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[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/parasitology*
[The first monkey malaria in Turkey: a case of Plasmodium knowlesi]

Özbilgin A, Çavuş İ, Yıldırım A, Gündüz C

Mikrobiyol Bul, 2016 Jul;50(3):484-90.
PMID: 27525405

Plasmodium knowlesi is now added to the known four Plasmodium species (P.vivax, P.falciparum, P.malariae, P.ovale) as a cause of malaria in humans because of the recent increasing rate of cases reported from countries of southeastern Asia. P.knowlesi which infects macaque monkeys (Macaca fascicularis and M.nemestrina) is transmitted to humans especially by Anopheles leucosphyrus and An.hackeri mosquitos. First human cases of P.knowlesi malaria have been detected in Malaysia which have reached high numbers in recent years and also have been reported from countries of Southeast Asia such as Thailand, Philippines, Myanmar, Singapore and Vietnam. However the number of cases reported from western countries are rare and limited only within voyagers. This report is the first presentation of an imported case of P.knowlesi malaria in Turkey and aims to draw attention to the point that it could also be detected in future. A 33-year-old male patient from Myanmar who has migrated to Turkey as a refugee, was admitted to a health center with the complaints of fever with a periodicity of 24 hours, headache, fatigue, cough, sore throat, anorexia, myalgia and arthralgia. He was prediagnosed as upper respiratory tract infection, however because of his periodical fever and background in Myanmar, thick and thin blood films were prepared and sent to our laboratory for further examinations. Microscopic examination of the thin blood films revealed erythrocytic stages compatible with P.knowlesi (three large early trophozoites in an erythrocyte, three late trophozoites with compact view, and three late band-form trophozoites). Upon this, both real-time polymerase chain reaction (Rt-PCR) targeting the small subunit ribosomal RNA (SSU-rRNA) genes of Plasmodium genus and DNA sequence analysis targeting P.knowlesi rRNA gene were performed. As a result, the suspected identification of P.knowlesi by microscopy was confirmed by Rt-PCR and DNA sequencing. The patient was treated with chloroquine and primaquine combination and in the follow-up on the seventh day after the treatment, his parasitemia and symptoms had ceased. Although there were some previous reports concerning about imported patients infected with different Plasmodium species in our country, no cases of P.knowlesi have been reported. This first case presented here emphasizes the occurence of P.knowlesi malaria in Turkey hereinafter due to the increasing number of refugees.

Matched MeSH terms: Malaria/parasitology*
[Plasmodium knowlesi--the fifth species causing human malaria]

Kantele A, Jokiranta S

Duodecim, 2010;126(4):427-34.
PMID: 20486493

Four species have been known to bring on human malaria, the most severe disease being caused by Plasmodium falciparum. In 2007, after returning from Malaysia, a Finnish tourist was found to be infected with a fifth Plasmodium species, P. knowlesi which usually infects macaques. Over the past few years, hundreds of human cases have been found in Malaysia. The clinical disease caused by P. knowlesi appears less severe than P. falciparum infection, but more severe than infection with other malaria-causing species. Diagnosis is based both on PCR and microscopy. P. knowlesi is currently. considered as the fifth species causing malaria in humans.

Matched MeSH terms: Malaria/parasitology*
Fulltext World Malaria Report: time to acknowledge Plasmodium knowlesi malaria

Barber BE, Rajahram GS, Grigg MJ, William T, Anstey NM

Malar J, 2017 03 31;16(1):135.
PMID: 28359340 DOI: 10.1186/s12936-017-1787-y

BACKGROUND: The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report.
MAIN TEXT: Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation.
CONCLUSION: The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.

Matched MeSH terms: Malaria/parasitology*
Fulltext Within-population genetic diversity and population structure of Plasmodium knowlesi merozoite surface protein 1 gene from geographically distinct regions of Malaysia and Thailand

Ahmed MA, Chu KB, Vythilingam I, Quan FS

Malar J, 2018 Nov 29;17(1):442.
PMID: 30497496 DOI: 10.1186/s12936-018-2583-z

BACKGROUND: The C-terminal 42 kDa domain of Plasmodium knowlesi merozoite surface protein 1 (PkMSP1) is a potential asexual blood-stage vaccine candidate, however, only a limited number of clinical isolates have been analysed from Malaysia and no inter-country comparative diversity study has been conducted. In the present study, nucleotide diversity, haplotypes and natural selection levels of pkmsp1 in clinical samples from geographically distinct regions of Malaysia and Thailand were investigated. The overall population structure of the parasite from the region was determined.
METHODS: Eleven full-length pkmsp1 sequences obtained from clinical isolates of Malaysia along with the H-strain were downloaded from the database for domain wise characterization of pkmsp1 gene. Additionally, 76 pkmsp-142 sequences from Thailand and Malaysia were downloaded from the database for intra and inter-population analysis. DnaSP 5.10 and MEGA 5.0 software were used to determine genetic diversity, polymorphism, haplotypes and natural selection. Genealogical relationships were determined using haplotype network tree in NETWORK software v5.0. Population genetic differentiation index (FST) of parasites were analysed using Arlequin v3.5.
RESULTS: Sequence analysis of 11 full-length pkmsp1 sequences along with the H-strain identified 477 (8.4%) polymorphic sites, of which 107 were singleton sites. The overall diversity observed in the full-length genes were high in comparison to its ortholog pvmsp1 and the 4 variable domains showed extensive size variations. The nucleotide diversity was low towards the pkmsp1-42 compared to the conserved domains. The 19 kDa domain was less diverse and completely conserved among isolates from Malaysian Borneo. The nucleotide diversity of isolates from Peninsular Malaysia and Thailand were higher than Malaysian Borneo. Network analysis of pkmsp1-42 haplotypes showed geographical clustering of the isolates from Malaysian Borneo and grouping of isolates from Peninsular Malaysia and Thailand. Population differentiation analysis indicated high FST values between parasite populations originating from Malaysian Borneo, Peninsular Malaysia and Thailand attributing to geographical distance. Moderate genetic differentiation was observed for parasite populations from Thailand and Peninsular Malaysia. Evidence of population expansion and purifying selection were observed in all conserved domains with strongest selection within the pkmsp1-42 domain.
CONCLUSIONS: This study is the first to report on inter country genetic diversity and population structure of P. knowlesi based on msp1. Strong evidence of negative selection was observed in the 42 kDa domain, indicating functional constrains. Geographical clustering of P. knowlesi and moderate to high genetic differentiation values between populations identified in this study highlights the importance of further evaluation using larger number of clinical samples from Southeast Asian countries.

Matched MeSH terms: Malaria/parasitology*
Fulltext Whole genome sequencing of amplified Plasmodium knowlesi DNA from unprocessed blood reveals genetic exchange events between Malaysian Peninsular and Borneo subpopulations

Benavente ED, Gomes AR, De Silva JR, Grigg M, Walker H, Barber BE, et al.

Sci Rep, 2019 07 08;9(1):9873.
PMID: 31285495 DOI: 10.1038/s41598-019-46398-z

The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.

Matched MeSH terms: Malaria/parasitology
Fulltext Updates on malaria incidence and profile in Malaysia from 2013 to 2017

Hussin N, Lim YA, Goh PP, William T, Jelip J, Mudin RN

Malar J, 2020 Jan 31;19(1):55.
PMID: 32005228 DOI: 10.1186/s12936-020-3135-x

BACKGROUND: To date, most of the recent publications on malaria in Malaysia were conducted in Sabah, East Malaysia focusing on the emergence of Plasmodium knowlesi. This analysis aims to describe the incidence, mortality and case fatality rate of malaria caused by all Plasmodium species between Peninsular Malaysia and East Malaysia (Sabah and Sarawak) over a 5-year period (2013-2017).
METHODS: This is a secondary data review of all diagnosed and reported malaria confirmed cases notified to the Ministry of Health, Malaysia between January 2013 and December 2017.
RESULTS: From 2013 to 2017, a total of 16,500 malaria cases were notified in Malaysia. The cases were mainly contributed from Sabah (7150; 43.3%) and Sarawak (5684; 34.4%). Majority of the patients were male (13,552; 82.1%). The most common age group in Peninsular Malaysia was 20 to 29 years (1286; 35.1%), while Sabah and Sarawak reported highest number of malaria cases in age group of 30 to 39 years (2776; 21.6%). The top two races with malaria in Sabah and Sarawak were Bumiputera Sabah (5613; 43.7%) and Bumiputera Sarawak (4512; 35.1%), whereas other ethnic group (1232; 33.6%) and Malays (1025; 28.0%) were the two most common races in Peninsular Malaysia. Plasmodium knowlesi was the commonest species in Sabah and Sarawak (9902; 77.1%), while there were more Plasmodium vivax cases (1548; 42.2%) in Peninsular Malaysia. The overall average incidence rate, mortality rate and case fatality rates for malaria from 2013 to 2017 in Malaysia were 0.106/1000, 0.030/100,000 and 0.27%, respectively. Sarawak reported the highest average incidence rate of 0.420/1000 population followed by Sabah (0.383/1000). Other states in Peninsular Malaysia reported below the national average incidence rate with less than 0.100/1000.
CONCLUSIONS: There were different trends and characteristics of notified malaria cases in Peninsular Malaysia and Sabah and Sarawak. They provide useful information to modify current prevention and control measures so that they are customised to the peculiarities of disease patterns in the two regions in order to successfully achieve the pre-elimination of human-only species in the near future.

Matched MeSH terms: Malaria/parasitology
Fulltext Two sympatric types of Plasmodium ovale and discrimination by molecular methods

Zaw MT, Lin Z

J Microbiol Immunol Infect, 2017 Oct;50(5):559-564.
PMID: 28065415 DOI: 10.1016/j.jmii.2016.08.004

Plasmodium ovale is widely distributed in tropical countries, whereas it has not been reported in the Americas. It is not a problem globally because it is rarely detected by microscopy owing to low parasite density, which is a feature of clinical ovale malaria. P.o. curtisi and P.o. wallikeri are widespread in both Africa and Asia, and were known to be sympatric in many African countries and in southeast Asian countries. Small subunit ribosomal RNA (SSUrRNA) gene, cytochrome b (cytb) gene, and merozoite surface protein-1 (msp-1) gene were initially studied for molecular discrimination of P.o. curtisi and P.o. wallikeri using polymerase chain reaction (PCR) and DNA sequencing. DNA sequences of other genes from P. ovale in Southeast Asia and the southwestern Pacific regions were also targeted to differentiate the two sympatric types. In terms of clinical manifestations, P.o. wallikeri tended to produce higher parasitemia levels and more severe symptoms. To date, there have been a few studies that used the quantitative PCR method for discrimination of the two distinct P. ovale types. Conventional PCR with consequent DNA sequencing is the common method used to differentiate these two types. It is necessary to identify these two types because relapse periodicity, drug susceptibility, and mosquito species preference need to be studied to reduce ovale malaria. In this article, an easier method of molecular-level discrimination of P.o. curtisi and P.o. wallikeri is proposed.

Matched MeSH terms: Malaria/parasitology
Fulltext Two Genetically Distinct Plasmodium knowlesi Duffy Binding Protein Alpha Region II (PkDBPαII) Haplotypes Demonstrate Higher Binding Level to Fy(a+b+) Erythrocytes than Fy(a+b--) Erythrocytes

Liew CC, Lau YL, Fong MY, Cheong FW

Am J Trop Med Hyg, 2020 05;102(5):1068-1071.
PMID: 32189613 DOI: 10.4269/ajtmh.19-0836

Invasion of human erythrocytes by merozoites of Plasmodium knowlesi involves interaction between the P. knowlesi Duffy binding protein alpha region II (PkDBPαII) and Duffy antigen receptor for chemokines (DARCs) on the erythrocytes. Information is scarce on the binding level of PkDBPαII to different Duffy antigens, Fya and Fyb. This study aims to measure the binding level of two genetically distinct PkDBPαII haplotypes to Fy(a+b-) and Fy(a+b+) human erythrocytes using erythrocyte-binding assay. The binding level of PkDBPαII of Peninsular Malaysian and Malaysian Borneon haplotypes to erythrocytes was determined by counting the number of rosettes formed in the assay. Overall, the Peninsular Malaysian haplotype displayed higher binding activity than the Malaysian Borneon haplotype. Both haplotypes exhibit the same preference to Fy(a+b+) compared with Fy(a+b-), hence justifying the vital role of Fyb in the binding to PkDBPαII. Further studies are needed to investigate the P. knowlesi susceptibility on individuals with different Duffy blood groups.

Matched MeSH terms: Malaria/parasitology
Fulltext Three Divergent Subpopulations of the Malaria Parasite Plasmodium knowlesi

Divis PC, Lin LC, Rovie-Ryan JJ, Kadir KA, Anderios F, Hisam S, et al.

Emerg Infect Dis, 2017 04;23(4):616-624.
PMID: 28322705 DOI: 10.3201/eid2304.161738

Multilocus microsatellite genotyping of Plasmodium knowlesi isolates previously indicated 2 divergent parasite subpopulations in humans on the island of Borneo, each associated with a different macaque reservoir host species. Geographic divergence was also apparent, and independent sequence data have indicated particularly deep divergence between parasites from mainland Southeast Asia and Borneo. To resolve the overall population structure, multilocus microsatellite genotyping was conducted on a new sample of 182 P. knowlesi infections (obtained from 134 humans and 48 wild macaques) from diverse areas of Malaysia, first analyzed separately and then in combination with previous data. All analyses confirmed 2 divergent clusters of human cases in Malaysian Borneo, associated with long-tailed macaques and pig-tailed macaques, and a third cluster in humans and most macaques in peninsular Malaysia. High levels of pairwise divergence between each of these sympatric and allopatric subpopulations have implications for the epidemiology and control of this zoonotic species.

Matched MeSH terms: Malaria/parasitology
Fulltext The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern?

Sabbatani S, Fiorino S, Manfredi R

Braz J Infect Dis, 2010 May-Jun;14(3):299-309.
PMID: 20835518

After examining the most recent scientific evidences, which assessed the role of some malaria plasmodia that have monkeys as natural reservoirs, the authors focus their attention on Plasmodium knowlesi. The infective foci attributable to this last Plasmodium species have been identified during the last decade in Malaysia, in particular in the states of Sarawak and Sabah (Malaysian Borneo), and in the Pahang region (peninsular Malaysia). The significant relevance of molecular biology assays (polymerase chain reaction, or PCR, performed with specific primers for P. knowlesi), is underlined, since the traditional microscopic examination does not offer distinguishing features, especially when the differential diagnosis with Plasmodium malariae is of concern. Furthermore, Plasmodium knowlesi disease may be responsible of fatal cases, since its clinical presentation and course is more severe compared with those caused by P. malariae, paralleling a more elevated parasitemia. The most effective mosquito vector is represented by Anopheles latens; this mosquito is a parasite of both humans and monkeys. Among primates, the natural hosts are Macaca fascicularis, M. nemestina, M. inus, and Saimiri scirea. When remarking the possible severe evolution of P. knowlesi malaria, we underline the importance of an early recognition and a timely management, especially in patients who have their first onset in Western Hospitals, after journeys in Southeast Asian countries, and eventually participated in trekking excursions in the tropical forest. When malaria-like signs and symptoms are present, a timely diagnosis and treatment become crucial. In the light of its emerging epidemiological features, P. knowlesi may be added to the reknown human malaria parasites, whith includes P. vivax, P. ovale, P. malariae, and P. falciparum, as the fifth potential ethiologic agent of human malaria. Over the next few years, it will be mandatory to support an adequate surveillance and epidemiological network. In parallel with epidemiological and health care policy studies, also an accurate appraisal of the clinical features of P. knowlesi-affected patients will be strongly needed, since some preliminary experiences seem to show an increased disease severity, associated with increased parasitemia, in parallel with the progressive increase of inter-human infectious passages of this emerging Plasmodium.

Matched MeSH terms: Malaria/parasitology*
Fulltext The effect of regularly dosed paracetamol versus no paracetamol on renal function in Plasmodium knowlesi malaria (PACKNOW): study protocol for a randomised controlled trial

Cooper DJ, Plewes K, Grigg MJ, Rajahram GS, Piera KA, William T, et al.

Trials, 2018 Apr 24;19(1):250.
PMID: 29690924 DOI: 10.1186/s13063-018-2600-0

BACKGROUND: Plasmodium knowlesi is the most common cause of human malaria in Malaysia. Acute kidney injury (AKI) is a frequent complication. AKI of any cause can have long-term consequences, including increased risk of chronic kidney disease, adverse cardiovascular events and increased mortality. Additional management strategies are therefore needed to reduce the frequency and severity of AKI in malaria. In falciparum malaria, cell-free haemoglobin (CFHb)-mediated oxidative damage contributes to AKI. The inexpensive and widely available drug paracetamol inhibits CFHb-induced lipid peroxidation via reduction of ferryl haem to the less toxic Fe3+ state, and has been shown to reduce oxidative damage and improve renal function in patients with sepsis complicated by haemolysis as well as in falciparum malaria. This study aims to assess the ability of regularly dosed paracetamol to reduce the incidence and severity of AKI in knowlesi malaria by attenuating haemolysis-induced oxidative damage.
METHODS: PACKNOW is a two-arm, open-label randomised controlled trial of adjunctive paracetamol versus no paracetamol in patients aged ≥ 5 years with knowlesi malaria, conducted over a 2-year period at four hospital sites in Sabah, Malaysia. The primary endpoint of change in creatinine from enrolment to 72 h will be evaluated by analysis of covariance (ANCOVA) using enrolment creatinine as a covariate. Secondary endpoints include longitudinal changes in markers of oxidative stress (plasma F2-isoprostanes and isofurans) and markers of endothelial activation/Weibel-Palade body release (angiopoietin-2, von Willebrand Factor, P-selectin, osteoprotegerin) over 72 h, as well as blood and urine biomarkers of AKI. This study will be powered to detect a difference between the two treatment arms in a clinically relevant population including adults and children with knowlesi malaria of any severity.
DISCUSSION: Paracetamol is widely available and has an excellent safety profile; if a renoprotective effect is demonstrated, this trial will support the administration of regularly dosed paracetamol to all patients with knowlesi malaria. The secondary outcomes in this study will provide further insights into the pathophysiology of haemolysis-induced oxidative damage and acute kidney injury in knowlesi malaria and other haemolytic diseases.
TRIAL REGISTRATION: Clinicaltrials.gov, NCT03056391 . Registered on 12 October 2016.

Matched MeSH terms: Malaria/parasitology
The Antimalarial Effect of Curcumin Is Mediated by the Inhibition of Glycogen Synthase Kinase-3β

Ali AH, Sudi S, Basir R, Embi N, Sidek HM

J Med Food, 2017 Feb;20(2):152-161.
PMID: 28146408 DOI: 10.1089/jmf.2016.3813

Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.

Matched MeSH terms: Malaria/parasitology
Fulltext Swedish traveller with Plasmodium knowlesi malaria after visiting Malaysian Borneo

Bronner U, Divis PC, Färnert A, Singh B

Malar J, 2009 Jan 16;8:15.
PMID: 19146706 DOI: 10.1186/1475-2875-8-15

Plasmodium knowlesi is typically found in nature in macaques and has recently been recognized as the fifth species of Plasmodium causing malaria in human populations in south-east Asia. A case of knowlesi malaria is described in a Swedish man, who became ill after returning from a short visit to Malaysian Borneo in October 2006. His P. knowlesi infection was not detected using a rapid diagnostic test for malaria, but was confirmed by PCR and molecular characterization. He responded rapidly to treatment with mefloquine. Evaluation of rapid diagnostic kits with further samples from knowlesi malaria patients are necessary, since early identification and appropriate anti-malarial treatment of suspected cases are essential due to the rapid growth and potentially life-threatening nature of P. knowlesi. Physicians should be aware that knowlesi infection is an important differential diagnosis in febrile travellers, with a recent travel history to forested areas in south-east Asia, including short-term travellers who tested negative with rapid diagnostic tests.

Matched MeSH terms: Malaria/parasitology
Fulltext Susceptibility of human Plasmodium knowlesi infections to anti-malarials

Fatih FA, Staines HM, Siner A, Ahmed MA, Woon LC, Pasini EM, et al.

Malar J, 2013;12:425.
PMID: 24245918 DOI: 10.1186/1475-2875-12-425

Evidence suggests that Plasmodium knowlesi malaria in Sarawak, Malaysian Borneo remains zoonotic, meaning anti-malarial drug resistance is unlikely to have developed in the absence of drug selection pressure. Therefore, adequate response to available anti-malarial treatments is assumed.

Matched MeSH terms: Malaria/parasitology*
Fulltext Suppression of Plasmodium berghei parasitemia by LiCl in an animal infection model

Nurul Aiezzah Z, Noor E, Hasidah MS

Trop Biomed, 2010 Dec;27(3):624-31.
PMID: 21399604 MyJurnal

Malaria, caused by the Plasmodium parasite is still a health problem worldwide due to resistance of the pathogen to current anti-malarials. The search for new anti-malarial agents has become more crucial with the emergence of chloroquine-resistant Plasmodium falciparum strains. Protein kinases such as mitogen-activated protein kinase (MAPK), MAPK kinase, cyclin-dependent kinase (CDK) and glycogen synthase kinase- 3(GSK-3) of parasitic protozoa are potential drug targets. GSK-3 is an enzyme that plays a vital role in multiple cellular processes, and has been linked to pathogenesis of several diseases such as type II diabetes and Alzheimer's disease. In the present study, the antiplasmodial property of LiCl, a known GSK-3 inhibitor, was evaluated in vivo for its antimalarial effect against mice infected with Plasmodium berghei. Infected ICR mice were intraperitoneally administered with LiCl for four consecutive days before (prophylactic test) and after (suppressive test) inoculation of P. berghei-parasitised erythrocytes. Results from the suppressive test (post-infection LiCl treatment) showed inhibition of erythrocytic parasitemia development by 62.06%, 85.67% and 85.18% as compared to nontreated controls for the 100 mg/kg, 300 mg/kg and 600 mg/kg dosages respectively. Both 300 mg/kg and 600 mg/kg LiCl showed similar significant (P<0.05) suppressive values to that obtained with chloroquine-treated mice (86% suppression). The prophylactic test indicated a significantly (P<0.05) high protective effect on mice pre-treated with LiCl with suppression levels relatively comparable to chloroquine (84.07% and 86.26% suppression for the 300 mg/kg and 600 mg/kg LiCl dosages respectively versus 92.86% suppression by chloroquine). In both the suppressive and prophylactic tests, LiCl-treated animals survived longer than their non-treated counterparts. Mortality of the non-treated mice was 100% within 6 to 7 days of parasite inoculation whereas mice administered with LiCl survived beyond 9 days. Healthy non-infected mice administered with 600 mg/ kg LiCl for four consecutive days also showed decreased mortality compared to animals receiving lower doses of LiCl; three of the seven mice intraperitoneally injected with the former dose of LiCl did not survive more than 24 h after administration of LiCl whereas animals given the lower LiCl doses survived beyond four days of LiCl administration. To date, no direct evidence of anti-malarial activity in vivo or in vitro has been reported for LiCl. Evidence of anti-plasmodial activity of lithium in a mouse infection model is presented in this study.

Matched MeSH terms: Malaria/parasitology
Fulltext Studies on the biology of Anopheles letifer Sandosham (Diptera, Culicidae) and its response to residual spraying, carried out in Sarawak, Malaysia

Thevasagayam ES, Liaw CF

Med J Malaysia, 1980 Mar;34(3):254-64.
PMID: 7191047
Matched MeSH terms: Malaria/parasitology
Fulltext Specific, sensitive and rapid detection of human plasmodium knowlesi infection by loop-mediated isothermal amplification (LAMP) in blood samples

Lau YL, Fong MY, Mahmud R, Chang PY, Palaeya V, Cheong FW, et al.

Malar J, 2011;10:197.
PMID: 21774805 DOI: 10.1186/1475-2875-10-197

The emergence of Plasmodium knowlesi in humans, which is in many cases misdiagnosed by microscopy as Plasmodium malariae due to the morphological similarity has contributed to the needs of detection and differentiation of malaria parasites. At present, nested PCR targeted on Plasmodium ssrRNA genes has been described as the most sensitive and specific method for Plasmodium detection. However, this method is costly and requires trained personnel for its implementation. Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method was developed for the clinical detection of P. knowlesi. The sensitivity and specificity of LAMP was evaluated in comparison to the results obtained via microscopic examination and nested PCR.

Matched MeSH terms: Malaria/parasitology*
Fulltext Spatial distribution of malaria in Peninsular Malaysia from 2000 to 2009

Alias H, Surin J, Mahmud R, Shafie A, Mohd Zin J, Mohamad Nor M, et al.

Parasit Vectors, 2014;7:186.
PMID: 24735583 DOI: 10.1186/1756-3305-7-186

Malaria is still an endemic disease of public health importance in Malaysia. Populations at risk of contracting malaria includes indigenous people, traditional villagers, mobile ethnic groups and land scheme settlers, immigrants from malaria endemic countries as well as jungle workers and loggers. The predominant species are Plasmodium falciparum and P. vivax. An increasing number of P. knowlesi infections have also been encountered. The principal vectors in Peninsular Malaysia are Anopheles maculatus and An. cracens. This study aims to determine the changes in spatial distribution of malaria in Peninsular Malaysia from year 2000-2009.

Matched MeSH terms: Malaria/parasitology
Simian malaria infection in wild caught Macaca fascicularis and Presbytis spp in Malaysia

Rain AN, Mak JW, Zamri R

Southeast Asian J. Trop. Med. Public Health, 1993 Jun;24(2):386-7.
PMID: 8266247
Matched MeSH terms: Malaria/parasitology

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