Safety and toxicity of sulfadoxine/pyrimethamine: Implications for malaria prevention in pregnancy using intermittent preventive treatment

Drug Safety

Volumn 30, Issue 6, 2007, Pages 481-501

  Peters, Philip J ^a,c   Thigpen, Michael C ^a,b   Parise, Monica E ^b   Newman, Robert D ^b  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CENTERS FOR DISEASE CONTROL AND PREVENTION   (United States)

^c EMORY UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COTRIMOXAZOLE; DAPSONE; FANSIDAR; FOLIC ACID ANTAGONIST; PYRIMETHAMINE; SULFONAMIDE;

AFRICA; ALLERGIC PNEUMONITIS; ANEMIA; ANTIBIOTIC RESISTANCE; BILIRUBIN METABOLISM; BLOOD DYSCRASIA; BREAST FEEDING; BREAST FEEDING EDUCATION; CLINICAL TRIAL; CONGENITAL MALFORMATION; CONGENITAL TOXOPLASMOSIS; DRUG CONTRAINDICATION; DRUG FEVER; DRUG MEGADOSE; DRUG SAFETY; DRUG SURVEILLANCE PROGRAM; ERYTHEMA MULTIFORME; FETUS OUTCOME; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; KERNICTERUS; LIVER NECROSIS; LIVER TOXICITY; LOW BIRTH WEIGHT; MALARIA; MEGALOBLASTIC ANEMIA; NEURAL TUBE DEFECT; ORGANOGENESIS; PREGNANCY; PREGNANT WOMAN; PRIORITY JOURNAL; RECOMMENDED DRUG DOSE; REVIEW; SINGLE DRUG DOSE; SKIN MANIFESTATION; STEVENS JOHNSON SYNDROME; TERATOGENESIS; TERATOGENICITY; TOXIC EPIDERMAL NECROLYSIS; VITAMIN SUPPLEMENTATION;

ABNORMALITIES, DRUG-INDUCED; AFRICA; ANIMALS; ANTIMALARIALS; DRUG ADMINISTRATION SCHEDULE; DRUG COMBINATIONS; DRUG RESISTANCE; FEMALE; HUMANS; INFANT, NEWBORN; KERNICTERUS; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM; PREGNANCY; PREGNANCY COMPLICATIONS, PARASITIC; PYRIMETHAMINE; SULFADOXINE;

EID: 34249889049     PISSN: 01145916     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002018-200730060-00003     Document Type: Review

References (188)

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. Beeson JG, Brown GV. Plasmodium falciparum-infected 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): 169-79
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): 535-9
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): 37-43
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.): 33-41
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): 1580-3
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.): 28-35
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.): 36-44
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. 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.): 50-6
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): 1374-82
12. WHO. WHO Expert Committee on Malaria. World Health Organ Tech Rep Ser 2000; 92: i-v, 1-74
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. 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): 109-16
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): 632-6
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): 277-82
17. Parise ME, Ayisi JG, Nahlen BL, et al. 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 1998 Nov; 59 (5): 813-22
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): 515-22
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): 1066-73
20. van Eijk AM, Ayisi JG, ter Kuile FO, et al. Effectiveness of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in western Kenya: a hospital-based study. Trop Med Int Health 2004 Mar; 9 (3): 351-60
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): 549-53
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): 286-93
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): 205-11
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): 141-50
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. 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. 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]
28. Nosten F, McGready R, Looareesuwan S, et al. Editorial: Maternal malaria: time for action. Trop Med Int Health 2003 Jun; 8 (6): 485-7
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): 409-18
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: 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): 279-89
32. Sibley CH, Hyde JE, Sims PF, et al. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 2001 Dec; 17 (12): 582-8
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): 292-8
34. Hyde JE. Exploring the folate pathway in Plasmodium falciparum. Acta Trop 2005 Jun; 94 (3): 191-206
35. Ferone R, Burchall JJ, Hitchings GH. Plasmodium berghei dihydrofolate reductase. Isolation, properties, and inhibition by antifolates. Mol Pharmacol 1969 Jan; 5 (1): 49-59
36. Zhang K, Rathod PK. Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science 2002 Apr 19; 296 (5567): 545-7
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
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): 459-64
39. Rollo IM. The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum. Br J Pharmacol Chemother 1955 Jun; 10 (2): 208-14
40. Hurly MG. Potentiation of pyrimethamine by sulphadiazine in human malaria. Trans R Soc Trop Med Hyg 1959 Sep; 53: 412-3
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): 115-22
42. Edstein MD. Pharmacokinetics of sulfadoxine and pyrimethamine after Fansidar administration in man. Chemotherapy 1987; 33 (4): 229-33
43. PDR guide to drug interactions, side effects, indications, contra-indications. Montvale (NJ): Medical Economics, 1997: 2281-2
44. Barnes KI, Little F, Smith PJ, et al. Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications. Clin Pharmacol Ther 2006 Dec; 80 (6): 582-96
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): 3794-800
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): 469-72
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 nonsevere falciparum malaria. Br J Clin Pharmacol 1992 Feb; 33 (2): 143-8
48. Trenque T, Marx C, Quereux C, et al. Human maternofoetal distribution of pyrimethamine-sulphadoxine. Br J Clin Pharmacol 1998 Feb; 45 (2): 179-80
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): 83-5
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. Ringwald P, Global Partnership to Roll Back Malaria. Susceptibility of plasmodium falciparum to antimalarial drugs: report global monitoring, 1996-2004. Geneva: World Health Organization, 2005
52. White NJ. Intermittent presumptive treatment for malaria. PLoS Med 2005 Jan; 2 (1): e3
53. Gregson A, Plowe CV. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 2005 Mar; 57 (1): 117-45
54. Hankins EG, Warhurst DC, Sibley CH. Novel alleles of the Plasmodium falciparum dhfr highly resistant to pyrimethamine and chlorcycloguanil, but not WR99210. Mol Biochem Parasitol 2001 Sep 28; 117 (1): 91-102
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): 189-97
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): 341-6
57. Bloland 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, 2003
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): 569-77
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): 545
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): 727-33
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): 280-3
62. Goodman LS, Gilman A, Brunton LL, et al. Goodman & Gilman's the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill, 2006
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): 284-9
64. Khoo KK. The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah. Ann Trop Med Parasitol 1981 Dec; 75 (6): 591-5
65. Bjorkman A, Phillips-Howard PA. Adverse reactions to sulfa drugs: implications for malaria chemotherapy. Bull World Health Organ 1991; 69 (3): 297-304
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): 451-8
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): 505-9
68. Oduro-Boatey C, Rodrigues O. Stevens-Johnson syndrome in two children in Ghana following anti-malarial treatment. Trop Doct 2005 Apr; 35 (2): 118-9
69. Nair SS, Kaplan JM, Levine LH, et al. Trimethoprim-sulfamethoxazole- induced intrahepatic cholestasis. Ann Intern Med 1980 Apr; 92 (4): 511-2
70. Munoz SJ, Martinez-Hernandez A, Maddrey WC. Intrahepatic cholestasis and phospholipidosis associated with the use of trimethoprim-sulfamethoxazole. Hepatology 1990 Aug; 12 (2): 342-7
71. Thies PW, Dull WL. Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis. Inadvertent rechallenge. Arch Intern Med 1984 Aug; 144 (8): 1691-2
72. Zitelli BJ, Alexander J, Taylor S, et al. Fatal hepatic necrosis due to pyrimethamine-sulfadoxine (Fansidar). Ann Intern Med 1987 Mar; 106 (3): 393-5
73. McCormack D, Morgan WK. Fansidar hypersensitivity pneumonitis. Br J Dis Chest 1987 Apr; 81 (2): 194-6
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): 1876
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): 365-6
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): 82-5
77. Steffen R, Somaini B. Severe cutaneous adverse reactions to sulfadoxine-pyrimethamine in Switzerland. Lancet 1986 Mar 15; 1 (8481): 610
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, 2002
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): 738-43
80. Hernborg A. Stevens-Johnson syndrome after mass prophylaxis with sulfadoxine for cholera in Mozambique. Lancet 1985 Nov 9; 2 (8463): 1072-3
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): 179-84
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): 77-82
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. ter Kuile FO, Parise ME, Verhoeff FH, et al. The burden of coinfection 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.): 41-54
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): 960-4
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): 127-31
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): 1860-7
88. Steketee RW, Wirima JJ, Bloland 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.): 42-9
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. 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): 529-35
91. Carr A, Gross AS, Hoskins JM, et al. Acetylation phenotype and cutaneous hypersensitivity to trimethoprim-sulphamethox-sulfadoxine azole in HIV-infected patients. Aids 1994 Mar; 8 (3): 333-7
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): 21-5
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): 260-5
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): 1469-75
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): 1428-34
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):1865-71
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): 1510-8
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. 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/ copublications/ documents/care/ general/recommendation-eng.pdf [Accessed 2006 Mar 6]
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): 1463-8
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): 1823-9
102. Malamba SS, Mermin J, Reingold A, et al. Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members. Am J Trop Med Hyg 2006 Sep; 75 (3): 375-80
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): 100-11
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): 130-6
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
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): 1053-61
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): 163-8
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): 2683-5
109. Fansidar-associated fatal reaction in an HIV-infected man. MMWR Morb Mortal Wkly Rep 1988 Sep 23; 37 (37): 571-2, 7
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): 595-6
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): 353-61
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, DC
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): 131-7
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): 1485-90
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): 195-226
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): 151-2
117. Kato T, Kitagawa S. Production of congenital anomalies in fetuses of rats and mice with various sulfonamides. Cong Anom 1973; 13 (1): 7-15
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: 1005-19
119. Wolkowski-Tyl R, Jones-Price C, Kimmel C, et al. Teratologic evaluation of sulfamethazine in CD rats. Teratology 1982; 25: 81A-2A
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): 17-23
121. Paget GE, Thorpe E. A teratogenic effect of a sulphonamide in experimental animals. Br J Pharmacol Chemother 1964 Oct; 23: 305-12
122. Uche-Nwachi EO, Caxton-Martins AE. Sulfadoxine-pyrimethamine embryopathy in Wistar rats. Kaibogaku Zasshi 1998 Apr; 73 (2): 135-9
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): 1514-7
124. Sullivan GE, Takacs E. Comparative teratogenicity of pyrimethamine in rats and hamsters. Teratology 1971; 4 (2): 205-9
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): 134-45
126. Schvartsman S. Teratogenicity of pyrimethamine. Toxicol Applied Pharmacol 1979; 48: A123
127. Misawa J, Kanda S, Kokue E, et al. Teratogenic activity of pyrimethamine in Gottingen minipig. Toxicol Lett 1982 Jan; 10 (1): 51-4
128. Tangapregassom AM, Tangapregassom MJ, Horvath C, et al. Vascular anomalies and pyrimethamine-induced malformations in the rat. Teratog Carcinog Mutagen 1985; 5 (1): 55-62
129. Petter C, Bourbon J. Foetal red cell macrocytosis induced by pyrimethamine; its teratogenic role. Experientia 1975 Mar 15; 31 (3): 369-70
130. Kudo G, Tsunematsu K, Shimoda M, et al. Effects of folic acid on pyrimethamine teratogenesis in rats. Adv Exp Med Biol 1993; 338: 469-72
131. Uche-Nwachi EO. Effect of intramuscular sulfadoxine-pyrimethamine on pregnant Wistar rats. Anat Rec 1998 Apr; 250 (4): 426-9
132. Hengst P. Teratogenicity of daraprim (pyrimethamine) in man [in German]. Zentralbl Gynakol 1972 Apr 29; 94 (17): 551-5
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): 589-94
134. Morley D, Woodland M, Cuthbertson WF. Controlled trial of pyrimethamine in pregnant women in an African village. BMJ 1964 Mar 14; 5384: 667-8
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): 830-4
136. Phillips-Howard PA, Wood D. The safety of antimalarial drugs in pregnancy. Drug Saf 1996 Mar; 14 (3): 131-45
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): 1608-14
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): 961-8
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): 637-46
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): 79-86
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): 441-3
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): 121-6
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
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): 617-24
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: 134-5
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): CD001056
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. Mahomed K. Iron and folate supplementation in pregnancy. Cochrane Database Syst Rev 2000; (2): CD001135
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): 1-10
150. Krungkrai J, Webster HK, Yuthavong Y. De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. Mol Biochem Parasitol 1989 Jan 1; 32 (1): 25-37
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): 325-30
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 Parasitol 1985 Jan; 14 (1): 55-61
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): 1254-62
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): 672-6
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): 166-70
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): e28
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): 960-4
158. Ip S, Chung M, Kulig J, et al. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004 Jul; 114 (1): e130-53
159. Ostrow JD, Pascolo L, Shapiro SM, et al. New concepts in bilirubin encephalopathy. Eur J Clin Invest 2003 Nov; 3 (11): 988-97
160. Odell GB. The dissociation of bilirubin from albumin and its clinical implications. J Pediatr 1959 Sep; 55: 268-79
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: 322-49
162. Schutta HS, Johnson L. Clinical signs and morphologic abnormalities in Gunn rats treated with sulfadimethoxine. J Pediatr 1969 Dec; 75 (6): 1070-9
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 87-9
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): 614-25
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): 859-62
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): 1040-8
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): 1858-63
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): 993-4
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): 295-300
170. Wallon M, Kodjikian L, Binquet C, et al. Long-term ocular prognosis in 327 children with congenital toxoplasmosis. Pediatrics 2004 Jun; 113 (6): 1567-72
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): 1383-94
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): 765-9
173. Heckel GP. Chemotherapy in pregnancy. JAMA 1941; 117 (16): 1314-6
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: 46-55
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: 128-31
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
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: 153-5
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): 222-5
179. Little PJ. The incidence of urinary infection in 5000 pregnant women. Lancet 1966 Oct 29; 2 (7470): 925-8
180. Bailey RR. Single-dose antibacterial treatment for bacteriuria in pregnancy. Drugs 1984 Feb; 27 (2): 183-6
181. Clyde DF, Press J, Shute GT. Transfer of pyrimethamine in human milk. J Trop Med Hyg 1956 Dec; 59 (12): 277-84
182. Kauffman RE, O'Brien C, Gilford P. Sulfisoxazole secretion into human milk. J Pediatr 1980 Nov; 97 (5): 839-41
183. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001 Sep; 108 (3): 776-89
184. Nahlen BL. Rolling back malaria in pregnancy. N Engl J Med 2000 Aug 31; 343 (9): 651-2
185. Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs; notice. Fed Regist 1993 Jul 22; 58 (139): 39406-16
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): 369-451
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): 167-91
188. Simooya O. The WHO 'Roll Back Malaria Project': planning for adverse event monitoring in Africa. Drug Saf 2005; 28 (4): 277-86