Skip to main content
Top
Published in: Malaria Journal 1/2017

Open Access 01-12-2017 | Research

Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso

Authors: Mamoudou Cisse, Gordon A. Awandare, Alamissa Soulama, Halidou Tinto, Marie-Pierre Hayette, Robert T. Guiguemdé

Published in: Malaria Journal | Issue 1/2017

Login to get access

Abstract

Background

The impact of sulfadoxine–pyrimethamine (SP) used as intermittent preventive treatment during pregnancy (IPTp-SP) on mutant parasite selection has been poorly documented in Burkina Faso. This study sought first to explore the relationship between IPTp-SP and the presence of mutant parasites. Second, to assess the relationship between the mutant parasites and adverse pregnancy outcomes.

Methods

From September to December 2010, dried blood spots (DBS) were collected during antenatal care visits and at delivery from 109 pregnant women with microscopically confirmed falciparum malaria infection. DBS were analysed by PCR–restriction fragment length polymorphism (PCR–RFLP) for the polymorphisms at codons 51, 59, 108, and 164 of the Pfdhfr gene and codons 437 and 540 in the Pfdhps gene.

Results

Both the Pfdhfr and Pfdhps genes were successfully genotyped in 92.7% (101/109) of the samples. The prevalence of Pfdhfr mutations N51I, C59R and S108N was 71.3, 42.6 and 64.4%, respectively. Overall, 80.2% (81/101) of samples carried the Pfdhps A437G mutation. None of the samples had the Pfdhfr I164L and the Pfdhps K540E mutations. The prevalence of the triple mutation N51I + C59R + S108N was 25.7% (26/101). The use of IPTp-SP was associated with a threefold increased odds of Pfdhfr C59R mutation [crude OR 3.29; 95% CI (1.44–7.50)]. Pregnant women with recent uptake of IPTp-SP were at higher odds of both the Pfdhfr C59R mutation [adjusted OR 4.26; 95% CI (1.64–11.07)] and the Pfdhfr intermediate-to-high resistance, i.e., ≥ 2 Pfdhfr mutations [adjusted OR 3.45; 95% CI (1.18–10.07)]. There was no statistically significant association between the presence of the Pfdhfr intermediate-to-high resistance and parasite densities or both maternal haemoglobin level and anaemia.

Conclusion

The data indicate that despite the possibility that IPTp-SP contributes to the selection of resistant parasites, it did not potentiate pregnancy-associated malaria morbidity, suggesting the continuation of SP use as IPTp in Burkina Faso.
Appendix
Available only for authorised users
Literature
1.
go back to reference Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001;64:28–35.PubMed Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001;64:28–35.PubMed
4.
go back to reference Diakite OS, Kayentao K, Traoré BT, Djimde A, Traoré B, Diallo M, et al. Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial. Clin Infect Dis. 2011;53:215–23.CrossRefPubMed Diakite OS, Kayentao K, Traoré BT, Djimde A, Traoré B, Diallo M, et al. Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine–pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial. Clin Infect Dis. 2011;53:215–23.CrossRefPubMed
5.
go back to reference Mockenhaupt FP, Bedu-Addo G, Eggelte TA, Hommerich L, Holmberg V, von Oertzen C, et al. Rapid increase in the prevalence of sulfadoxine–pyrimethamine resistance among Plasmodium falciparum isolated from pregnant women in Ghana. J Infect Dis. 2008;198:1545–9.CrossRefPubMed Mockenhaupt FP, Bedu-Addo G, Eggelte TA, Hommerich L, Holmberg V, von Oertzen C, et al. Rapid increase in the prevalence of sulfadoxine–pyrimethamine resistance among Plasmodium falciparum isolated from pregnant women in Ghana. J Infect Dis. 2008;198:1545–9.CrossRefPubMed
6.
go back to reference Peterson D, Walliker D, Wellems T. Evidence that a point mutation in dihydrofolate reductase–thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA. 1988;85:9114–8.CrossRefPubMedPubMedCentral Peterson D, Walliker D, Wellems T. Evidence that a point mutation in dihydrofolate reductase–thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA. 1988;85:9114–8.CrossRefPubMedPubMedCentral
7.
go back to reference Triglia T, Menting JG, Wilson C, Cowman AF. Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proc Natl Acad Sci USA. 1997;94:13944–9.CrossRefPubMedPubMedCentral Triglia T, Menting JG, Wilson C, Cowman AF. Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proc Natl Acad Sci USA. 1997;94:13944–9.CrossRefPubMedPubMedCentral
8.
go back to reference Marks F, Evans J, Meyer CG, Browne EN, Flessner C, Von Kalckreuth V, et al. High prevalence of markers for sulfadoxine and pyrimethamine resistance in Plasmodium falciparum in the absence of drug pressure in the Ashanti Region of Ghana. Antimicrob Agents Chemother. 2005;49:1101–5.CrossRefPubMedPubMedCentral Marks F, Evans J, Meyer CG, Browne EN, Flessner C, Von Kalckreuth V, et al. High prevalence of markers for sulfadoxine and pyrimethamine resistance in Plasmodium falciparum in the absence of drug pressure in the Ashanti Region of Ghana. Antimicrob Agents Chemother. 2005;49:1101–5.CrossRefPubMedPubMedCentral
9.
go back to reference Iwalokun BA, Iwalokun SO, Adebodun V, Balogun M. Carriage of mutant dihydrofolate reductase and dihydropteroate synthase genes among Plasmodium falciparum isolates recovered from pregnant women with asymptomatic infection in Lagos, Nigeria. Med Princ Pract. 2015;24:436–43.CrossRefPubMed Iwalokun BA, Iwalokun SO, Adebodun V, Balogun M. Carriage of mutant dihydrofolate reductase and dihydropteroate synthase genes among Plasmodium falciparum isolates recovered from pregnant women with asymptomatic infection in Lagos, Nigeria. Med Princ Pract. 2015;24:436–43.CrossRefPubMed
10.
go back to reference Menéndez C, Serra-Casas E, Scahill MD, Sanz S, Nhabomba A, Bardají A, et al. HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment. Clin Infect Dis. 2011;52:41–8.CrossRefPubMed Menéndez C, Serra-Casas E, Scahill MD, Sanz S, Nhabomba A, Bardají A, et al. HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment. Clin Infect Dis. 2011;52:41–8.CrossRefPubMed
11.
go back to reference Taylor SM, Antonia AL, Chaluluka E, Mwapasa V, Feng G, Molyneux ME, et al. Antenatal receipt of sulfadoxine–pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study. Clin Infect Dis. 2012;55:42–50.CrossRefPubMedPubMedCentral Taylor SM, Antonia AL, Chaluluka E, Mwapasa V, Feng G, Molyneux ME, et al. Antenatal receipt of sulfadoxine–pyrimethamine does not exacerbate pregnancy-associated malaria despite the expansion of drug-resistant Plasmodium falciparum: clinical outcomes from the QuEERPAM study. Clin Infect Dis. 2012;55:42–50.CrossRefPubMedPubMedCentral
12.
go back to reference Siame MNP, Mharakurwa S, Chipeta J, Thuma P, Michelo C. High prevalence of dhfr and dhps molecular markers in Plasmodium falciparum in pregnant women of Nchelenge district, Northern Zambia. Malar J. 2015;14:190.CrossRefPubMedPubMedCentral Siame MNP, Mharakurwa S, Chipeta J, Thuma P, Michelo C. High prevalence of dhfr and dhps molecular markers in Plasmodium falciparum in pregnant women of Nchelenge district, Northern Zambia. Malar J. 2015;14:190.CrossRefPubMedPubMedCentral
13.
go back to reference Mockenhaupt FP, Eggelte TA, Tamara B, Thompson WNA, Bienzle U. Plasmodium falciparum dihydrofolate reductase alleles and pyrimethamine use in pregnant ghanaian women. Am J Trop Med Hyg. 2001;65:21–6.PubMed Mockenhaupt FP, Eggelte TA, Tamara B, Thompson WNA, Bienzle U. Plasmodium falciparum dihydrofolate reductase alleles and pyrimethamine use in pregnant ghanaian women. Am J Trop Med Hyg. 2001;65:21–6.PubMed
14.
go back to reference Mockenhaupt FP, Bedu-Addo G, Junge C, Hommerich L, Eggelte TA, Bienzle U. Markers of sulfadoxine–pyrimethamine-resistant Plasmodium falciparum in placenta and circulation of pregnant women. Antimicrob Agents Chemother. 2007;51:332–4.CrossRefPubMed Mockenhaupt FP, Bedu-Addo G, Junge C, Hommerich L, Eggelte TA, Bienzle U. Markers of sulfadoxine–pyrimethamine-resistant Plasmodium falciparum in placenta and circulation of pregnant women. Antimicrob Agents Chemother. 2007;51:332–4.CrossRefPubMed
15.
go back to reference Harrington WE, Mutabingwa TK, Muehlenbachs A, Sorensen B, Bolla MC, Fried M, et al. Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women. Proc Natl Acad Sci USA. 2009;106:9027–32.CrossRefPubMedPubMedCentral Harrington WE, Mutabingwa TK, Muehlenbachs A, Sorensen B, Bolla MC, Fried M, et al. Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women. Proc Natl Acad Sci USA. 2009;106:9027–32.CrossRefPubMedPubMedCentral
16.
go back to reference Bouyou-Akotet MK, Mawili-Mboumba DP, Tchantchou TDD, Kombila M. High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium falciparum isolates in pregnant women at the time of introduction of intermittent preventive treatment with sulfadoxine/pyrimethamine in Gabon. J Antimicrob Chemother. 2010;65:438–41.CrossRefPubMed Bouyou-Akotet MK, Mawili-Mboumba DP, Tchantchou TDD, Kombila M. High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium falciparum isolates in pregnant women at the time of introduction of intermittent preventive treatment with sulfadoxine/pyrimethamine in Gabon. J Antimicrob Chemother. 2010;65:438–41.CrossRefPubMed
17.
go back to reference Coulibaly SO, Kayentao K, Taylor S, Guirou EA, Khairallah C, Guindo N, et al. Parasite clearance following treatment with sulphadoxine–pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study. Malar J. 2014;13:41.CrossRefPubMedPubMedCentral Coulibaly SO, Kayentao K, Taylor S, Guirou EA, Khairallah C, Guindo N, et al. Parasite clearance following treatment with sulphadoxine–pyrimethamine for intermittent preventive treatment in Burkina-Faso and Mali: 42-day in vivo follow-up study. Malar J. 2014;13:41.CrossRefPubMedPubMedCentral
18.
go back to reference Tahita MC, Tinto H, Erhart A, Kazienga A, Fitzhenry R, VanOvermeir C, et al. Prevalence of the dhfr and dhps mutations among pregnant women in Rural Burkina Faso five years after the introduction of intermittent preventive treatment with sulfadoxine–pyrimethamine. PLoS ONE. 2015;10:e0137440.CrossRefPubMedPubMedCentral Tahita MC, Tinto H, Erhart A, Kazienga A, Fitzhenry R, VanOvermeir C, et al. Prevalence of the dhfr and dhps mutations among pregnant women in Rural Burkina Faso five years after the introduction of intermittent preventive treatment with sulfadoxine–pyrimethamine. PLoS ONE. 2015;10:e0137440.CrossRefPubMedPubMedCentral
19.
go back to reference Cisse M, Sangare I, Lougue G, Bamba S, Bayane D, Guiguemde RT. Prevalence and risk factors for Plasmodium falciparum malaria in pregnant women attending antenatal clinic in Bobo-Dioulasso (Burkina Faso). BMC Infect Dis. 2014;14:631.CrossRefPubMedPubMedCentral Cisse M, Sangare I, Lougue G, Bamba S, Bayane D, Guiguemde RT. Prevalence and risk factors for Plasmodium falciparum malaria in pregnant women attending antenatal clinic in Bobo-Dioulasso (Burkina Faso). BMC Infect Dis. 2014;14:631.CrossRefPubMedPubMedCentral
20.
go back to reference Cisse M, Diallo AH, Somé DA, Poda A, Awandare AG, Guiguemdé TR. Association of placental Plasmodium falciparum parasitaemia with maternal and newborn outcomes in the periurban area of Bobo-Dioulasso, Burkina Faso. Parasitol Open. 2016;2:e15.CrossRef Cisse M, Diallo AH, Somé DA, Poda A, Awandare AG, Guiguemdé TR. Association of placental Plasmodium falciparum parasitaemia with maternal and newborn outcomes in the periurban area of Bobo-Dioulasso, Burkina Faso. Parasitol Open. 2016;2:e15.CrossRef
21.
go back to reference Jonathan V, Sunil P, Chris D, Grant D, Daniel K, Sam N, et al. Protocols for detecting mutations conferring resistance to the antifolate class of antimalarial drugs: DHFR Ile-51, Arg-59, Asn-108, Leu-164, and DHPS Gly-437, Glu-540: April, 2004. http://www.muucsf.org/protocols/pdf/Molecular markers of antifolate resistance (dhfr, dhps).pdf. Accessed 25 Mar 2013. Jonathan V, Sunil P, Chris D, Grant D, Daniel K, Sam N, et al. Protocols for detecting mutations conferring resistance to the antifolate class of antimalarial drugs: DHFR Ile-51, Arg-59, Asn-108, Leu-164, and DHPS Gly-437, Glu-540: April, 2004. http://​www.​muucsf.​org/​protocols/​pdf/​Molecular markers of antifolate resistance (dhfr, dhps).pdf. Accessed 25 Mar 2013.
22.
go back to reference Geiger C, Compaore G, Coulibaly B, Sie A, Dittmer M, Sanchez C, et al. Substantial increase in mutations in the genes pfdhfr and pfdhps puts sulphadoxine–pyrimethamine-based intermittent preventive treatment for malaria at risk in Burkina Faso. Trop Med Int Health. 2014;19:690–7.CrossRefPubMed Geiger C, Compaore G, Coulibaly B, Sie A, Dittmer M, Sanchez C, et al. Substantial increase in mutations in the genes pfdhfr and pfdhps puts sulphadoxine–pyrimethamine-based intermittent preventive treatment for malaria at risk in Burkina Faso. Trop Med Int Health. 2014;19:690–7.CrossRefPubMed
23.
go back to reference Tinto H, Ouédraogo JB, Zongo I, van Overmeir C, van Marck E, Guiguemdé TR, et al. Sulfadoxine–pyrimethamine efficacy and selection of Plasmodium falciparum DHFR mutations in Burkina Faso before its introduction as intermittent preventive treatment for pregnant women. Am J Trop Med Hyg. 2007;76:608–13.PubMed Tinto H, Ouédraogo JB, Zongo I, van Overmeir C, van Marck E, Guiguemdé TR, et al. Sulfadoxine–pyrimethamine efficacy and selection of Plasmodium falciparum DHFR mutations in Burkina Faso before its introduction as intermittent preventive treatment for pregnant women. Am J Trop Med Hyg. 2007;76:608–13.PubMed
24.
25.
go back to reference Bertin G, Briand V, Bonaventure D, Carrieu A, Massougbodji A, Cot M, et al. Molecular markers of resistance to sulphadoxine–pyrimethamine during intermittent preventive treatment of pregnant women in Benin. Malar J. 2011;10:196.CrossRefPubMedPubMedCentral Bertin G, Briand V, Bonaventure D, Carrieu A, Massougbodji A, Cot M, et al. Molecular markers of resistance to sulphadoxine–pyrimethamine during intermittent preventive treatment of pregnant women in Benin. Malar J. 2011;10:196.CrossRefPubMedPubMedCentral
26.
go back to reference Chauvin P, Menard S, Iriart X, Nsango SE, Tchioffo MT, Abate L, et al. Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles. J Antimicrob Chemother. 2015;70:2566–71.CrossRefPubMed Chauvin P, Menard S, Iriart X, Nsango SE, Tchioffo MT, Abate L, et al. Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles. J Antimicrob Chemother. 2015;70:2566–71.CrossRefPubMed
27.
go back to reference Diallo DA, Sutherland C, Nebié I, Konaté AT, Ord R, Pota H, et al. Sustained use of insecticide-treated curtains is not associated with greater circulation of drug-resistant malaria parasites, or with higher risk of treatment failure among children with uncomplicated malaria in Burkina Faso. Am J Trop Med Hyg. 2007;76:237–44.PubMed Diallo DA, Sutherland C, Nebié I, Konaté AT, Ord R, Pota H, et al. Sustained use of insecticide-treated curtains is not associated with greater circulation of drug-resistant malaria parasites, or with higher risk of treatment failure among children with uncomplicated malaria in Burkina Faso. Am J Trop Med Hyg. 2007;76:237–44.PubMed
28.
go back to reference Dokomajilar C, Lankoande ZM, Dorsey G, Zongo I, Ouedraogo J-B, Rosenthal PJ. Roles of specific Plasmodium falciparum mutations in resistance to amodiaquine and sulfadoxine–pyrimethamine in Burkina Faso. Am J Trop Med Hyg. 2006;75:162–5.PubMed Dokomajilar C, Lankoande ZM, Dorsey G, Zongo I, Ouedraogo J-B, Rosenthal PJ. Roles of specific Plasmodium falciparum mutations in resistance to amodiaquine and sulfadoxine–pyrimethamine in Burkina Faso. Am J Trop Med Hyg. 2006;75:162–5.PubMed
29.
go back to reference Somé AF, Séré YY, Dokomajilar C, Zongo I, Rouamba N, Greenhouse B, et al. Selection of known Plasmodium falciparum resistance-mediating polymorphisms by artemether–lumefantrine and amodiaquine-sulfadoxine–pyrimethamine but not dihydroartemisinin–piperaquine in Burkina Faso. Antimicrob Agents Chemother. 2010;54:1949–54.CrossRefPubMedPubMedCentral Somé AF, Séré YY, Dokomajilar C, Zongo I, Rouamba N, Greenhouse B, et al. Selection of known Plasmodium falciparum resistance-mediating polymorphisms by artemether–lumefantrine and amodiaquine-sulfadoxine–pyrimethamine but not dihydroartemisinin–piperaquine in Burkina Faso. Antimicrob Agents Chemother. 2010;54:1949–54.CrossRefPubMedPubMedCentral
30.
go back to reference Diourté Y, Djimdé A, Doumbo OK, Sagara I, Coulibaly Y, Dicko A, et al. Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali. Am J Trop Med Hyg. 1999;60:475–8.PubMed Diourté Y, Djimdé A, Doumbo OK, Sagara I, Coulibaly Y, Dicko A, et al. Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali. Am J Trop Med Hyg. 1999;60:475–8.PubMed
31.
go back to reference Hastings I, Donnelly M. The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance. Drug Resist Updat. 2005;8:43–50.CrossRefPubMed Hastings I, Donnelly M. The impact of antimalarial drug resistance mutations on parasite fitness, and its implications for the evolution of resistance. Drug Resist Updat. 2005;8:43–50.CrossRefPubMed
32.
go back to reference Iriemenam NC, Shah M, Gatei W, van Eijk AM, Ayisi J, Kariuki S, et al. Temporal trends of sulphadoxine–pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malar J. 2012;11:134.CrossRefPubMedPubMedCentral Iriemenam NC, Shah M, Gatei W, van Eijk AM, Ayisi J, Kariuki S, et al. Temporal trends of sulphadoxine–pyrimethamine (SP) drug-resistance molecular markers in Plasmodium falciparum parasites from pregnant women in western Kenya. Malar J. 2012;11:134.CrossRefPubMedPubMedCentral
33.
go back to reference Ochiel DO, Awandare GA, Keller CC, Hittner JB, Kremsner PG, Weinberg JBPD. Differential regulation of beta-chemokines in children with Plasmodium falciparum malaria. Infect Immun. 2005;73:4190–7.CrossRefPubMedPubMedCentral Ochiel DO, Awandare GA, Keller CC, Hittner JB, Kremsner PG, Weinberg JBPD. Differential regulation of beta-chemokines in children with Plasmodium falciparum malaria. Infect Immun. 2005;73:4190–7.CrossRefPubMedPubMedCentral
Metadata
Title
Recent uptake of intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine is associated with increased prevalence of Pfdhfr mutations in Bobo-Dioulasso, Burkina Faso
Authors
Mamoudou Cisse
Gordon A. Awandare
Alamissa Soulama
Halidou Tinto
Marie-Pierre Hayette
Robert T. Guiguemdé
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2017
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-017-1695-1

Other articles of this Issue 1/2017

Malaria Journal 1/2017 Go to the issue