About and Welcome
The IMPROVE Consortium was established to evaluate whether intermittent preventive therapy (IPTp) with dihydroartemisinin-piperaquine (DP), with or without azithromycin (AZ), is a viable alternative to current policy for the prevention of malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) in pregnancy in high sulphadoxine pyrimrthamine resistance areas in Kenya, Malawi, and Tanzania.
The Consortium is undertaking two multicentre trials, one conducted among HIV-uninfected women (IMPROVE) and one among HIV-infected women taking co-trimoxazole (CTX) (IMPROVE-2), together with three nested studies and capacity development.
Why is this research important
Malaria in pregnancy has devastating consequences for both mother and her baby. In countries with stable transmission in sub-Saharan Africa, most malaria infections in pregnant women remain asymptomatic, yet are associated with foetal loss, maternal anaemia, and intrauterine growth retardation and preterm birth, which are risk factors for neonatal and infant mortality.
To prevent these adverse consequences WHO currently recommends IPTp sulphadoxine pyrimethamine (SP), for asymptomatic women, but high-level SP resistance threatens its efficacy. Over the last decade, several trials ruled out amodiaquine, mefloquine, and chloroquine-azithromycin as suitable replacements for SP because of their poor tolerability when used as IPTp. Similarly, a potential alternative strategy of intermittent screening for malaria and treatment with artemisinin-based combination therapies was shown to be non-superior to IPTp-SP, even in areas with very high SP resistance.
Sexually transmitted and reproductive tract infections (STIs/RTIs) also cause poor birth outcomes and are highly prevalent in East and Southern Africa, and similar to malaria, remain mostly asymptomatic, and therefore undetected and untreated. We will therefore determine whether combining DP with AZ, a broad spectrum antibiotic active against STIs/RTIs, can further improve birth outcomes, potentially paving the way for integrated control strategies for malaria and curable sexually transmitted and reproductive tract co-infections.
A multi-centre, individually-randomized, 3-arm, superiority trial comparing the efficacy, safety and tolerance of IPTp and DP, alone or combined with azithromycin, to IPTp-SP (current policy) to reduce the adverse effects of malaria and curable STIs/RTIs in 4,680 HIV-uninfected women in 10 sites in high SP resistance areas in Kenya, Malawi, and Tanzania.
The project includes cardiac monitoring for safety, nested studies of antimalarial drug resistance and macrolide resistance, the impact of SP and AZ on vaginal and intestinal microbiota, and health economics, feasibility and acceptability components. The project also includes four African PhD-studentships and a Post-Doctoral fellowship.
A multi-centre, 3-arm, parallel, placebo-controlled, individually randomised Phase-3, superiority trial to compare the efficacy of weekly IPTp with DP, alone or combined with AZ, to CTX alone (current policy) to reduce the adverse effects of malaria and curable STIs/RTIs in ~1000 HIV-infected pregnant women in 6-8 sites in high SP resistance areas in Kenya and Malawi. The project includes health economics, feasibility and acceptability components and one African PhD-studentship.
IMPROVE is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2). Grant number TRIA-2015-1076-IMPROVE