Displaying publications 1 - 20 of 34 in total

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  1. 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
  2. Tan HS, Tan PE
    Ann Acad Med Singap, 1984 Apr;13(2):170-4.
    PMID: 6388486
    One hundred and ten consecutive patients with falciparum malaria were treated with Fansidar and primaquine. Of the 61 patients who were followed up at one week, 4 (6.6%) failed to clear their parasitaemia (1 R III and 3 R II treatment failures). Of the subsequent 40 patients who were seen again at one month, another 3 (7.5%) had recrudesced (R I treatment failure). A total of 7 patients thus experienced some form of treatment failure in the cohort of 40 who completed the one month follow up. Only 1 of these 7 patients (with R III treatment failure) failed to respond to repeat Fansidar treatment, and may be the only one with true Fansidar resistance. The overall treatment failure rate of 17.5% (95% confidence interval: 6-29%) in the cohort who completed the study is consistent with the known clinical efficacy of Fansidar. These results suggest no significant Fansidar resistance in falciparum malaria found in Sabah.
    Matched MeSH terms: Primaquine/therapeutic use
  3. Soo GW, Law JH, Kan E, Tan SY, Lim WY, Chay G, et al.
    Anticancer Drugs, 2010 Aug;21(7):695-703.
    PMID: 20629201
    Imatinib, a selective inhibitor of c-KIT and Bcr-Abl tyrosine kinases, approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, shows further therapeutic potential for gliomas, glioblastoma, renal cell carcinoma, autoimmune nephritis and other neoplasms. It is metabolized by CYP3A4, is highly bound to alpha-1-acid glycoprotein and is a P-glycoprotein substrate limiting its brain distribution. We assess imatinib's protein binding interaction with primaquine, which also binds to alpha-1-acid glycoprotein, and its metabolic interaction with ketoconazole, which is a CYP3A4 inhibitor, on its pharmacokinetics and biodistribution. Male ICR mice, 9-12 weeks old were given imatinib PO (50 mg/kg) alone or co-administered with primaquine (12.5 mg/kg), ketoconazole (50 mg/kg) or both, and imatinib concentration in the plasma, kidney, liver and brain was measured at prescheduled time points by HPLC. Noncompartmental pharmacokinetic parameters were estimated. Primaquine increased 1.6-fold plasma AUC(0)--> infinity, C(Max) decreased 24%, T(Max) halved and t(1/2) and mean residence time were longer. Ketoconazole increased plasma AUC(0)-->infinity 64% and doubled the C(Max), but this dose did not affect t(1/2) or mean residence time. When ketoconazole and primaquine were co-administered, imatinib AUC(0)-->infinity and C(Max) increased 32 and 35%, respectively. Ketoconazole did not change imatinib's distribution efficiency in the liver and kidney, primaquine increased it two-fold and it was larger when both the drugs were co-administered with imatinib. Ketoconazole did not change brain penetration but primaquine increased it approximately three-fold. Ketoconazole and primaquine affect imatinib clearance, bioavailability and distribution pattern, which could improve the treatment of renal and brain tumors, but also increase toxicity. This would warrant hepatic and renal functions monitoring.
    Matched MeSH terms: Primaquine/administration & dosage; Primaquine/pharmacology*
  4. 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
  5. Commons RJ, Simpson JA, Thriemer K, Chu CS, Douglas NM, Abreha T, et al.
    BMC Med, 2019 08 01;17(1):151.
    PMID: 31366382 DOI: 10.1186/s12916-019-1386-6
    BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.

    METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.

    RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p  25% to  5 g/dL.

    CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.

    TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

    Matched MeSH terms: Primaquine/adverse effects*
  6. 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*
  7. 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*
  8. Hong, Eric Qiu Weng, Cheo, Seng Wee, Low, Qin Jian
    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
  9. Daneshvar C, Davis TM, Cox-Singh J, Rafa'ee MZ, Zakaria SK, Divis PC, et al.
    Clin Infect Dis, 2009 Sep 15;49(6):852-60.
    PMID: 19635025 DOI: 10.1086/605439
    BACKGROUND: Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections.

    METHODS: In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.

    RESULTS: Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).

    CONCLUSIONS: Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.

    Matched MeSH terms: Primaquine/therapeutic use
  10. 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
  11. Elbashir AA, Saad B, Ali AS, Saleh MI
    J AOAC Int, 2008 6 24;91(3):536-41.
    PMID: 18567298
    A capillary electrophoresis (CE) method has been developed that allows the separation and estimation of primaquine enantiomers using hydroxypropyl-gamma-cyclodextrin (HP-gamma -CD) as a chiral selector. The influence of chemical and instrumental parameters on the separation, such as type and concentration of CD, buffer concentration, buffer pH, applied voltage, capillary temperature, and injection time, were investigated. Good separation of the racemic mixture of primaquine was achieved using a fused-silica capillary (52.5 cm effective length x 50 microm id) and a background electrolyte composed of tris-phosphate buffer solution (50 mM, pH 2.5) containing 15 mM HP-gamma-CD as a chiral selector. The recommended applied voltage, capillary temperature, and injection time were 15 kV, 25 degrees C, and 6 s, respectively. Within-day and interday reproducibility of peak area and migration time gave relative standard deviation values ranging from 1.05-3.30%. Good recoveries (range of 96.8-104.9%) were obtained from the determination of placebos that were spiked with 0.25-1.00 mg/L primaquine. The proposed CE method was successfully applied to the assay of primaquine diphosphate in pharmaceutical formulations (tablets).
    Matched MeSH terms: Primaquine/isolation & purification*; Primaquine/standards; Primaquine/chemistry*
  12. 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
  13. 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
  14. 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
  15. 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
  16. Cowan GO, Parry ES
    Lancet, 1968 Nov 02;2(7575):946-8.
    PMID: 4176265
    Matched MeSH terms: Primaquine/therapeutic use
  17. Daneshvar C, Davis TM, Cox-Singh J, Rafa'ee MZ, Zakaria SK, Divis PC, et al.
    Malar J, 2010;9:238.
    PMID: 20723228 DOI: 10.1186/1475-2875-9-238
    Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs.
    Matched MeSH terms: Primaquine/therapeutic use*
  18. 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
  19. Atroosh WM, Al-Mekhlafi HM, Snounou G, Al-Jasari A, Sady H, Nasr NA, et al.
    Malar J, 2016 05 27;15(1):295.
    PMID: 27234587 DOI: 10.1186/s12936-016-1344-0
    BACKGROUND: In Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes.

    METHODS: A 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification.

    RESULTS: Eighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced.

    CONCLUSION: In Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria.

    Matched MeSH terms: Primaquine
  20. Ley B, Thriemer K, Jaswal J, Poirot E, Alam MS, Phru CS, et al.
    Malar J, 2017 08 10;16(1):329.
    PMID: 28797255 DOI: 10.1186/s12936-017-1981-y
    BACKGROUND: Primaquine is essential for the radical cure of vivax malaria, however its broad application is hindered by the risk of drug-induced haemolysis in individuals with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Rapid diagnostic tests capable of diagnosing G6PD deficiency are now available, but these are not used widely.

    METHODS: A series of qualitative interviews were conducted with policy makers and healthcare providers in four vivax-endemic countries. Routine G6PD testing is not part of current policy in Bangladesh, Cambodia or China, but it is in Malaysia. The interviews were analysed with regard to respondents perceptions of vivax malaria, -primaquine based treatment for malaria and the complexities of G6PD deficiency.

    RESULTS: Three barriers to the roll-out of routine G6PD testing were identified in all sites: (a) a perceived low risk of drug-induced haemolysis; (b) the perception that vivax malaria was benign and accordingly treatment with primaquine was not regarded as a priority; and, (c) the additional costs of introducing routine testing. In Malaysia, respondents considered the current test and treat algorithm suitable and the need for an alternative approach was only considered relevant in highly mobile and hard to reach populations.

    CONCLUSIONS: Greater efforts are needed to increase awareness of the benefits of the radical cure of Plasmodium vivax and this should be supported by economic analyses exploring the cost effectiveness of routine G6PD testing.

    Matched MeSH terms: Primaquine/adverse effects*; Primaquine/therapeutic use*
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