High Efficacy of Primaquine Treatment for Plasmodium vivax in Western Thailand

Abstract

Abstract. Primaquine is the only licensed antimalarial drug that is capable of clearing dormant Plasmodium vivax liver stage parasites. To date, there is no clear evidence of resistance of the liver stage parasite against this drug, because of the difficulty in ascertaining the cause of recurrent infection. We followed 52 Thai P. vivax patients for 9 months after directly observed treatment of 15 mg primaquine daily for 14 days. Blood samples taken at 2-4 weekly intervals were assessed by microscopy and polymerase chain reaction (PCR) for the presence of parasites. Only four of 52 (7.7%) volunteers had recurrent P. vivax infections, all at least 8 weeks after treatment. This demonstrates that primaquine retains a high efficacy in this population. Although a risk of new infections could not be ruled out, parasite genotyping at two polymorphic markers suggested a high probability of late relapsing infections in these volunteers. Continued monitoring of primaquine efficacy in this region is advisable.Plasmodium vivax is widespread throughout southeast Asia, and is now considered the dominant parasite causing malaria within Thailand.

<p>Pharmacogene Variation in Thai <em>Plasmodium vivax</em> Relapse Patients Treated with a Combination of Primaquine and Chloroquine</p>

“…This study investigated the frequencies of sequence variations in eleven drug-metabolizing enzymes contributing to phase I (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3A5) and Phase II (COMT, SULT1A1, SULT1A4 and UGT2B7) metabolism of PQ and CQ as well as seven drug transporter genes (ABCB1, ABCA1, ABCC2, ABCC4, ABCG2, SLCO1B1 and SLC25A40) in 51 Thai patients infected with P. vivax. Although the influence of drug-metabolizing enzymes and drug transporters on the efficacy of PQ treatment on P. vivax infection has been studied, 7,14,16,27 their contribution to relapse is still unclear.…”

“…It has been reported that CYP2D6 metabolizer status influences PQ efficacy. 7,14 Bennette et al 7 first described that two study participants (6%), one PM with a CYP2D6*5/*6 genotype and one IM with a CYP2D6*4/*41 genotype signifying considerable decreased activity, had multiple relapses of P. vivax while participants with genotypes predicting normal metabolizer (NM) status were not found to relapse. Furthermore, relapse patients had significantly higher amounts of the parent drug PQ AUC inf (p<0.001) compared with non-relapse patients.…”

“…This exploratory investigation included 51 Thai patients from a previous study. 14 The study was approved by the Internal Ethics Review Committee on Human Research of the Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Thailand (MURA 2016/657) and conducted in accordance with the Declaration of Helsinki. Briefly, symptomatic P. vivax patients from the Tha Song Yang malaria clinic, Tak province, Thailand were recruited from April 2014 to September 2015; all patients gave written informed consent.…”

Naturally acquired antibody responses to more than 300 Plasmodium vivax proteins in three geographic regions

“…The longitudinal study in Thailand was conducted from April 2014 to September 2015, as described [ 21 ]. Briefly, 57 symptomatic P .…”

Dual Loading Of Primaquine And Chloroquine Into Liposome

“…In addition, the latent phase of hypnozoites in the liver often found in Plasmodium ovale and Plasmodium vivax infection can cause relapses in about 50-80% of malaria sufferers (Chu and White, 2016). Primaquine (PQ), recognized as the primary treatment for the hepatic phase of malaria (Longley et al, 2016), is an antimalarial pro-drug compound belonging to the 8-aminoquinoline group that actively works against sporozoites, hypnozoites, asexual phases and gametocytes through inhibition of the metabolic activity of mitochondrial parasites and the production of reactive metabolites, which are toxic to cells (Chu and White, 2016;Marcsisin et al, 2016). PQ constitutes a drug with a short half-life, which is rapidly metabolized by the liver into a carboxylic acid derivative ultimately excreted in the urine.…”