MyMedR

Plasmodium knowlesi, a simian malaria parasite, is now recognised as the fifth cause of human malaria and can lead to fatal infections in humans. Knowlesi malaria cases are widely distributed in East and West Malaysia and account for more than 50% of admissions for malaria in certain hospitals in the state of Sarawak. This paper will begin with a description of the early studies on P. knowlesi, followed by a review of the epidemiology, diagnosis, clinical and laboratory features, and treatment of knowlesi malaria.

Matched MeSH terms: Malaria/drug therapy

Fulltext Human Plasmodium knowlesi infections in Klang Valley, Peninsula Malaysia: a case series

Lee CE, Adeeba K, Freigang G

Med J Malaysia, 2010 Mar;65(1):63-5.

PMID: 21265252

We report seven cases of naturally acquired human Plasmodium knowlesi infections which were admitted to our centre from July 2007 till June 2008. Diagnosis was confirmed by nested PCR. Cases of P. knowlesi infections, dubbed the fifth type of human malaria, have been reported in East Malaysia (Sabah and Sarawak) as well as in the state of Pahang in Peninsula Malaysia. These seven patients appear to be the first few reported cases of P. knowlesi infection in the Klang valley, Peninsula Malaysia. We then discuss the characteristics of human P. knowlesi infections, which include its natural hosts, responsible vectors, clinical presentation, and the treatment of such infections.

Matched MeSH terms: Malaria/drug therapy

Pharmacokinetics of artemisinin-type compounds

Navaratnam V, Mansor SM, Sit NW, Grace J, Li Q, Olliaro P

Clin Pharmacokinet, 2000 Oct;39(4):255-70.

PMID: 11069212

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.

Matched MeSH terms: Malaria/drug therapy

[Various general aspects of of the problem of chloroquine-resistant Plasmodium falciparum malaria in the South-East Asia]

Orlov VS

Med Parazitol (Mosk), 1980 Jul-Aug;49(4):11-5.

PMID: 6999319

Matched MeSH terms: Malaria/drug therapy

Chloroquine-resistant P. falciparum infections

Lundie AR

J Clin Pathol, 1969 Jul;22(4):509.

PMID: 4894850

Matched MeSH terms: Malaria/drug therapy*

Fulltext Drug interaction between cyclosporine A and quinine in a renal transplant patient with malaria

Tan HW, Ch'ng SL

Singapore Med J, 1991 Jun;32(3):189-90.

PMID: 1876897

We report a previously undocumented drug interaction between cyclosporine A and quinine. A 39 year old Asian with a recent renal transplant was diagnosed to have a mild cerebral falciparum malaria. He was treated with seven days of oral quinine (600 mg, 8 hourly), followed by a stat dose of pyrimethamine (75 mg)--sulfadoxime (1200mg) because of a strong suspicion of chloroquine resistant falciparum malaria. Using a polyclonal radioimmunoassay method, we measured morning trough cyclosporine A level before, during and after the quinine treatment. Results showed a gradual decrease in the cyclosporine A level from a baseline value of 328 ng/ml to 107 ng/ml after seven days of oral quinine with a subsequent rise to pre-treatment level after discontinuation of quinine. There was no significant change in the dose of cyclosporine A administered during the period of quinine treatment (4.05 to 3.83 mg/kg body weight). Biochemical liver function tests, serum creatinine and hematological parameters were also essentially unchanged during this period. In vitro study showed no significant methodological interference in the cyclosporine assay by quinine dihydrochloride. These findings suggest an in vivo drug interaction between cyclosporine A and quinine. The mechanism of this interaction is not clear. Further studies are required to confirm the significance of this observation. Quinine and its stereoisomer, quinidine should be used with caution until further information is available.

Matched MeSH terms: Malaria/drug therapy*

Fulltext A study protocol for a randomised open-label clinical trial of artesunate-mefloquine versus chloroquine in patients with non-severe Plasmodium knowlesi malaria in Sabah, Malaysia (ACT KNOW trial)

Grigg MJ, William T, Dhanaraj P, Menon J, Barber BE, von Seidlein L, et al.

BMJ Open, 2014 Aug 19;4(8):e006005.

PMID: 25138814 DOI: 10.1136/bmjopen-2014-006005

INTRODUCTION: Malaria due to Plasmodium knowlesi is reported throughout South-East Asia, and is the commonest cause of it in Malaysia. P. knowlesi replicates every 24 h and can cause severe disease and death. Current 2010 WHO Malaria Treatment Guidelines have no recommendations for the optimal treatment of non-severe knowlesi malaria. Artemisinin-combination therapies (ACT) and chloroquine have each been successfully used to treat knowlesi malaria; however, the rapidity of parasite clearance has not been prospectively compared. Malaysia's national policy for malaria pre-elimination involves mandatory hospital admission for confirmed malaria cases with discharge only after two negative blood films; use of a more rapidly acting antimalarial agent would have health cost benefits. P. knowlesi is commonly microscopically misreported as P. malariae, P. falciparum or P. vivax, with a high proportion of the latter two species being chloroquine-resistant in Malaysia. A unified ACT-treatment protocol would provide effective blood stage malaria treatment for all Plasmodium species.

METHODS AND ANALYSIS: ACT KNOW, the first randomised controlled trial ever performed in knowlesi malaria, is a two-arm open-label trial with enrolments over a 2-year period at three district sites in Sabah, powered to show a difference in proportion of patients negative for malaria by microscopy at 24 h between treatment arms (clinicaltrials.gov #NCT01708876). Enrolments started in December 2012, with completion expected by September 2014. A total sample size of 228 is required to give 90% power (α 0.05) to determine the primary end point using intention-to-treat analysis. Secondary end points include parasite clearance time, rates of recurrent infection/treatment failure to day 42, gametocyte carriage throughout follow-up and rates of anaemia at day 28, as determined by survival analysis.

ETHICS AND DISSEMINATION: This study has been approved by relevant institutional ethics committees in Malaysia and Australia. Results will be disseminated to inform knowlesi malaria treatment policy in this region through peer-reviewed publications and academic presentations.

TRIAL REGISTRATION NUMBER: NCT01708876.

Matched MeSH terms: Malaria/drug therapy*

Fulltext In vitro and in vivo antimalarial evaluations of myrtle extract, a plant traditionally used for treatment of parasitic disorders

Naghibi F, Esmaeili S, Abdullah NR, Nateghpour M, Taghvai M, Kamkar S, et al.

Biomed Res Int, 2013;2013:316185.

PMID: 24455686 DOI: 10.1155/2013/316185

Based on the collected ethnobotanical data from the Traditional Medicine and Materia Medica Research Center (TMRC), Iran, Myrtus communis L. (myrtle) was selected for the assessment of in vitro and in vivo antimalarial and cytotoxic activities. Methanolic extract of myrtle was prepared from the aerial parts and assessed for antiplasmodial activity, using the parasite lactate dehydrogenase (pLDH) assay against chloroquine-resistant (K1) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. The 4-day suppressive test was employed to determine the parasitemia suppression of the myrtle extract against P. berghei in vivo. The IC50 values of myrtle extract were 35.44 µg/ml against K1 and 0.87 µg/ml against 3D7. Myrtle extract showed a significant suppression of parasitaemia (84.8 ± 1.1% at 10 mg/kg/day) in mice infected with P. berghei after 4 days of treatment. Cytotoxic activity was carried out against mammalian cell lines using methyl thiazol tetrazolium (MTT) assay. No cytotoxic effect on mammalian cell lines up to 100 µg/mL was shown. The results support the traditional use of myrtle in malaria. Phytochemical investigation and understanding the mechanism of action would be in our upcoming project.

Matched MeSH terms: Malaria/drug therapy*

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: Malaria/drug therapy

Fulltext First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia

Ta TT, Salas A, Ali-Tammam M, Martínez Mdel C, Lanza M, Arroyo E, et al.

Malar J, 2010;9:219.

PMID: 20663184 DOI: 10.1186/1475-2875-9-219

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old.

Matched MeSH terms: Malaria/drug therapy

[Monkey malaria in a traveller from Malaysia]

van Hellemond JJ, van Genderen PJ

Ned Tijdschr Geneeskd, 2010;154:A1353.

PMID: 20456798

Matched MeSH terms: Malaria/drug therapy

Ethnobotanical study on some Malaysian anti-malarial plants: a community based survey

Al-Adhroey AH, Nor ZM, Al-Mekhlafi HM, Mahmud R

J Ethnopharmacol, 2010 Oct 28;132(1):362-4.

PMID: 20723596 DOI: 10.1016/j.jep.2010.08.006

Various plants species are used in the traditional medicine for the treatment of malaria. This is the first community based ethnobotanical study in Peninsular Malaysia.

Matched MeSH terms: Malaria/drug therapy

Fulltext A retrospective prevalence study of malaria in an aborigine hospital in Gombak, Selangor, Malaysia

Jamaiah I, Rohela M, Nissapatorn V, Mohamad Azlan H, Nor Adli AR, Shahrul Rizan I, et al.

Southeast Asian J. Trop. Med. Public Health, 2006;37 Suppl 3:1-4.

PMID: 17547040

This was a five-year retrospective study (1999-2004) on the prevalence of malaria at the Aborigine Hospital, Gombak, Malaysia. A total of 94 malaria cases was analysed. The highest case reports were for the year 2000, with 32 cases (34%), and the lowest was in 2004, with only 1 (1%). The majority of cases reported were among the Semai tribe (44%), followed by the Temiar tribe (34%) and the unspecified tribe (s) (20%). Females (53%) were more commonly affected than males (47%). The majority of cases were within the age group 1-5 years (51%). Plasmodium falciparum was the most common species reported in this study, at 57%, followed by Plasmodium vivax (38%) and 5% mixed infection of P. falciparum and P. vivax. Most patients (27%) stayed for more than one month in hospital. Most patients came from Kuala Lipis, Pahang, (78%). The most common complication was anemia (38%) followed by splenomegaly (18%); only 2% had cerebral malaria. All patients were treated with the standard anti-malarial drugs. No deaths were reported in this study.

Matched MeSH terms: Malaria/drug therapy

Fulltext A systematic review of the efficacy of a single dose artemisinin-naphthoquine in treating uncomplicated malaria

Naing C, Whittaker MA, Mak JW, Aung K

Malar J, 2015;14:392.

PMID: 26445424 DOI: 10.1186/s12936-015-0919-5

This study aimed to synthesize the existing evidence on the efficacy and safety of a single dose artemisinin-naphthoquine (ASNQ) for treatment of uncomplicated malaria in endemic countries.

Matched MeSH terms: Malaria/drug therapy*

Fulltext Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of Plasmodium chabaudi Malaria to various drugs and their combinations

Rahman NNNA

Med J Malaysia, 1997 Dec;52(4):390-8.

PMID: 10968116

K1 strain of Plasmdoium falciparum is resistant in vitro to chloroquine, pyrimethamine and sulfadoxine. Response of this strain to combinations of antimalarial drugs in the in vitro hypoxanthine incorporation test was coupled with that of a line of strain NF54 relatively sensitive to chloroquine and fully sensitive to other antimalarials. Pyrimethamine and sulfadoxine showed potentiative synergism against NF54 and less marked against K1. Erythromycin and chloroquine showed potentiation, but less marked against NF54. Quinine and clindamycin had an additive effect against NF54 but potentiated against K1. Combinations of chloroquine with quinine or amodiaquine or of amodiaquine with clindamycin or erythromycin showed mild antagonistic or additive effects. In vivo studies in mice, using the 4-day suppressive test, the AS(3CQ) clone of Plasmodium chabaudi was resistant to pyrimethamine and chloroquine but sensitive to sulfadoxine. Similar combinations as above were carried out and their responses were compared between the resistant and sensitive strains. For both strains, the combinations of chloroquine-erythromycin, pyrimethamine-sulfadoxine, quinine-clindamycin showed potentiation; antagonistic effects were observed in chloroquine-amodiaquine combinations whereas when amodiaquine combined with erythromycin the effect was additive. Amodiaquine-clindamycin and chloroquine-quinine combinations have an antagonistic effect against the sensitive strain but additive against the resistant strain.

Matched MeSH terms: Malaria/drug therapy*

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: Malaria/drug therapy

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