Project Title

Safety and Efficacy of Intermittent Presumptive Treatment with Sulfadoxine-Pyrimethamine using Rapid Diagnostic Test Screening And Treatment at First Antenatal Care Visit

EDCTP Project Call

Career Development Fellowship (CDF)

Project Objectives

Primary Objective: To evaluate the impact of adding, at first ANC, mRDT screening and treatment with DHA-PPQ to the current IPTp-SP (IPTp-SP+) on IPT-SP efficacy at clearing maternal peripheral parasitemia and at preventing maternal anemia, LBW and neonatal mortality. Specific Objectives: To compare: • IPTp-SP+ and IPTp-SP PCR treatment failure rates at Days 28, 42, 63 and at delivery • IPTp-SP+ and IPTp-SP maternal anemia and low birth weight rates at delivery • IPTp-SP+ and IPTp-SP neonatal mortality rates at 28 post delivery • Proportion of pregnancy losses between the groups • PCR median time to recrudescence between the two groups • PCR re-infection rates between the two groups • Incidences of post-treatment clinical malaria during pregnancy between the two groups • Prevalence of asymptomatic malaria during pregnancy between the two groups • Prevalence of malaria at delivery between the two groups • Prevalence of congenital malaria and anaemia between the two groups • Overtime SP resistance prevalence and mutant haplotypes types between the two groups • Placental infection rates between the two groups • Proportions of Acute infection, Chronic infection /Past infection between the two groups, using placental biopsies Describe the Incidence of adverse events until one year post-partum Determine the overtime prevalence of asymptomatic malaria and their impact on birth outcomes Exploratory objectives: Assess the impact of screen and treat with one dose DHA-PQ on antimalarial drug resistance development To determine the relationship between the prevalence of infections with mutant transporter genotypes and the plasma concentration of PQ

Study Design

A phase IIIB open-label, two arms randomized controlled superiority trial will be carried out to assess the safety and efficacy of adding to the current IPTp-SP, at first ANC visit, mRDT screening and treatment of positive mothers with Dihydroartemisinin-Piperaquine (DHA-PQ)). After obtaining the informed consent and assessing for eligibility criteria. HIV-negative mothers will be randomly allocated to IPTp-SP+ or to the standard of care IPTp-SP upon provision of a voluntary informed consent. Mothers in IPTp-SP+ group will be tested with mRDT at first ANC visit; If they test positive they will be treated with DHA-PQ followed with 2 doses of SP given at days 35 and 63; if negative they will be given three doses of SP at enrollment, days 35 and 63. Mothers in the IPTp-SP group will receive 3 doses of SP at enrollment, day 35 and day 63. All mothers will be followed up to day 63 and thereafter at delivery. Their babies will be followed up to one year after delivery.

Project Summary

Intermittent Preventive Treatment in Pregnancy (IPTp) with Sulfadoxine-Pyrimethamine (SP) is recommended in moderate to high transmission areas of sub-Saharan Africa. However IPTp with SP (IPTp-SP) efficacy is threatened by the ever increasing parasite resistance to SP. The continued use of SP for IPTp would result to further reduction of IPTp-SP efficacy and completely compromise its effectiveness at preventing malaria in pregnancy (MIP) associated adverse outcomes. This constitutes a serious threat for mothers and their offspring’s in sub-Saharan Africa. Reducing SP interaction with the already mutated parasite would prevent further selection of mutated parasites, reduce SP resistance and improve IPTp-SP efficacy. This can be achieved by introducing at first Antenatal (ANC) visit, malaria Rapid Diagnostic Testing (mRDT) and treatment of positive mothers with a safe and fully effective anti-malarial drug before they are administered with SP while negative mothers receive SP as per current standard practices; a package labeled as IPTp-SP+ henceforth. This clinical trial proposes to compare the current standard of care IPTp-SP with IPTp-SP+ in terms of their efficacy at clearing peripheral maternal and placental parasitemia and at preventing adverse outcomes associated with malaria in pregnancy. Volunteer HIV non-infected mothers meeting the inclusion criteria will be recruited. Relevant socio-demographic and clinical information will be obtained and blood samples will be taken for Hemoglobin (Hb) and malaria molecular testing at enrollment; days 14, 28, 42 and 63 and at delivery. Cord blood for malaria parasitology will be collected, babies’ Hb will be measured and placental biopsy for malaria parasitology and histopathology will be collected. In addition blood for pharmacokinetic testing will be collected from mothers in the IPTp-SP+ group treated with DHA-PQ,

Host Organisation

Sites

Results & Outcomes

Current Organisation

Tropical Diseases research Centre

Current Job Title

Senior Scientific Officer

Biography