- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- Prevalence of pfcrt K76T, pfmdr1 N86Y, and pfmdr1 F184Y genotypes at Day 0.
- Sequencing.
- Selection of pfcrt 76T by CQ and AQ.
- Selection of pfmdr1 86Y.
- Selection of pfmdr1 184F.
- Linkage disequilibrium and selection of SNP combinations.
- Other pfcrt and pfmdr1 alleles identified.
- Recrudescent pfcrt 76K carrying parasites.
- Re-infections occurred after day 14.
- DISCUSSION
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1
Hellgren U, Johansson I, Dias F, Ericsson O, Stenbeck J, Rombo L, 1991. Chloroquine resistant Plasmodium falciparum malaria in Guinea-Bissau. Trans R Soc Trop Med Hyg 85 :36.
-
2
Kofoed PE, Co F, Johansson P, Dias F, Cabral C, Hedegaard K, Aaby P, Rombo L, 2002. Treatment of uncomplicated malaria in children in Guinea-Bissau with chloroquine, quinine, and sulfadoxine-pyrimethamine. Trans R Soc Trop Med Hyg 96 :304–309.
-
3
Kofoed PE, Lopez F, Johansson P, Sandstrom A, Hedegaard K, Aaby P, Rombo L, 2002. Treatment of children with Plasmodium falciparum malaria with chloroquine in Guinea-Bissau. Am J Trop Med Hyg 67 :28–31.
-
4
Kofoed PE, Poulsen A, Co F, Hedegaard K, Aaby P, Rombo L, 2003. No benefits from combining chloroquine with artesunate for three days for treatment of Plasmodium falciparum in Guinea-Bissau. Trans R Soc Trop Med Hyg 97 :29–33.
-
5
Kofoed PE, Ursing J, Poulsen A, Rodrigues A, Bergquist Y, Aaby P, Rombo L, 2006. Different doses of amodiaquine and chloroquine for treatment of uncomplicated malaria in children in Guinea-Bissau. Implications for future treatment recommendations. Trans R Soc Trop Med Hyg 101 :231–238.
-
6
Jaenson TG, Gomes MJ, Barreto dos Santos RC, Petrarca V, Fortini D, Evora J, Crato J, 1994. Control of endophagic Anopheles mosquitoes and human malaria in Guinea Bissau, West Africa by permethrin-treated bed nets. Trans R Soc Trop Med Hyg 88 :620–624.
-
7
Cooper RA, Hartwig CL, Ferdig MT, 2005. Pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective. Acta Trop 94 :170–180.
-
8
Wootton JC, Feng X, Ferdig MT, Cooper RA, Mu J, Baruch DI, Magill AJ, Su XZ, 2002. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum.Nature 418 :320–323.
-
9
Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for Pfcrt in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15 :867–877.
-
10
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D, 2001. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1.J Infect Dis 183 :1535–1538.
-
11
Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bjorkman A, 2006. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 6 :309–314.
-
12
Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.Nature 403 :906–909.
-
13
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 :257–263.
-
14
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108 :13–23.
-
15
Veiga IM, Ferreira PE, Bjorkman A, Gil JP, 2006. Multiplex PCR-RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium falciparum.Mol Cell Probes 20 :100–104.
-
16
Cox-Singh J, Singh B, Alias A, Abdullah MS, 1995. Assessment of the association between three pfmdr1 point mutations and chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg 89 :436–437.
-
17
Snounou G, Zhu X, Siripoon N, Jarra W, Thaitong S, Brown KN, Viriyakasol S, 1999. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93 :369–374.
-
18
Daily JP, Roberts C, Thomas SM, Ndir O, Dieng T, Mboup S, Wirth DF, 2003. Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal. Parasitology 126 :401–405.
-
19
Thomas SM, Ndir O, Dieng T, Mboup S, Wypij D, Maguire JH, Wirth DF, 2002. In vitro chloroquine susceptibility and PCR analysis of pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from Senegal. Am J Trop Med Hyg 66 :474–480.
-
20
Ginsburg H, 2005. Should chloroquine be laid to rest? Acta Trop 96 :16–23.
-
21
Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355 :1959–1966.
-
22
Djimde A, Doumbo OK, Steketee RW, Plowe CV, 2001. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 358 :890–891.
-
23
Tinto H, Sanou B, Dujardin JC, Ouedraogo JB, Van Overmeir C, Erhart A, Van Marck E, Guiquemde TR, D’Alessandro U, 2005. Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso. Am J Trop Med Hyg 73 :171–173.
-
24
Adagu IS, Dias F, Pinheiro L, Rombo L, do Rosario V, Warhurst DC, 1996. Guinea-Bissau: association of chloroquine resistance of Plasmodium falciparum with the Tyr86 allele of the multiple drug-resistance gene Pfmdr1.Trans R Soc Trop Med Hyg 90 :90–91.
-
25
World Health Organization. Available at: www.who.int/malaria/amdp/amdp_afro.htm. Assessed at 22 March 2007.
-
26
Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP, 2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365 :1467–1473.
-
27
Sisowath C, Strömberg J, Mårtensson A, Msellem M, Obondo C, Bjorkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 91 :1014–1017.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 282 | 257 | 106 |
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PLASMODIUM FALCIPARUM GENOTYPES ASSOCIATED WITH CHLOROQUINE AND AMODIAQUINE RESISTANCE IN GUINEA-BISSAU
JOHAN URSING
JOHAN URSING
Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Kolding Hospital, Denmark; Projecto de Saúde de Bandim, Bissau, Guinea-Bissau; Division of Infectious Diseases, Thoracic Medicine and Dermatology, Mälarsjukhuset, Eskilstuna, Sweden, Centre of Molecular and Structural Biomedicine, University of Algarve, Portugal
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POUL-ERIK KOFOED
POUL-ERIK KOFOED
Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Kolding Hospital, Denmark; Projecto de Saúde de Bandim, Bissau, Guinea-Bissau; Division of Infectious Diseases, Thoracic Medicine and Dermatology, Mälarsjukhuset, Eskilstuna, Sweden, Centre of Molecular and Structural Biomedicine, University of Algarve, Portugal
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AMABELIA RODRIGUES
AMABELIA RODRIGUES
Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Kolding Hospital, Denmark; Projecto de Saúde de Bandim, Bissau, Guinea-Bissau; Division of Infectious Diseases, Thoracic Medicine and Dermatology, Mälarsjukhuset, Eskilstuna, Sweden, Centre of Molecular and Structural Biomedicine, University of Algarve, Portugal
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LARS ROMBO
LARS ROMBO
Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Kolding Hospital, Denmark; Projecto de Saúde de Bandim, Bissau, Guinea-Bissau; Division of Infectious Diseases, Thoracic Medicine and Dermatology, Mälarsjukhuset, Eskilstuna, Sweden, Centre of Molecular and Structural Biomedicine, University of Algarve, Portugal
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JOSÉ PEDRO GIL
JOSÉ PEDRO GIL
Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Kolding Hospital, Denmark; Projecto de Saúde de Bandim, Bissau, Guinea-Bissau; Division of Infectious Diseases, Thoracic Medicine and Dermatology, Mälarsjukhuset, Eskilstuna, Sweden, Centre of Molecular and Structural Biomedicine, University of Algarve, Portugal
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Chloroquine is the most commonly used antimalarial in Guinea-Bissau and high doses are routinely prescribed. Blood from 497 patients treated with different doses of chloroquine or amodiaquine were genotyped. Pfcrt and pfmdr1 polymorphisms were identified. Pfmsp2 analysis identified recrudescent infections. The pfcrt 72–76 haplotypes were CVIET and CVMNK. The pfcrt 76T prevalence was 23% at day 0 and 96%, 83% and 100% at recrudescence following treatment with 25mg/kg and 50mg/kg of chloroquine and 15mg/kg of amodiaquine respectively. When treating pfcrt 76T carrying P. falciparum the efficacy of 50 mg/kg and 25mg/kg of chloroquine was 78% and 34% respectively (P = 0.007). The genetic basis of chloroquine resistance is probably the same in Guinea-Bissau as in the rest of Africa. The low pfcrt 76T prevalence suggests that resistance to normal dose chloroquine does not confer a major advantage to falciparum in Bissau and could be a result of treatment with high-dose chloroquine.
Author Notes
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- Prevalence of pfcrt K76T, pfmdr1 N86Y, and pfmdr1 F184Y genotypes at Day 0.
- Sequencing.
- Selection of pfcrt 76T by CQ and AQ.
- Selection of pfmdr1 86Y.
- Selection of pfmdr1 184F.
- Linkage disequilibrium and selection of SNP combinations.
- Other pfcrt and pfmdr1 alleles identified.
- Recrudescent pfcrt 76K carrying parasites.
- Re-infections occurred after day 14.
- DISCUSSION
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1
Hellgren U, Johansson I, Dias F, Ericsson O, Stenbeck J, Rombo L, 1991. Chloroquine resistant Plasmodium falciparum malaria in Guinea-Bissau. Trans R Soc Trop Med Hyg 85 :36.
-
2
Kofoed PE, Co F, Johansson P, Dias F, Cabral C, Hedegaard K, Aaby P, Rombo L, 2002. Treatment of uncomplicated malaria in children in Guinea-Bissau with chloroquine, quinine, and sulfadoxine-pyrimethamine. Trans R Soc Trop Med Hyg 96 :304–309.
-
3
Kofoed PE, Lopez F, Johansson P, Sandstrom A, Hedegaard K, Aaby P, Rombo L, 2002. Treatment of children with Plasmodium falciparum malaria with chloroquine in Guinea-Bissau. Am J Trop Med Hyg 67 :28–31.
-
4
Kofoed PE, Poulsen A, Co F, Hedegaard K, Aaby P, Rombo L, 2003. No benefits from combining chloroquine with artesunate for three days for treatment of Plasmodium falciparum in Guinea-Bissau. Trans R Soc Trop Med Hyg 97 :29–33.
-
5
Kofoed PE, Ursing J, Poulsen A, Rodrigues A, Bergquist Y, Aaby P, Rombo L, 2006. Different doses of amodiaquine and chloroquine for treatment of uncomplicated malaria in children in Guinea-Bissau. Implications for future treatment recommendations. Trans R Soc Trop Med Hyg 101 :231–238.
-
6
Jaenson TG, Gomes MJ, Barreto dos Santos RC, Petrarca V, Fortini D, Evora J, Crato J, 1994. Control of endophagic Anopheles mosquitoes and human malaria in Guinea Bissau, West Africa by permethrin-treated bed nets. Trans R Soc Trop Med Hyg 88 :620–624.
-
7
Cooper RA, Hartwig CL, Ferdig MT, 2005. Pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a functional and evolutionary perspective. Acta Trop 94 :170–180.
-
8
Wootton JC, Feng X, Ferdig MT, Cooper RA, Mu J, Baruch DI, Magill AJ, Su XZ, 2002. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum.Nature 418 :320–323.
-
9
Johnson DJ, Fidock DA, Mungthin M, Lakshmanan V, Sidhu AB, Bray PG, Ward SA, 2004. Evidence for a central role for Pfcrt in conferring Plasmodium falciparum resistance to diverse antimalarial agents. Mol Cell 15 :867–877.
-
10
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D, 2001. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1.J Infect Dis 183 :1535–1538.
-
11
Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bjorkman A, 2006. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 6 :309–314.
-
12
Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.Nature 403 :906–909.
-
13
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 :257–263.
-
14
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108 :13–23.
-
15
Veiga IM, Ferreira PE, Bjorkman A, Gil JP, 2006. Multiplex PCR-RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium falciparum.Mol Cell Probes 20 :100–104.
-
16
Cox-Singh J, Singh B, Alias A, Abdullah MS, 1995. Assessment of the association between three pfmdr1 point mutations and chloroquine resistance in vitro of Malaysian Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg 89 :436–437.
-
17
Snounou G, Zhu X, Siripoon N, Jarra W, Thaitong S, Brown KN, Viriyakasol S, 1999. Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand. Trans R Soc Trop Med Hyg 93 :369–374.
-
18
Daily JP, Roberts C, Thomas SM, Ndir O, Dieng T, Mboup S, Wirth DF, 2003. Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal. Parasitology 126 :401–405.
-
19
Thomas SM, Ndir O, Dieng T, Mboup S, Wypij D, Maguire JH, Wirth DF, 2002. In vitro chloroquine susceptibility and PCR analysis of pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from Senegal. Am J Trop Med Hyg 66 :474–480.
-
20
Ginsburg H, 2005. Should chloroquine be laid to rest? Acta Trop 96 :16–23.
-
21
Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355 :1959–1966.
-
22
Djimde A, Doumbo OK, Steketee RW, Plowe CV, 2001. Application of a molecular marker for surveillance of chloroquine-resistant falciparum malaria. Lancet 358 :890–891.
-
23
Tinto H, Sanou B, Dujardin JC, Ouedraogo JB, Van Overmeir C, Erhart A, Van Marck E, Guiquemde TR, D’Alessandro U, 2005. Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso. Am J Trop Med Hyg 73 :171–173.
-
24
Adagu IS, Dias F, Pinheiro L, Rombo L, do Rosario V, Warhurst DC, 1996. Guinea-Bissau: association of chloroquine resistance of Plasmodium falciparum with the Tyr86 allele of the multiple drug-resistance gene Pfmdr1.Trans R Soc Trop Med Hyg 90 :90–91.
-
25
World Health Organization. Available at: www.who.int/malaria/amdp/amdp_afro.htm. Assessed at 22 March 2007.
-
26
Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP, 2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365 :1467–1473.
-
27
Sisowath C, Strömberg J, Mårtensson A, Msellem M, Obondo C, Bjorkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 91 :1014–1017.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 282 | 257 | 106 |
| Full Text Views | 229 | 3 | 1 |
| PDF Downloads | 54 | 3 | 1 |