BACKGROUND: Molecular markers for sulfadoxine-pyrimethamine (SP) resistance in Plasmodium vivax have been reported. However, data on the molecular correlates involved in the development of resistance to 4-aminoquinolines and their association with the in vivo treatment response are scarce. METHODS: We assessed pvdhfr (F57L/I, S58R, T61M, S117T/N, and I173F/L) and pvmdr1 (Y976F and F1076L) mutations in 94 patients who received amodiaquine (AQ) plus SP in Papua New Guinea (PNG). We then investigated the association between parasite genotype and treatment response. RESULTS: The treatment failure (TF) rate reached 13%. Polymorphisms in pvdhfr F57L, S58R, T61M, and S117T/N and in pvmdr1 Y976F were detected in 60%, 67%, 20%, 40%, and 39% of the samples, respectively. The single mutant pvdhfr 57 showed the strongest association with TF (odds ratio [OR], 9.04; P= .01). The combined presence of the quadruple mutant pvdhfr 57L+58R+61M+117T and pvmdr1 mutation 976F was the best predictor of TF (OR, 8.56; P= .01). The difference in TF rates between sites was reflected in the genetic drug-resistance profile of the respective parasites. CONCLUSIONS: The present study identified a new molecular marker in pvmdr1 that is associated with the in vivo response to AQ+SP. We suggest suitable marker sets with which to monitor P. vivax resistance against AQ+SP in countries where these drugs are used.
BACKGROUND: Molecular markers for sulfadoxine-pyrimethamine (SP) resistance in Plasmodium vivax have been reported. However, data on the molecular correlates involved in the development of resistance to 4-aminoquinolines and their association with the in vivo treatment response are scarce. METHODS: We assessed pvdhfr (F57L/I, S58R, T61M, S117T/N, and I173F/L) and pvmdr1 (Y976F and F1076L) mutations in 94 patients who received amodiaquine (AQ) plus SP in Papua New Guinea (PNG). We then investigated the association between parasite genotype and treatment response. RESULTS: The treatment failure (TF) rate reached 13%. Polymorphisms in pvdhfr F57L, S58R, T61M, and S117T/N and in pvmdr1 Y976F were detected in 60%, 67%, 20%, 40%, and 39% of the samples, respectively. The single mutant pvdhfr 57 showed the strongest association with TF (odds ratio [OR], 9.04; P= .01). The combined presence of the quadruple mutant pvdhfr 57L+58R+61M+117T and pvmdr1 mutation 976F was the best predictor of TF (OR, 8.56; P= .01). The difference in TF rates between sites was reflected in the genetic drug-resistance profile of the respective parasites. CONCLUSIONS: The present study identified a new molecular marker in pvmdr1 that is associated with the in vivo response to AQ+SP. We suggest suitable marker sets with which to monitor P. vivax resistance against AQ+SP in countries where these drugs are used.
Authors: Celine Barnadas; Cristian Koepfli; Harin A Karunajeewa; Peter M Siba; Timothy M E Davis; Ivo Mueller Journal: Antimicrob Agents Chemother Date: 2011-06-27 Impact factor: 5.191
Authors: Saad M Bin Dajem; Adel Ali H Al-Sheikh; Marie Fe Bohol; Mohammad Alhawi; Mohammed N Al-Ahdal; Ahmed Al-Qahtani Journal: Parasitol Res Date: 2011-02-25 Impact factor: 2.289
Authors: Pamela Orjuela-Sánchez; Nadira D Karunaweera; Mônica da Silva-Nunes; Natal S da Silva; Kézia K G Scopel; Raquel M Gonçalves; Chanaki Amaratunga; Juliana M Sá; Duong Socheat; Rick M Fairhust; Sharmini Gunawardena; Thuraisamy Thavakodirasah; Gawrie L N Galapaththy; Rabindra Abeysinghe; Fumihiko Kawamoto; Dyann F Wirth; Marcelo U Ferreira Journal: BMC Genet Date: 2010-07-13 Impact factor: 2.797
Authors: Jessica T Lin; Jaymin C Patel; Oksana Kharabora; Jetsumon Sattabongkot; Sinuon Muth; Ratawan Ubalee; Anthony L Schuster; William O Rogers; Chansuda Wongsrichanalai; Jonathan J Juliano Journal: Am J Trop Med Hyg Date: 2013-03-18 Impact factor: 2.345
Authors: Rosa del Carmen Miluska Vargas-Rodríguez; Melissa da Silva Bastos; Maria José Menezes; Pamela Orjuela-Sánchez; Marcelo U Ferreira Journal: Am J Trop Med Hyg Date: 2012-09-04 Impact factor: 2.345