Displaying publications 81 - 100 of 143 in total

Abstract:
Sort:
  1. Molecular markers associated with resistance to commonly used antimalarial drugs among Plasmodium falciparum isolates from a malaria-endemic area in Taiz governorate-Yemen during the transmission season
    Alareqi LMQ, Mahdy MAK, Lau YL, Fong MY, Abdul-Ghani R, Mahmud R
    Acta Trop, 2016 Oct;162:174-179.
    PMID: 27343362 DOI: 10.1016/j.actatropica.2016.06.016
    Since 2005, artesunate (AS) plus sulfadoxine/pyrimethamine (SP) combination has been adopted as the first-line treatment for uncomplicated malaria in Yemen in response to the high level of Plasmodium falciparum resistance to chloroquine (CQ). Therefore, the aim of the present study was to determine the frequency distribution of molecular markers associated with resistance to CQ and AS plus SP combination among P. falciparum isolates from a malaria-endemic area in Taiz governorate, Yemen. Fifty P. falciparum isolates were collected during a cross-sectional study in Mawza district, Taiz, in the period from October 2013 to April 2014. The isolates were investigated for drug resistance-associated molecular markers in five genes, including P. falciparum CQ resistance transporter (pfcrt) 76T and P. falciparum multidrug resistance 1 (pfmdr1) 86Y as markers of resistance to CQ, mutations in the Kelch 13 (K13) propeller domain for resistance to AS, and P. falciparum dihydrofolate reductase (pfdhfr) and P. falciparum dihydropteroate synthase (pfdhps) genes for resistance to SP. Nested polymerase chain reaction was used to amplify target genes in DNA extracts of the isolates followed by restriction fragment length polymorphism for detecting 76T and 86Y mutations in pfcrt and pfmdr1, respectively, and by DNA sequencing for detecting mutations in K13, pfdhfr and pfdhps. All the investigated isolates from Mawza district were harboring the pfcrt 76T mutant and the pfmdr1 N86 wild-type alleles. The pfdhfr 51I/108N double mutant allele was found in 2.2% (1/45) of the isolates; however, no mutations were detected at codons 436, 437, 540, 581 and 613 of pfdhps. All P. falciparum isolates that were successfully sequenced (n=47) showed the K13 Y493, R539, I543 and C580 wild-type alleles. In conclusion, the pfcrt 76T mutant allele is fixed in the study area about six years after the official withdrawal of CQ, possibly indicating its over-the-counter availability and continued use as a self-medication in the study area. However, the almost predominant wild-type alleles of the genes associated with resistance to AS and SP among P. falciparum isolates in the present study indicates the sustained efficacy of the currently adopted first-line treatment of AS plus SP in the study area.
    Matched MeSH terms: Chloroquine/pharmacology
  2. Nephropathy in Malaria
    Wolthuis FH
    Trop Geogr Med, 1968 Mar;20(1):21-7.
    PMID: 4868143
    Matched MeSH terms: Chloroquine/therapeutic use
  3. Fulltext No Association between the Plasmodium vivax crt-o MS334 or In9pvcrt Polymorphisms and Chloroquine Failure in a Pre-Elimination Clinical Cohort from Malaysia with a Large Clonal Expansion
    Rumaseb A, Moraes Barros RR, Sá JM, Juliano JJ, William T, Braima KA, et al.
    Antimicrob Agents Chemother, 2023 Jul 18;67(7):e0161022.
    PMID: 37314336 DOI: 10.1128/aac.01610-22
    Increasing reports of resistance to a frontline malaria blood-stage treatment, chloroquine (CQ), raises concerns for the elimination of Plasmodium vivax. The absence of an effective molecular marker of CQ resistance in P. vivax greatly constrains surveillance of this emerging threat. A recent genetic cross between CQ sensitive (CQS) and CQ resistant (CQR) NIH-1993 strains of P. vivax linked a moderate CQR phenotype with two candidate markers in P. vivax CQ resistance transporter gene (pvcrt-o): MS334 and In9pvcrt. Longer TGAAGH motif lengths at MS334 were associated with CQ resistance, as were shorter motifs at the In9pvcrt locus. In this study, high-grade CQR clinical isolates of P. vivax from a low endemic setting in Malaysia were used to investigate the association between the MS334 and In9pvcrt variants and treatment efficacy. Among a total of 49 independent monoclonal P. vivax isolates assessed, high-quality MS334 and In9pvcrt sequences could be derived from 30 (61%) and 23 (47%), respectively. Five MS334 and six In9pvcrt alleles were observed, with allele frequencies ranging from 2 to 76% and 3 to 71%, respectively. None of the clinical isolates had the same variant as the NIH-1993 CQR strain, and none of the variants were associated with CQ treatment failure (all P > 0.05). Multi-locus genotypes (MLGs) at 9 neutral microsatellites revealed a predominant P. vivax strain (MLG6) accounting for 52% of Day 0 infections. The MLG6 strain comprised equal proportions of CQS and CQR infections. Our study reveals complexity in the genetic basis of CQ resistance in the Malaysian P. vivax pre-elimination setting and suggests that the proposed pvcrt-o MS334 and In9pvcrt markers are not reliable markers of CQ treatment efficacy in this setting. Further studies are needed in other endemic settings, applying hypothesis-free genome-wide approaches, and functional approaches to understand the biological impact of the TGAAGH repeats linked to CQ response in a cross are warranted to comprehend and track CQR P. vivax.
    Matched MeSH terms: Chloroquine/pharmacology; Chloroquine/therapeutic use
  4. Opisthorchis viverrini (Poirier, 1886) a trematode parasite of man in West Malaysia
    Bisseru B, Chong LK
    Trop Geogr Med, 1969 Jun;21(2):138-46.
    PMID: 5816416
    Matched MeSH terms: Chloroquine/therapeutic use
  5. Phagocytosis of malaria-infected erythrocytes in rodent malaria
    Rain AN, Roxas CC, Mak JW
    Southeast Asian J. Trop. Med. Public Health, 1993 Jun;24(2):388-90.
    PMID: 8266248
    Matched MeSH terms: Chloroquine/therapeutic use
  6. Fulltext Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as MPro inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
    Law WY, Asaruddin MR, Bhawani SA, Mohamad S
    BMC Res Notes, 2020 Nov 11;13(1):527.
    PMID: 33176880 DOI: 10.1186/s13104-020-05379-6
    OBJECTIVES: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions.

    RESULTS: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent MPro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant MPro inhibition.

    Matched MeSH terms: Chloroquine/pharmacology*; Chloroquine/chemistry; Hydroxychloroquine/pharmacology; Hydroxychloroquine/chemistry
  7. Fulltext Pharmacotherapeutic considerations for systemic rheumatic diseases amid the COVID-19 pandemic: more questions than answers
    Kow CS, Hasan SS
    Drugs Ther Perspect, 2020 Aug 16.
    PMID: 32837197 DOI: 10.1007/s40267-020-00767-1
    Thus far, associations between the presence of systemic rheumatic disease and an increased risk of novel coronavirus disease 2019 (COVID-19) acquisition or a worse prognosis from COVID-19 have not been conclusive. It is not known for certain if there is an association between any pharmacological agent used for rheumatologic treatment, including biological and non-biological disease-modifying antirheumatic drugs (DMARDs), and an increased risk of COVID-19 acquisition or adverse outcomes from COVID-19, although these agents have been associated with an overall higher risk of infections. The pharmacological management of patients with a rheumatic disease without COVID-19 should currently follow usual treatment approaches. Individualized approaches to adjusting DMARD regimens in patients with documented COVID-19 seems prudent, with specific attention paid to the severity of the infection. Patients receiving antimalarials (hydroxychloroquine/chloroquine) may continue treatment with these agents. Treatment with sulfasalazine, methotrexate, leflunomide, immunosuppressants and biological agents other than interluekin-6 receptor inhibitors and JAK inhibitors should be stopped or withheld. It should be reasonable to resume DMARD treatment when patients are no longer symptomatic and at least 2 weeks after documentation of COVID-19, although the decision should be individualized, preferably based on infection severity.
    Matched MeSH terms: Chloroquine; Hydroxychloroquine
  8. Fulltext Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology
    Callaghan PS, Siriwardana A, Hassett MR, Roepe PD
    Malar J, 2016;15(1):186.
    PMID: 27036417 DOI: 10.1186/s12936-016-1238-1
    Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT).
    Matched MeSH terms: Chloroquine
  9. Plasmodium falciparum: increased proportion of severe resistance (RII and RIII) to chloroquine and high rate of resistance to sulfadoxine-pyrimethamine in Peninsular Malaysia after two decades
    Lokman Hakim S, Sharifah Roohi SW, Zurkurnai Y, Noor Rain A, Mansor SM, Palmer K, et al.
    Trans R Soc Trop Med Hyg, 1996 5 1;90(3):294-7.
    PMID: 8758083
    Uncomplicated falciparum malaria patients were randomly assigned to receive either 25 mg/kg chloroquine (CHL) over 3 d or a statim dose of 25 mg/kg sulfadoxine (SDX) plus 1.25 mg/kg pyrimethamine (PYR). Patients were followed up for 28 d and the parasite response graded according to World Health Organization criteria. Overall resistance to CHL was 63.3% and 47.4% to SDX/PYR. RI, RII and RIII rates were 9.1%, 42.4% and 12.1% for CHL and 10.5%, 21.1% and 15.8% for SDX/PYR, respectively. Degree and rates of resistance to CHL were significantly correlated with pre-treatment parasite density, but not those to SDX/PYR. Plasma CHL and SDX/PYR levels were within the reported ranges and were not significantly different in patients with sensitive and resistant responses.
    Matched MeSH terms: Chloroquine/blood; Chloroquine/therapeutic use*
  10. Plasmodium hylobati: a malaria parasite of the gibbon
    Collins WE, Contacos PG, Garnham PC, Warren M, Skinner JC
    J Parasitol, 1972 Feb;58(1):123-8.
    PMID: 4335047
    Matched MeSH terms: Chloroquine/therapeutic use
  11. Fulltext Plasmodium knowlesi infection: a diagnostic challenge
    Fan L, Lee SY, Koay E, Harkensee C
    BMJ Case Rep, 2013;2013:bcr2013009558.
    PMID: 23608876 DOI: 10.1136/bcr-2013-009558
    Plasmodium knowlesi malaria is an uncommon, but highly prevalent parasitic infection in parts of Malaysia. This is the case of a 14-year-old Singaporean boy presenting to our emergency department with an 11-day history of fever following a school trip to Malaysia. Hepatosplenomegaly was the only clinical finding; laboratory tests showed thrombocytopaenia, lymphopaenia, mild anaemia and liver transaminitis. Specific malaria antigen tests were negative, but the peripheral blood film showed plasmodia with atypical features, with a parasite load of 0.5%. PCR confirmed the diagnosis of P knowlesi. The patient was successfully treated with chloroquine. The clinical course of P knowlesi malaria is indistinguishable from that of Plasmodium falciparum. This case highlights the importance of taking detailed travel history, careful examination of malaria blood films and judicious use of molecular techniques. Antigen tests alone may have missed a malaria diagnosis altogether, while blood film examination may wrongly identify the species as Plasmodium malariae or P falciparum. Third-generation PCR assays can be used to reliably identify P knowlesi.
    Matched MeSH terms: Chloroquine/therapeutic use
  12. 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: Chloroquine/therapeutic use
  13. Plasmodium knowlesi: from Malaysia, a novel health care threat
    Sabbatani S, Fiorino S, Manfredi R
    Infez Med, 2012 Mar;20(1):5-11.
    PMID: 22475654
    Epidemic foci of Plasmodium knowlesi malaria have been identified during the past ten years in Malaysia, in particular in the States of Sarawak and Sabah (Malaysia Borneo), and in the Pahang region (peninsular Malaysia). Based on a review of the available recent international literature, the authors underline the importance of molecular biology examinations, polymerase chain reactions (PCR), performed with primers specific for P. knowlesi, since the current microscopic examination (haemoscope) may fail to distinguish P. knowlesi from Plasmodium malariae, due to the very similar appearance of the two parasites. P. knowlesi has been described as the causal agent of life-threatening and lethal forms of malaria: its clinical picture is more severe when compared with that of P. malariae, since the disease is characterized by greater parasitaemia, as opposed to that documented in the course of P. malariae disease. The most effective carrier is Anopheles leucosphyrus: this mosquito is attracted by both humans and monkeys. Among primates, the natural hosts of P. knowlesi are Macaca fascicularis and Macaca nemestina, while Saimiri scirea and Macaca mulatta, which cannot become infected in nature, may be useful in experimental models. When underlining the potentially severe evolution, we note the key role played by prompt disease recognition, which is expected to be more straightforward in patients monitored in endemic countries at high risk, but should be carefully implemented for subjects being admitted to hospital in Western countries suffering from the typical signs and symptoms of malaria, after travelling in South-East Asia where they were engaged in excursions in the tropical forest (trekking, and similar outdoor activities). In these cases, the diagnosis should be prompt, and suitable treatment should follow. According to data in the literature, in non-severe cases chloroquine proves very effective against P. knowlesi, achieving the disappearance of signs and symptoms in 96% of cases after only 24 hours after treatment start. In the light of the emerging epidemiological data, P. knowlesi should be added to Plasmodium vivax, Plasmodium ovale, P. malariae, and Plasmodium falciparum, as the fifth aetiological agent of malaria. During the next few years, it will become mandatory to plan an appropriate surveillance program of the epidemiological evolution, paying also great attention to the clinical features of patients affected by P. knowlesi malaria, which are expected to worsen according to the time elapsed; some studies seem to point out greater severity according to increased parasitaemia, paralleling the increased interhuman infectious passages of the plasmodium.
    Matched MeSH terms: Chloroquine/therapeutic use
  14. Plasmodium knowlesi: the emerging zoonotic malaria parasite
    Antinori S, Galimberti L, Milazzo L, Corbellino M
    Acta Trop, 2013 Feb;125(2):191-201.
    PMID: 23088834 DOI: 10.1016/j.actatropica.2012.10.008
    Plasmodium knowlesi was initially identified in the 30s as a natural Plasmodium of Macaca fascicularis monkey also capable of experimentally infecting humans. It gained a relative notoriety in the mid-30s as an alternative to Plasmodium vivax in the treatment of the general paralysis of the insane (neurosyphilis). In 1965 the first natural human infection was described in a US military surveyor coming back from the Pahang jungle of the Malaysian peninsula. P. knowlesi was again brought to the attention of the medical community when in 2004, Balbir Singh and his co-workers reported that about 58% of malaria cases observed in the Kapit district of the Malaysian Borneo were actually caused by P. knowlesi. In the following years several reports showed that P. knowlesi is much more widespread than initially thought with cases reported across Southeast Asia. This infection should also be considered in the differential diagnosis of any febrile travellers coming back from a recent travel to forested areas of Southeast Asia. P. knowlesi can cause severe malaria with a rate of 6-9% and with a case fatality rate of 3%. Respiratory distress, acute renal failure, shock and hyperbilirubinemia are the most frequently observed complications of severe P. knowlesi malaria. Chloroquine is considered the treatment of choice of uncomplicated malaria caused by P. knowlesi.
    Matched MeSH terms: Chloroquine/pharmacology
  15. Plasmodium vivax drug resistance markers: Genetic polymorphisms and mutation patterns in isolates from Malaysia
    Cheong FW, Dzul S, Fong MY, Lau YL, Ponnampalavanar S
    Acta Trop, 2020 Jun;206:105454.
    PMID: 32205132 DOI: 10.1016/j.actatropica.2020.105454
    Transmission of Plasmodium vivax still persist in Malaysia despite the government's aim to eliminate malaria in 2020. High treatment failure rate of chloroquine monotherapy was reported recently. Hence, parasite drug susceptibility should be kept under close monitoring. Mutation analysis of the drug resistance markers is useful for reconnaissance of anti-malarial drug resistance. Hitherto, information on P. vivax drug resistance marker in Malaysia are limited. This study aims to evaluate the mutations in four P. vivax drug resistance markers pvcrt-o (putative), pvmdr1 (putative), pvdhfr and pvdhps in 44 isolates from Malaysia. Finding indicates that 27.3%, 100%, 47.7%, and 27.3% of the isolates were carrying mutant allele in pvcrt-o, pvmdr1, pvdhfr and pvdhps genes, respectively. Most of the mutant isolates had multiple point mutations rather than single point mutation in pvmdr1 (41/44) and pvdhfr (19/21). One novel point mutation V111I was detected in pvdhfr. Allelic combination analysis shows significant strong association between mutations in pvcrt-o and pvmdr1 (X2 = 9.521, P < 0.05). In the present study, 65.9% of the patients are non-Malaysians, with few of them arrived in Malaysia 1-2 weeks before the onset of clinical manifestations, or had previous history of malaria infection. Besides, few Malaysian patients had travel history to vivax-endemic countries, suggesting that these patients might have acquired the infections during their travel. All these possible imported cases could have placed Malaysia in a risk to have local transmission or outbreak of malaria. Six isolates were found to have mutations in all four drug resistance markers, suggesting that the multiple-drugs resistant P. vivax strains are circulating in Malaysia.
    Matched MeSH terms: Chloroquine
  16. Polymorphism in the pvcrt-o and pvmdr-1 genes of Plasmodium vivax associated with a better prognosis for malaria
    Alves-Junior ER, Dombroski TCD, Nakazato L, Dutra V, Neves-Costa JD, Katsuragawa TH, et al.
    Trop Biomed, 2022 Sep 01;39(3):421-427.
    PMID: 36214439 DOI: 10.47665/tb.39.3.012
    The early molecular identification of strains of Plasmodium vivax that have a worse prognosis is important to stratify the risk of complications and choice of conduct made by medical teams. Thus, the aim of the present study was to associate the presence of polymorphisms in the pvmdr-1 and pvcrt-o resistance genes of P. vivax in patients with better or worse prognosis. This cross-sectional epidemiological study was conducted based on data obtained from the records of 120 patients diagnosed with malaria in the Brazilian Amazon. The T958M and F1076L mutations of the pvmdr-1 gene had a frequency of 3.3 and 4.2%, respectively, and primo-infected patients had a 17 times greater chance of being infected with protozoa with the T958M mutation compared to patients with previous episodes. Regarding pvcrt-o, the C393T and T786C polymorphisms had a frequency of 14.2 and 3.3%, respectively, and self-declared white patients had a 3.1 times greater chance of being infected with protozoa with the C393T polymorphism. In addition, patients with this pvcrt-o polymorphism had lower concentrations of C-reactive protein, indicating a better prognosis. These data present clues of genetic indicators useful for assessing the virulence of the parasite and the prognosis of patients with vivax malaria.
    Matched MeSH terms: Chloroquine/therapeutic use
  17. Fulltext Potential benefits of combination of Nigella sativa and Zn supplements to treat COVID-19
    Rahman MT
    J Herb Med, 2020 Oct;23:100382.
    PMID: 32834942 DOI: 10.1016/j.hermed.2020.100382
    An effective vaccine to prevent the SARS-CoV-2 causing COVID-19 is yet to be approved. Further there is no drug that is specific to treat COVID-19. A number of antiviral drugs such as Ribavirin, Remdesivir, Lopinavir/ritonavir, Azithromycin and Doxycycline have been recommended or are being used to treat COVID-19 patients. In addition to these drugs, rationale and evidence have been presented to use chloroquine to treat COVID-19, arguably with certain precautions and criticism. In line with the proposed use of chloroquine, Nigella sativa (black seed) could be considered as a natural substitute that contains a number of bioactive components such as thymoquinone, dithymoquinone, thymohydroquinone, and nigellimine. Further benefits to use N. sativa could be augmented by Zn supplement. Notably, Zn has been proven to improve innate and adaptive immunity in the course of any infection, be it by pathogenic virus or bacteria. The effectiveness of the Zn salt supplement could also be enhanced with N. sativa as its major bioactive component might work as ionophore to allow Zn2+ to enter pneumocytes - the target cell for SARSCoV-2. Given those benefits, this review paper describes how N. sativa in combination with Zn could be useful as a complement to COVID-19 treatment.
    Matched MeSH terms: Chloroquine
  18. Potential of repurposing chloroquine as an adjunct therapy for melioidosis based on a murine model of Burkholderia pseudomallei infection
    Ganesan N, Embi N, Hasidah MS
    Trop Biomed, 2020 Jun 01;37(2):303-317.
    PMID: 33612800
    Burkholderia pseudomallei is the etiologic agent of melioidosis, a major cause of community-acquired pneumonia and sepsis in the endemic areas. The overall mortality of patients with severe melioidosis remains high due to severe sepsis attributed to overwhelming inflammatory cytokine response in spite of recommended antibiotic therapy. It is crucial that therapeutic approaches beyond just effective antibiotic treatment such as adjunct therapy be considered to mitigate the dysregulated inflammatory signaling and augment host defenses. In an acute B. pseudomallei infection model, we have previously demonstrated that treatment with anti-malarial drug, chloroquine, modulated inflammatory cytokine levels and increased animal survivability via Akt-mediated inhibition of glycogen synthase kinase-3β (GSK3β). GSK3β is a downstream effector molecule within the phosphatidylinositol 3-kinase (PI3K)/ Akt axis which plays a pivotal role in regulating the production of pro- and anti-inflammatory cytokines. Here we evaluate the effect of chloroquine treatment in combination with a subtherapeutic dose of the antibiotic doxycycline on animal survivability, cytokine levels and phosphorylation states of GSK3β (Ser9) in a murine model of acute melioidosis infection to investigate whether chloroquine could be used as an adjunct therapy along with doxycycline for the treatment of melioidosis. Our findings revealed that 50 mg/kg b.w. chloroquine treatment together with a dose of 20 mg/kg b.w. doxycycline improved survivability (100%) of mice infected with 3 X LD50 of B. pseudomallei and significantly (P<0.05) lowered the bacterial loads in spleen, liver and blood compared to controls. B. pseudomallei-infected mice subjected to adjunct treatment with chloroquine and doxycycline significantly (P<0.05) reduced serum levels of pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) but increased levels of antiinflammatory cytokines (IL-4 and IL-10). Western blot analysis demonstrated that the intensities of pGSK3β (Ser9) in liver samples from mice treated with chloroquine and doxycycline combination were significantly (P<0.05) higher suggesting that the adjunct treatment resulted in significant inhibition of GSK3β. Taken together the bacteriostatic action of doxycycline coupled with the cytokine-modulating effect of chloroquine gave full protection to B. pseudomallei-infected mice and involved inhibition of GSK3β. Findings from the present study using B. pseudomallei-infected BALB/c mice suggest that chloroquine is a plausible candidate for repurposing as adjunct therapy to treat acute B. pseudomallei infection.
    Matched MeSH terms: Chloroquine/therapeutic use*
  19. Fulltext Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia
    Norahmad NA, Mohd Abd Razak MR, Abdullah NR, Sastu UR, Imwong M, Muniandy PK, et al.
    PLoS One, 2016;11(10):e0165515.
    PMID: 27788228 DOI: 10.1371/journal.pone.0165515
    Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.
    Matched MeSH terms: Chloroquine/pharmacology; Chloroquine/therapeutic use
  20. 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: Chloroquine
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links