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Antimicrobial Agents and Chemotherapy, August 2009, p. 3405-3410, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00024-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Novel pfdhps Haplotypes among Imported Cases of Plasmodium falciparum Malaria in the United Kingdom {triangledown}

Colin J. Sutherland,1,2,3* Helen Fifer,1 Richard J. Pearce,4 Faisal bin Reza,1 Meredydd Nicholas,1 Thomas Haustein,1 Njah E. Njimgye-Tekumafor,3 Justin F. Doherty,1 Philip Gothard,1 Spencer D. Polley,1,2 and Peter L. Chiodini1,2

Hospital for Tropical Diseases,1 HPA Malaria Reference Laboratory,2 Immunology Unit,3 Pathogen Molecular Biology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom4

Received 7 January 2009/ Returned for modification 19 March 2009/ Accepted 3 May 2009

Treatment of acute malaria caused by Plasmodium falciparum may include long-half-life drugs, such as the antifolate combination sulfadoxine-pyrimethamine (SP), to provide posttreatment chemoprophylaxis against parasite recrudescence or delayed emergence from the liver. An unusual case of P. falciparum recrudescence in a returned British traveler who received such a regimen, as well as a series of 44 parasite isolates from the same hospital, was analyzed by PCR and direct DNA sequencing for the presence of markers of parasite resistance to chloroquine and antifolates. The index patient harbored a mixture of wild-type and resistant pfdhfr and pfdhps alleles upon initial presentation. During his second malaria episode, he harbored only resistant parasites, with the haplotypes IRNI (codons 51, 59, 108, and 164) and SGEAA (codons 436, 437, 540, 581, and 613) at these two loci, respectively. Analysis of isolates from 44 other patients showed that the pfdhfr haplotype IRNI was common (found in 81% of cases). The SGEAA haplotype of pfdhps was uncommon (found only in eight cases of East African origin [17%]). A previously undescribed mutation, I431V, was observed for seven cases of Nigerian origin, occurring as one of two haplotypes, VAGKGS or VAGKAA. The presence of this mutation was also confirmed in isolates of Nigerian origin from the United Kingdom Malaria Reference Laboratory. The presence of the pfdhps haplotype SGEAA in P. falciparum parasites of East African origin appears to compromise the efficacy of treatment regimens that include SP as a means to prevent recrudescence. Parasites with novel pfdhps haplotypes are circulating in West Africa. The response of these parasites to chemotherapy needs to be evaluated.

* Corresponding author. Mailing address: HPA Parasite Reference Laboratory, Department of Clinical Parasitology, Hospital for Tropical Diseases, Mortimer Market Centre, Capper St., London WC1E 6JB, United Kingdom. Phone: 44 20 7387 4411, ext. 5965. Fax: 44 20 7388 0041. E-mail: colin.sutherland{at}lshtm.ac.uk

{triangledown} Published ahead of print on 11 May 2009.

Antimicrobial Agents and Chemotherapy, August 2009, p. 3405-3410, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00024-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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