Patients’ adherence and clinical effectiveness of a 14-day course of primaquine when given with a 3-day chloroquine in patients with Plasmodium vivax at the Thai–Myanmar border

Cheoymang, Anurak; Ruenweerayut, Ronnatrai; Muhamad, Phunuch; Rungsihirunrat, Kanchana; Na‐Bangchang, Kesara

doi:10.1016/j.actatropica.2015.08.008

Cited by 19 publications

(26 citation statements)

References 39 publications

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“…Apart from the Indian subcontinent, there is very little use of primaquine in the private sector [ 37 , 38 ], which in many countries is the main source of antimalarial treatment. Reported adherence to unobserved 14-day radical cure regimens varies between different studies (adherence was considered poor in Papua Indonesia [ 48 ], where most patients are children; in 2 studies in Thailand [ 49 , 50 ]; and in studies from India, but good in other studies in Pakistan [an Afghan refugee camp] [ 51 ], Brazil [ 52 ], and the Thailand-Myanmar border [ 53 ]). This suggests that adherence is dependent on context and education practices.…”

Section: Discussionmentioning

confidence: 99%

Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries

2018

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Primaquine is the only available antimalarial drug that kills dormant liver stages of Plasmodium vivax and Plasmodium ovale malarias and therefore prevents their relapse (‘radical cure’). It is also the only generally available antimalarial that rapidly sterilises mature P. falciparum gametocytes. Radical cure requires extended courses of primaquine (usually 14 days; total dose 3.5–7 mg/kg), whereas transmissibility reduction in falciparum malaria requires a single dose (formerly 0.75 mg/kg, now a single low dose [SLD] of 0.25 mg/kg is recommended). The main adverse effect of primaquine is dose-dependent haemolysis in glucose 6-phosphate dehydrogenase (G6PD) deficiency, the most common human enzymopathy. X-linked mutations conferring varying degrees of G6PD deficiency are prevalent throughout malaria-endemic regions. Phenotypic screening tests usually detect <30% of normal G6PD activity, identifying nearly all male hemizygotes and female homozygotes and some heterozygotes. Unfortunately, G6PD deficiency screening is usually unavailable at point of care, and, as a consequence, radical cure is greatly underused. Both haemolytic risk (determined by the prevalence and severity of G6PD deficiency polymorphisms) and relapse rates vary, so there has been considerable uncertainty in both policies and practices related to G6PD deficiency testing and use of primaquine for radical cure. Review of available information on the prevalence and severity of G6PD variants together with countries’ policies for the use of primaquine and G6PD deficiency testing confirms a wide range of practices. There remains lack of consensus on the requirement for G6PD deficiency testing before prescribing primaquine radical cure regimens. Despite substantially lower haemolytic risks, implementation of SLD primaquine as a P. falciparum gametocytocide also varies. In Africa, a few countries have recently adopted SLD primaquine, yet many with areas of low seasonal transmission do not use primaquine as an antimalarial at all. Most countries that recommended the higher 0.75 mg/kg single primaquine dose for falciparum malaria (e.g., most countries in the Americas) have not changed their recommendation. Some vivax malaria–endemic countries where G6PD deficiency testing is generally unavailable have adopted the once-weekly radical cure regimen (0.75 mg/kg/week for 8 weeks), known to be safer in less severe G6PD deficiency variants. There is substantial room for improvement in radical cure policies and practices.

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Section: Discussionmentioning

confidence: 99%

Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries

2018

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“…35 Primaquine effectiveness is impacted not only by the dosing but also by the adherence of patients to the regimen for which robust data are also limited. [23][24][25]36 We assumed that in the referral strategy, women not using their referrals would not be given the option of primaquine at their initial consultation. Although this was chosen because it was economically conservative and programmatically straightforward, it would be problematic because it involves denying women the standard of care in Afghanistan, Indonesia, and Vietnam.…”

Section: Discussionmentioning

confidence: 99%

“…A value of 62% was used for the base case analysis of PQ7 based on a study conducted in Peru, 23 with a range of 25-95% around this estimate taken from the results of two studies of adherence in Thailand. 24,25 An assumption was made that the adherence to a complete course of treatment was reduced by 25% for PQ14 as compared with PQ7, and PQ8W was reduced by 50% ( Table 2). The equations used to calculate the expected number of recurrences are presented in the Supplemental Appendix.…”

Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness Analysis of Sex-Stratified Plasmodium vivax Treatment Strategies Using Available G6PD Diagnostics to Accelerate Access to Radical Cure

Devine

Howes

Price

et al. 2020

The American Journal of Tropical Medicine and Hygiene

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Tafenoquine has been licensed for the single-dose radical cure of Plasmodium vivax in adults; however, it is only recommended in patients with > 70% of normal glucose-6-phosphate dehydrogenase (G6PD) activity. Because this may hinder widespread use, we investigated sex-based treatment strategies in which all adult patients are tested with a qualitative G6PD rapid diagnostic test (RDT). Glucose-6-phosphate dehydrogenase normal males are prescribed tafenoquine in all three strategies, whereas G6PD normal females are prescribed either a low-dose 14-day primaquine regimen (PQ14, total dose 3.5 mg/kg) or a high-dose 7-day primaquine regimen (PQ7, total dose 7 mg/kg), or referred to a healthcare facility for quantitative G6PD testing before prescribing tafenoquine. Patients testing G6PD deficient are prescribed a weekly course of primaquine for 8 weeks. We compared the cost-effectiveness of these three strategies to usual care in four countries using a decision tree model. Usual care in Ethiopia does not include radical cure, whereas Afghanistan, Indonesia, and Vietnam prescribe PQ14 without G6PD screening. The cost per disability-adjusted life-year (DALY) averted was expressed through incremental cost-effectiveness ratios (ICERs).

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“…The most common cause of a recurrence is poor adherence to treatment. In the case of primaquine, this is highly variable in endemic areas, ranging from 62 to 95% of adherence [ 42 – 44 ]. Nevertheless, the patient of this study reinforced that she had completed the full dosage of primaquine in all episodes, and she attended to all follow-up doctor’s appointments.…”

Section: Discussionmentioning

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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Patients’ adherence and clinical effectiveness of a 14-day course of primaquine when given with a 3-day chloroquine in patients with Plasmodium vivax at the Thai–Myanmar border

Cited by 19 publications

References 39 publications

Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries

Use of primaquine and glucose-6-phosphate dehydrogenase deficiency testing: Divergent policies and practices in malaria endemic countries

Cost-Effectiveness Analysis of Sex-Stratified Plasmodium vivax Treatment Strategies Using Available G6PD Diagnostics to Accelerate Access to Radical Cure

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

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