Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Research Square
Abstract
Declines in malaria burden in Uganda have slowed. Modelling predicts that
indoor residual spraying (IRS) and mass drug administration (MDA), when
co-timed, have synergistic impact. This study investigated additional protective
impact of population-based MDA on malaria prevalence, if any, when added to
IRS, as compared with IRS alone and with standard of care (SOC).
Methods:
The 32-month prospective controlled community trial enrolled an open cohort
of residents (46,765 individuals, 1st enumeration and 52,133, 4th enumeration) in
Katakwi District in northeastern Uganda. Consented participants were assigned
to three arms based on residential subcounty: MDA+IRS, IRS, and SOC
(insecticide treated bednets and case management). IRS with pirimiphos methyl
and MDA with dihydroartemisinin- piperaquine were delivered in 4 co-timed
campaign-style rounds 8 months apart. The primary endpoint was population
prevalence of malaria, estimated by 6 cross-sectional surveys, starting at baseline
and preceding each subsequent round.
Results:
Comparing malaria prevalence in MDA+IRS and IRS only arms over all 6
surveys (intention-to-treat analysis), roughly every 6 months, post-interventions,
a geostatistical model found a significant additional 15.5% (95% confidence
interval (CI): [13.7%, 17.5%], Z=9.6, p= 5e-20) decrease in the adjusted odds
ratio (aOR) due to MDA for all ages, a 13.3% reduction in under 5’s (95% CI:
[10.5%, 16.8%], Z=4.02, p= 5e-5), and a 10.1% reduction in children 5-15 (95%
CI: [8.5%, 11.8%], Z=4.7, p= 2e-5). All ages residents of the MDA + IRS arm
enjoyed an overall 80.1% reduction (95% CI: [80.0%,83.0%, p¡.0001] in odds of
qPCR confirmed malaria compared with SOC residents. Secondary
difference-in-difference analyses comparing surveys at different timepoints to
baseline showed aOR (MDA + IRS vs IRS) of qPCR positivity between 0.28 and
0.66 (p<.001). Of three serious adverse events, one (nonfatal) was considered
related to study medications. Limitations include the initial non-random
assignment of MDA+IRS, which may have understated the impact of MDA, and
lack of MDA-only arm, considered to violate equipoise.
Conclusions:
Despite being assessed at long timepoints 5-7 months post-round, MDA plus
IRS provided significant additional protection from malaria infection over IRS
alone. Future cohort studies of impact on incidence recommended.
Description
Keywords
MDA, Malaria, IRS, High burden, Uganda, Controlled trial, Pirimiphos, Dihydroartemisinin
Citation
Echodu, DC, Yeka, A., Eganyu, T., Odude, W., Bukenya, F., Amoah, B., ... & Opigo, J. (2022). Impact of population based indoor residual spraying with and without mass drug administration with dihydroartemisinin-piperaquine on malaria prevalence in a high transmission setting: a controlled trial in northeastern Uganda. https://doi.org/10.21203/rs.3.rs-1510812/v1