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Evaluation of dihydrofolate reductase and dihydropteroate synthetase genotypes that confer resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum in Haiti

Tamar E Carter123, Megan Warner104, Connie J Mulligan12, Alexander Existe5, Yves S Victor6, Gladys Memnon7, Jacques Boncy5, Roland Oscar8, Mark M Fukuda9 and Bernard A Okech104*

Author Affiliations

1 Genetics Institute, University of Florida, 2033 Mowry Road, PO Box 103610, Gainesville, FL 32610, USA

2 Department of Anthropology, University of Florida, Turlington Hall, Room 1112, PO Box 117305, Gainesville, FL 32611, USA

3 Department of Epidemiology, College of Public Health and Health Professions, University of Florida, 1225 Center Drive, Room 3101, PO Box 100231, Gainesville, FL 32611, USA

4 Emerging Pathogens Institute, University of Florida, 2055 Mowry Rd, P.O. Box 100009, Gainesville, FL 32610, USA

5 National Public Health Laboratory, Ministry of Public Health and Population (MSPP), Port au Prince, Haiti

6 Blanchard Clinic, Family Health Ministries Haiti, Terre Noire, Port au Prince, Haiti

7 Hospital Saint Croix, Leogane, Haiti

8 National Malaria Control Program, Ministry of Public Health and Population, Port au Prince, Haiti

9 Armed Forces Health Sciences Surveillance Center, 11800 Tech Road, Suite 220, Silver Spring, MD 20904, USA

10 Department of Environmental and Global Health, University of Florida, PO Box 100188, Gainesville, FL 32610, USA

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Malaria Journal 2012, 11:275  doi:10.1186/1475-2875-11-275

Published: 13 August 2012

Abstract

Background

Malaria caused by Plasmodium falciparum infects roughly 30,000 individuals in Haiti each year. Haiti has used chloroquine (CQ) as a first-line treatment for malaria for many years and as a result there are concerns that malaria parasites may develop resistance to CQ over time. Therefore it is important to prepare for alternative malaria treatment options should CQ resistance develop. In many other malaria-endemic regions, antifolates, particularly pyrimethamine (PYR) and sulphadoxine (SDX) treatment combination (SP), have been used as an alternative when CQ resistance has developed. This study evaluated mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes that confer PYR and SDX resistance, respectively, in P. falciparum to provide baseline data in Haiti. This study is the first comprehensive study to examine PYR and SDX resistance genotypes in P. falciparum in Haiti.

Methods

DNA was extracted from dried blood spots and genotyped for PYR and SDX resistance mutations in P. falciparum using PCR and DNA sequencing methods. Sixty-one samples were genotyped for PYR resistance in codons 51, 59, 108 and 164 of the dhfr gene and 58 samples were genotyped for SDX resistance codons 436, 437, 540 of the dhps gene in P. falciparum.

Results

Thirty-three percent (20/61) of the samples carried a mutation at codon 108 (S108N) of the dhfr gene. No mutations in dhfr at codons 51, 59, 164 were observed in any of the samples. In addition, no mutations were observed in dhps at the three codons (436, 437, 540) examined. No significant difference was observed between samples collected in urban vs rural sites (Welch’s T-test p-value = 0.53 and permutations p-value = 0.59).

Conclusion

This study has shown the presence of the S108N mutation in P. falciparum that confers low-level PYR resistance in Haiti. However, the absence of SDX resistance mutations suggests that SP resistance may not be present in Haiti. These results have important implications for ongoing discussions on alternative malaria treatment options in Haiti.

Keywords:
Malaria; Hispaniola; Folic acid antagonists; Anti-malarials; Drug resistance; Transmission; Fansidar