Prevention Malawi – ISTp versus IPTp-SP

Principal Investigator: Prof. Feiko Ter Kuile (UK)

Project Collaborators:

Dr. Linda Kalilani (Malawi), Mwayiwawo Madanitsa (Malawi), Doreen Ali (Malawi), Brian Faragher (UK), Kara Hanson (UK), Silke Lutzelschwab (UK), Stephen Rogerson (Australia)

Objective:

The objective of the project was to determine how scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (ISTp-DP) compared with IPTp-SP in the second and third trimesters of pregnancy among HIV-negative pregnant women protected by insecticide–treated bed nets (ITNs) in an area with decreasing malaria transmission and high levels of SP resistance in southern Malawi is associated with:

>=27.5% reduction in adverse birth outcome (composite of miscarriage, stillbirth, low birth weight or preterm birth) in women in their first and second pregnancies (G1+2)

>=50% reduction in active or recent infection assessed at delivery by placental histopathology or RDT in multigravidae (G3+).

Method:

The study was being undertaken in three semi-rural and rural antenatal clinics in southern Malawi in an area with moderate year-round malaria transmission (no IRS programs implemented yet), high levels of SP resistance, and high ITN coverage.  Additional sub-studies include a cost-effectiveness, acceptability and implementability study and an immunological study.

Results:

The results demonstrated that ISTp is not a suitable alternative to IPTp-SP even in areas with high levels of resistance to SP.

Publications

Desai M, Gutman J, Taylor S, Wiegand R, Khairallah C, Kayentao K, Ouma P, Coulibaly S, Kalilani L, Mace K, Arinaitwe E, Mathanga D, Doumbo O, Otieno K, Edgar D, Chaluluka E, Kamuliwo M, Ades V, Skarbinski J, Shi YP, Magnussen P, Meshnick S, ter Kuile FO. Impact of sulfadoxine-pyrimethamine resistance on effectiveness of intermittent preventive therapy in pregnancy at clearing peripheral blood Plasmodium falciparum parasites and preventing low birth weight: A prospective, multi-country observational study across Africa. Clin Infect Dis. 

Gutman J, Taylor S, Meshnick SR, Ter Kuile FO.  Reply to Harrington et al. J Infect Dis. 2015 Aug 19

Gutman, J., Kalilani, L., Taylor, S., Zhou, Z., Wiegand, R. E., Thwai, K. L., Mwandama, D., Khairallah, C., Madanitsa, M., Chaluluka, E., Dzinjalamala, F., Ali, D., Mathanga, D. P., Skarbinski, J., Shi, Y. P., Meshnick, S., ter Kuile, F. O. he A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women J Infect Dis. (2015)

Coulibaly, S. O., Kayentao, K., Taylor, S., Guirou, E. A., Khairallah, C., Guindo, N., Djimde, M., Bationo, R., Soulama, A., Dabira, E., Barry, B., Niangaly, M., Diakite, H., Konate, S., Keita, M., Traore, B., Meshnick, S. R., Magnussen, P., Doumbo, O. K., ter Kuile, F. O.  Parasite clearance following treatment with sulphadoxine-pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study. Malaria Journal, 2014, 13:41

Taylor, S. M., Antonia, A. L., Harrington, W. E., Goheen, M. M., Mwapasa, V., Chaluluka, E., Fried, M., Kabyemela, E., Madanitsa, M., Khairallah, C., Kalilani-Phiri, L., Tshefu, A. K., Rogerson, S. J., ter Kuile, F. O., Duffy P. E., Meshnick, S. R.  Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa. Emerg Infect Dis, 2014, 20(7), 1140-1148. 

Kayentao K, Garner P, van Eijk AM, Naidoo I, Roper C, Mulokozi A, MacArthur JR, Luntamo M, Ashorn P, Doumbo OK, ter Kuile FO. Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis.JAMA. 2013 Feb 13;309(6):594-604. doi:10.1001/jama.2012.216231. PMID: 23403684