Assessment of the safety of antimalarial drug use during early pregnancy (ASAP): protocol for a multicenter prospective cohort study in Burkina Faso, Kenya and Mozambique

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Tinto, Halidou ; Sevene, Esperança ; Dellicour, Stephanie ; Calip, Gregory S. ; d’Alessandro, Umberto ; Macete, Eusébio ; Nakanabo-Diallo, Seydou ; Kazienga, Adama ; Valea, Innocent ; Sorgho, Hermann ; Valá, Anifa ; Augusto, Orvalho ; Ruperez, Maria ; Menendez, Clara ; Ouma, Peter ; Desai, Meghna ; Ter Kuile, Feiko ; Stergachis, Andy (2015)
  • Publisher: BioMed Central
  • Journal: Reproductive Health, volume 12 (eissn: 1742-4755)
  • Related identifiers: pmc: PMC4670540, doi: 10.1186/s12978-015-0101-0
  • Subject: Malària | qv_256 | Pregnancy | Medicina prenatal | qv_771 | wa_395 | Estudi de casos | Case studies | Malaria | ACTs | Embaràs | wq_200 | Obstetrics and Gynaecology | Anti-infective agents | Prenatal medicine | Reproductive Medicine | Study Protocol | Agents antiinfecciosos
    mesheuropmc: parasitic diseases

BACKGROUND: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. METHODS: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. DISCUSSION: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. TRIAL REGISTRATION: NCT01232530.
  • References (39)
    39 references, page 1 of 4

    1. www.who.int/malaria/areas/treatment/en. Accessed 28 May 2014.

    2. McGready R, Phyo AP, Rijken MJ, Tarning J, Lindegardh N, Hanpithakpon W, et al. Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: Absorption, bioavailability, disposition and disease effects. Br J Clin Pharmacol. 2012;73:467-77.

    3. Tarning J, Kloprogge F, Piola P, Dhorda M, Muwanga S, Turyakira E, et al. Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda. Malar J. 2012;11:293.

    4. Yartey JE. Malaria in pregnancy: Access to effective interventions in Africa. Int J Gynecol Obstet. 2006;94:364-73.

    5. Muehlenbachs A, Nabasumba C, McGready R, Turyakira E, Tumwebaze B, Dhorda M, et al. Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial. Malar J. 2012;11:150.

    6. Finaurini S, Basilico N, Corbett Y, D'Alessandro S, Parapini S, Olliaro P, et al. Dihydroartemisinin inhibits the human erythroid cell differentiation by altering the cell cycle. Toxicology. 2012;300:57-66.

    7. Li Q, Si Y, Xie L, Zhang J, Weina P. Severe embryolethality of artesunate related to pharmacokinetics following intravenous and intramuscular doses in pregnant rats. Birth Defects Res Part B - Dev Reprod Toxicol. 2009;86:385-93.

    8. Clark RL, Brannen KC, Sanders JE, Hoberman AM. Artesunate and artelinic acid: Association of embryotoxicity, reticulocytopenia, and delayed stimulation of hematopoiesis in pregnant rats. Birth Defects Res Part B - Dev Reprod Toxicol. 2011;92:52-68.

    9. White TEK, Clark RL. Sensitive periods for developmental toxicity of orally administered artesunate in the rat. Birth Defects Res Part B - Dev Reprod Toxicol. 2008;83:407-17.

    10. Boareto AC, Müller JC, Lourenço EL, Lombardi N, Lourenço AC, Rabitto I, et al. Effects of the combined artesunate and mefloquine antimalarial drugs on rat embryos. Hum Exp Toxicol. 2013;32:930-41.

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