Malaria in the Pregnant Woman

  • P. E. Duffy
  • M. Fried
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 295)


Women become more susceptible to Plasmodium falciparum malaria during pregnancy, and the risk of disease and death is high for both the mother and her fetus. In low transmission areas, women of all parities are at risk for severe syndromes like cerebral malaria, and maternal and fetal mortality are high. In high transmission areas, where women are most susceptible during their first pregnancies, severe syndromes like cerebral malaria are uncommon, but severe maternal anemia and low birth weight are frequent sequelae and account for an enormous loss of life. P. falciparum-infected red cells sequester in the intervillous space of the placenta, where they adhere to chondroitin sulfate A but not to receptors like CD36 that commonly support adhesion of parasites infecting nonpregnant hosts. Poor pregnancy outcomes due to malaria are related to the macrophage-rich infiltrates and pro-inflammatory cytokines such as tumor necrosis factor-α that accumulate in the intervillous space. Women who acquire antibodies against chrondroitin sulfate A (CSA)-binding parasites are less likely to have placental malaria, and are more likely to deliver healthy babies. In areas of stable transmission, women acquire antibodies against CSA-binding parasites over successive pregnancies, explaining the high susceptibility to malaria during first pregnancy, and suggesting that a vaccine to prevent pregnancy malaria should target placental parasites. Prevention and treatment of malaria are essential components of antenatal care in endemic areas, but require special considerations during pregnancy. Recrudescence after drug treatment is more common during pregnancy, and the spread of drug-resistant parasites has eroded the usefulness of the few drugs known to be safe for the woman and her fetus. Determining the safety and effectiveness of newer antimalarials in pregnant women is an urgent priority. A vaccine that prevents pregnancy malaria due to P. falciparum could be delivered before first pregnancy, and would have an enormous impact on mother-child health in tropical areas.


Cerebral Malaria Placental Malaria Poor Pregnancy Outcome High Transmission Area Plasmodium Falciparum Erythrocyte Membrane Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Abrams ET, Brown H, Chensue SW, Turner GD, Tadesse E, Lema VM, Molyneux ME, Rochford R, Meshnick SR, Rogerson SJ (2003) Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression. J Immunol 170:2759–2764PubMedGoogle Scholar
  2. Archibald HM (1956) The influence of malarial infection of the placenta on the incidence of prematurity. Bull WHO 15:842–845PubMedGoogle Scholar
  3. Ayisi JG, Newman RD, ter Kuile FO, Shi YP, Yang C, et al. (2004) Maternal malaria and perinatal HIV transmission, western Kenya. Emerg Infect Dis 10:643–652PubMedGoogle Scholar
  4. Baruch DI, Gormely JA, Ma C, Howard RJ, Pasloske BL (1996) Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1. Proc Natl Acad Sci USA 93:3497–3502PubMedCrossRefGoogle Scholar
  5. Beeson JG, Brown GV (2004) Plasmodium falciparum-infected erythrocytes demonstrate dual specificity for adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive properties. J Infect Dis 189:169–179PubMedGoogle Scholar
  6. Beeson JG, Brown GV, Molyneux ME, Mhango C, Dzinjalamala F, Rogerson SJ (1999) Plasmodium falciparum isolates from infected pregnant women and children are associated with distinct adhesive and antigenic properties. J Infect Dis 180:464–472PubMedCrossRefGoogle Scholar
  7. Beeson JG, Rogerson SJ, Cooke BM, Reeder JC, Chai W, Lawson AM, Molyneux ME, Brown GV (2000) Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nat Med 6:86–90PubMedCrossRefGoogle Scholar
  8. Bignami A (1898) Al Policlinico (Supplemento) 4:763–767Google Scholar
  9. Bounyasong S (2001) Randomized trial of artesunate and mefloquine in comparison with quinine sulfate to treat P. falciparum malaria pregnant women. J Med Assoc Thai 84:1289–1299PubMedGoogle Scholar
  10. Brabin BJ (1983) An analysis of malaria in pregnancy in Africa. Bull WHO 61:1005–1016PubMedGoogle Scholar
  11. Brabin BJ, Hakimi M, Pelletier D (2001) An analysis of anemia and pregnancy-related maternal mortality. J Nutr 131:604S–614S; discussion 614S–615SPubMedGoogle Scholar
  12. Brabin BJ, Rogerson SJ (2001) The epidemiology and outcomes of maternal malaria. In: Duffy PE, Fried M (eds) Malaria in pregnancy: deadly parasite, susceptible host. Taylor & Francis, New YorkGoogle Scholar
  13. Brahmbhatt H, Kigozi G, Wabwire-Mangen F, Serwadda D, Sewankambo N, Lutalo T, Wawer MJ, Abramowsky C, Sullivan D, Gray R (2003) The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS 17:2539–2541PubMedCrossRefGoogle Scholar
  14. Bray RS, Sinden RE (1979) The sequestration of Plasmodium falciparum infected erythrocytes in the placenta. Trans R Soc Trop Med Hyg 73:716–719PubMedGoogle Scholar
  15. Browne EN, Maude GH, Binka FN (2001) The impact of insecticide-treated bednets on malaria and anaemia in pregnancy in Kassena-Nankana district, Ghana: a randomized controlled trial. Trop Med Int Health 6:667–676PubMedCrossRefGoogle Scholar
  16. Bruce-Chwatt LJ (1952) Malaria in African infants and children in Southern Nigeria. Ann Trop Med Parasitol 46:173–200PubMedGoogle Scholar
  17. Buffet PA, Gamain B, Scheidig C, Baruch D, Smith JD, Hernandez-Rivas R, Pouvelle B, Oishi S, Fujii N, Fusai T, Parzy D, Miller LH, Gysin J, Scherf A (1999) Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection. Proc Natl Acad Sci USA 96:12743–12748PubMedCrossRefGoogle Scholar
  18. Cannon DSH (1958) Malaria and prematurity in the western region of Nigeria. BMJ ii:877–878Google Scholar
  19. Creasey AM, Staalsoe T, Raza A, Arnot DE, Rowe JA (2003) Nonspecific immunoglobulin M binding and chondroitin sulfate A binding are linked phenotypes of Plasmodium falciparum isolates implicated in malaria during pregnancy. Infect Immun 71:4767–4771PubMedCrossRefGoogle Scholar
  20. D’Alessandro U, Langerock P, Bennett S, Francis N, Cham K, Greenwood BM (1996) The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia. Trans R Soc Trop Med Hyg 90:487–492PubMedGoogle Scholar
  21. Deen JL, von Seidlein L, Pinder M, Walraven GE, Greenwood BM (2001) The safety of the combination artesunate and pyrimethamine-sulfadoxine given during pregnancy. Trans R Soc Trop Med Hyg 95:424–428PubMedCrossRefGoogle Scholar
  22. Diagne N, Rogier C, Cisse B, Trape JF (1997) Incidence of clinical malaria in pregnant women exposed to intense perennial transmission. Trans R Soc Trop Med Hyg 91:166–170PubMedCrossRefGoogle Scholar
  23. Dolan G, ter Kuile FO, Jacoutot V, White NJ, Luxemburger C, Malankirii L, Chongsuphajaisiddhi T, Nosten F (1993) Bed nets for the prevention of malaria and anaemia in pregnancy. Trans R Soc Trop Med Hyg 87:620–626PubMedCrossRefGoogle Scholar
  24. Duffy MF, Brown GV, Basuki W, Krejany EO, Noviyanti R, Cowman AF, Reeder JC (2002) Transcription of multiple var genes by individual, trophozoite-stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype. Mol Microbiol 43:1285–1293PubMedCrossRefGoogle Scholar
  25. Duffy PE (2001) Immunity to malaria during pregnancy: Different host, different parasite. In: Duffy PE, Fried M (eds) Malaria in pregnancy: deadly parasite, susceptible host. Taylor & Francis, New York, pp 71–126Google Scholar
  26. Duffy PE, Desowitz RS (2001) Pregnancy malaria throughout history: Dangerous labors. In: Duffy PE, Fried M (eds) Malaria in pregnancy: deadly parasite, susceptible host. Taylor & Francis, New York, pp 1–25Google Scholar
  27. Duffy PE, Fried M(2003) Antibodies that inhibit Plasmodium falciparum adhesion to chondroitin sulfate A are associated with increased birth weight and the gestational age of newborns. Infect Immun 71:6620–6623PubMedCrossRefGoogle Scholar
  28. Fievet N, Tami G, Maubert B, Moussa M, Shaw IK, Cot M, Holder AA, Chaouat G, Deloron P (2002) Cellular immune response to Plasmodium falciparum after pregnancy is related to previous placental infection and parity. Malaria J 1:16Google Scholar
  29. Flick K, Scholander C, Chen Q, Fernandez V, Pouvelle B, Gysin J, Wahlgren M (2001) Role of nonimmune IgG bound to PfEMP1 in placental malaria. Science 293:2098–2100PubMedCrossRefGoogle Scholar
  30. Florens L, Liu X, Wang Y, Yang S, Schwartz O, Peglar M, Carucci DJ, Yates JR, Wub Y (2004) Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes. Mol Biochem Parasitol 135:1–11PubMedCrossRefGoogle Scholar
  31. Fried M, Duffy PE (1996) Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272:1502–1504PubMedGoogle Scholar
  32. Fried M, Duffy PE (1998) Maternal malaria and parasite adhesion. J Mol Med 76:162–171PubMedCrossRefGoogle Scholar
  33. Fried M, Duffy PE (2002) Two DBLgamma subtypes are commonly expressed by placental isolates of Plasmodium falciparum. Mol Biochem Parasitol 122:201–210PubMedCrossRefGoogle Scholar
  34. Fried M, Lauder RM, Duffy PE (2000) Plasmodium falciparum: adhesion of placental isolates modulated by the sulfation characteristics of the glycosaminoglycan receptor. Exp Parasitol 95:75–78PubMedCrossRefGoogle Scholar
  35. Fried M, Muga RO, Misore AO, Duffy PE (1998a) Malaria elicits type 1 cytokines in the human placenta: IFN-gamma and TNF-alpha associated with pregnancy outcomes. J Immunol 160:2523–2530PubMedGoogle Scholar
  36. Fried M, Nosten F, Brockman A, Brabin BJ, Duffy PE (1998b) Maternal antibodies block malaria. Nature 395:851–852PubMedCrossRefGoogle Scholar
  37. Fried M, Wendler JP, Mutabingwa TK, Duffy PE (2004) Mass spectrometric analysis of Plasmodium falciparum erythrocyte membrane protein-1 variants expressed by placental malaria parasites. Proteomics 4:1086–1093PubMedCrossRefGoogle Scholar
  38. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K, Salzberg SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J, Angiuoli S, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM, Fairlamb AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM, Subramanian GM, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW, Fraser CM, Barrell B (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511PubMedGoogle Scholar
  39. Garner P, Gulmezoglu AM (2003) Drugs for preventing malaria-related illness in pregnant women and death in the newborn. Cochrane Database Syst Rev CD000169Google Scholar
  40. Garnham PCC (1938) Transact R Soc Trop Med Hyg 32:13–48Google Scholar
  41. Greenwood AM, Armstrong JR, Byass P, Snow RW, Greenwood BM (1992) Malaria chemoprophylaxis, birth weight and child survival. Trans R Soc Trop Med Hyg 86:483–485PubMedGoogle Scholar
  42. Greenwood AM, Menendez C, Todd J, Greenwood BM (1994) 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 88: 311–312PubMedGoogle Scholar
  43. Greenwood BM, Greenwood AM, Snow RW, Byass P, Bennett S, Hatib-N’Jie AB (1989) The effects of malaria chemoprophylaxis given by traditional birth attendants on the course and outcome of pregnancy. Trans R Soc Trop Med Hyg 83:589–594PubMedGoogle Scholar
  44. Guyatt HL, Snow RW (2001) The epidemiology and burden of Plasmodium falciparum related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 64:36–44PubMedGoogle Scholar
  45. Hammerich A, Campbell OM, Chandramohan D (2002) Unstable malaria transmission and maternal mortality—experiences from Rwanda. Trop Med Int Health 7:573–576PubMedCrossRefGoogle Scholar
  46. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA (2000) Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 343:1608–1614PubMedCrossRefGoogle Scholar
  47. Hinderaker SG, Olsen BE, Bergsjo PB, Gasheka P, Lie RT, Havnen J, Kvale G (2003) Avoidable stillbirths and neonatal deaths in rural Tanzania. BJOG 110:616–623PubMedGoogle Scholar
  48. Inion I, Mwanyumba F, Gaillard P, Chohan V, Verhofstede C, Claeys P, Mandaliya K, Van Marck E, Temmerman M (2003) Placental malaria and perinatal transmission of human immunodeficiency virus type 1. J Infect Dis 188:1675–1678PubMedCrossRefGoogle Scholar
  49. Jensen AT, Zornig HD, Buhmann C, Salanti A, Koram KA, Riley EM, Theander TG, Hviid L, Staalsoe T (2003) Lack of gender-specific antibody recognition of products from domains of a var gene implicated in pregnancy-associated Plasmodium falciparum malaria. Infect Immun 71:4193–4196PubMedCrossRefGoogle Scholar
  50. Jilly P (1969) Anaemia in parturient women, with special reference to malaria infection of the placenta. Ann Trop Med Parasitol 63:109–116PubMedGoogle Scholar
  51. Keuter M, van Eijk A, Hoogstrate M, Raasveld M, van de Ree M, Ngwawe WA, Watkins WM, Were JB, Brandling-Bennett AD (1990) Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya. BMJ 301:466–470PubMedCrossRefGoogle Scholar
  52. Kochar DK, Kumawat BL, Kochar SK, Sanwal V (1995) Hypoglycemia after oral quinine administration. J Assoc Physicians India 43:654, 657PubMedGoogle Scholar
  53. Kulmala T, Vaahtera M, Ndekha M, Koivisto AM, Cullinan T, Salin ML, Ashorn P (2000) The importance of preterm births for peri-and neonatal mortality in rural Malawi. Paediatr Perinat Epidemiol 14:219–226PubMedCrossRefGoogle Scholar
  54. Kyes SA, Christodoulou Z, Raza A, Horrocks P, Pinches R, Rowe JA, Newbold CI (2003) A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern. Mol Microbiol 48:1339–1348PubMedCrossRefGoogle Scholar
  55. Ladner J, Leroy V, Simonon A, Karita E, Bogaerts J, De Clercq A, Van De Perre P, Dabis F (2002) HIV infection, malaria, and pregnancy: a prospective cohort study in Kigali, Rwanda. Am J Trop Med Hyg 66:56–60PubMedGoogle Scholar
  56. Laveran A (1882) Bulletins et Memoires de la Societe Medicale des hopitaux de Paris 18:168–176Google Scholar
  57. Lekana Douki JB, Traore B, Costa FT, Fusai T, Pouvelle B, Sterkers Y, Scherf A, Gysin J (2002) Sequestration of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A, a receptor for maternal malaria: monoclonal antibodies against the native parasite ligand reveal pan-reactive epitopes in placental isolates. Blood 100:1478–1483PubMedCrossRefGoogle Scholar
  58. Leopardi O, Naughten W, Salvia L, Colecchia M, Matteelli A, Zucchi A, Shein A, Muchi JA, Carosi G, Ghione M (1996) Malaric placentas. A quantitative study and clinico-pathological correlations. Pathol Res Pract 192, 892–898; discussion 899–900PubMedGoogle Scholar
  59. Looareesuwan S, Phillips RE, White NJ, Kietinun S, Karbwang J, Rackow C, Turner RC, Warrell DA (1985) Quinine and severe falciparum malaria in late pregnancy. Lancet 2:4–8PubMedGoogle Scholar
  60. Luxemburger C, Ricci F, Nosten F, Raimond D, Bathet S, White NJ (1997) The epidemiology of severe malaria in an area of low transmission in Thailand. Trans R Soc Trop Med Hyg 91:256–262PubMedCrossRefGoogle Scholar
  61. MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA (1985) Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119:385–401PubMedGoogle Scholar
  62. Maitra N, Joshi M, Hazra M (1993) Maternal manifestations of malaria in pregnancy: a review. Indian J Matern Child Health 4:98–101PubMedGoogle Scholar
  63. Malhotra M, Sharma JB, Batra S, Sharma S, Murthy NS, Arora R (2002) Maternal and perinatal outcome in varying degrees of anemia. Int J Gynaecol Obstet 79:93–100PubMedCrossRefGoogle Scholar
  64. Marchant T, Schellenberg JA, Edgar T, Nathan R, Abdulla S, Mukasa O, Mponda H, Lengeler C (2002) Socially marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania. Trop Med Int Health 7:149–158PubMedCrossRefGoogle Scholar
  65. Marchiafava E, Bignami A (1894) On summer-autmnal fevers. In: Charles TE (ed.) Two monographs on malaria and the parasites of malarial fevers. The New Sydenham Society, LondonGoogle Scholar
  66. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, Clerici M (1996) Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol 106:127–133PubMedCrossRefGoogle Scholar
  67. Maubert B, Fievet N, Tami G, Boudin C, Deloron P (1998) Plasmodium falciparum isolates from Cameroonian pregnant women do not rosette. Parasite 5:281–283PubMedGoogle Scholar
  68. Maubert B, Fievet N, Tami G, Boudin C, Deloron P (2000) Cytoadherence of Plasmodium falciparum-infected erythrocytes in the human placenta. Parasite Immunol 22:191–199PubMedCrossRefGoogle Scholar
  69. McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looareesuwan S, White NJ, Nosten F (2001a) Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 33:2009–2016PubMedCrossRefGoogle Scholar
  70. McGready R, Cho T, Samuel D, Villegas L, Brockman A, van Vugt M, Looareesuwan S, White NJ, Nosten F (2001b) Trans R Soc Trop Med Hyg 95:651–656PubMedGoogle Scholar
  71. McGready R, Hamilton KA, Simpson JA, Cho T, Luxemburger C, Edwards R, Looareesuwan S, White NJ, Nosten F, Lindsay SW (2001c) Safety of the insect repellent N,N-diethyl-M-toluamide (DEET) in pregnancy. Am J Trop Med Hyg 65:285–289PubMedGoogle Scholar
  72. McGready R, Stepniewska K, Edstein MD, Cho T, Gilveray G, Looareesuwan S, White NJ, Nosten F (2003) The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. Eur J Clin Pharmacol 59:545–552PubMedGoogle Scholar
  73. McGregor IA (1984) Epidemiology, malaria and pregnancy. Am J Trop Med Hyg 33:517–525PubMedGoogle Scholar
  74. Menendez C, Todd J, Alonso PL, Lulat S, Francis N, Greenwood BM (1994) Malaria chemoprophylaxis, infection of the placenta and birth weight in Gambian primigravidae. J Trop Med Hyg 97:244–248PubMedGoogle Scholar
  75. Meuris S, Piko BB, Eerens P, Vanbellinghen AM, Dramaix M, Hennart P (1993) Gestational malaria: assessment of its consequences on fetal growth. Am J Trop Med Hyg 48:603–609PubMedGoogle Scholar
  76. Moore JM, Nahlen BL, Misore A, Lal AA, Udhayakumar V (1999) Immunity to placental malaria. I. Elevated production of interferon-gamma by placental blood mononuclear cells is associated with protection in an area with high transmission of malaria. J Infect Dis 179:1218–1225PubMedCrossRefGoogle Scholar
  77. Moormann AM, Sullivan AD, Rochford RA, Chensue SW, Bock PJ, Nyirenda T, Meshnick SR (1999) Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation. J Infect Dis 180:1987–1993PubMedCrossRefGoogle Scholar
  78. Murphy SC, Breman JG (2001) Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64:57–67PubMedGoogle Scholar
  79. Mutabingwa TK, Malle LN, de Geus A, Oosting J (1993a) Malaria chemosuppression in pregnancy. I. The effect of chemosuppressive drugs on maternal parasitaemia. Trop Geogr Med 45:6–14PubMedGoogle Scholar
  80. Mutabingwa TK, Malle LN, de Geus A, Oosting J (1993b) Malaria chemosuppression in pregnancy. II. Its effect on maternal haemoglobin levels, placental malaria and birth weight. Trop Geogr Med 45:49–55PubMedGoogle Scholar
  81. Newman RD, Hailemariam A, Jimma D, Degifie A, Kebede D, Rietveld AE, Nahlen BL, Barnwell JW, Steketee RW, Parise ME (2003) Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis 187:1765–1772PubMedGoogle Scholar
  82. Nosten F, McGready R (2001) The treatment of malaria in pregnancy. In: Duffy PE, Fried M (eds) Malaria in pregnancy: deadly parasite, susceptible host. Taylor & Francis, New York, ppGoogle Scholar
  83. Nosten F, McGready R (2003) Burden of malaria during pregnancy in areas of stable and unstable transmission in Ethiopia during a nonepidemic year. J Infect Dis 188:1259–1261; author reply 1561–1562PubMedCrossRefGoogle Scholar
  84. Nosten F, McGready R, Simpson JA, Thwai KL, Balkan S, Cho T, Hkirijaroen L, Looareesuwan S, White NJ (1999a) Effects of Plasmodium vivax malaria in pregnancy. Lancet 354:546–549PubMedCrossRefGoogle Scholar
  85. Nosten F, Vincenti M, Simpson J, Yei P, Thwai KL, de Vries A, Chongsuphajaisiddhi T, White NJ (1999b) The effects of mefloquine treatment in pregnancy. Clin Infect Dis 28:808–815PubMedGoogle Scholar
  86. Ordi J, Ismail MR, Ventura PJ, Kahigwa E, Hirt R, Cardesa A, Alonso PL, Menendez C (1998) Massive chronic intervillositis of the placenta associated with malaria infection. Am J Surg Pathol 22:1006–1011PubMedGoogle Scholar
  87. Ordi J, Menendez C, Ismail MR, Ventura PJ, Palacin A, Kahigwa E, Ferrer B, Cardesa A, Alonso PL (2001) Placental malaria is associated with cell-mediated inflammatory responses with selective absence of natural killer cells. J Infect Dis 183:1100–1107PubMedCrossRefGoogle Scholar
  88. Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, Muga R, Oloo AJ, Steketee RW (1998) Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg 59:813–822PubMedGoogle Scholar
  89. Piper C, Brabin BJ, Alpers MP (2001) Higher risk of post-partum hemorrhage in malarious than in non-malarious areas of Papua New Guinea. Int J Gynaecol Obstet 72:77–78PubMedCrossRefGoogle Scholar
  90. Pongponratn E, Riganti M, Punpoowong B, Aikawa M (1991) Microvascular sequestration of parasitized erythrocytes in human falciparum malaria: a pathological study. Am J Trop Med Hyg 44:168–175PubMedGoogle Scholar
  91. Rasheed FN, Bulmer JN, Morrison L, Jawla MF, Hassan-King M, Riley EM, Greenwood BM (1992) Isolation of maternal mononuclear cells from placentas for use in in vitro functional assays. J Immunol Methods 146:185–193PubMedCrossRefGoogle Scholar
  92. Redd SC, Wirima JJ, Steketee RW, Breman JG, Heymann DL (1996) Transplacental transmission of Plasmodium falciparum in rural Malawi. Am J Trop Med Hyg 55:57–60PubMedGoogle Scholar
  93. Reeder JC, Cowman AF, Davern KM, Beeson JG, Thompson JK, Rogerson SJ, Brown GV (1999) The adhesion of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A is mediated by P. falciparum erythrocyte membrane protein 1. Proc Natl Acad Sci USA 96:5198–5202PubMedCrossRefGoogle Scholar
  94. Reeder JC, Hodder AN, Beeson JG, Brown GV (2000) Identification of glycosaminoglycan binding domains in Plasmodium falciparum erythrocyte membrane protein 1 of a chondroitin sulfate A-adherent parasite. Infect Immun 68:3923–3926PubMedCrossRefGoogle Scholar
  95. Ricke CH, Staalsoe T, Koram K, Akanmori BD, Riley EM, Theander TG, Hviid L (2000) Plasma antibodies from malaria-exposed pregnant women recognize variant surface antigens on Plasmodium falciparum-infected erythrocytes in a parity dependent manner and block parasite adhesion to chondroitin sulfate A. J Immunol 165:3309–3316PubMedGoogle Scholar
  96. Rogerson SJ, Beeson JG, Mhango CG, Dzinjalamala FK, Molyneux ME (2000) Plasmodium falciparum rosette formation is uncommon in isolates from pregnant women. Infect Immun 68:391–393PubMedCrossRefGoogle Scholar
  97. Rogerson SJ, Brown HC, Pollina E, Abrams ET, Tadesse E, Lema VM, Molyneux ME (2003) Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women. Infect Immun 71:267–270PubMedCrossRefGoogle Scholar
  98. Rowe JA, Kyes SA, Rogerson SJ, Babiker HA, Raza A(2002) Identification of a conserved Plasmodium falciparum var gene implicated in malaria in pregnancy. J Infect Dis 185:1207–1211PubMedCrossRefGoogle Scholar
  99. Salanti A, Jensen AT, Zornig HD, Staalsoe T, Joergensen L, Nielsen MA, Khattab A, Arnot DE, Klinkert MQ, Hviid L, Theander TG (2002) A sub-family of common and highly conserved Plasmodium falciparum var genes. Mol Biochem Parasitol 122:111–115PubMedCrossRefGoogle Scholar
  100. Salanti A, Staalsoe T, Lavstsen T, Jensen AT, Sowa MP, Arnot DE, Hviid L, Theander TG (2003) Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy associated malaria. Mol Microbiol 49:179–191PubMedCrossRefGoogle Scholar
  101. Salihu HM, Naik EG, Tchuinguem G, Bosny JP, Dagne G (2002) Weekly chloroquine prophylaxis and the effect on maternal haemoglobin status at delivery. Trop Med Int Health 7:29–34PubMedCrossRefGoogle Scholar
  102. Schultz LJ, Steketee RW, Macheso A, Kazembe P, Chitsulo L, Wirima JJ (1994) The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. Am J Trop Med Hyg 51:515–522PubMedGoogle Scholar
  103. Sereni S (1902) Bullettino della Reale Accademia Medica di Roma 29:55–88Google Scholar
  104. Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, Marsh K (1999) Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet 353:632–636PubMedCrossRefGoogle Scholar
  105. Shulman CE, Dorman EK, Talisuna AO, Lowe BS, Nevill C, Snow RW, Jilo H, Peshu N, Bulmer JN, Graham S, Marsh K (1998) A community randomized controlled trial of insecticide-treated bednets for the prevention of malaria and anaemia among primigravid women on the Kenyan coast. Trop Med Int Health 3:197–204PubMedCrossRefGoogle Scholar
  106. Simister NE (2003) Placental transport of immunoglobulin G. Vaccine 21:3365–3369Google Scholar
  107. Singh N, Saxena A, Chand SK, Valecha N, Sharma VP (1998) Studies on malaria during pregnancy in a tribal area of central India (Madhya Pradesh). Southeast Asian J Trop Med Public Health 29:10–17PubMedGoogle Scholar
  108. Singh N, Shukla MM, Sharma VP (1999) Epidemiology of malaria in pregnancy in central India. Bull WHO 77:567–572PubMedGoogle Scholar
  109. Smoak BL, Writer JV, Keep LW, Cowan J, Chantelois JL (1997) The effects of inadvertent exposure of mefloquine chemoprophylaxis on pregnancy outcomes and infants of US Army servicewomen. J Infect Dis 176:831–833PubMedCrossRefGoogle Scholar
  110. Staalsoe T, Shulman CE, Bulmer JN, Kawuondo K, Marsh K, Hviid L (2004) Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria. Lancet 363:283–289PubMedCrossRefGoogle Scholar
  111. Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG (1996a) The effect of malaria and malaria prevention in pregnancy on offspring birthweight, prematurity, and intrauterine growth retardation in rural Malawi. Am J Trop Med Hyg 55:33–41PubMedGoogle Scholar
  112. Steketee RW, Wirima JJ, Slutsker L, Khoromana CO, Heymann DL, Breman JG (1996b) Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine. Am J Trop Med Hyg 55:50–56PubMedGoogle Scholar
  113. Steketee RW, Wirima JJ, Slutsker WL, Khoromana CO, Breman JG, Heymann DL (1996c) Objectives and methodology in a study of malaria treatment and prevention in pregnancy in rural Malawi: The Mangochi Malaria Research Project. Am J Trop Med Hyg 55:8–16PubMedGoogle Scholar
  114. Suguitan AL Jr, Leke RG, Fouda G, Zhou A, Thuita L, Metenou S, Fogako J, Megnekou R, Taylor DW (2003) Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. J Infect Dis 188:1074–1982PubMedGoogle Scholar
  115. Sullivan AD, Nyirenda T, Cullinan T, Taylor T, Harlow SD, James SA, Meshnick SR (1999) Malaria infection during pregnancy: intrauterine growth retardation and preterm delivery in Malawi. J Infect Dis 179:1580–1583PubMedCrossRefGoogle Scholar
  116. Sullivan AD, Nyirenda T, Cullinan T, Taylor T, Lau A, Meshnick SR (2000) Placental haemozoin and malaria in pregnancy. Placenta 21:417–421PubMedCrossRefGoogle Scholar
  117. Taylor HM, Kyes SA, Harris D, Kriek N, Newbold CI (2000) A study of var gene transcription in vitro using universal var gene primers. Mol Biochem Parasitol 105:13–23PubMedCrossRefGoogle Scholar
  118. Taylor WR, White NJ (2004) Antimalarial drug toxicity: a review. Drug Saf 27 25–61PubMedGoogle Scholar
  119. ter Kuile FO, Terlouw DJ, Phillips-Howard PA, Hawley WA, Friedman JF, Kariuki SK, Shi YP, Kolczak MS, Lal AA, Vulule JM, Nahlen BL (2003) 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 68:50–60PubMedGoogle Scholar
  120. Tkachuk AN, Moormann AM, Poore JA, Rochford RA, Chensue SW, Mwapasa V, Meshnick SR (2001) Malaria enhances expression of CC chemokine receptor 5 on placental macrophages. J Infect Dis 183:967–972PubMedCrossRefGoogle Scholar
  121. Valiyaveettil M, Achur RN, Alkhalil A, Ockenhouse CF, Gowda DC (2001) Plasmodium falciparum cytoadherence to human placenta: evaluation of hyaluronic acid and chondroitin 4-sulfate for binding of infected erythrocytes. Exp Parasitol 99:57–65PubMedCrossRefGoogle Scholar
  122. van den Broek N (1996) The aetiology of anaemia in pregnancy in West Africa. Trop Doct 26:5–7PubMedGoogle Scholar
  123. van Eijk AM, Ayisi JG, ter Kuile FO, Misore AO, Otieno JA, Rosen DH, Kager PA, Steketee RW, Nahlen BL (2003) HIV increases the risk of malaria in women of all gravidities in Kisumu, Kenya. AIDS 17:595–603PubMedGoogle Scholar
  124. van Hung L (1951) Revue du Paludisme at de Medecine Tropicale 9:75–112Google Scholar
  125. Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Russell WB, Broadhead RL (1998) An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi. Ann Trop Med Parasitol 92:141–150PubMedGoogle Scholar
  126. Verhoeff FH, Brabin BJ, Hart CA, Chimsuku L, Kazembe P, Broadhead RL (1999) Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control. Trop Med Int Health 4:5–12PubMedCrossRefGoogle Scholar
  127. Verhoeff FH, Brabin BJ, van Buuren S, Chimsuku L, Kazembe P, Wit JM, Broadhead RL (2001) An analysis of intra-uterine growth retardation in rural Malawi. Eur J Clin Nutr 55:682–689PubMedCrossRefGoogle Scholar
  128. Wegmann TG, Lin H, Guilbert L, Mosmann TR (1993) Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 14:353–536PubMedCrossRefGoogle Scholar
  129. Wickramasuriya GAW (1935) J Obstet Gynaecol BE 42:816–834Google Scholar
  130. Wickramasuriya GAW (1936) Malaria and ankylostomiasis in the pregnant woman. Oxford University Press, LondonGoogle Scholar
  131. Winstanley P (2003) The contribution of clinical pharmacology to antimalarial drug discovery and development. Br J Clin Pharmacol 55:464–468PubMedCrossRefGoogle Scholar
  132. Winter G, Chen Q, Flick K, Kremsner P, Fernandez V, Wahlgren M (2003) The 3D7var5.2 (var COMMON) type var gene family is commonly expressed in non-placental Plasmodium falciparum malaria. Mol Biochem Parasitol 127:179–191PubMedCrossRefGoogle Scholar
  133. Winter G, Chen Q, Wahlgren M (2004) Meeting report: the molecular background of severe and complicated malaria. Mol Biochem Parasitol 134:37–41PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • P. E. Duffy
    • 1
    • 2
  • M. Fried
    • 1
  1. 1.Seattle Biomedical Research InstituteSeattleUSA
  2. 2.Walter Reed Army Institute of ResearchSilver SpringUSA

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