# Long-term health and socioeconomic impact of interventions targeting low-density malaria infection (LMI) among children in Tanzania

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $1,206,533

## Abstract

Project Summary/Abstract
 As malaria transmission declines, an increasing proportion of infections persist in the body at low levels.
Low-density malaria infection (LMI) are often chronic and represent a high proportion of infections among
children in the community and children presenting with fever, but they have been largely ignored because
standard point-of-care diagnostics have limited sensitivity to detect them, and they are considered incidental or
beneficial in that they may provide protective immunity again future malaria illness. However, much of this data
comes for high transmission settings and results are mixed. Also data from lower transmission settings
suggests negative health consequences. There is a growing body evidence to suggest that LMI are associated
with recurrent malaria, chronic anemia, poor growth, co-infection with invasive bacterial disease, and cognitive
impairment. Data from trials of intermittent preventative therapy (IPT) and mass drug administration (MDA)
also suggest benefits of treating LMI. However, these presumptive treatment strategies can also promote drug
resistance and are not practical in low transmission settings. More sensitive detection methods including
molecular approaches are increasingly available, but evidence of their effectiveness to reduce disease burden
is lacking. To inform policy and practice, there is an urgent need for evidence on the impact and safety of
detecting and treating LMI in children. The objective of the proposed project is to determine the long-term
health and socioeconomic effects of detecting and treating LMI in children. We hypothesize that compared to a
standard of care where malaria detection is passive and based on standard diagnostics (PCD), detecting and
treating LMI through use molecular detection methods in active case detection (ACDm) and passive case
detection (PCDm) in children will improve all-cause morbidity and have cognitive and socioeconomic benefits.
To test this hypothesis, we propose to conduct an open-label randomized controlled trial in children 6 months
to 10 years of age at an established trial site in Bagamoyo, Tanzania, where transmission is low and we have
found that a high proportion of infections are low-density. The effects of treating Plasmodium falciparum LMI
through active or passive case detection may differ. As such, we will study these as separate interventions and
compare each to the standard of care. A population representative sample of 600 children total will be recruited
(n=200 per arm, inclusive of 15% loss to follow-up) enabling at least 85% power (two-sided a=0.05) to detect a
20% effect size for each of the interventions compared to control. Children will be randomized into one of three
study arms: 1) standard of care PCD (Control) whereby children presenting with fever will receive artemether
lumefantrine (AL) based on positive rapid diagnostic test (RDT) result, 2) ACDm (Arm 2) whereby children will
receive testing for malaria (usi...

## Key facts

- **NIH application ID:** 10609863
- **Project number:** 5U01AI155315-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Michelle Sang Hsiang
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,206,533
- **Award type:** 5
- **Project period:** 2022-04-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609863

## Citation

> US National Institutes of Health, RePORTER application 10609863, Long-term health and socioeconomic impact of interventions targeting low-density malaria infection (LMI) among children in Tanzania (5U01AI155315-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10609863. Licensed CC0.

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