8-Aminoquinoline Therapy for Latent Malaria

Baird, J. Kevin

doi:10.1128/cmr.00011-19

Cited by 103 publications

(128 citation statements)

References 267 publications

(352 reference statements)

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“…Thus, other strategy of drug implementation was not considered. But, due to the risk of primaquine-induced G6PD deficiency-mediated haemolytic anaemia, the consideration for the use of other chemotherapy or chemoprophylaxis such as 8-aminoquinoline is also needed [14].…”

Section: Introductionmentioning

confidence: 99%

Investigation of glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence in a Plasmodium vivax-endemic area in the Republic of Korea (ROK)

Lee

Lee³

et al. 2020

Malar J

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with haemolytic anaemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine administration, testing for G6PD deficiency was not mandatory. In this study, to evaluate the risk from malaria chemoprophylaxis in the ROK, G6PD deficiency prevalence was investigated. Methods: Blood specimens from 1632 soldiers entering training camp for the 3 rd Infantry of the ROK Army were collected. CareStart ™ Biosensor for G6PD and haemoglobin (Hb) was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined. Results: Of 1632 blood specimens tested, none was observed to be G6PD deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants was analysed and categorized as partially low normal [n = 131, 30-80% (2.27-6.05 U/g Hb) of the median value], high [n = 3, > 150% (> 11.373 U/g Hb) of the median value], or normal [n = 36, 80-150% (6.05-11.373 U/g Hb) of the median value], and none was amplified by the DiaPlexC kit. Five silent mutations (C→T) in 131 partially low normal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 131 partially low normal specimens. Thus, it is inferred that these silent mutations could be related to G6PD activity. Conclusions: This G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. This study showed that the prevalence of G6PD deficiency among 1632 young soldiers was wholly absent. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, it is inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated haemolytic anaemia. However, given the number of individuals whose G6PD were at the partially low normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.

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Section: Introductionmentioning

confidence: 99%

Investigation of glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence in a Plasmodium vivax-endemic area in the Republic of Korea (ROK)

Lee

Lee³

et al. 2020

Malar J

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“…For example, in countries with P. vivax, the radical cure of hypnozoites is of great importance. Effective drugs such as primaquine and tafenoquine are available; however, their use is limited by the lack of point-of-care test for G6PD-deficient patients [75]. Population-based surveys looking at the different mutation variants associated with G6PD deficiency could provide useful baseline data for radical cure treatment policy in the absence of a validated POC test [76].…”

Section: Discussionmentioning

confidence: 99%

Strengthening Surveillance Systems for Malaria Elimination by Integrating Molecular and Genomic Data

Nsanzabana

2019

TropicalMed

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Unprecedented efforts in malaria control over the last 15 years have led to a substantial decrease in both morbidity and mortality in most endemic settings. However, these progresses have stalled over recent years, and resurgence may cause dramatic impact on both morbidity and mortality. Nevertheless, elimination efforts are currently going on with the objective of reducing malaria morbidity and mortality by 90% and malaria elimination in at least 35 countries by 2030. Strengthening surveillance systems is of paramount importance to reach those targets, and the integration of molecular and genomic techniques into routine surveillance could substantially improve the quality and robustness of data. Techniques such as polymerase chain reaction (PCR) and quantitative PCR (qPCR) are increasingly available in malaria endemic countries, whereas others such as sequencing are already available in a few laboratories. However, sequencing, especially next-generation sequencing (NGS), requires sophisticated infrastructure with adequate computing power and highly trained personnel for data analysis that require substantial investment. Different techniques will be required for different applications, and cost-effective planning must ensure the appropriate use of available resources. The development of national and sub-regional reference laboratories could help in minimizing the resources required in terms of equipment and trained staff. Concerted efforts from different stakeholders at national, sub-regional, and global level are needed to develop the required framework to establish and maintain these reference laboratories.

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“…Another factor to take into account is the possibility of failures in the metabolic activation of primaquine. To eliminate Plasmodium hypnozoites, primaquine has to be activated by the isoenzyme 2D6 of human cytochrome P450 (CYP2D6), which is converted to oxidized metabolites which are responsible for the anti-hypnozoites activity [ 21 – 23 ]. CYP2D6 is responsible for the metabolism of 20–25% of clinically used drugs, and there are more than 46 known major CYP2D6 alleles which can be determined and predict a CYP2D6 phenotype of metabolization (poor, intermediate, normal and ultrarapid) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function

Ramírez

González²,

Maniega

et al. 2020

Malar J

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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.

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8-Aminoquinoline Therapy for Latent Malaria

Cited by 103 publications

References 267 publications

Investigation of glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence in a Plasmodium vivax-endemic area in the Republic of Korea (ROK)

Investigation of glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence in a Plasmodium vivax-endemic area in the Republic of Korea (ROK)

Strengthening Surveillance Systems for Malaria Elimination by Integrating Molecular and Genomic Data

Several Plasmodium vivax relapses after correct primaquine treatment in a patient with impaired cytochrome P450 2D6 function

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