Drug Safety

, Volume 30, Issue 6, pp 481–501 | Cite as

Safety and Toxicity of Sulfadoxine/Pyrimethamine

Implications for Malaria Prevention in Pregnancy using Intermittent Preventive Treatment
  • Philip J. Peters
  • Michael C. Thigpen
  • Monica E. Parise
  • Robert D. Newman
Review Article

Abstract

Plasmodium falciparum infection during pregnancy is strongly associated with maternal anaemia and low birth weight, contributing to substantial morbidity and mortality in sub-Saharan Africa. Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine (IPTp-SP) has been one of the most effective approaches to reduce the burden of malaria during pregnancy in Africa. IPTp-SP is based on administering ≥2 treatment doses of sulfadoxine/pyrimethamine to pregnant women at predefined intervals after quickening (around 18–20 weeks). Randomised, controlled trials have demonstrated decreased rates of maternal anaemia and low birth weight with this approach. The WHO currently recommends IPTp-SP in malaria-endemic areas of sub-Saharan Africa. However, implementation has been suboptimal in part because of concerns of potential drug toxicities. This review evaluates the toxicity data of sulfadoxine/pyrimethamine, including severe cutaneous adverse reactions, teratogenicity and alterations in bilirubin metabolism. Weekly sulfadoxine/pyrimethamine prophylaxis is associated with rare but potentially fatal cutaneous reactions. Fortunately, sulfadoxine/pyrimethamine use in IPTp programmes in Africa, with 2–4 treatment doses over 6 months, has been well tolerated in multiple IPTp trials. However, sulfadoxine/pyrimethamine should not be administered concurrently with cotrimoxazole given their redundant mechanisms of action and synergistic worsening of adverse drug reactions. Therefore, HIV-infected pregnant women in malaria endemic areas who are already receiving cotrimoxazole prophylaxis should not also receive IPTp-SP. Although folate antagonist use in the first trimester is associated with neural tube defects, large case-control studies have demonstrated that sulfadoxine/pyrimethamine administered as IPTp (exclusively in the second and third trimesters and after organogenesis) does not result in an increased risk of teratogenesis. Folic acid supplementation is recommended for all pregnant women to reduce the rate of congenital anomalies but high doses of folic acid (5 mg/day) may interfere with the antimalarial efficacy of sulfadoxine/pyrimethamine. However, the recommended standard dose of folic acid supplementation (0.4 mg/day) does not affect antimalarial efficacy and may provide the optimal balance to prevent neural tube defects and maintain the effectiveness of IPTp-SP. No clinical association between sulfadoxine/pyrimethamine use and kernicterus has been reported despite the extensive use of sulfadoxine/pyrimethamine and related compounds to treat maternal malaria and congenital toxoplasmosis in near-term pregnant women and newborns. Although few drugs in pregnancy can be considered completely safe, sulfadoxine/pyrimethamine — when delivered as IPTp — has a favourable safety profile. Improved pharmacovigilance programmes throughout Africa are now needed to confirm its safety as access to IPTp-SP increases. Given the documented benefits of IPTp-SP in malaria endemic areas of Africa, access to this treatment for pregnant women should continue to expand.

Keywords

Pregnant Woman Folic Acid Malaria Folic Acid Supplementation Pyrimethamine 

Notes

Acknowledgements

The authors have no conflicts of interest that are directly relevant to the content of this manuscript. No sources of funding were used in the preparation of this review. The findings and conclusions in this publication are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. The authors are grateful to Dr Laurence Slutsker for helpful comments on drafts of this review.

References

  1. 1.
    WHO. Lives at risk: malaria in pregnancy [online]. Available from URL: http://www.who.int/features/2003/04b/en/ [Accessed 2006 Mar 6]
  2. 2.
    Beeson JG, Brown GV. Plasmodium falciparum-imfected erythrocytes demonstrate dual specificity for adhesion to hyaluronic acid and chondroitin sulfate A and have distinct adhesive properties. J Infect Dis 2004 Jan 15; 189(2): 169–79PubMedGoogle Scholar
  3. 3.
    Shulman CE, Graham WJ, Jilo H, et al. Malaria is an important cause of anaemia in primigravidae: evidence from a district hospital in coastal Kenya. Trans R Soc Trop Med Hyg 1996 Sep–Oct; 90(5): 535–9PubMedGoogle Scholar
  4. 4.
    Cot M, le Hesran JY, Miailhes P, et al. Effect of chloroquine prophylaxis during pregnancy on maternal haematocrit. Ann Trop Med Parasitol 1998 Jan; 92(1): 37–43PubMedGoogle Scholar
  5. 5.
    Steketee RW, Wirima JJ, Hightower AW, et al. 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 1996; 55 (1 Suppl.): 33–41PubMedGoogle Scholar
  6. 6.
    Sullivan AD, Nyirenda T, Cullinan T, et al. Malaria infection during pregnancy: intrauterine growth retardation and preterm delivery in Malawi. J Infect Dis 1999 Jun; 179(6): 1580–3PubMedGoogle Scholar
  7. 7.
    Steketee RW, Nahlen BL, Parise ME, et al. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg 2001 Jan–Feb; 64 (1-2 Suppl.): 28–35PubMedGoogle Scholar
  8. 8.
    Guyatt HL, Snow RW. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg 2001 Jan–Feb; 64 (1–2 Suppl.): 36–44PubMedGoogle Scholar
  9. 9.
    Marchesini P, Crawley J. Reducing the burden of malaria in pregnancy [online]. Available from URL: http://www.who.int/malaria/rbm/Attachment/20040713/MeraJan2003.pdf [Accessed 2006 Jan 6]
  10. 10.
    Steketee RW, Wirima JJ, Slutsker L, et al. Malaria treatment and prevention in pregnancy: indications for use and adverse events associated with use of chloroquine or mefloquine. Am J Trop Med Hyg 1996; 55 (1 Suppl.): 50–6PubMedGoogle Scholar
  11. 11.
    Sirima SB, Sawadogo R, Moran AC, et al. Failure of a chloroquine chemoprophylaxis program to adequately prevent malaria during pregnancy in Koupela District, Burkina Faso. Clin Infect Dis 2003 Jun 1; 36(11): 1374–82PubMedGoogle Scholar
  12. 12.
    WHO. WHO Expert Committee on Malaria. World Health Organ Tech Rep Ser 2000; 92: i-v, 1–74Google Scholar
  13. 13.
    World Health Organization. A strategic framework for malaria prevention and control during pregnancy in the African region. Brazzaville: WHO Regional Office for Africa, 2004. AFR/ MAL/04/01 [online]. Available from URL: http://www.cdc.gov/malaria/pdf/strategic_framework_mip_04.pdf [Accessed 2006 Jan 6]
  14. 14.
    Kayentao K, Kodio M, Newman RD, et al. Comparison of intermittent preventive treatment with chemoprophylaxis for the prevention of malaria during pregnancy in Mali. J Infect Dis 2005 Jan 1; 191(1): 109–16PubMedGoogle Scholar
  15. 15.
    Shulman CE, Dorman EK, Cutts F, et al. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet 1999 Feb 20; 353(9153): 632–6PubMedGoogle Scholar
  16. 16.
    Njagi JK, Magnussen P, Estambale B, et al. Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial. Trans R Soc Trop Med Hyg 2003 May–Jun; 97(3): 277–82PubMedGoogle Scholar
  17. 17.
    Parise ME, Ayisi JG, Nahlen BL, et al. Efficacy of sulfadoxinepyrimethamine 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 1998 Nov; 59(5): 813–22PubMedGoogle Scholar
  18. 18.
    Schultz LJ, Steketee RW, Macheso A, et al. 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 1994 Nov; 51(5): 515–22PubMedGoogle Scholar
  19. 19.
    Challis K, Osman NB, Cotiro M, et al. Impact of a double dose of sulphadoxine-pyrimethamine to reduce prevalence of pregnancy malaria in southern Mozambique. Trop Med Int Health 2004 Oct; 9(10): 1066–73PubMedGoogle Scholar
  20. 20.
    van Eijk AM, Ayisi JG, ter Kuile FO, et al. Effectiveness of intermittent preventive treatment with sulphadoxinepyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study. Trop Med Int Health 2004 Mar; 9(3): 351–60PubMedGoogle Scholar
  21. 21.
    Rogerson SJ, Chaluluka E, Kanjala M, et al. Intermittent sulfadoxine-pyrimethamine in pregnancy: effectiveness against malaria morbidity in Blantyre, Malawi, in 1997–99. Trans R Soc Trop Med Hyg 2000 Sep–Oct; 94(5): 549–53PubMedGoogle Scholar
  22. 22.
    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 Aug 1; 194(3): 286–93PubMedGoogle Scholar
  23. 23.
    Sirima SB, Cotte AH, Konate A, et al. Malaria prevention during pregnancy: assessing the disease burden one year after implementing a program of intermittent preventive treatment in Koupela District, Burkina Faso. Am J Trop Med Hyg 2006 Aug; 75(2): 205–11PubMedGoogle Scholar
  24. 24.
    Verhoeff FH, Brabin BJ, Chimsuku L, et al. 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 1998 Mar; 92(2): 141–50PubMedGoogle Scholar
  25. 25.
    WHO/AFRO. Global Antimalarial Drug Database [online]. Available from URL: http://www.who.int/malaria/amdp/amdp_afro.htm [Accessed 2007 Jan 10]
  26. 26.
    Korenromp E, Miller J, Nahlen B, et al., for World Health Organization (WHO). World Malaria Report 2005 [online]. Available from URL: http://rbm.who.int/wmr2005/index.html [Accessed 2007 Jan 10]
  27. 27.
    Dodoo A. Safety challenges of preventing malaria during pregnancy. WHO Drug Information 2005; 19(4): 286–7 [online]. Available from URL: http://www.who.int/druginformation/vol19num4_2005/DI19-4.pdf [Accessed 2007 Jan 10]Google Scholar
  28. 28.
    Nosten F, McGready R, Looareesuwan S, et al. Editorial: Maternal malaria: time for action. Trop Med Int Health 2003 Jun; 8(6): 485–7PubMedGoogle Scholar
  29. 29.
    Hill J, Kazembe P. Reaching the Abuja target for intermittent preventive treatment of malaria in pregnancy in African women: a review of progress and operational challenges. Trop Med Int Health 2006 Apr; 11(4): 409–18PubMedGoogle Scholar
  30. 30.
    Mubyazi G, Bloch P, Kamugisha M, et al. Intermittent preventive treatment of malaria during pregnancy: a qualitative study of knowledge, attitudes and practices of district health managers, antenatal care staff and pregnant women in Korogwe District, North-Eastern Tanzania. Malar J 2005; 4: 31PubMedGoogle Scholar
  31. 31.
    Mbonye AK, Neema S, Magnussen P. Perceptions on use of sulfadoxine-pyrimethamine in pregnancy and the policy implications for malaria control in Uganda. Health Policy 2006 Aug; 77(3): 279–89PubMedGoogle Scholar
  32. 32.
    Sibley CH, Hyde JE, Sims PF, et al. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 2001 Dec; 17(12): 582–8PubMedGoogle Scholar
  33. 33.
    Nzila A, Ward SA, Marsh K, et al. Comparative folate metabolism in humans and malaria parasites (part I): pointers for malaria treatment from cancer chemotherapy. Trends Parasitol 2005 Jun; 21(6): 292–8PubMedGoogle Scholar
  34. 34.
    Hyde JE. Exploring the folate pathway in Plasmodium falciparum. Acta Trop 2005 Jun; 94(3): 191–206PubMedGoogle Scholar
  35. 35.
    Ferone R, Burchall JJ, Hitchings GH. Pkismodium berghei dihydrofolate reductase. Isolation, properties, and inhibition by antifolates. Mol Pharmacol 1969 Jan; 5(1): 49–59PubMedGoogle Scholar
  36. 36.
    Zhang K, Rathod PK. Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science 2002 Apr 19; 296(5567): 545–7PubMedGoogle Scholar
  37. 37.
    Hitchings GH, Burchall JJ. Inhibition of folate biosynthesis and function as a basis for chemotherapy. Adv Enzymol Relat Areas Mol Biol 1965; 27: 417–68 497PubMedGoogle Scholar
  38. 38.
    Watkins WM, Mberu EK, Winstanley PA, et al. The efficacy of antifolate antimalarial combinations in Africa: a predictive model based on pharmacodynamic and pharmacokinetic analyses. Parasitol Today 1997 Dec; 13(12): 459–64PubMedGoogle Scholar
  39. 39.
    Rollo IM. The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum. Br J Pharmacol Chemother 1955 Jun; 10(2): 208–14PubMedGoogle Scholar
  40. 40.
    Hurly MG. Potentiation of pyrimethamine by sulphadiazine in human malaria. Trans R Soc Trop Med Hyg 1959 Sep; 53: 412–3PubMedGoogle Scholar
  41. 41.
    Weidekamm E, Plozza-Nottebrock H, Forgo I, et al. Plasma concentrations in pyrimethamine and sulfadoxine and evaluation of pharmacokinetic data by computerized curve fitting. Bull World Health Organ 1982; 60(1): 115–22PubMedGoogle Scholar
  42. 42.
    Edstein MD. Pharmacokinetics of sulfadoxine and pyrimethamine after Fansidar administration in man. Chemotherapy 1987; 33(4): 229–33PubMedGoogle Scholar
  43. 43.
    PDR guide to drug interactions, side effects, indications, contraindications. Montvale (NJ): Medical Economics, 1997: 2281–2Google Scholar
  44. 44.
    Barnes KI, Little F, Smith PJ, et al. Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications. Clin Pharmacol Ther 2006 Dec; 80(6): 582–96PubMedGoogle Scholar
  45. 45.
    Corvaisier S, Charpiat B, Mounier C, et al. Population pharmacokinetics of pyrimethamine and sulfadoxine in children treated for congenital toxoplasmosis. Antimicrob Agents Chemother 2004 Oct; 48(10): 3794–800PubMedGoogle Scholar
  46. 46.
    Hellgren U, Kihamia CM, Bergqvist Y, et al. Standard and reduced doses of sulfadoxine-pyrimethamine for treatment of Plasmodium falciparum in Tanzania, with determination of drug concentrations and susceptibility in vitro. Trans R Soc Trop Med Hyg 1990 Jul–Aug; 84(4): 469–72PubMedGoogle Scholar
  47. 47.
    Winstanley PA, Watkins WM, Newton CR, et al. The disposition of oral and intramuscular pyrimethamine/sulphadoxine in Kenyan children with high parasitaemia but clinically non-severe falciparum malaria. Br J Clin Pharmacol 1992 Feb; 33(2): 143–8PubMedGoogle Scholar
  48. 48.
    Trenque T, Marx C, Quereux C, et al. Human maternofoetal distribution of pyrimethamine-sulphadoxine. Br J Clin Pharmacol 1998 Feb; 45(2): 179–80PubMedGoogle Scholar
  49. 49.
    Peytavin G, Leng JJ, Forestier F, et al. Placental transfer of pyrimethamine studied in an ex vivo placental perfusion model. Biol Neonate 2000; 78(2): 83–5PubMedGoogle Scholar
  50. 50.
    Roche. Fansidar® brand of sulfadoxine and pyrimethamine tablets: complete product information [online]. Available from URL: http://www.rocheusa.com/products/fansidar/ [Accessed 2006 May 7]
  51. 51.
    Ringwald P, Global Partnership to Roll Back Malaria. Susceptibility of plasmodium falciparum to antimalarial drugs: report on global monitoring, 1996–2004. Geneva: World Health Organization, 2005Google Scholar
  52. 52.
    White NJ. Intermittent presumptive treatment for malaria. PLoS Med 2005 Jan; 2(1): e3PubMedGoogle Scholar
  53. 53.
    Gregson A, Plowe CV. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 2005 Mar; 57(1): 117–45PubMedGoogle Scholar
  54. 54.
    Hankins EG, Warhurst DC, Sibley CH. Novel alleles of the Plasmodium falciparum dhfr highly resistant to pyrimethamine and chlorcycloguanil, but not WR 99210. Mol Biochem Parasitol 2001 Sep 28; 117(1): 91–102PubMedGoogle Scholar
  55. 55.
    McCollum AM, Poe AC, Hamel M, et al. Antifolate resistance in Plasmodium falciparum: multiple origins and identification of novel dhfr alleles. J Infect Dis 2006 Jul 15; 194(2): 189–97PubMedGoogle Scholar
  56. 56.
    Nzila A, Ochong E, Nduati E, et al. Why has the dihydrofolate reductase 164 mutation not consistently been found in Africa yet? Trans R Soc Trop Med Hyg 2005 May; 99(5): 341–6PubMedGoogle Scholar
  57. 57.
    Bioland PB, Ringwald P, Snow RW, World Health Organization. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Geneva: World Health Organization, 2003Google Scholar
  58. 58.
    Kalanda GC, Hill J, Verhoeff FH, et al. Comparative efficacy of chloroquine and sulphadoxine: pyrimethamine in pregnant women and children: a meta-analysis. Trop Med Int Health 2006 May; 11(5): 569–77PubMedGoogle Scholar
  59. 59.
    Plowe CV, Kublin JG, Dzinjalamala FK, et al. Sustained clinical efficacy of sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Malawi after 10 years as first line treatment: five year prospective study. BMJ 2004 Mar 6; 328(7439): 545PubMedGoogle Scholar
  60. 60.
    Chandramohan D, Owusu-Agyei S, Carneiro I, et al. Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. BMJ 2005 Oct 1; 331(7519): 727–33PubMedGoogle Scholar
  61. 61.
    Matthews JI, Molitor JT, Hunt KK, et al. Pyrimethamine-induced leukopenia and thrombocytopenia in a patient with malaria and tropical sprue: case report. Mil Med 1973 May; 138(5): 280–3PubMedGoogle Scholar
  62. 62.
    Goodman LS, Gilman A, Brunton LL, et al. Goodman & Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006Google Scholar
  63. 63.
    Waxman S, Metz J, Herbert V. Defective DNA synthesis in human megaloblastic bone marrow: effects of homocysteine and methionine. J Clin Invest 1969 Feb; 48(2): 284–9PubMedGoogle Scholar
  64. 64.
    Khoo KK. The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah. Ann Trop Med Parasitol 1981 Dec; 75(6): 591–5PubMedGoogle Scholar
  65. 65.
    Bjorkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull World Health Organ 1991; 69(3): 297–304PubMedGoogle Scholar
  66. 66.
    Miller KD, Lobel HO, Satriale RF, et al. Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. Am J Trop Med Hyg 1986 May; 35(3): 451–8PubMedGoogle Scholar
  67. 67.
    Aguemon AR, Houngbe F, Yameogo TM, et al. Toxic epidermal necrolysis. Epidemiologic, clinic and therapeutic aspects at Cotonou University and National Teaching Hospital [in French]. Ann Fr Anesth Reanim 2006 May; 25(5): 505–9PubMedGoogle Scholar
  68. 68.
    Oduro-Boatey C, Rodrigues O. Stevens-Johnson syndrome in two children in Ghana following anti-malarial treatment. Trop Doct 2005 Apr; 35(2): 118–9PubMedGoogle Scholar
  69. 69.
    Nair SS, Kaplan JM, Levine LH, et al. Trimethoprimsulfamethoxazole-induced intrahepatic cholestasis. Ann Intern Med 1980 Apr; 92(4): 511–2PubMedGoogle Scholar
  70. 70.
    Munoz SJ, Martinez-Hernandez A, Maddrey WC. Intrahepatic cholestasis and phospholipidosis associated with the use of trimethoprim-sulfamethoxazole. Hepatology 1990 Aug; 12(2): 342–7PubMedGoogle Scholar
  71. 71.
    Thies PW, Dull WL. Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis. Inadvertent rechallenge. Arch Intern Med 1984 Aug; 144(8): 1691–2PubMedGoogle Scholar
  72. 72.
    Zitelli BJ, Alexander J, Taylor S, et al. Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar). Ann Intern Med 1987 Mar; 106(3): 393–5PubMedGoogle Scholar
  73. 73.
    McCormack D, Morgan WK. Fansidar hypersensitivity pneumonitis. Br J Dis Chest 1987 Apr; 81(2): 194–6 498PubMedGoogle Scholar
  74. 74.
    Svanbom M, Rombo L, Gustafsson L. Unusual pulmonary reaction during short term prophylaxis with pyrimethamine-sulfadoxine (Fansidar). BMJ (Clin Res Ed). 1984 Jun 23; 288(6434): 187Google Scholar
  75. 75.
    Hellgren U, Rombo L, Berg B, et al. Adverse reactions to sulphadoxine-pyrimethamine in Swedish travellers: implications for prophylaxis. BMJ (Clin Res Ed) 1987 Aug 8; 295(6594): 365–6Google Scholar
  76. 76.
    Phillips-Howard PA, West LJ. Serious adverse drug reactions to pyrimethamine-sulphadoxine, pyrimethamine-dapsone and to amodiaquine in Britain. J R Soc Med 1990 Feb; 83(2): 82–5PubMedGoogle Scholar
  77. 77.
    Steffen R, Somaini B. Severe cutaneous adverse reactions to sulfadoxine-pyrimethamine in Switzerland. Lancet 1986 Mar 15; 1(8481): 610PubMedGoogle Scholar
  78. 78.
    World Health Organization. WHO Collaborating Centre for International Drug Monitoring. The importance of pharmacovigilance. Geneva: World Health Organization Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, 2002Google Scholar
  79. 79.
    Gimnig JE, MacArthur JR, M’Bang’ombe M, et al. Severe cutaneous reactions to sulfadoxine-pyrimethamine and trimethoprim-sulfamethoxazole in Blantyre District, Malawi. Am J Trop Med Hyg 2006 May; 74(5): 738–43PubMedGoogle Scholar
  80. 80.
    Hernborg A. Stevens-Johnson syndrome after mass prophylaxis with sulfadoxine for cholera in Mozambique. Lancet 1985 Nov 9; 2(8463): 1072–3PubMedGoogle Scholar
  81. 81.
    Shear NH, Spielberg SP, Grant DM, et al. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med 1986 Aug; 105(2): 179–84PubMedGoogle Scholar
  82. 82.
    Holtz TH, Kachur SP, Roberts JM, et al. Use of antenatal care services and intermittent preventive treatment for malaria among pregnant women in Blantyre District, Malawi. Trop Med Int Health 2004 Jan; 9(1): 77–82PubMedGoogle Scholar
  83. 83.
    UNAIDS. AIDS epidemic update: December 2005 [online]. Available from URL: http://www.unaids.org/epi/2005/doc/report_pdf.asp [Accessed 2006 Mar 6]
  84. 84.
    ter Kuile FO, Parise ME, Verhoeff FH, et al. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-saharan Africa. Am J Trop Med Hyg 2004 Aug; 71 (2 Suppl.): 41–54PubMedGoogle Scholar
  85. 85.
    Moore JM, Ayisi J, Nahlen BL, et al. Immunity to placental malaria: II. Placental antigen-specific cytokine responses are impaired in human immunodeficiency virus-infected women. J Infect Dis 2000 Sep; 182(3): 960–4PubMedGoogle Scholar
  86. 86.
    Chaisavaneeyakorn S, Moore JM, Otieno J, et al. Immunity to placental malaria: III. Impairment of interleukin(IL)-12, not IL-18, and interferon-inducible protein-10 responses in the placental intervillous blood of human immunodeficiency virus/malaria-coinfected women. J Infect Dis 2002 Jan 1; 185(1): 127–31PubMedGoogle Scholar
  87. 87.
    Mount AM, Mwapasa V, Elliott SR, et al. Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection. Lancet 2004 Jun 5; 363(9424): 1860–7PubMedGoogle Scholar
  88. 88.
    Steketee RW, Wirima JJ, Bioland PB, et al. Impairment of a pregnant woman’s acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1. Am J Trop Med Hyg 1996; 55 (1 Suppl.): 42–9PubMedGoogle Scholar
  89. 89.
    WHO. Malaria and HIV interactions and their implications for public health policy [online]. Available from URL: http://www.who.int/malaria/malariandhivaids.html [Accessed 2006 Mar 5]
  90. 90.
    Lee BL, Wong D, Benowitz NL, et al. Altered patterns of drug metabolism in patients with acquired immunodeficiency syndrome. Clin Pharmacol Ther 1993 May; 53(5): 529–35PubMedGoogle Scholar
  91. 91.
    Carr A, Gross AS, Hoskins JM, et al. Acetylation phenotype and cutaneous hypersensitivity to trimethoprim-sulphamethoxazole in HIV-infected patients. Aids 1994 Mar; 8(3): 333–7PubMedGoogle Scholar
  92. 92.
    Carr A, Tindall B, Penny R, et al. In vitro cytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HIV. Clin Exp Immunol 1993 Oct; 94(1): 21–5PubMedGoogle Scholar
  93. 93.
    Carr A, Vasak E, Munro V, et al. Immunohistological assessment of cutaneous drug hypersensitivity in patients with HIV infection. Clin Exp Immunol 1994 Aug; 97(2): 260–5PubMedGoogle Scholar
  94. 94.
    Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d’Ivoire: a randomised controlled trial. Lancet 1999 May 1; 353(9163): 1469–75PubMedGoogle Scholar
  95. 95.
    Mermin J, Lule J, Ekwaru JP, et al. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004 Oct 16–22; 364(9443): 1428–34PubMedGoogle Scholar
  96. 96.
    Chintu C, Bhat GJ, Walker AS, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet 2004 Nov 20–26; 364(9448): 1865–71PubMedGoogle Scholar
  97. 97.
    Walter J, Mwiya M, Scott N, et al. Reduction in preterm delivery and neonatal mortality after the introduction of antenatal cotrimoxazole prophylaxis among HIV-infected women with low CD4 cell counts. J Infect Dis 2006 Dec 1; 194(11): 1510–8PubMedGoogle Scholar
  98. 98.
    WHO. Guidelines for cotrimoxazole prophylaxis for HIV-related infections in children, adolescents and adults in resource limited settings [online]. Available from URL: http://www.who.int/hiv/pub/guidelines/ctxguidelines.pdf [Accessed 2006 Mar 5]
  99. 99.
    UNAIDS/WHO. Provisional WHO/UNAIDS secreteriat recommendations on the widespread use of co-trimoxazole prophylaxis in adults and children living with HIV/AIDS in Africa, 2000 [online]. Available from URL: http://www.unaids.org/publications/documents/care/general/recommendationeng.pdf [Accessed 2006 Mar 6]
  100. 100.
    Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d’Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet 1999 May 1; 353(9163): 1463–8PubMedGoogle Scholar
  101. 101.
    Thera MA, Sehdev PS, Coulibaly D, et al. Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease. J Infect Dis 2005 Nov 15; 192(10): 1823–9PubMedGoogle Scholar
  102. 102.
    Malamba SS, Mermin J, Reingold A, et al. Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HlV)-infected persons on the selection of sulfadoxinepyrimethamine-resistant malaria parasites among HIV-uninfected household members. Am J Trop Med Hyg 2006 Sep; 75(3): 375–80PubMedGoogle Scholar
  103. 103.
    Brentlinger PE, Behrens CB, Micek MA. Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa. Lancet Infect Dis 2006 Feb; 6(2): 100–11PubMedGoogle Scholar
  104. 104.
    Maynart M, Lievre L, Sow PS, et al. Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal. J Acquir Immune Defic Syndr 2001 Feb 1; 26(2): 130–6PubMedGoogle Scholar
  105. 105.
    Watera C, Todd J, Muwonge R, et al. Feasibility and effectiveness of cotrimoxazole prophylaxis for HIV-1-infected adults attending an HIV/AIDS clinic in Uganda. J Acquir Immune Defic Syndr 2006 Jul; 42(3): 373–8 499PubMedGoogle Scholar
  106. 106.
    Zachariah R, Spielmann MP, Chinji C, et al. Voluntary counselling, HIV testing and adjunctive cotrimoxazole reduces mortality in tuberculosis patients in Thyolo, Malawi. AIDS 2003 May 2; 17(7): 1053–61PubMedGoogle Scholar
  107. 107.
    Grimwade K, Sturm AW, Nunn AJ, et al. Effectiveness of cotrimoxazole prophylaxis on mortality in adults with tuberculosis in rural South Africa. AIDS 2005 Jan 28; 19(2): 163–8PubMedGoogle Scholar
  108. 108.
    Raviglione MC, Dinan WA, Pablos-Mendez A, et al. Fatal toxic epidermal necrolysis during prophylaxis with pyrimethamine and sulfadoxine in a human immunodeficiency virus-infected person. Arch Intern Med 1988 Dec; 148(12): 2683–5PubMedGoogle Scholar
  109. 109.
    Fansidar-associated fatal reaction in an HIV-infected man. MMWR Morb Mortal Wkly Rep 1988 Sep 23; 37(37): 571–2, 7Google Scholar
  110. 110.
    Teira R, Virosta M, Munoz J, et al. The safety of pyrimethamine and sulfadoxine for the prevention of Pneumocystis carinii pneumonia. Scand J Infect Dis 1997; 29(6): 595–6PubMedGoogle Scholar
  111. 111.
    Schurmann D, Bergmann F, Albrecht H, et al. Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection. Eur J Clin Microbiol Infect Dis 2002 May; 21(5): 353–61PubMedGoogle Scholar
  112. 112.
    Hamer DH, Mwanakasale V, Chalwe V, et al. Intermittent presumptive therapy of malaria with SP in HIV-seropositive Zambian women: a placebo-controlled, randomized trial [abstract no. 54]. 54th Annual Meeting of the American Society Tropical Medicine and Hygiene; 2005 Dec 11–15; Washington, DCGoogle Scholar
  113. 113.
    MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991 Jul 20; 338(8760): 131–7Google Scholar
  114. 114.
    Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999 Nov 11; 341(20): 1485–90PubMedGoogle Scholar
  115. 115.
    Bohni E, Fust B, Rieder J, et al. Comparative toxicological, chemotherapeutic and pharmacokinetic studies with sulphormethoxine and other sulphonamides in animals and man. Chemotherapy 1969; 14(4): 195–226PubMedGoogle Scholar
  116. 116.
    Bertazzoli C, Chieli T, Grandi M. Absence of tooth malformation in offspring of rats treated with a long-acting sulphonamide. Experientia 1965 Mar 15; 21(3): 151–2PubMedGoogle Scholar
  117. 117.
    Kato T, Kitagawa S. Production of congenital anomalies in fetuses of rats and mice with various sulfonamides. Cong Anom 1973; 13(1): 7–15Google Scholar
  118. 118.
    Suzuki Y, Wakita Y, Kondo S, et al. Effects of sulfamethopyrazine administered to pregnant animals upon the development of their fetuses and neonates. Oyo Yakuri 1973; 7: 1005–19Google Scholar
  119. 119.
    Wolkowski-Tyl R, Jones-Price C, Kimmel C, et al. Teratologic evaluation of sulfamethazine in CD rats. Teratology 1982; 25: 81A-2AGoogle Scholar
  120. 120.
    Kato T, Kitagawa S. Production of congenital skeletal anomalies in the fetuses of pregnant rats and mice treated with various sulfonamides. Cong Anom 1973; 13(1): 17–23Google Scholar
  121. 121.
    Paget GE, Thorpe E. A teratogenic effect of a sulphonamide in experimental animals. Br J Pharmacol Chemother 1964 Oct; 23: 305–12PubMedGoogle Scholar
  122. 122.
    Uche-Nwachi EO, Caxton-Martins AE. Sulfadoxinepyrimethamine embryopathy in Wistar rats. Kaibogaku Zasshi 1998 Apr; 73(2): 135–9PubMedGoogle Scholar
  123. 123.
    Dyban AP, Akimova IM, Svetlova VA. Embryonal development of rats acted upon with 2,4-diamino-5-chlorphenyl-6-ethylpyrimidine [in Russian]. Dokl Akad Nauk SSSR 1965 Aug 21; 163(6): 1514–7PubMedGoogle Scholar
  124. 124.
    Sullivan GE, Takacs E. Comparative teratogenicity of pyrimethamine in rats and hamsters. Teratology 1971; 4(2): 205–9Google Scholar
  125. 125.
    Anderson I, Morse LM. The influence of solvent on the teratogenic effect of folic acid antagonist in the rat. Exp Mol Pathol 1966 Apr; 5(2): 134–45PubMedGoogle Scholar
  126. 126.
    Schvartsman S. Teratogenicity of pyrimethamine. Toxicol Applied Pharmacol 1979; 48: A123Google Scholar
  127. 127.
    Misawa J, Kanda S, Kokue E, et al. Teratogenic activity of pyrimethamine in Gottingen minipig. Toxicol Lett 1982 Jan; 10(1): 51–4PubMedGoogle Scholar
  128. 128.
    Tangapregassom AM, Tangapregassom MJ, Horvath C, et al. Vascular anomalies and pyrimethamine-induced malformations in the rat. Teratog Carcinog Mutagen 1985; 5(1): 55–62PubMedGoogle Scholar
  129. 129.
    Petter C, Bourbon J. Foetal red cell macrocytosis induced by pyrimethamine; its teratogenic role. Experientia 1975 Mar 15; 31(3): 369–70PubMedGoogle Scholar
  130. 130.
    Kudo G, Tsunematsu K, Shimoda M, et al. Effects of folic acid on pyrimethamine teratogenesis in rats. Adv Exp Med Biol 1993; 338: 469–72PubMedGoogle Scholar
  131. 131.
    Uche-Nwachi EO. Effect of intramuscular sulfadoxinepyrimethamine on pregnant Wistar rats. Anat Rec 1998 Apr; 250(4): 426–9PubMedGoogle Scholar
  132. 132.
    Hengst P. Teratogenicity of daraprim (pyrimethamine) in man [in German]. Zentralbl Gynakol 1972 Apr 29; 94(17): 551–5PubMedGoogle Scholar
  133. 133.
    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 Sep-Oct; 83(5): 589–94PubMedGoogle Scholar
  134. 134.
    Morley D, Woodland M, Cuthbertson WF. Controlled trial of pyrimethamine in pregnant women in an African village. BMJ 1964 Mar 14; 5384: 667–8Google Scholar
  135. 135.
    Nahlen BL, Akintunde A, Alakija T, et al. Lack of efficacy of pyrimethamine prophylaxis in pregnant Nigerian women. Lancet 1989 Oct 7; 2(8667): 830–4PubMedGoogle Scholar
  136. 136.
    Phillips-Howard PA, Wood D. The safety of antimalarial drugs in pregnancy. Drug Saf 1996 Mar; 14(3): 131–45PubMedGoogle Scholar
  137. 137.
    Hernandez-Diaz S, Werler MM, Walker AM, et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000 Nov 30; 343(22): 1608–14PubMedGoogle Scholar
  138. 138.
    Hernandez-Diaz S, Werler MM, Walker AM, et al. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001 May 15; 153(10): 961–8PubMedGoogle Scholar
  139. 139.
    Czeizel AE, Rockenbauer M, Sorensen HT, et al. The teratogenic risk of trimethoprim-sulfonamides: a population based case-control study. Reprod Toxicol 2001 Nov-Dec; 15(6): 637–46PubMedGoogle Scholar
  140. 140.
    Czeizel AE, Puho E, Sorensen HT, et al. Possible association between different congenital abnormalities and use of different sulfonamides during pregnancy. Congenit Anom (Kyoto) 2004 Jun; 44(2): 79–86Google Scholar
  141. 141.
    Jungmann EM, Mercey D, DeRuiter A, et al. Is first trimester exposure to the combination of antiretroviral therapy and folate antagonists a risk factor for congenital abnormalities? Sex Transm Infect 2001 Dec; 77(6): 441–3PubMedGoogle Scholar
  142. 142.
    Phillips-Howard PA, Steffen R, Kerr L, et al. Safety of mefloquine and other antimalarial agents in the first trimester of pregnancy. J Travel Med 1998 Sep; 5(3): 121–6PubMedGoogle Scholar
  143. 143.
    Slama R, Bouyer J, Windham G, et al. Influence of paternal age on the risk of spontaneous abortion. Am J Epidemiol 2005 May 1; 161(9): 816–23 500PubMedGoogle Scholar
  144. 144.
    Correa-Villasenor A, Cragan J, Kucik J, et al. The Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects surveillance at the Centers for Disease Control and Prevention. Birth Defects Res A Clin Mol Teratol 2003 Sep; 67(9): 617–24PubMedGoogle Scholar
  145. 145.
    Barbosa J, Ferreira I. Sulfadoxine-pyrimethamine (Fansidar) in pregnant women with toxoplasma antibody titers. In: Siegenthaler W, Luthy R, editors. The 10th International Congress of Chemotherapy, 1977. Zürich: American Society of Microbiology, 1977: 134–5Google Scholar
  146. 146.
    Lumley J, Watson L, Watson M, et al. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev 2001 (3): CD001056Google Scholar
  147. 147.
    WHO. Integrated management of pregnancy and childbirth: pregnancy, childbirth, postpartum and newborn care: a guide for essential practice [online]. Available from URL: http://www.who.int/reproductive-health/publications/pcpnc/pcpnc.pdf [Accessed 2007 Jan 22]
  148. 148.
    Mahomed K. Iron and folate supplementation in pregnancy. Cochrane Database Syst Rev 2000; (2): CD001135Google Scholar
  149. 149.
    Asawamahasakda W, Yuthavong Y. The methionine synthesis cycle and salvage of methyltetrahydrofolate from host red cells in the malaria parasite (Plasmodium falciparum). Parasitology 1993 Jul; 107 (Pt 1): 1–10PubMedGoogle Scholar
  150. 150.
    Krungkrai J, Webster HK, Yuthavong Y. De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. Mol Biochem Parasitai 1989 Jan 1; 32(1): 25–37Google Scholar
  151. 151.
    Chulay JD, Watkins WM, Sixsmith DG. Synergistic antimalarial activity of pyrimethamine and sulfadoxine against Plasmodium falciparum in vitro. Am J Trop Med Hyg 1984 May; 33(3): 325–30PubMedGoogle Scholar
  152. 152.
    Watkins WM, Sixsmith DG, Chulay JD, et al. Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by p-aminobenzoic acid, p-aminobenzoylglutamic acid and folic acid. Mol Biochem Parasitai 1985 Jan; 14(1): 55–61Google Scholar
  153. 153.
    Wang P, Brobey RK, Horii T, et al. Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy. Mol Microbiol 1999 Jun; 32(6): 1254–62PubMedGoogle Scholar
  154. 154.
    van Hensbroek MB, Morris-Jones S, Meisner S, et al. Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria. Trans R Soc Trop Med Hyg 1995 Nov–Dec; 89(6): 672–6PubMedGoogle Scholar
  155. 155.
    Carter JY, Loolpapit MP, Lema OE, et al. Reduction of the efficacy of antifolate antimalarial therapy by folic acid supplementation. Am J Trop Med Hyg 2005 Jul; 73(1): 166–70PubMedGoogle Scholar
  156. 156.
    Ouma P, Parise ME, Hamel MJ, et al. A randomized controlled trial of folate supplementation when treating malaria in pregnancy with sulfadoxine-pyrimethamine. PLoS Clin Trials 2006 Oct 20; 1(6): e28PubMedGoogle Scholar
  157. 157.
    Mbaye A, Richardson K, Balajo B, et al. Lack of inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for intermittent preventive treatment in Gambian primigravidae. Am J Trop Med Hyg 2006 Jun; 74(6): 960–4PubMedGoogle Scholar
  158. 158.
    Ip S, Chung M, Kulig J, et al. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004 Jul; 114(1): el30–53Google Scholar
  159. 159.
    Ostrow JD, Pascolo L, Shapiro SM, et al. New concepts in bilirubin encephalopathy. Eur J Clin Invest 2003 Nov; 3(11): 988–97Google Scholar
  160. 160.
    Odell GB. The dissociation of bilirubin from albumin and its clinical implications. J Pediatr 1959 Sep; 55: 268–79PubMedGoogle Scholar
  161. 161.
    Johnson L, Garcia ML, Figueroa E, et al. Kernicterus in rats lacking glucuronyl transferase: II. Factors which alter bilirubin concentration and frequency of kernicterus. Am J Dis Child 1961 Mar; 101: 322–49PubMedGoogle Scholar
  162. 162.
    Schutta HS, Johnson L. Clinical signs and morphologic abnormalities in Gunn rats treated with sulfadimethoxine. J Pediatr 1969 Dec; 75(6): 1070–9PubMedGoogle Scholar
  163. 163.
    Blanc WA, Johnson L. Studies on kernicterus; relationship with sulfonamide intoxication, report on kernicterus in rats with glucuronyl transferase deficiency and review of pathogenesis. J Neuropathol Exp Neurol 1959 Jan; 18(1): 165–87; discussion 87–9PubMedGoogle Scholar
  164. 164.
    Silverman WA, Andersen DH, Blanc WA, et al. A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics 1956 Oct; 18(4): 614–25PubMedGoogle Scholar
  165. 165.
    Maisonneuve H, Faber C, Piens MA, et al. Congenital toxoplasmosis. Tolerability of the sulfadoxine-pyrimethamine combination. 24 cases [in French]. Presse Med 1984 Mar 31; 13(14): 859–62PubMedGoogle Scholar
  166. 166.
    McLeod R, Mack D, Foss R, et al. Levels of pyrimethamine in sera and cerebrospinal and ventricular fluids from infants treated for congenital toxoplasmosis. Toxoplasmosis Study Group. Antimicrob Agents Chemother 1992 May; 36(5): 1040–8PubMedGoogle Scholar
  167. 167.
    Guerina NG, Hsu HW, Meissner HC, et al. Neonatal serologic screening and early treatment for congenital Toxoplasma gondii infection. The New England Regional Toxoplasma Working Group. N Engl J Med 1994 Jun 30; 330(26): 1858–63PubMedGoogle Scholar
  168. 168.
    Peyron F, Wallon M, Bernardoux C. Long-term follow-up of patients with congenital ocular toxoplasmosis. N Engl J Med 1996 Apr 11; 334(15): 993–4PubMedGoogle Scholar
  169. 169.
    Villena I, Aubert D, Leroux B, et al. Pyrimethamine-sulfadoxine treatment of congenital toxoplasmosis: follow-up of 78 cases between 1980 and 1997. Reims Toxoplasmosis Group. Scand J Infect Dis 1998; 30(3): 295–300PubMedGoogle Scholar
  170. 170.
    Wallon M, Kodjikian L, Binquet C, et al. Long-term ocular prognosis in 327 children with congenital toxoplasmosis. Pediatrics 2004 Jun; 113(6): 1567–72PubMedGoogle Scholar
  171. 171.
    McLeod R, Boyer K, Karrison T, et al. Outcome of treatment for congenital toxoplasmosis, 1981–2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis 2006 May 15; 42(10): 1383–94PubMedGoogle Scholar
  172. 172.
    Hohlfeld P, Daffos F, Thulliez P, et al. Fetal toxoplasmosis: outcome of pregnancy and infant follow-up after in utero treatment. J Pediatr 1989 Nov; 115 (5 Pt 1): 765–9PubMedGoogle Scholar
  173. 173.
    Heckel GP. Chemotherapy in pregnancy. JAMA1941; 117(16): 1314–6Google Scholar
  174. 174.
    Ginzler AM, Cherner C. Toxic manifestations in the newborn infant following placental transmission of sulfanilamide: with a report of 2 cases simulating erythroblastosis fetalis. Am J Obstet Gynecol 1942; 44: 46–55Google Scholar
  175. 175.
    Dunn PM. The possible relationship between the maternal administration of sulphamethoxypyridazine and hyperbilirubinaemia in the newborn. J Obstet Gynaecol Br Commonw 1964 Feb; 71: 128–31PubMedGoogle Scholar
  176. 176.
    Kantor HI, Sutherland DA, Leonard JT, et al. Effect on bilirubin metabolism in the newborn of sulfisoxazole administered to the mother. Obstet Gynecol 1961 Apr; 17: 494–500 501PubMedGoogle Scholar
  177. 177.
    Morgan AD, Wenger NK. Sulfadiazine prophylaxis against rheumatic fever during pregnancy: its safety as regards the infant. J Med Assoc Ga 1965 May; 54: 153–5PubMedGoogle Scholar
  178. 178.
    Baskin CG, Law S, Wenger NK. Sulfadiazine rheumatic fever prophylaxis during pregnancy: does it increase the risk of kernicterus in the newborn? Cardiology 1980; 65(4): 222–5PubMedGoogle Scholar
  179. 179.
    Little PJ. The incidence of urinary infection in 5000 pregnant women. Lancet 1966 Oct 29; 2(7470): 925–8PubMedGoogle Scholar
  180. 180.
    Bailey RR. Single-dose antibacterial treatment for bacteriuria in pregnancy. Drugs 1984 Feb; 27(2): 183–6PubMedGoogle Scholar
  181. 181.
    Clyde DF, Press J, Shute GT. Transfer of pyrimethamine in human milk. J Trop Med Hyg 1956 Dec; 59(12): 277–84PubMedGoogle Scholar
  182. 182.
    Kauffman RE, O’Brien C, Gilford P. Sulfisoxazole secretion into human milk. J Pediatr 1980 Nov; 97(5): 839–41PubMedGoogle Scholar
  183. 183.
    American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001 Sep; 108(3): 776–89Google Scholar
  184. 184.
    Nahlen BL. Rolling back malaria in pregnancy. N Engl J Med 2000 Aug 31; 343(9): 651–2PubMedGoogle Scholar
  185. 185.
    Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs; notice. Fed Regist 1993 Jul 22; 58(139): 39406–16Google Scholar
  186. 186.
    Merton V. The exclusion of pregnant, pregnable, and once-pregnable people (a.k.a. women) from biomedical research. Am J Law Med 1993; 19(4): 369–451PubMedGoogle Scholar
  187. 187.
    Mastroianni AC. HIV, women, and access to clinical trials: tort liability and lessons from DES. Duke J Gend Law Policy 1998 Spring; 5(1): 167–91PubMedGoogle Scholar
  188. 188.
    Simooya O. The WHO ‘Roll Back Malaria Project’: planning for adverse event monitoring in Africa. Drug Saf 2005; 28(4): 277–86PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Philip J. Peters
    • 1
  • Michael C. Thigpen
    • 1
    • 2
  • Monica E. Parise
    • 2
  • Robert D. Newman
    • 2
  1. 1.Division of Infectious DiseasesEmory University School of MedicineAtlantaUSA
  2. 2.Malaria BranchAtlantaUSA

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