Volume 69, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The prevalence of pre-term deliveries (PTDs) is increased in women who become infected with during pregnancy. Because prematurity is a risk factor for newborns, it is important to identify conditions that contribute to malaria-associated PTDs. –infected erythrocytes sequester in the placenta and attract activated mononuclear cells that secrete pro-inflammatory cytokines. Increased inflammatory cytokine levels in other microbial infections are associated with PTDs. To determine if such is the case in women with placental malaria, concentrations of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10 were measured in placental plasma of 391 malaria-infected and -uninfected Cameroonian women with premature and full-term deliveries. Risk factors for malaria-associated PTDs included peripheral and placental parasitemias greater than 1%, maternal anemia, elevated IL-10 levels, and low TNF-α:IL-10 ratios due to over-expression of IL-10. Alterations in cytokine levels may contribute to PTDs through the induction of anemia and/or altering cellular immune responses required for eliminating placental parasites.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Brabin BJ, 1983. An analysis of malaria in pregnancy in Africa. Bull World Health Organ 61: 1005–1016. [Google Scholar]
  2. McGregor IA, 1984. Epidemiology, malaria, and pregnancy. Am J Trop Med Hyg 33 : 517–525. [Google Scholar]
  3. Kaushik A, Sharma VK, Sadhana, Kumar R, 1992. Malarial placental infection and low birth weight babies. J Commum Dis 24 : 65–69. [Google Scholar]
  4. Steketee RW, Nahlen BL, Parise ME, Menendez C, 2001. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 64 : 28–35. [Google Scholar]
  5. Goldenberg RL, 2002. The management of preterm labor. Obstet Gynecol 100 : 1020–1037. [Google Scholar]
  6. McCormick MC, 1985. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med 312 : 82–90. [Google Scholar]
  7. Romero R, Espinoza J, Chaiworapongsa T, Kalache K, 2002. Infection and prematurity and the role of preventive strategies. Semin Neonatol 7 : 259–274. [Google Scholar]
  8. Menendez C, Ordi J, Ismail MR, Ventura PJ, Aponte JJ, Kahigwa E, Font F, Alonso PL, 2000. The impact of placental malaria on gestational age and birth weight. J Infect Dis 181 : 1740–1745. [Google Scholar]
  9. Steketee RW, Wirima JJ, Hightower AW, Slutsker L, Heymann DL, Breman JG, 1996. 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 : 33–41. [Google Scholar]
  10. 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 : 1580–1583. [Google Scholar]
  11. Bennett WA, Lagoo-Deenadayalan S, Whitworth NS, Stopple JA, Barber WH, Hale E, Brackin MN, Cowan BD, 1999. First-trimester human chorionic villi express both immunoregulatory and inflammatory cytokines: a role for interleukin-10 in regulating the cytokine network of pregnancy. Am J Reprod Immunol 41 : 70–78. [Google Scholar]
  12. Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG, 1993. Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol 151 : 4562–4573. [Google Scholar]
  13. Baggia S, Gravett MG, Witkin SS, Haluska GJ, Novy MJ, 1996. Interleukin-1β intra-amniotic infusion induces tumour necrosis factor-α, prostaglandin production, and pre-term contractions in pregnant rhesus monkeys. J Soc Gynecol Investig 3 : 121–126. [Google Scholar]
  14. Dudley DJ, 1997. Pre-term labor: an intra-uterine inflammatory response syndrome? J Reprod Immunol 36 : 93–109. [Google Scholar]
  15. Fried M., Muga RO, Misore AO, Duffy, PE, 1998. Malaria elicits type 1 cytokines in the human placenta: IFN-γ and TNF-α associated with pregnancy outcomes. J Immunol 160 : 2523–2530. [Google Scholar]
  16. Fievet N, Moussa M, Tami G, Maubert B, Cot M, Deloron P, Chaouat G, 2001. Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta. J Infect Dis 183 : 1530–1534. [Google Scholar]
  17. Suguitan AJL Jr, Leke RGF, Fouda G, Zhou A, Thuita L, Metenou S, Fogako J, Megnekou R, Taylor DW, 2003. Changes in the level of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. J Infect Dis 188 : 1074–1082. [Google Scholar]
  18. Clark IA, Chaudhri G, 1988. Tumor necrosis factor in malaria-induced abortion. Am J Trop Med Hyg 39 : 246–249. [Google Scholar]
  19. 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 : 1987–1993. [Google Scholar]
  20. Tilg H, Ulmer H, Kaser A, Weiss G, 2002. Role of IL-10 for induction of anemia during inflammation. J Immunol 169 : 2204–2209. [Google Scholar]
  21. Means RT Jr, 2003. Recent developments in the anemia of chronic disease. Curr Hematol Rep 2 : 116–121. [Google Scholar]
  22. Jason J, Archibald LK, Nwanyanwu OC, Bell M, Buchanan I, Larned J, Kazembe PN, Dobbie H, Parekh B, Byrd MG, Eick A, Han A, Jarvis WR, 2001. Cytokines and malaria parasitemia. Clin Immunol 100 : 208–218. [Google Scholar]
  23. Gosi P, Khusmith S, Looareesuwan S, Sitachamroom U, Glanarongran R, Buchachart K, Walsh DS, 1999. Complicated malaria is associated with differential elevations in serum levels of interleukins 10, 12, and 15. Southeast Asian J Trop Med Public Health. 30 : 412–417. [Google Scholar]
  24. Casey ML, Cox SM, Beutler B, Milewich L, MacDonald PC, 1989. Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor. J Clin Invest 83 : 430–436. [Google Scholar]
  25. Entrican G, 2002. Immune regulation during pregnancy and hostpathogen interactions in infectious abortions. J Comp Pathol 126 : 79–94. [Google Scholar]
  26. 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 : 1006–1011. [Google Scholar]
  27. Matteelli A, Donato F, Shein A, Muchi JA, Leopardi O, Astori L, Carosi G, 1994. Malaria and anaemia in pregnant women in urban Zanzibar, Tanzania. Ann Trop Med Parasitol 88 : 475–483. [Google Scholar]
  28. Ndyomugyenyi R, Magnussen P, 1999. Anaemia in pregnancy: Plasmodium falciparum infection is an important cause in primigravidae in Hoima district, western Uganda. Ann Trop Med Parasitol 93 : 457–465. [Google Scholar]
  29. Othoro C, Lal AA, Nahlen B, Koech D, Orago SS, Udhayakumar V, 1999. A low interleukin-10 tumor necrosis factor-α ratio is associated with malaria anemia in children residing in a holoendemic malaria region in Western Kenya. J Infect Dis 179 : 279–282. [Google Scholar]
  30. May J, Lell B, Luty AJF, Meyer CG, Kremsner PG, 2000. Plasma interleukin-10:tumor necrosis factor (TNF)-α ratio is associated with TNF promoter variants and predicts malarial complications. J Infect Dis 182 : 1570–1573. [Google Scholar]
  31. Nussenblatt V, Mukasa G, Metzger A, Ndeezi G, Garrett E, Semba RD, 2001. Anemia and interleukin-10, tumor necrosis factor alpha, and erythropoietin levels among children with acute, uncomplicated Plasmodium falciparum malaria. Clin Diagn Lab Immun 8 : 1164–1170. [Google Scholar]
  32. Peyron F, Burdin N, Ringwald P, Vuillez JP, Rousset F, Banchereau J, 1994. High levels of circulating IL-10 in human malaria. Clin Exp Immunol 95 : 300–303. [Google Scholar]
  33. Perkins DJ, Kremsner PG, Weinberg JB, 2001. Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria. J Infect Dis 183 : 113–118. [Google Scholar]
  34. Kobayashi F, Ishida H, Matsui T, Tsuji M, 2000. Effects of in vivo administration of anti-IL-10 or anti-IFN-gamma monoclonal antibody on the host defense mechanism against Plasmodium yoelii yoelii infection. J Vet Med Sci 62 : 583–587. [Google Scholar]
  35. Opal SM, Wherry JC, Grint P, 1998. Interleukin-10: potential benefits and possible risks in clinical infectious diseases. Clin Infect Dis 27 : 1497–1507. [Google Scholar]
  36. 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 : 353–356. [Google Scholar]
  37. Raghupathy R, 1997. Th1-type immunity is incompatible with successful pregnancy. Immunol Today 18 : 478–482. [Google Scholar]
  38. 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. [Google Scholar]
  39. 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 : 1006–1011. [Google Scholar]
  40. 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 : 1100–1107. [Google Scholar]
  41. Clark IA, Chaudhri G, 1988. Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. Br J Haematol 70 : 99–103. [Google Scholar]
  42. Ludwiczek S, Aigner E, Theurl I, Weiss G, 2003. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101 : 4148–4154. [Google Scholar]
  43. Bulmer JN, Rasheed FN, Francis N, Morrison L, Greenwood BM, 1993. Placental malaria. I. Pathological classification. Histopathology 22 : 211–218. [Google Scholar]
  44. Robinson JN, Regan JA, Norwitz ER, 2001. The epidemiology of pre-term labor. Semin Perinatol 25 : 204–214. [Google Scholar]
  45. Oehler L, Kollars M, Bohle B, Berer A, Reiter E, Lechner K, Geissler K, 1999. Interleukin-10 inhibits burst-forming uniterythroid growth by suppression of endogenous granulocyte-macrophage colony-stimulating factor production from T cells. Exp Hematol 27: 217–223. [Google Scholar]
  46. World Health Organization, Report on the Global HIV/AIDS Epidemic, 2002. Available at http://www.who.int/hiv/pub/epidemiology/hiv_aids_2001.xls . Accessed April 4, 2003.
  47. Leke RF, Djokam RR, Mbu R, Leke RJ, Fogako J, Megnekou R, Metenou S, Sama G, Zhou Y, Cadigan T, Parra M, Taylor DW, 1999. Detection of the Plasmodium falciparum antigen histidine-rich protein 2 in blood of pregnant women: implications for diagnosing placental malaria. J Clin Microbiol 37 : 2992–2996. [Google Scholar]

Data & Media loading...

  • Received : 12 Jun 2003
  • Accepted : 18 Sep 2003

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error