IPTI-plus. An efficacy trial of the incremental mortality benefit of IPTi plus azithromycin.
The main objectives of this project are:
- To evaluate the impact of azithromycin, plus intermittent preventive treatment with sulphadoxine-pyrimethamine administered through the Expanded Program on Immunisation on all-cause mortality at 18 months of age in young children living in areas of high mortality and malaria burden in Sub-Saharan Africa.
- To identify implementation bottlenecks for intermittent preventive treatment with sulphadoxine-pyrimethamine administered through the Expanded Program on Immunisation scale-up in Sierra Leone.
Half of the 5.4 million children under 5 years of age (U5) who die in the world annually live in the African region where falciparum malaria is a major cause of death. Intermittent preventive treatment of malaria in infants (IPTi), consisting of the administration of sulphadoxine-pyrimethamine to infants, is a safe, efficacious and cost-effective intervention in reducing malaria. Despite the WHO recommendation (2010) to administer IPTi alongside routine vaccinations in areas of high to moderate perennial transmission, IPTi is not implemented in most of African malaria endemic countries. Recent studies in some African countries showed that azithromycin (AZi)– is associated with a significant reduction in child mortality when used for mass drug administration in the elimination of trachoma. Evaluation of the impact on mortality reduction of the addition of AZi to IPTi (ITPi+) and assessment of bottlenecks for IPTi scale-up are needed before promoting their large scale-up.
An individually randomized double-blinded placebo-controlled superiority clinical trial will be carried out to evaluate the impact of azithromycin administered through the Expanded Program on Immunization on all-cause mortality at 18 months of age. AZi will be administrated in (20,000) infants exposed to high malaria endemicity and mortality burden in Sierra Leone (SL). This approach will enable to obtain conclusive evidence of the effect of IPTi together with AZi in U5’s mortality reduction and address knowledge and implementation gaps to scale-up ITPi/IPTi+: 1.
Evaluation of the Expanded Program on Immunisation (EPI) as a delivery channel to ensure the long-term sustainability of interventions targeted to young children 2. Evaluation of knowledge gaps related to the effect of AZi as a tool to reduce infant mortality, such as: a) potential development of macrolide resistance; b) understanding the mechanisms of action of AZi in reducing mortality; c) Ascertaining the seasonality effect on mortality and the frequency of adverse events; and d) Determining the potential interactions of the drug with the vaccines routinely given through the EPI system.