Reducing malaria in pregnancy through focal drug administration in household members: A pilot feasibility trial

PROJECT SUMMARY/ABSTRACT
Malaria in pregnancy (MiP) carries substantial - but largely preventable - risks for both the pregnant woman
and unborn child. Despite rigorous evidence supporting the efficacy of current interventions, such as long-lasting
insecticidal nets (LLIN) and intermittent preventive treatment of malaria in pregnancy (IPTp), MiP is estimated to
occur in more than 40% of livebirths in endemic areas of sub-Saharan Africa. Therefore, additional interventions
that would complement existing strategies are urgently needed One intriguing, but largely unexplored strategy
for preventing MiP would be to reduce the risk of malaria transmission in the home environment, essentially
creating a “safe zone” around the pregnant woman. This strategy has many potential advantages, including (i)
leveraging the spatiotemporal clustering of malaria risk, (ii) bridging gaps in the existing package of interventions
(i.e., imperfect LLIN use and missed IPTp doses), and (iii) the established safety and effectiveness of mass drug
administration (MDA) programs. Therefore, the scientific objective of this Exploratory/Developmental
Grant (R21) application is to demonstrate the feasibility, acceptability, and preliminary effectiveness of a focal
mass drug administration (fMDA) program for household members of pregnant women to protect against MiP.
Our hypothesis is that eliminating the parasite reservoir within the household will provide a complementary layer
of protection against MiP especially when access to care is limited and visits may be delayed or missed. To
achieve this, we will conduct a pilot randomized controlled trial to:
Aim 1: Determine the feasibility and acceptability of a fMDA program with dihydroartemisinin-
piperaquine (DP) as a novel component of the MiP prevention package. We will conduct an open-label,
randomized pilot study at a primary health center in rural western Uganda. Women presenting to their first
antenatal clinic visit will be randomized 1:1:1: to (i) monthly fMDA, (ii) one-time fMDA, or (iii) usual care. Using
an established implementation framework, we will assess process measures such as the proportion of household
members reached, adherence to the course of treatment, and frequency of adverse events.
Aim 2: Estimate the efficacy of fMDA to create a “safe zone” in the immediate home environment
and ultimately prevent MiP. Using the study design outlined in Aim 1, we will follow participating pregnant
women and associated households through delivery, including longitudinal assessments of P. falciparum
infection. As a pilot study, the trial is deliberately not powered for statistical tests of significance, but we will
measure the incidence of (i) clinical malaria, defined as the presence of typical symptoms (e.g., fever, lethargy)
and a positive malaria rapid diagnostic test (RDT), (ii) asymptomatic P. falciparum parasitemia and placental
malaria by PCR throughout pregnancy and (iii) the incidence of adverse birth outcomes (e.g., stillbirth, low birth
weight). In addition, we will measure the prevalence of asymptomatic parasitemia in household members using
RDTs at three time points in order to estimate the effectiveness of fMDA at maintaining a parasite free zone.

Grant Number: 3R21AI180728-02S1
NIH Institute/Center: NIH
Principal Investigator: Ross Boyce