IPTp Effectiveness multicentre study

A baby being weighed on a scaleTitle:
Monitoring Sulphadoxine-Pyrimethamine (SP) Resistance and the Effectiveness of Intermittent Preventive Treatment (IPT) for the Control of Malaria in Pregnancy

Project Coordinator(s):
Principal Investigator: Prof. Feiko Ter Kuile (UK)

Project Collaborators:

Dr. Linda Kalilani (Malawi), Prof. Brian Greenwood/Dr. Daniel Chandramohan (UK), Dr. Pascal Magnussen (Denmark), Dr. Sheick Coulibaly (Burkina Faso), Dr. Abraham Hodgson (Ghana), Dr. Kalifa Bojang (The Gambia), Dr. Kassoum Kayentao (Mali), PMI, USAID and CDC, USA.

Study aims:

The goal of this project is to explore the relationship between the level of SP resistance in the population of pregnant women, the efficacy of intermittent preventive treatment in pregnancy (IPTp) with SP in clearing parasites and preventing new infections and the effectiveness of IPTp-SP in reducing the adverse effects of malaria at birth.

IPTp with SP is recommended by the World Health Organization (WHO) for reducing the risks associated with malaria in pregnancy. Parasite resistance has compromised the efficacy of SP in the case-management of symptomatic children, but SP currently appears to remain effective for IPTp in pregnant women probably because they have more immunity than young children. It is unclear at what level of resistance alternative regimens for IPTp should be considered and it is therefore important to monitor the development of SP resistance in the population and develop an understanding of the potential implications for the effectiveness of IPTp. There are no standardized methods yet to do this.

Study objectives:

  1. To determine the relationship between the degree of SP resistance in the population as assessed by molecular markers and its impact on the ability of IPTp with SP to clear existing infections, prevent new infections and prevent the adverse malaria associated morbidity.
  2. To design a practical operational tool to monitor SP effectiveness that can be used outside of research settings.

This is a multi-centre study to monitor the effectiveness of IPTp by determining the relationship between the level of SP resistance as assessed by molecular markers, the efficacy of SP in clearing existing malaria infections (in-vivo module: 42 day follow-up of asymptomatic parasitaemic women) and the ability of IPTp-SP to reduce the adverse effect of malaria at birth (delivery module).

Study sites include:

MiP Consortium sites: Malawi (Blantyre), Burkina Faso (Ziniare), Ghana (Navrongo), Mali (San & Kita) and The Gambia (Basse).

PMI,USAID and CDC sites: Zambia, Malawi, Mali, [Uganda].

 

Specific objectives:

  1. To characterize the degree of resistance of P. falciparum to SP in the population using molecular markers in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS).
  2. To determine the efficacy of SP IPTp in clearing peripheral parasitaemia in asymptomatic parasitaemic pregnant women.
  3. To determine the effectiveness of SP IPTp in preventing placental malaria, maternal anaemia and low birth weight, by comparing these among women who have received 2 or more versus less than 2 doses of IPTp based on their antenatal clinic records.
  4. To determine which parasite genotypes recrudesce, cause new infections, and persist in the placenta in women receiving IPTp-SP.
  5. To model the pharmacodynamic relationship between drug levels, parasite SP resistance genotype, recrudescence, and new infection and to validate the model using the pooled data from the different study sites.
  6. To use the pooled experience and ‘rich’ in-vivo data from the weekly follow-up to determine the potential validity of a ‘sparse’ ‘population’ sampling methodology for future therapeutic in-vivo follow-up studies.