Prevention and treatment of malaria in pregnant women
- Peter A Chedraui, MD, MSc, PhD
Peter A Chedraui, MD, MSc, PhD
- Director of the Institute of Biomedicine, Faculty of Medicine
- Catholic University
- Guayaquil, Ecuador
- Johanna Daily, MD, MSc
Johanna Daily, MD, MSc
- Section Editor — Malaria
- Associate Professor, Department of Medicine, Division of Infectious Diseases
- Albert Einstein College of Medicine
- Blair J Wylie, MD, MPH
Blair J Wylie, MD, MPH
- Assistant Professor
- Harvard Medical School
- Department of Obstetrics and Gynecology
- Division of Maternal-Fetal Medicine
- Massachusetts General Hospital
- Section Editors
- Peter F Weller, MD, FACP
Peter F Weller, MD, FACP
- Editor-in-Chief — Infectious Diseases
- Section Editor — Tropical Medicine
- William Bosworth Castle Professor of Medicine
- Harvard Medical School
- Professor of Immunology and Infectious Diseases
- Harvard T. H. Chan School of Public Health
- Susan M Ramin, MD
Susan M Ramin, MD
- Section Editor — Obstetrics
- Professor of Obstetrics and Gynecology
- Baylor College of Medicine
- Deputy Editors
- Vanessa A Barss, MD, FACOG
Vanessa A Barss, MD, FACOG
- Senior Deputy Editor — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Associate Clinical Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- Elinor L Baron, MD, DTMH
Elinor L Baron, MD, DTMH
- Deputy Editor — Infectious Diseases
- Assistant Clinical Professor of Medicine
- Tufts University School of Medicine
Malaria during pregnancy is a major cause of maternal morbidity worldwide and leads to poor birth outcomes. Pregnant women are more prone to complications of malaria infection than nongravid women. Prevention involves chemoprophylaxis and mosquito avoidance. Treatment involves antimalarial drugs and supportive measures.
Issues related to prevention and treatment of malaria in pregnant women will be reviewed here. Issues related to the prevalence, epidemiology, pathogenesis, clinical manifestations, diagnosis, and outcome of malaria in pregnancy are discussed separately, as are general details on treatment of uncomplicated and severe malaria.
- Hill J, Hoyt J, van Eijk AM, et al. Factors affecting the delivery, access, and use of interventions to prevent malaria in pregnancy in sub-Saharan Africa: a systematic review and meta-analysis. PLoS Med 2013; 10:e1001488.
- Centers for Disease Control and Prevention. Health Information for International Travel 2016: The Yellow Book. http://wwwnc.cdc.gov/travel/page/yellowbook-home (Accessed on August 19, 2015).
- Greenwood BM, Greenwood AM, Snow RW, et al. The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy. Trans R Soc Trop Med Hyg 1989; 83:589.
- Greenwood AM, Menendez C, Todd J, Greenwood BM. The distribution of birth weights in Gambian women who received malaria chemoprophylaxis during their first pregnancy and in control women. Trans R Soc Trop Med Hyg 1994; 88:311.
- Greenwood AM, Menendez C, Alonso PL, et al. Can malaria chemoprophylaxis be restricted to first pregnancies? Trans R Soc Trop Med Hyg 1994; 88:681.
- Menendez C, Todd J, Alonso PL, et al. Malaria chemoprophylaxis, infection of the placenta and birth weight in Gambian primigravidae. J Trop Med Hyg 1994; 97:244.
- Mola GL, Wanganapi A. Failure of chloroquine malaria prophylaxis in pregnancy. Aust N Z J Obstet Gynaecol 1987; 27:24.
- Nosten F, ter Kuile F, Maelankiri L, et al. Mefloquine prophylaxis prevents malaria during pregnancy: a double-blind, placebo-controlled study. J Infect Dis 1994; 169:595.
- Garner P, Gülmezoglu AM. Drugs for preventing malaria-related illness in pregnant women and death in the newborn. Cochrane Database Syst Rev 2003; :CD000169.
- Radeva-Petrova D, Kayentao K, ter Kuile FO, et al. Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment. Cochrane Database Syst Rev 2014; 10:CD000169.
- McClure EM, Goldenberg RL, Dent AE, Meshnick SR. A systematic review of the impact of malaria prevention in pregnancy on low birth weight and maternal anemia. Int J Gynaecol Obstet 2013; 121:103.
- Menéndez C, Bardají A, Sigauque B, et al. Malaria prevention with IPTp during pregnancy reduces neonatal mortality. PLoS One 2010; 5:e9438.
- Taylor SM, Antonia AL, Chaluluka E, et al. Antenatal receipt of sulfadoxine-pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study. Clin Infect Dis 2012; 55:42.
- World Health Organization; Global Malaria Program. Updated WHO Policy Recommendation (October 2012): Intermittent Preventive Treatment of Malaria in Pregnancy Using Sulfadoxine-Pyrimethamine (IPTp-SP). Geneva, Switzerland: World Health Organization; 2012.
- World Health Organization. Guidelines for the treatment of malaria, 3rd ed, WHO, Geneva 2015. http://www.who.int/malaria/publications/atoz/9789241549127/en/ (Accessed on September 10, 2015).
- Kayentao K, Garner P, van Eijk AM, et al. 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; 309:594.
- Harrington WE, Mutabingwa TK, Kabyemela E, et al. Intermittent treatment to prevent pregnancy malaria does not confer benefit in an area of widespread drug resistance. Clin Infect Dis 2011; 53:224.
- Desai M, Gutman J, Taylor SM, et al. Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight. Clin Infect Dis 2016; 62:323.
- Desai M, Gutman J, L'lanziva A, et al. Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial. Lancet 2015; 386:2507.
- Kakuru A, Jagannathan P, Muhindo MK, et al. Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy. N Engl J Med 2016; 374:928.
- Malaria Policy Advisory Committee to the WHO: conclusions and recommendations of September 2013 meeting http://www.malariajournal.com/content/12/1/456 (Accessed on January 07, 2014).
- González R, Mombo-Ngoma G, Ouédraogo S, et al. Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial. PLoS Med 2014; 11:e1001733.
- Tagbor H, Bruce J, Agbo M, et al. Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial. PLoS One 2010; 5:e14425.
- Tagbor H, Cairns M, Bojang K, et al. A Non-Inferiority, Individually Randomized Trial of Intermittent Screening and Treatment versus Intermittent Preventive Treatment in the Control of Malaria in Pregnancy. PLoS One 2015; 10:e0132247.
- González R, Desai M, Macete E, et al. Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial. PLoS Med 2014; 11:e1001735.
- Filler SJ, Kazembe P, Thigpen M, et al. Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi. J Infect Dis 2006; 194:286.
- ter Kuile FO, van Eijk AM, Filler SJ. Effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy: a systematic review. JAMA 2007; 297:2603.
- ter Kuile FO, Terlouw DJ, Phillips-Howard PA, et al. Reduction of malaria during pregnancy by permethrin-treated bed nets in an area of intense perennial malaria transmission in western Kenya. Am J Trop Med Hyg 2003; 68:50.
- Gamble C, Ekwaru JP, ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database Syst Rev 2006; :CD003755.
- Orton LC, Omari AA. Drugs for treating uncomplicated malaria in pregnant women. Cochrane Database Syst Rev 2008; :CD004912.
- Taylor WR, White NJ. Antimalarial drug toxicity: a review. Drug Saf 2004; 27:25.
- Mosha D, Mazuguni F, Mrema S, et al. Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort. Malar J 2014; 13:197.
- McGready R, Lee SJ, Wiladphaingern J, et al. Adverse effects of falciparum and vivax malaria and the safety of antimalarial treatment in early pregnancy: a population-based study. Lancet Infect Dis 2012; 12:388.
- Manyando C, Mkandawire R, Puma L, et al. Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia. Malar J 2010; 9:249.
- Adam I, Elhassan EM, Omer EM, et al. Safety of artemisinins during early pregnancy, assessed in 62 Sudanese women. Ann Trop Med Parasitol 2009; 103:205.
- Kovacs SD, Rijken MJ, Stergachis A. Treating severe malaria in pregnancy: a review of the evidence. Drug Saf 2015; 38:165.
- PREGACT Study Group, Pekyi D, Ampromfi AA, et al. Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. N Engl J Med 2016; 374:913.
- Dellicour S, Hall S, Chandramohan D, Greenwood B. The safety of artemisinins during pregnancy: a pressing question. Malar J 2007; 6:15.
- McGready R, Tan SO, Ashley EA, et al. A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated plasmodium falciparum treatment in pregnancy. PLoS Med 2008; 5:e253.
- Guidelines for the treatment of malaria. 3rd ed. Geneva: World Health Organization, 2015. http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf?ua=1&ua=1 (Accessed on October 22, 2015).
- Clark RL, White TE, A Clode S, et al. Developmental toxicity of artesunate and an artesunate combination in the rat and rabbit. Birth Defects Res B Dev Reprod Toxicol 2004; 71:380.
- White TE, Bushdid PB, Ritter S, et al. Artesunate-induced depletion of embryonic erythroblasts precedes embryolethality and teratogenicity in vivo. Birth Defects Res B Dev Reprod Toxicol 2006; 77:413.
- Clark RL, Lerman SA, Cox EM, et al. Developmental toxicity of artesunate in the rat: comparison to other artemisinins, comparison of embryotoxicity and kinetics by oral and intravenous routes, and relationship to maternal reticulocyte count. Birth Defects Res B Dev Reprod Toxicol 2008; 83:397.
- Boareto AC, Muller JC, Bufalo AC, et al. Toxicity of artemisinin [Artemisia annua L.] in two different periods of pregnancy in Wistar rats. Reprod Toxicol 2008; 25:239.
- McGready R, Brockman A, Cho T, et al. Randomized comparison of mefloquine-artesunate versus quinine in the treatment of multidrug-resistant falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 2000; 94:689.
- McGready R, Ashley EA, Moo E, et al. A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy. J Infect Dis 2005; 192:846.
- McGready R, Cho T, Keo NK, et al. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 2001; 33:2009.
- McGready R, Cho T, Villegas L, et al. Randomized comparison of quinine-clindamycin versus artesunate in the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 2001; 95:651.
- McGready R, Cho T, Cho JJ, et al. Artemisinin derivatives in the treatment of falciparum malaria in pregnancy. Trans R Soc Trop Med Hyg 1998; 92:430.
- McGready R, Keo NK, Villegas L, et al. Artesunate-atovaquone-proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report. Trans R Soc Trop Med Hyg 2003; 97:592.
- González R, Hellgren U, Greenwood B, Menéndez C. Mefloquine safety and tolerability in pregnancy: a systematic literature review. Malar J 2014; 13:75.
- Tagbor H, Bruce J, Browne E, et al. Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial. Lancet 2006; 368:1349.
- Nosten F, McGready R, d'Alessandro U, et al. Antimalarial drugs in pregnancy: a review. Curr Drug Saf 2006; 1:1.
- Baird JK, Hoffman SL. Primaquine therapy for malaria. Clin Infect Dis 2004; 39:1336.
- White NJ. The treatment of malaria. N Engl J Med 1996; 335:800.
- Griffin JB, Lokomba V, Landis SH, et al. Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study. Malar J 2012; 11:319.
- Schmiegelow C, Minja D, Oesterholt M, et al. Malaria and fetal growth alterations in the 3(rd) trimester of pregnancy: a longitudinal ultrasound study. PLoS One 2013; 8:e53794.
- Women living in endemic areas
- - Intermittent preventive treatment during pregnancy
- - Intermittent screening and treatment during pregnancy
- - Women infected with HIV
- Mosquito avoidance
- P. falciparum
- - Uncomplicated malaria
- First trimester
- Second and third trimesters
- - Severe malaria
- Non-falciparum malaria
- DRUG SAFETY
- MANAGEMENT OF PREGNANCY
- SUMMARY AND RECOMMENDATIONS