Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function
Abstract Background Plasmodium vivax malaria is characterized by the presence of dormant liver-stage parasites, called hypnozoites, which can cause malaria relapses after an initial attack. Primaquine, which targets liver hypnozoites, must be used in combination with a schizonticidal agent to get th...
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doaj-17759ba5dac54973b30ab68c4112c01c2020-11-25T03:45:19ZengBMCMalaria Journal1475-28752020-07-011911710.1186/s12936-020-03326-1Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 functionAlexandra Martin Ramírez0Carlos Lombardia González1Tamara Soler Maniega2Ángela Gutierrez Liarte3Diego Domingo García4Marta Lanza Suárez5María Josefa Bernal Fernández6José Miguel Rubio7Malaria and Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos IIIGenetics Department, CatLabMicrobiology and Parasitology Department, Hospital Universitario de la PrincesaInternal Medicine Department, Hospital Universitario de la PrincesaMicrobiology and Parasitology Department, Hospital Universitario de la PrincesaMalaria and Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos IIIMalaria and Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos IIIMalaria and Parasitic Diseases Laboratory, National Microbiology Center, Instituto de Salud Carlos IIIAbstract Background Plasmodium vivax malaria is characterized by the presence of dormant liver-stage parasites, called hypnozoites, which can cause malaria relapses after an initial attack. Primaquine, which targets liver hypnozoites, must be used in combination with a schizonticidal agent to get the radical cure. However, relapses can sometimes occur in spite of correct treatment, due to different factors such as a diminished metabolization of primaquine. Case presentation In January 2019, a 21 years old woman with residence in Madrid, returning from a trip to Venezuela with clinical symptoms compatible with malaria infection, was diagnosed with vivax malaria. Chloroquine for 3 days plus primaquine for 14 days was the elected treatment. Two months later and after a second trip to Venezuela, the patient presented a second P. vivax infection, which was treated as the previous one. A third P. vivax malaria episode was diagnosed 2 months later, after returning from a trip to Morocco, receiving chloroquine for 3 days but increasing to 28 days the primaquine regimen, and with no more relapses after 6 months of follow up. The genotyping of P. vivax in the three malaria episodes revealed that the same strain was present in the different relapses. Upon confirmation of correct adherence to the treatment, non-description of resistance in the infection area and the highly unlikely re-infection on subsequent trips or stays in Spain, a possible metabolic failure was considered. CYP2D6 encodes the human cytochrome P450 isoenzyme 2D6 (CYP2D6), responsible for primaquine activation. The patient was found to have a CYP2D6*4/*1 genotype, which turns out in an intermediate metabolizer phenotype, which has been related to P. vivax relapses. Conclusions The impairment in CYP2D6 enzyme could be the most likely cause of P. vivax relapses in this patient. This highlights the importance of considering the analysis of CYP2D6 gene polymorphisms in cases of P. vivax relapses after a correct treatment and, especially, it should be considered in any study of dosage and duration of primaquine treatment.http://link.springer.com/article/10.1186/s12936-020-03326-1Plasmodium vivaxMalariaRelapseCYP2D6Primaquine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandra Martin Ramírez Carlos Lombardia González Tamara Soler Maniega Ángela Gutierrez Liarte Diego Domingo García Marta Lanza Suárez María Josefa Bernal Fernández José Miguel Rubio |
spellingShingle |
Alexandra Martin Ramírez Carlos Lombardia González Tamara Soler Maniega Ángela Gutierrez Liarte Diego Domingo García Marta Lanza Suárez María Josefa Bernal Fernández José Miguel Rubio Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function Malaria Journal Plasmodium vivax Malaria Relapse CYP2D6 Primaquine |
author_facet |
Alexandra Martin Ramírez Carlos Lombardia González Tamara Soler Maniega Ángela Gutierrez Liarte Diego Domingo García Marta Lanza Suárez María Josefa Bernal Fernández José Miguel Rubio |
author_sort |
Alexandra Martin Ramírez |
title |
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function |
title_short |
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function |
title_full |
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function |
title_fullStr |
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function |
title_full_unstemmed |
Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function |
title_sort |
several plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome p450 2d6 function |
publisher |
BMC |
series |
Malaria Journal |
issn |
1475-2875 |
publishDate |
2020-07-01 |
description |
Abstract Background Plasmodium vivax malaria is characterized by the presence of dormant liver-stage parasites, called hypnozoites, which can cause malaria relapses after an initial attack. Primaquine, which targets liver hypnozoites, must be used in combination with a schizonticidal agent to get the radical cure. However, relapses can sometimes occur in spite of correct treatment, due to different factors such as a diminished metabolization of primaquine. Case presentation In January 2019, a 21 years old woman with residence in Madrid, returning from a trip to Venezuela with clinical symptoms compatible with malaria infection, was diagnosed with vivax malaria. Chloroquine for 3 days plus primaquine for 14 days was the elected treatment. Two months later and after a second trip to Venezuela, the patient presented a second P. vivax infection, which was treated as the previous one. A third P. vivax malaria episode was diagnosed 2 months later, after returning from a trip to Morocco, receiving chloroquine for 3 days but increasing to 28 days the primaquine regimen, and with no more relapses after 6 months of follow up. The genotyping of P. vivax in the three malaria episodes revealed that the same strain was present in the different relapses. Upon confirmation of correct adherence to the treatment, non-description of resistance in the infection area and the highly unlikely re-infection on subsequent trips or stays in Spain, a possible metabolic failure was considered. CYP2D6 encodes the human cytochrome P450 isoenzyme 2D6 (CYP2D6), responsible for primaquine activation. The patient was found to have a CYP2D6*4/*1 genotype, which turns out in an intermediate metabolizer phenotype, which has been related to P. vivax relapses. Conclusions The impairment in CYP2D6 enzyme could be the most likely cause of P. vivax relapses in this patient. This highlights the importance of considering the analysis of CYP2D6 gene polymorphisms in cases of P. vivax relapses after a correct treatment and, especially, it should be considered in any study of dosage and duration of primaquine treatment. |
topic |
Plasmodium vivax Malaria Relapse CYP2D6 Primaquine |
url |
http://link.springer.com/article/10.1186/s12936-020-03326-1 |
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