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  1. Enantioselective analysis of primaquine and its impurity quinocide by capillary electrophoresis
    Elbashir AA, Saad B, Ali AS, Saleh MI, Aboul-Enein HY
    Biomed Chromatogr, 2009 Mar;23(3):295-301.
    PMID: 18816453 DOI: 10.1002/bmc.1113
    A capillary electrophoretic (CE) method for the baseline separation of the enantiomers of primaquine diphosphate (PQ) and quinocide (QC) (a major contaminant) in pharmaceutical formulations is proposed. Both components were separated under the following conditions: 50 mm tris phosphate buffer (pH 3.0) containing 15 mm hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as background electrolyte; applied voltage, 16 kV; capillary temperature, 25 degrees C; detection wavelength, 254 nm; hydrostatic injection, 10 s. The separations were conducted using a 35 cm length and 50 microm i.d. uncoated fused silica capillary column. Under the optimized conditions, the components were successfully separated in about 5 min. Intraday precision of migration time and corrected peak areas when expressed as relative standard deviation ranged from 0.17 to 0.45 and 2.60 to 3.94%, respectively, while the interday precision ranged from 2.59 to 4.20 and 3.15 to 4.21%, respectively. After the validation exercise, the proposed method was applied for the determination of QC impurity in PQ formulations.
    Matched MeSH terms: Primaquine/chemistry*
  2. Determination of quinocide as impurity in primaquine tablets by capillary zone electrophoresis
    Elbashir AA, Saad B, Ali AS, Saleh MI, Aboul-Enein HY
    Biomed Chromatogr, 2009 May;23(5):464-71.
    PMID: 19016231 DOI: 10.1002/bmc.1137
    A capillary zone electrophoretic method has been developed and validated for the determination of the impurity quinocide (QC) in the antimalarial drug primaquine (PQ). Different buffer additives such as native cyclodextrins and crown ethers were evaluated. Promising results were obtained when either beta-cyclodextrin (beta-CD) or 18-crown-6 ether (18C6) were used. Their separation conditions such as type of buffer and its pH, buffer additive concentration, applied voltage capillary temperature and injection time were optimized. The use of 18C6 offers slight advantages over beta-CD such as faster elution times and improved resolution. Nevertheless, migration times of less than 5 min and resolution factors (R(s)) in the range of 2-4 were obtained when both additives were used. The method was validated with respect to selectivity, linearity, limits of detection and quantitation, analytical precision (intra- and inter-day variability) and repeatability. Concentrations of 2.12 and 2.71% (w/w) of QC were found in pharmaceutical preparations of PQ from two different manufacturers. A possible mechanism for the successful separation of the isomers is also discussed.
    Matched MeSH terms: Primaquine/chemistry*
  3. Fulltext Plasmodium knowlesi malaria in children
    Barber BE, William T, Jikal M, Jilip J, Dhararaj P, Menon J, et al.
    Emerg Infect Dis, 2011 May;17(5):814-20.
    PMID: 21529389 DOI: 10.3201/eid1705.101489
    Plasmodium knowlesi can cause severe malaria in adults; however, descriptions of clinical disease in children are lacking. We reviewed case records of children (age <15 years) with a malaria diagnosis at Kudat District Hospital, serving a largely deforested area of Sabah, Malaysia, during January-November 2009. Sixteen children with PCR-confirmed P. knowlesi monoinfection were compared with 14 children with P. falciparum monoinfection diagnosed by microscopy or PCR. Four children with knowlesi malaria had a hemoglobin level at admission of <10.0 g/dL (minimum lowest level 6.4 g/dL). Minimum level platelet counts were lower in knowlesi than in falciparum malaria (median 76,500/μL vs. 156,000/mL; p = 0.01). Most (81%) children with P. knowlesi malaria received chloroquine and primaquine; median parasite clearance time was 2 days (range 1-5 days). P. knowlesi is the most common cause of childhood malaria in Kudat. Although infection is generally uncomplicated, anemia is common and thrombocytopenia universal. Transmission dynamics in this region require additional investigation.
    Matched MeSH terms: Primaquine/therapeutic use
  4. Prophylaxis Failure Against Vivax Malaria in Guyana, South America
    Barrett JP, Behrens RH
    J Travel Med, 1996 Mar 01;3(1):60-61.
    PMID: 9815425
    Chloroquine-resistant Plasmodium vivax was originally reported in Papua, New Guinea by Reickman in 1989.1 In the same year, in Colombia, South America, Arias and Corredor2 reported relapses of 11 patients suffering from vivax malaria, following a chloroquine-primaquine regimen. Garavelli and Corti3 suggested chloroquine-resistant Plasmodium vivax may be present in Brazil following these therapeutic relapses. Further therapeutic failures in returned travelers from South America were reported by Moore et al (1994).4 We report vivax malaria in a group of expeditioners visiting Guyana who, whereas compliant with antimalarial chemoprophylaxis, developed clinical malaria, adding evidence to the presence of chloroquine-resistant Plasmodium vivax in South America. Raleigh International is a youth development charity that undertakes environmental and community projects around the world. These are usually in remote locations. Nine expeditions in countries such as Chile, Belize, Zimbabwe, Uganda, and Malaysia are organized annually. A project manager and a medical officer are placed at each site, along with approximately 10 venturers (age 17-25.) Participants are of all nationalities, but, at present, they are predominantly British.
    Matched MeSH terms: Primaquine
  5. Fulltext Cytochrome P450 2D6 (CYP2D6) and glucose-6-phosphate dehydrogenase (G6PD) genetic variations in Thai vivax malaria patients: Implications for 8-aminoquinoline radical cure
    Chamchoy K, Sudsumrit S, Thita T, Krudsood S, Patrapuvich R, Boonyuen U
    PLoS Negl Trop Dis, 2022 Dec;16(12):e0010986.
    PMID: 36508454 DOI: 10.1371/journal.pntd.0010986
    BACKGROUND: Primaquine and tafenoquine are the only licensed drugs that effectively kill the hypnozoite stage and are used to prevent Plasmodium vivax malaria relapse. However, both primaquine and tafenoquine can cause acute hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient people with varying degrees of severity depending on G6PD variants. Additionally, primaquine efficacy against malaria parasites was decreased in individuals with impaired cytochrome P450 2D6 (CYP2D6) activity due to genetic polymorphisms. This study aimed to characterize G6PD and CYP2D6 genetic variations in vivax malaria patients from Yala province, a malaria-endemic area along the Thai-Malaysian border, and determine the biochemical properties of identified G6PD variants.

    METHODOLOGY/PRINCIPLE FINDINGS: Multiplexed high-resolution melting assay and DNA sequencing detected five G6PD variants, including G6PD Kaiping, G6PD Vanua Lava, G6PD Coimbra, G6PD Mahidol, and G6PD Kerala-Kalyan. Biochemical and structural characterization revealed that G6PD Coimbra markedly reduced catalytic activity and structural stability, indicating a high susceptibility to drug-induced hemolysis. While Kerala-Kalyan had minor effects, it is possible to develop mild adverse effects when receiving radical treatment. CYP2D6 genotyping was performed using long-range PCR and DNA sequencing, and the phenotypes were predicted using the combination of allelic variants. Decreased and no-function alleles were detected at frequencies of 53.4% and 14.2%, respectively. The most common alleles were CYP2D6*36+*10 (25.6%), *10 (23.9%), and *1 (22.2%). Additionally, 51.1% of the intermediate metabolizers showed CYP2D6*10/*36+*10 as the predominant genotype (15.9%).

    CONCLUSIONS/SIGNIFICANCE: Our findings provide insights about genetic variations of G6PD and CYP2D6 in 88 vivax malaria patients from Yala, which may influence the safety and effectiveness of radical treatment. Optimization of 8-aminoquinoline administration may be required for safe and effective treatment in the studied population, which could be a significant challenge in achieving the goal of eliminating malaria.

    Matched MeSH terms: Primaquine/adverse effects
  6. A large focus of naturally acquired Plasmodium knowlesi infections in human beings
    Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, et al.
    Lancet, 2004 Mar 27;363(9414):1017-24.
    PMID: 15051281
    About a fifth of malaria cases in 1999 for the Kapit division of Malaysian Borneo had routinely been identified by microscopy as Plasmodium malariae, although these infections appeared atypical and a nested PCR assay failed to identify P malariae DNA. We aimed to investigate whether such infections could be attributable to a variant form of P malariae or a newly emergent Plasmodium species.
    Matched MeSH terms: Primaquine/therapeutic use
  7. Fulltext The challenges of introducing routine G6PD testing into radical cure: a workshop report
    Ley B, Luter N, Espino FE, Devine A, Kalnoky M, Lubell Y, et al.
    Malar J, 2015 Sep 29;14:377.
    PMID: 26416229 DOI: 10.1186/s12936-015-0896-8
    The only currently available drug that effectively removes malaria hypnozoites from the human host is primaquine. The use of 8-aminoquinolines is hampered by haemolytic side effects in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Recently a number of qualitative and a quantitative rapid diagnostic test (RDT) format have been developed that provide an alternative to the current standard G6PD activity assays. The WHO has recently recommended routine testing of G6PD status prior to primaquine radical cure whenever possible. A workshop was held in the Philippines in early 2015 to discuss key challenges and knowledge gaps that hinder the introduction of routine G6PD testing. Two point-of-care (PoC) test formats for the measurement of G6PD activity are currently available: qualitative tests comparable to malaria RDT as well as biosensors that provide a quantitative reading. Qualitative G6PD PoC tests provide a binomial test result, are easy to use and some products are comparable in price to the widely used fluorescent spot test. Qualitative test results can accurately classify hemizygous males, heterozygous females, but may misclassify females with intermediate G6PD activity. Biosensors provide a more complex quantitative readout and are better suited to identify heterozygous females. While associated with higher costs per sample tested biosensors have the potential for broader use in other scenarios where knowledge of G6PD activity is relevant as well. The introduction of routine G6PD testing is associated with additional costs on top of routine treatment that will vary by setting and will need to be assessed prior to test introduction. Reliable G6PD PoC tests have the potential to play an essential role in future malaria elimination programmes, however require an improved understanding on how to best integrate routine G6PD testing into different health settings.
    Matched MeSH terms: Primaquine/adverse effects; Primaquine/therapeutic use
  8. Fulltext Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax
    Anjani QK, Volpe-Zanutto F, Hamid KA, Sabri AHB, Moreno-Castellano N, Gaitán XA, et al.
    J Control Release, 2023 Sep;361:385-401.
    PMID: 37562555 DOI: 10.1016/j.jconrel.2023.08.009
    Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine and chloroquine, but they have limitations, such as poor adherence due to frequent oral administration and gastrointestinal side effects. To overcome these limitations, we have developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) for the intradermal delivery of these drugs. In vitro testing showed that these systems can deliver to skin and receiver compartment up to ≈60% of the payload for CQ-based dissolving MAPs and a total of ≈42% of drug loading for PQ-based dissolving MAPs. MAPs also displayed acceptable biocompatibility in cell tests. Pharmacokinetic studies in rats showed that dissolving MAPs could deliver sustained plasma levels of both PQ and CQ for over 7 days. Efficacy studies in a murine model for malaria showed that mice treated with PQ-MAPs and CQ-MAPs had reduced parasitaemia by up to 99.2%. This pharmaceutical approach may revolutionise malaria vivax treatment, especially in developing countries where the disease is endemic. The development of these dissolving MAPs may overcome issues associated with current pharmacotherapy and improve patient outcomes.
    Matched MeSH terms: Primaquine/pharmacology; Primaquine/therapeutic use
  9. An Australian experience with malaria
    George CR, O'Neill BJ, Garth JM
    Med J Aust, 1971 May 22;1(21):1110-3.
    PMID: 4932319
    Matched MeSH terms: Primaquine/therapeutic use
  10. [The first monkey malaria in Turkey: a case of Plasmodium knowlesi]
    Özbilgin A, Çavuş İ, Yıldırım A, Gündüz C
    Mikrobiyol Bul, 2016 Jul;50(3):484-90.
    PMID: 27525405
    Plasmodium knowlesi is now added to the known four Plasmodium species (P.vivax, P.falciparum, P.malariae, P.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern Asia. P.knowlesi which infects macaque monkeys (Macaca fascicularis and M.nemestrina) is transmitted to humans especially by Anopheles leucosphyrus and An.hackeri mosquitos. First human cases of P.knowlesi malaria have been detected in Malaysia which have reached high numbers in recent years and also have been reported from countries of Southeast Asia such as Thailand, Philippines, Myanmar, Singapore and Vietnam. However the number of cases reported from western countries are rare and limited only within voyagers. This report is the first presentation of an imported case of P.knowlesi malaria in Turkey and aims to draw attention to the point that it could also be detected in future. A 33-year-old male patient from Myanmar who has migrated to Turkey as a refugee, was admitted to a health center with the complaints of fever with a periodicity of 24 hours, headache, fatigue, cough, sore throat, anorexia, myalgia and arthralgia. He was prediagnosed as upper respiratory tract infection, however because of his periodical fever and background in Myanmar, thick and thin blood films were prepared and sent to our laboratory for further examinations. Microscopic examination of the thin blood films revealed erythrocytic stages compatible with P.knowlesi (three large early trophozoites in an erythrocyte, three late trophozoites with compact view, and three late band-form trophozoites). Upon this, both real-time polymerase chain reaction (Rt-PCR) targeting the small subunit ribosomal RNA (SSU-rRNA) genes of Plasmodium genus and DNA sequence analysis targeting P.knowlesi rRNA gene were performed. As a result, the suspected identification of P.knowlesi by microscopy was confirmed by Rt-PCR and DNA sequencing. The patient was treated with chloroquine and primaquine combination and in the follow-up on the seventh day after the treatment, his parasitemia and symptoms had ceased. Although there were some previous reports concerning about imported patients infected with different Plasmodium species in our country, no cases of P.knowlesi have been reported. This first case presented here emphasizes the occurence of P.knowlesi malaria in Turkey hereinafter due to the increasing number of refugees.
    Matched MeSH terms: Primaquine/therapeutic use
  11. Fulltext Factors Affecting Primaquine Combination Treatment in Malaria Patients in Selangor, Malaysia
    Ariffin NM, Islahudin F, Makmor-Bakry M, Kumolosasi E, Hamid MHA
    J Pharm Bioallied Sci, 2017 Oct-Dec;9(4):239-245.
    PMID: 29456374 DOI: 10.4103/jpbs.JPBS_48_17
    Introduction: Primaquine is vital for the management of liver-stagePlasmodium vivaxandPlasmodium ovalemalaria. However, primaquine effectiveness is dependent on various factors and differs between populations. Therefore, this study was conducted to identify factors that affect the length of stay and relapse during primaquine combination treatment in malaria-infected patients in the local setting.

    Materials and Methods: A retrospective study on the use of primaquine combination amongP. vivaxandP. ovaleinfected patients in Selangor, Malaysia within a 5-year period from 2011 to 2015 was obtained from the National Malaria Case Registry, Malaysia. Data collected were patient characteristics (age, gender, nationality, glucose-6-phosphate dehydrogenase, pregnancy); disease characteristics (survival, past malaria infection, parasite type, presence of gametocyte, parasite count, week onset, severity, transmission type); and treatment characteristics (type of antimalarial, treatment completion). Outcome measures were length of stay and relapse during a 1-year follow-up.

    Results: A total of 635 patients were included in the study. Based on a multivariate logistic regression analysis, the significant predictors for length of stay were gender (P= 0.009) and indigenous transmission (P< 0.001). Male patients had a shorter length of stay than females by 0.868 days (P= 0.009), and indigenous transmission took 1.82 days more compared to nonindigenous transmission (P< 0.001). Predictors for relapse were indigenous transmission of malaria (P= 0.019), which was 15.83 times more likely to relapse than nonindigenous transmission (P< 0.01).

    Conclusions: This study reveals that the effectiveness of primaquine was clinically associated with gender and indigenous transmission. To that end, vigilant monitoring of primaquine use is required to reduce relapse and future transmission.
    Matched MeSH terms: Primaquine
  12. Fulltext Malaria resurgence after significant reduction by mass drug administration on Ngodhe Island, Kenya
    Kagaya W, Gitaka J, Chan CW, Kongere J, Md Idris Z, Deng C, et al.
    Sci Rep, 2019 12 13;9(1):19060.
    PMID: 31836757 DOI: 10.1038/s41598-019-55437-8
    Although WHO recommends mass drug administration (MDA) for malaria elimination, further evidence is required for understanding the obstacles for the optimum implementation of MDA. Just before the long rain in 2016, two rounds of MDA with artemisinin/piperaquine (Artequick) and low-dose primaquine were conducted with a 35-day interval for the entire population of Ngodhe Island (~500 inhabitants) in Lake Victoria, Kenya, which is surrounded by areas with moderate and high transmission. With approximately 90% compliance, Plasmodium prevalence decreased from 3% to 0% by microscopy and from 10% to 2% by PCR. However, prevalence rebounded to 9% by PCR two months after conclusion of MDA. Besides the remained local transmission, parasite importation caused by human movement likely contributed to the resurgence. Analyses of 419 arrivals to Ngodhe between July 2016 and September 2017 revealed Plasmodium prevalence of 4.6% and 16.0% by microscopy and PCR, respectively. Risk factors for infection among arrivals included age (0 to 5 and 11 to 15 years), and travelers from Siaya County, located to the north of Ngodhe Island. Parasite importation caused by human movement is one of major obstacles to sustain malaria elimination, suggesting the importance of cross-regional initiatives together with local vector control.
    Matched MeSH terms: Primaquine/adverse effects; Primaquine/pharmacology; Primaquine/therapeutic use
  13. The treatment of malaria in glucose-6-phosphate dehydrogenase deficient patients in Sabah
    Khoo KK
    Ann Trop Med Parasitol, 1981 Dec;75(6):591-5.
    PMID: 7325735 DOI: 10.1080/00034983.1981.11687489
    One hundred and nine (9·8%) out of 1103 malaria patients examined in Sabah were deficient in glucose-6-phosphate dehydrogenase (G6PD). Sixty-nine of these G6PD-deficient patients were randomly allocated to one of three treatment regimes with (a) chloroquine, (b) chloroquine and primaquine or (c) sulfadoxine-pyrimethamine (Fansidar). No haemolysis was observed in group (a); except for a single mild case, no haemolysis was seen in group (c). However, in the primaquine group (23 patients), haemolysis occurred in seven of the 16 patients who had complete G6PD deficiency. Of these seven, five required blood transfusion and the other two developed acute renal failure, one requiring peritoneal dialysis. In the Fansidar group (c), four of the 22 patients took more than 15 days to clear the parasitaemia. Chloroquine resistance to falciparum infection was common in the patients given this anti-malarial.
    Study site: Queen Elizabeth Hospital, Kola Kinabalu, Sabah, Malaysia
    Matched MeSH terms: Primaquine/adverse effects; Primaquine/therapeutic use
  14. Case report: recurrence of Plasmodium vivax malaria due to defective cytochrome P450 2D6 function in Pos Lenjang, Pahang, Malaysia
    Mat Salleh NH, Rahman MFA, Samsusah S, De Silva JR, Ng DC, Ghozali AH, et al.
    Trans R Soc Trop Med Hyg, 2020 Sep 01;114(9):700-703.
    PMID: 32511702 DOI: 10.1093/trstmh/traa042
    Five children in Pos Lenjang, Pahang, Malaysia were PCR-positive for vivax malaria and were admitted to the hospital from 5 to 26 July 2019. One of the patients experienced three episodes of recurrence of vivax malaria. Microsatellite analysis showed that reinfection is unlikely. Drug resistance analysis indicated that Riamet (artemether-lumefantrine) is effective. Cytochrome P450 2D6 (CYP2D6) testing showed that this patient has defective CYP2D6 function. Primaquine failure to clear the Plasmodium vivax hypnozoites may be the cause of recurring infections in this patient. This report highlights the need for the development of liver-stage curative antimalarials that do not require metabolism by the CYP2D6 enzyme.
    Matched MeSH terms: Primaquine/therapeutic use
  15. [Diagnosis and Treatment of the First Imported Case of Plasmodium knowlesi Infection in China]
    Pan B, Pei FQ, Ruan CW, Lin RX, Cen YZ, Liu MR, et al.
    Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi, 2016 12;34(6):513-6.
    PMID: 30141606
    Objective: To diagnose and treat the first imported active case of Plasmodium knowlesi infection in China.

    Methods: The clinical information of the patient was collected. Microscopy of blood smear was conducted after Giemsa staining. Genomic DNA was extracted from blood, and PCR was conducted to amplify rDNA. The PCR products were sequenced and analyzed with BLAST

    Results: The patient returned from a one-week tour in a tropical rain forest in Malaysia. The first disease attack occurred in Guangzhou on Oct. 16, 2014, with fever, shivering and sweating. The patient was initially diagnosed as malaria and hospitalized on Oct. 26, 2014. Microscopic observation revealed typical forms of P. knowlesi in blood smear. The red blood cells became enlarged, with big trophozoites appearing as a ring with dual cores and dark brown malaria pigment. The trophozoites were slightly bigger and thicker than P. falciparum. The schizont had 6-8 merozoites, with obvious brown malaria pigment. PCR resulted in a specific band of 1 099 bp. BLAST analysis showed that the sequence of the PCR product was 99% homologous to P. knowlesi (acession No. AM910985.1, L07560.1 and AY580317.1). The patient was diagnosed as P. knowlesi infection, and was then given an 8-day treatment with chloroquine and primaquine, together with dihydroartemisinin piperaquine phosphate tablet. The patient was discharged after recovery on Oct. 28, 2014.

    Conclusion: According to the clinical symptoms, epidemiological history and laboratory test, the patient has been confirmed as P. knowlesi infection. It may also be the first active case of knowlesi malaria reported in China.

    Matched MeSH terms: Primaquine
  16. Fulltext An unusual case of concurrent dengue and malaria infection
    Hong, Eric Qiu Weng, Cheo, Seng Wee, Low, Qin Jian
    Borneo Journal of Medical Sciences, 2021;15(1):57-60.
    MyJurnal
    Dengue and malaria infections are common mosquito-borne infectious diseases in tropical and subtropical regions. The clinical manifestations of dengue and malaria often mimic each other, causing the predicament of early diagnosis without laboratory investigations. Concurrent dengue and malaria infection are often rare scenarios when both diseases occur in a particular patient at the same time. A high index of suspicion is therefore required to establish an early diagnosis to ensure complete success in its management. This case report is about concurrent dengue and malaria infection in a 54-year-old Pakistani man who presented with high-grade fever for three days before admission. On examination, he was febrile (38.8°C) with no other findings. His blood investigations were positive for NS1 antigen and IgM but negative for IgG. His peripheral blood film revealed the presence of Plasmodium vivax. He was treated for dengue fever with supportive management and started with oral Riamet (artemether and lumefantrine) along with oral primaquine 30 mg daily for two weeks’ duration. Following treatment, the patient demonstrated progressive clinical improvement and was subsequently discharged back to the community clinic for the continuation of care.
    Matched MeSH terms: Primaquine
  17. Effects of MAO-A and CYP450 on primaquine metabolism in healthy volunteers
    Ariffin NM, Islahudin F, Kumolosasi E, Makmor-Bakry M
    Parasitol Res, 2019 Mar;118(3):1011-1018.
    PMID: 30706164 DOI: 10.1007/s00436-019-06210-3
    Eliminating the Plasmodium vivax malaria parasite infection remains challenging. One of the main problems is its capacity to form hypnozoites that potentially lead to recurrent infections. At present, primaquine is the only drug used for the management of hypnozoites. However, the effects of primaquine may differ from one individual to another. The aim of this work is to determine new measures to reduce P. vivax recurrence, through primaquine metabolism and host genetics. A genetic study of MAO-A, CYP2D6, CYP1A2 and CYP2C19 and their roles in primaquine metabolism was undertaken of healthy volunteers (n = 53). The elimination rate constant (Ke) and the metabolite-to-parent drug concentration ratio (Cm/Cp) were obtained to assess primaquine metabolism. Allelic and genotypic analysis showed that polymorphisms MAO-A (rs6323, 891G>T), CYP2D6 (rs1065852, 100C>T) and CYP2C19 (rs4244285, 19154G>A) significantly influenced primaquine metabolism. CYP1A2 (rs762551, -163C>A) did not influence primaquine metabolism. In haplotypic analysis, significant differences in Ke (p = 0.00) and Cm/Cp (p = 0.05) were observed between individuals with polymorphisms, GG-MAO-A (891G>T), CT-CYP2D6 (100C>T) and GG-CYP2C19 (19154G>A), and individuals with polymorphisms, TT-MAO-A (891G>T), TT-CYP2D6 (100C>T) and AA-CYP2C19 (19154G>A), as well as polymorphisms, GG-MAO-A (891G>T), TT-CYP2D6 (100C>T) and GA-CYP2C19 (19154G>A). Thus, individuals with CYP2D6 polymorphisms had slower primaquine metabolism activity. The potential significance of genetic roles in primaquine metabolism and exploration of these might help to further optimise the management of P. vivax infection.
    Matched MeSH terms: Primaquine/metabolism*
  18. Fulltext A clinical tool to predict Plasmodium vivax recurrence in Malaysia
    Mat Ariffin N, Islahudin F, Kumolosasi E, Makmor-Bakry M
    BMC Infect Dis, 2017 12 08;17(1):759.
    PMID: 29216842 DOI: 10.1186/s12879-017-2868-9
    BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia.

    METHODS: Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation.

    RESULTS: Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value 

    Matched MeSH terms: Primaquine/therapeutic use
  19. Prophylactic and sporontocidal treatment of chloroquine resistant Plasmodium falciparum from Malaya
    Clyde DF, DuPont HL, Miller RM, McCarthy VC
    Trans R Soc Trop Med Hyg, 1970;64(6):834-8.
    PMID: 4924648
    Matched MeSH terms: Primaquine/therapeutic use
  20. Choroquine-resistant Plasmodium falciparum malaria in the United Kingdom
    Cowan GO, Parry ES
    Lancet, 1968 Nov 02;2(7575):946-8.
    PMID: 4176265
    Matched MeSH terms: Primaquine/therapeutic use
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