# The Averting Readmissions for Malaria and Outpatient Reinfections (ARMOR) Trial

> **NIH NIH R34** · JOHNS HOPKINS UNIVERSITY · 2022 · $245,625

## Abstract

PROJECT SUMMARY/ABSTRACT
Malaria due to Plasmodium falciparum is a public health priority in sub-Saharan Africa and other endemic
areas, yet clinical interventions for severe malaria remain understudied. Children who survive a hospitalized
episode of severe malaria remain at increased risk of morbidity and mortality for as long as 18 months post-
discharge, mainly due to recurrent malaria. Thus, children who are convalescent from severe malaria represent
a high-risk population who stand to benefit from interventions that prevent recurrent malaria. A small number of
prior studies have tested intermittent preventive treatment-based approaches with equivocal results. We
propose to test the effectiveness of a novel approach using secondary chemoprophylaxis with the causally-
active antimalarial (i.e., against the liver-stage of the parasite), atovaquone-proguanil (AP), and reactive focal
vector control with indoor residual spraying (rf-IRS) both alone and in combination. The objective of this
proposal is to develop the study materials and prepare for the implementation of a randomized factorial design
clinical trial to test the role of secondary chemoprophylaxis and reactive focal vector control in improving
severe malaria outcomes during the post-discharge period where children are at high risk of hospital
readmission and death due to recurrent malaria. The trial site in Nchelenge District, Zambia is a high burden
area with sustained transmission throughout the year and where severe malaria accounts for up to one-third of
pediatric hospital admissions at any given time. This study will leverage substantial infrastructure from the NIH-
funded International Centers of Excellence for Malaria Research. The central hypothesis is that the risk of P.
falciparum reinfection following an episode of severe malaria can be averted by the combination of causal
prophylaxis using AP and vector control using rf-IRS. We expect that AP prophylaxis and rf-IRS will reduce
morbidity and mortality in children convalescent from severe falciparum malaria. The innovation of the study
includes in its use of AP for secondary chemoprophylaxis—uniquely notable for its hepatic as well as blood
schizonticidal activity, in contrast to other available agents which are limited to blood-stage parasites—and a
novel application of focal vector control in an understudied, high-risk population. The proposed trial is
significant because it will furnish evidence to inform the case management of severe malaria which has seen
little advancement in the preceding decades. It will test the effectiveness of secondary chemoprophylaxis and
rf-IRS, alone and in combination, among a high-risk patient population with the potential to prevent an
estimated 2.8 million rehospitalizations and over 100,000 deaths annually.

## Key facts

- **NIH application ID:** 10328316
- **Project number:** 1R34AI165307-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Matthew Michael Ippolito
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $245,625
- **Award type:** 1
- **Project period:** 2022-07-18 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328316

## Citation

> US National Institutes of Health, RePORTER application 10328316, The Averting Readmissions for Malaria and Outpatient Reinfections (ARMOR) Trial (1R34AI165307-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10328316. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
