high and low transmission
settings. In areas where malaria control efforts have achieved some success and transmission has declined, it
may be hard to make further progress without interventions targeting the asymptomatic infectious reservoir.
We have worked in rural Bagamoyo district in coastal Tanzania since 2018, characterizing the asymptomatic
reservoir and performing mosquito feeding studies to better understand human-to-mosquito transmission from
low density malaria infections (LMI). This work has involved direct skin feeding assays to measure the
infectivity of > 500 children and adults to Anopheles gambiae, with ongoing analyses examining the
relationship of gametocytemia and other covariates to the likelihood of transmission (infectiousness) and
mosquito infection rates. Now, in conjunction with the University of California San Francisco and the Ifakara
Health Institute, we have the opportunity to leverage this data to understand how treatment of LMI through
periodic active case detection in children can lead to a reduction in gametocyte carriage and the infectious
reservoir. The “Low-density malaria infection (LMI) trial among children in Tanzania” (U01AI155315, PI: Hsiang
and Olotu) will assess whether treating LMI in children results in clinical benefits on long-term health. Over two
years, 200 children in Bagamoyo district randomized to undergo malaria active case detection with molecular
testing (ACDm) will be screened 3 times each year (during biannual transmission peaks and at end of second
peak) using an ultrasensitive PCR, and receive antimalarial therapy if positive. They will also be followed
monthly and treated if they present with fever and are positive on a rapid test, as per standard passive case
detection (PCD). In the comparator arm, 200 children will receive PCD only. In this proposed project, we will
measure gametocytemia from monthly surveillance samples to determine the effects of proactive treatment of
LMI on gametocyte prevalence and gametocyte AUC (area under the curve) in each study arm (Aim 1). Since
reductions in gametocyte carriage will variably translate into reduced transmissibility across individuals based
on factors such as age, symptom status, and seasonality, we will use data from our Bagamoyo skin feed
cohort to model how reductions in gametocytemia translates to a reduction in human-to-mosquito transmission
in both study arms (Aim 2). We hypothesize that active case detection of LMI will reduce gametocyte carriage
and days of infectiousness in children to a greater extent than that achieved by PCD alone. The proposed work
will quantify the potential transmission-reducing benefit of using ultrasensitive diagnostics to actively detect and
treat LMI in African children. Findings will be important to policymake...

## Key facts

- **NIH application ID:** 10823319
- **Project number:** 5R03AI173899-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jessica Lin
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $77,750
- **Award type:** 5
- **Project period:** 2023-04-06 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823319

## Citation

> US National Institutes of Health, RePORTER application 10823319, Does treating low density malaria infections reduce malaria transmission? (5R03AI173899-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10823319. Licensed CC0.

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