Displaying publications 1 - 20 of 143 in total

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  1. 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: Chloroquine/therapeutic use
  2. van Hellemond JJ, van Genderen PJ
    Ned Tijdschr Geneeskd, 2010;154:A1353.
    PMID: 20456798
    Matched MeSH terms: Chloroquine/therapeutic use
  3. Zaid OI, Abd Majid R, Sidek HM, Noor SM, Abd Rachman-Isnadi MF, Bello RO, et al.
    Trop Biomed, 2020 Mar 01;37(1):29-49.
    PMID: 33612716
    Treatment Failure with chloroquine is one of the challenges that faced the dedicated efforts to eradicate malaria This study aims at investigating the impact of treatment failure with chloroquine on the progression of the disease-induced histo-pathogenic and immunogenic outcomes. To achieve this, Rane's protocol with modifications was applied on a model of Plasmodium berghei ANKA infected ICR mice to determine the dose response curve of chloroquine and to screen the treatment impact on the disease progression. Chloroquine was given at 1, 5, 10, 15 and 20 mg/kg once the parasitemia reached to 20-30% (the experimental initiation point). During the subsequent days, the mice were monitored for changes in the clinical signs, hematology parameters and the progress of the parasitemia until the parasitemia reached to 60-70% (the experimental termination point) or up to 10 days after chloroquine administration in case of achieving a complete eradication of the parasite. At the end, the mice were exsanguinated and their blood and organs were collected for the biochemistry and the histology study. A complete eradication of the parasite was achieved at 20 mg/kg while recrudescence was observed at the lower doses. At 1 mg/kg, the parasite growth was comparable to that of the positive control. The histo-pathogenic and immunogenic changes were stronger in the groups that experienced recrudescence (at 5 and 10 mg/kg). All in all, the study highlights the possibility of having a worsened clinical condition when chloroquine is given at its sub-therapeutic doses during malaria treatment.
    Matched MeSH terms: Chloroquine/administration & dosage*; Chloroquine/therapeutic use
  4. Zahari A, Cheah FK, Mohamad J, Sulaiman SN, Litaudon M, Leong KH, et al.
    Planta Med, 2014 May;80(7):599-603.
    PMID: 24723007 DOI: 10.1055/s-0034-1368349
    The crude extract of the bark of Dehaasia longipedicellata exhibited antiplasmodial activity against the growth of Plasmodium falciparum K1 isolate (resistant strain). Phytochemical studies of the extract led to the isolation of six alkaloids: two morphinandienones, (+)-sebiferine (1) and (-)-milonine (2); two aporphines, (-)-boldine (3) and (-)-norboldine (4); one benzlyisoquinoline, (-)-reticuline (5); and one bisbenzylisoquinoline, (-)-O-O-dimethylgrisabine (6). Their structures were determined on the basis of 1D and 2D NMR, IR, UV, and LCMS spectroscopic techniques and upon comparison with literature values. Antiplasmodial activity was determined for all of the isolated compounds. They showed potent to moderate activity with IC50 values ranging from 0.031 to 30.40 µM. (-)-O-O-dimethylgrisabine (6) and (-)-milonine (2) were the two most potent compounds, with IC50 values of 0.031 and 0.097 µM, respectively, that were comparable to the standard, chloroquine (0.090 µM). The compounds were also assessed for their antioxidant activities with di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (IC50 = 18.40-107.31 µg/mL), reducing power (27.40-87.40 %), and metal chelating (IC50 = 64.30 to 257.22 µg/mL) having good to low activity. (-)-O-O-dimethylgrisabine (6) exhibited a potent antioxidant activity of 44.3 % reducing power, while di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium and metal chelating activities had IC50 values of 18.38 and 64.30 µg/mL, respectively. Thus it may be considered as a good reductant with the ability to chelate metal and prevent pro-oxidant activity. In addition to the antiplasmodial and antioxidant activities, the isolated compounds were also tested for their cytotoxicity against a few cancer and normal cell lines. (-)-Norboldine (4) exhibited potent cytotoxicity towards pancreatic cancer cell line BxPC-3 with an IC50 value of 27.060 ± 1.037 µM, and all alkaloids showed no toxicity towards the normal pancreatic cell line (hTERT-HPNE).
    Matched MeSH terms: Chloroquine/pharmacology
  5. Yapp DT, Yap SY
    J Ethnopharmacol, 2003 Mar;85(1):145-50.
    PMID: 12576213
    Malaria remains a global problem in the light of chloroquine-resistant strains of Plasmodium falciparum. New compounds are needed for the development of novel antimalarial drugs. Seed, leaf, and fruit skin extracts of Lansium domesticum, a common fruit tree in South-East Asia, are used by indigenous tribes in Sabah, Malaysia for treating malaria. The skin and aqueous leaf extracts of the tree were found to reduce parasite populations of the drug sensitive strain (3D7) and the chloroquine-resistant strain (T9) of P. falciparum equally well. The skin extracts were also found to interrupt the lifecycle of the parasite. The data reported here indicate that extracts of L. domesticum are a potential source for compounds with activity towards chloroquine-resistant strains of P. falciparum.
    Matched MeSH terms: Chloroquine/pharmacology
  6. Wolthuis FH
    Trop Geogr Med, 1968 Mar;20(1):21-7.
    PMID: 4868143
    Matched MeSH terms: Chloroquine/therapeutic use
  7. William T, Menon J, Rajahram G, Chan L, Ma G, Donaldson S, et al.
    Emerg Infect Dis, 2011 Jul;17(7):1248-55.
    PMID: 21762579 DOI: 10.3201/eid1707.101017
    The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007-November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1-2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria.
    Matched MeSH terms: Chloroquine/administration & dosage; Chloroquine/therapeutic use
  8. Wiesmann UN, DiDonato S, Herschkowitz NN
    Biochem Biophys Res Commun, 1975 Oct 27;66(4):1338-43.
    PMID: 4
    Matched MeSH terms: Chloroquine/pharmacology*
  9. Wallace RB
    Med J Malaya, 1950;4:190-204.
    This work, carried out on a rubber estate in Malaya during 1949, was a Continuation of the trials begun in 1948 previously recorded [this Bulletin, 1949, v 46, 1116]. Full details concerning the terrain and the nature of the experiment were given in the previous publication. In 1949 the malaria rate in the area approached the rates which were customary in pre-war years, for the first time since the reoccupation of the country. The Indian population which was chosen for the experiment contains the survivors of the Japanese occupation; many had been in Siam and almost all had suffered from malaria. Treatment had been entirely lacking or very inadequate, with the result that the survivors had developed a high degree of immunity by the end of the war. These facts probably explain the low incidence of malaria in post-war years in spite of high prevalence of A. maculatus. No anti-larval measures have been carried out since 1941. Neo-premaline completely suppressed malaria in one group, the control group showing a high incidence. In other groups chloroquine, or chloroquine and pentaquine combined, given once a week, promptly brought to an end primary waves of malaria which were rising rapidly.
    Matched MeSH terms: Chloroquine
  10. WILSON T, EDESON JF
    Med J Malaya, 1954 Dec;9(2):115-31.
    PMID: 14355275
    Matched MeSH terms: Chloroquine/therapeutic use*
  11. WALLACE MF
    Med J Malaya, 1954 Mar;8(3):251-9.
    PMID: 13164695
    Matched MeSH terms: Chloroquine*
  12. Tindall SM, Vallières C, Lakhani DH, Islahudin F, Ting KN, Avery SV
    Sci Rep, 2018 02 06;8(1):2464.
    PMID: 29410428 DOI: 10.1038/s41598-018-20816-0
    Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
    Matched MeSH terms: Chloroquine/pharmacology
  13. T Thurai Rathnam J, Grigg MJ, Dini S, William T, Sakam SS, Cooper DJ, et al.
    Malar J, 2023 Feb 14;22(1):54.
    PMID: 36782162 DOI: 10.1186/s12936-023-04483-9
    BACKGROUND: The incidence of zoonotic Plasmodium knowlesi infections in humans is rising in Southeast Asia, leading to clinical studies to monitor the efficacy of anti-malarial treatments for knowlesi malaria. One of the key outcomes of anti-malarial drug efficacy is parasite clearance. For Plasmodium falciparum, parasite clearance is typically estimated using a two-stage method, that involves estimating parasite clearance for individual patients followed by pooling of individual estimates to derive population estimates. An alternative approach is Bayesian hierarchical modelling which simultaneously analyses all parasite-time patient profiles to determine parasite clearance. This study compared these methods for estimating parasite clearance in P. knowlesi treatment efficacy studies, with typically fewer parasite measurements per patient due to high susceptibility to anti-malarials.

    METHODS: Using parasite clearance data from 714 patients with knowlesi malaria and enrolled in three trials, the Worldwide Antimalarial Resistance Network (WWARN) Parasite Clearance Estimator (PCE) standard two-stage approach and Bayesian hierarchical modelling were compared. Both methods estimate the parasite clearance rate from a model that incorporates a lag phase, slope, and tail phase for the parasitaemia profiles.

    RESULTS: The standard two-stage approach successfully estimated the parasite clearance rate for 678 patients, with 36 (5%) patients excluded due to an insufficient number of available parasitaemia measurements. The Bayesian hierarchical estimation method was applied to the parasitaemia data of all 714 patients. Overall, the Bayesian method estimated a faster population mean parasite clearance (0.36/h, 95% credible interval [0.18, 0.65]) compared to the standard two-stage method (0.26/h, 95% confidence interval [0.11, 0.46]), with better model fits (compared visually). Artemisinin-based combination therapy (ACT) is more effective in treating P. knowlesi than chloroquine, as confirmed by both methods, with a mean estimated parasite clearance half-life of 2.5 and 3.6 h, respectively using the standard two-stage method, and 1.8 and 2.9 h using the Bayesian method.

    CONCLUSION: For clinical studies of P. knowlesi with frequent parasite measurements, the standard two-stage approach (WWARN's PCE) is recommended as this method is straightforward to implement. For studies with fewer parasite measurements per patient, the Bayesian approach should be considered. Regardless of method used, ACT is more efficacious than chloroquine, confirming the findings of the original trials.

    Matched MeSH terms: Chloroquine/pharmacology
  14. Supramaniam V, Datta GC, Singam V, Singh J
    Med J Malaysia, 1987 Mar;42(1):44-9.
    PMID: 3323860
    Malaria is the most important communicable disease in the field for the Malaysian soldier. His chief weapon is chemoprophylaxis. This was proguanil hydrochloride in the '50s, changed to Daraclor in 1962; since late 1985, Fansidar only is used. The incidence of malaria over the years has fluctuated widely and had its peak in 1977 at 29.7/1,000 soldiers and since then has shown a downward trend. Studies carried out to study the problem are noted briefly. Antimalarial discipline in the field, continued surveillance and integrated control measures in the base are emphasised in the fight against malaria.
    Matched MeSH terms: Chloroquine/therapeutic use*
  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: Chloroquine/therapeutic use
  16. Shankar PR, Palaian S, Gulam SM
    J Pharm Bioallied Sci, 2020 10 06;13(1):4-10.
    PMID: 34084043 DOI: 10.4103/jpbs.JPBS_404_20
    The corona virus disease-19 (COVID-19) pandemic has affected the entire world causing huge economic losses and considerable morbidity and mortality. Considering the explosive growth of the pandemic repurposing existing medicines may be cost-effective and may be approved for use in COVID-19 faster. Researchers and medical practitioners worldwide have explored the use of chloroquine and hydroxychloroquine, in few occasions combined with the macrolide antibiotic azithromycin, for COVID-19 treatment. These two drugs are economic and easily available, and hence gained attention as a potential option for COVID-19 management. As per the available evidence, the outcomes of treatments with these medications are conflicting from both the efficacy and safety (predominantly cardiac related) perspectives. Currently, multiple studies are underway to test the safety and efficacy of these medications and more results are expected in the near future. The retina, the endocrine system (with risk of hypoglycemia), the musculoskeletal system, the hematological system, and the neurological system may also be affected. The use of these drugs is contraindicated in patients with arrhythmias, known hypersensitivity, and in patients on amiodarone. In addition to the published literature, personal communication with doctors treating COVID-19 patients seems to suggest the drugs may be effective in reducing symptoms and hastening clinical recovery. The literature evidence is still equivocal and further results are awaited. There has been recent controversy including retraction of articles published in prestigious journals about these medicines. Their low cost, long history of use, and easy availability are positive factors with regard to use of these drugs in COVID-19.
    Matched MeSH terms: Chloroquine; Hydroxychloroquine
  17. Sandosham AA, Eyles DE, Pull JH, Seng LD
    Med J Malaya, 1966 Dec;21(2):115-24.
    PMID: 4227380
    Matched MeSH terms: Chloroquine/therapeutic use*
  18. Sandosham AA, Fredericks HJ, Ponnampalam JT, Seow CL, Ismail O, Othman AM, et al.
    J Trop Med Hyg, 1975 Mar;78(3):54-8.
    PMID: 1095776
    Chloroquine resistance is a well established entity in South East Asia, and presents a problem of increasing importance. Strains of P. falciparum resistant to chloroquine have also been found to be resistant to amodiaquine and a combination of pyrimethamine and sulphadoxine. Knowledge of the drug sensitivity of the strains of malaria parasite in a given locality is important so that the right choice of drugs can be made in treatment of the disease. The treatment of chloroquine resistant malaria in West Malaysia is a subject of another paper but suffice it to say that increased doses of chloroquine have still been found to be effective in treating many cases of falciparum malaria from areas of chloroquine resistance.
    Matched MeSH terms: Chloroquine/administration & dosage; Chloroquine/pharmacology; Chloroquine/therapeutic use*
  19. Sandosham AA
    Singapore Med J, 1963 Mar;4(1):3-5.
    PMID: 14162703
    Matched MeSH terms: Chloroquine*
  20. Safar HF, Ali AH, Zakaria NH, Kamal N, Hassan NI, Agustar HK, et al.
    Trop Biomed, 2022 Dec 01;39(4):552-558.
    PMID: 36602215 DOI: 10.47665/tb.39.4.011
    Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.
    Matched MeSH terms: Chloroquine
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