Different Patterns of pfcrt and pfmdr1 Polymorphisms in P. falciparum Isolates from Nigeria and Brazil: The Potential Role of Antimalarial Drug Selection Pressure

Grace O. Gbotosho Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Onikepe A. Folarin Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Carolina Bustamante Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Luis Hildebrando Pereira da Silva Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Elieth Mesquita Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Akintunde Sowunmi Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Mariano G. Zalis Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Ayoade M. J. Oduola Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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Christian T. Happi Malaria Research Laboratories, Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Nigeria; Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil; Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil; Special Program for Research and Training in Tropical Diseases (WHO/TDR), Geneva, Switzerland

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The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.

Author Notes

*Address correspondence to Christian T. Happi, Malaria Research Laboratories, IMRAT, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail: christianhappi@hotmail.com
†These two authors contributed equally to this work.

Financial support: This study was supported by the NIH/Fogarty International Centre, The European Union Developing Countries Clinical Trial Partnership (EDCTP), the UNICEF/UNDP/World Bank/WHO/TDR, and the Multilateral Initiative for Malaria in Africa (MIM)/TDR. The Nigerian Government Postgraduate Scholarship supports Onikepe Folarin. Christian T. Happi is recipient of the Exxon-Mobil Corporation Malaria Leadership Award and is supported by the EDCTP Grant Award no. TA2007/40200016 for Senior Research Fellowship, the Fogarty International Research Collaboration Award (FIRCA) no. NIH RO3TW007757-03, and the UNICEF/UNDP/World Bank/WHO/TDR Grant ID A50337. Grace O. Gbotosho is supported by the MIM/TDR project ID A20239.

Authors' addresses: Grace O. Gbotosho, Onikepe A. Folarin, Akintunde Sowunmi, and Christian T. Happi, Malaria Research Laboratories, Institute of Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria, E-mails: solagbotosho@yahoo.co.uk, onikepefolarin@yahoo.com, akinsowunmi@hotmail.com, and christianhappi@hotmail.com. Carolina Bustamante and Mariano G. Zalis, Laboratory of Molecular Infectiology and Parasitology, Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, E-mails: Carolina.bustamante@gmail.com and mgzalis@hucff.ufrj.br. Luis Hildebrando Pereira da Silva and Elieth Mesquita, Instituto de Pesquisa em Patologias Tropicais de Rondônia, Porto Velho, Brazil, E-mails: hildebrando.pereira@yahoo.com.br and eliethbio@hotmail.com. Ayoade M. J. Oduola, Strategic and Discovery Research, World Health Organization/Tropical Disease Research, Geneva, Switzerland, E-mail: oduolaa@who.int.

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