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Fulltext Increased detection of Plasmodium knowlesi in Sandakan division, Sabah as revealed by PlasmoNex™

Goh XT, Lim YA, Vythilingam I, Chew CH, Lee PC, Ngui R, et al.

Malar J, 2013 Jul 31;12:264.
PMID: 23902626 DOI: 10.1186/1475-2875-12-264

BACKGROUND: Plasmodium knowlesi is a simian malaria parasite that is widespread in humans in Malaysian Borneo. However, little is known about the incidence and distribution of this parasite in the Sandakan division, Malaysian Borneo. Therefore, the aim of the present epidemiological study was to investigate the incidence and distribution of P. knowlesi as well as other Plasmodium species in this division based on a most recent developed hexaplex PCR system (PlasmoNex™).
METHODS: A total of 189 whole blood samples were collected from Telupid Health Clinic, Sabah, Malaysia, from 2008 to 2011. All patients who participated in the study were microscopically malaria positive before recruitment. Complete demographic details and haematological profiles were obtained from 85 patients (13 females and 72 males). Identification of Plasmodium species was conducted using PlasmoNex™ targeting the 18S ssu rRNA gene.
RESULTS: A total of 178 samples were positive for Plasmodium species by using PlasmoNex™. Plasmodium falciparum was identified in 68 samples (38.2%) followed by 64 cases (36.0%) of Plasmodium vivax, 42 (23.6%) cases of P. knowlesi, two (1.1%) cases of Plasmodium malariae and two (1.1%) mixed-species infections (i e, P. vivax/P. falciparum). Thirty-five PlasmoNex™ positive P. knowlesi samples were misdiagnosed as P. malariae by microscopy. Plasmodium knowlesi was detected in all four districts of Sandakan division with the highest incidence in the Kinabatangan district. Thrombocytopaenia and anaemia showed to be the most frequent malaria-associated haematological complications in this study.
CONCLUSIONS: The discovery of P. knowlesi in Sandakan division showed that prospective studies on the epidemiological risk factors and transmission dynamics of P. knowlesi in these areas are crucial in order to develop strategies for effective malaria control. The availability of advanced diagnostic tool PlasmoNex™ enhanced the accuracy and accelerated the speed in the diagnosis of malaria.

Matched MeSH terms: Malaria/parasitology*
In vivo study of human Plasmodium knowlesi in Macaca fascicularis

Anderios F, Noorrain A, Vythilingam I

Exp Parasitol, 2010 Feb;124(2):181-9.
PMID: 19765587 DOI: 10.1016/j.exppara.2009.09.009

Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious to humans. In this study Macaca fascicularis was used as a model to understand the host response to P. knowlesi using parasitological and haematological parameters. Three M. fascicularis of either sex were experimentally infected with P. knowlesi erythrocytic parasites from humans. The pre-patent period for P. knowlesi infection in M. fascicularis ranged from seven to 14 days. The parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual stage and 88-264 parasites per microL of blood for sexual stage. Periodicity analysis adopted from microfilaria periodicity technique of asexual stage showed that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h. Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to display periodicity with a peak (24:00-06:00) that coincides with the peak biting activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late trophozoite. However, it may be distinguishable by observing the appliqué appearance of the cytoplasm and the chromatin lying inside the ring. Haematological analysis on macaques with knowlesi malaria showed clinical manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross examination of spleen and liver showed malaria pigments deposition in both organs.

Matched MeSH terms: Malaria/parasitology*
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/parasitology
Fulltext Identification of protein markers in patients infected with Plasmodium knowlesi, Plasmodium falciparum and Plasmodium vivax

Mu AK, Bee PC, Lau YL, Chen Y

Int J Mol Sci, 2014;15(11):19952-61.
PMID: 25372941 DOI: 10.3390/ijms151119952

Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. For this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. The aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various Plasmodium species, including P. knowlesi, P. vivax and P. falciparum. Sera from malaria-infected patients were pooled and compared to control sera obtained from healthy individuals using the isobaric tags for relative and absolute quantitation (iTRAQ) technique. Mass spectrometry was used to identify serum proteins and quantify their relative abundance. We found that the levels of several proteins were increased in pooled serum from infected patients, including cell adhesion molecule-4 and C-reactive protein. In contrast, the serum concentration of haptoglobin was reduced in malaria-infected individuals, which we verified by western blot assay. Therefore, these proteins might represent infectious markers of malaria, which could be used to develop novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum. However, these potential malarial markers will need to be validated in a larger population of infected individuals.

Matched MeSH terms: Malaria/parasitology
Fulltext Identification of circulating biomarkers in sera of Plasmodium knowlesi-infected malaria patients--comparison against Plasmodium vivax infection

Chen Y, Chan CK, Kerishnan JP, Lau YL, Wong YL, Gopinath SC

BMC Infect Dis, 2015;15:49.
PMID: 25656928 DOI: 10.1186/s12879-015-0786-2

Plasmodium knowlesi was identified as the fifth major malaria parasite in humans. It presents severe clinical symptoms and leads to mortality as a result of hyperparasitemia in a short period of time. This study aimed to improve the current understanding of P. knowlesi and identify potential biomarkers for knowlesi malaria.

Matched MeSH terms: Malaria/parasitology
Fulltext Hyperparasitaemic human Plasmodium knowlesi infection with atypical morphology in peninsular Malaysia

Lee WC, Chin PW, Lau YL, Chin LC, Fong MY, Yap CJ, et al.

Malar J, 2013;12:88.
PMID: 23496970 DOI: 10.1186/1475-2875-12-88

Plasmodium knowlesi is a potentially life-threatening zoonotic malaria parasite due to its relatively short erythrocytic cycle. Microscopic identification of P. knowlesi is difficult, with "compacted parasite cytoplasm" being one of the important identifying keys. This report is about a case of hyperparasitaemic human P. knowlesi infection (27% parasitaemia) with atypical amoeboid morphology. A peninsular Malaysian was admitted to the hospital with malaria. He suffered anaemia and acute kidney function impairment. Microscopic examination, assisted by nested PCR and sequencing confirmed as P. knowlesi infection. With anti-malarial treatment and several medical interventions, patient survived and recovered. One-month medical follow-up was performed after recovery and no recrudescence was noted. This case report highlights the extreme hyperparasitaemic setting, the atypical morphology of P. knowlesi in the patient's erythrocytes, as well as the medical interventions involved in this successfully treated case.

Matched MeSH terms: Malaria/parasitology*
Fulltext Human Plasmodium knowlesi infections in South-East Asian countries

Zaw MT, Lin Z

J Microbiol Immunol Infect, 2019 Oct;52(5):679-684.
PMID: 31320238 DOI: 10.1016/j.jmii.2019.05.012

Plasmodium knowlesi is now regarded as the fifth malaria parasite causing human malaria as it is widely distributed in South-East Asian countries especially east Malaysia where two Malaysian states namely Sabah and Sarawak are situated. In 2004, Polymerase Chain Reaction (PCR) was applied for diagnosing knowlesi malaria in the Kapit Division of Sarawak, Malaysia, so that human P. knowlesi infections could be detected correctly while blood film microscopy diagnosed incorrectly as Plasmodium malariae. This parasite is transmitted from simian hosts to humans via Anopheles vectors. Indonesia is the another country in South East Asia where knowlesi malaria is moderately prevalent. In the last decade, Sarawak and Sabah, the two states of east Malaysia became the target of P. knowlesi research due to prevalence of cases with occasional fatal infections. The host species of P. knowlesi are three macaque species namely Macaca fascicularis, Macaca nemestrina and Macaca leonina while the vector species are the Leucosphyrus Complex and the Dirus Complex of the Leucophyrus Group of Anopheles mosquitoes. Rapid diagnostic tests (RDT) are non-existent for knowlesi malaria although timely treatment is necessary for preventing complications, fatality and drug resistance. Development of RDT is essential in dealing with P. knowlesi infections in poor rural healthcare services. Genetic studies of the parasite on possibility of human-to-human transmission of P. knowlesi were recommended for further studies.

Matched MeSH terms: Malaria/parasitology
Fulltext High proportion of knowlesi malaria in recent malaria cases in Malaysia

Yusof R, Lau YL, Mahmud R, Fong MY, Jelip J, Ngian HU, et al.

Malar J, 2014;13:168.
PMID: 24886266 DOI: 10.1186/1475-2875-13-168

Plasmodium knowlesi is a simian parasite that has been recognized as the fifth species causing human malaria. Naturally-acquired P. knowlesi infection is widespread among human populations in Southeast Asia. The aim of this epidemiological study was to determine the incidence and distribution of malaria parasites, with a particular focus on human P. knowlesi infection in Malaysia.

Matched MeSH terms: Malaria/parasitology*
Fulltext Hexaplex PCR detection system for identification of five human Plasmodium species with an internal control

Chew CH, Lim YA, Lee PC, Mahmud R, Chua KH

J Clin Microbiol, 2012 Dec;50(12):4012-9.
PMID: 23035191 DOI: 10.1128/JCM.06454-11

Malaria remains one of the major killers of humankind and persists to threaten the lives of more than one-third of the world's population. Given that human malaria can now be caused by five species of Plasmodium, i.e., Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and the recently included Plasmodium knowlesi, there is a critical need not only to augment global health efforts in malaria control but also, more importantly, to develop a rapid, accurate, species-sensitive/species-specific, and economically effective diagnostic method for malaria caused by these five species. Therefore, in the present study, a straightforward single-step hexaplex PCR system targeting five human Plasmodium 18S small-subunit rRNAs (ssu rRNAs) was designed, and the system successfully detected all five human malaria parasites. In addition, this system enables the differentiation of single infection as well as mixed infections up to the two-species level. This assay was validated with 50 randomly blinded test and 184 clinical samples suspected to indicate malaria. This hexaplex PCR system is not only an ideal alternative for routine malaria diagnosis in laboratories with conventional PCR machines but also adds value to diagnoses when there is a lack of an experienced microscopist or/and when the parasite morphology is confusing. Indeed, this system will definitely enhance the accuracy and accelerate the speed in the diagnosis of malaria, as well as improve the efficacy of malaria treatment and control, in addition to providing reliable data from epidemiological surveillance studies.

Matched MeSH terms: Malaria/parasitology*
Fulltext Genotyping of the Duffy blood group among Plasmodium knowlesi-infected patients in Malaysia

De Silva JR, Lau YL, Fong MY

PLoS One, 2014;9(9):e108951.
PMID: 25268233 DOI: 10.1371/journal.pone.0108951

The Duffy blood group is of major interest in clinical medicine as it plays an important role in Plasmodium knowlesi and Plasmodium vivax infection. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Peninsular Malaysia were determined. The blood group of 60 healthy blood donors and 51 P. knowlesi malaria patients were genotyped using allele specific polymerase chain reaction (ASP-PCR). The data was analyzed using Fisher's exact test in order to assess the significance of the variables. Our results show a high proportion of the FY*A/FY*A genotype (>85% for both groups) and a high frequency of the FY*A allele (>90% for both groups). The FY*A/FY*A genotype was the most predominant genotype in both infected and healthy blood samples. The genotype frequency did not differ significantly between the donor blood and the malaria patient groups. Also, there was no significant correlation between susceptibility to P. knowlesi infection with any Duffy blood genotype.

Matched MeSH terms: Malaria/parasitology
Genetic polymorphism of circumsporozoite protein (CSP) in Plasmodium malariae isolates from Malaysia

Phang WK, Bukhari FDM, Zen LPY, Jaimin JJ, Dony JJF, Lau YL

Parasitol Int, 2022 Apr;87:102519.
PMID: 34800724 DOI: 10.1016/j.parint.2021.102519

Information about Plasmodium malariae is scanty worldwide due to its "benign" nature and low infection rates. Consequently, studies on the genetic polymorphisms of P. malariae are lacking. Here, we report genetic polymorphisms of 28 P. malariae circumsporozoite protein (Pmcsp) isolates from Malaysia which were compared with those in other regions in Asia as well as those from Africa. Phylogenetic analysis revealed that most Malaysian P. malariae isolates clustered together but independently from other Asian isolates. Low nucleotide diversity was observed in Pmcsp non-repeat regions in contrast to high nucleotide diversity observed in non-repeat regions of Plasmodium knowlesi CSP gene, the current major cause of malaria in Malaysia. This study contributes to the characterisation of naturally occurring polymorphisms in the P. malariae CSP gene.

Matched MeSH terms: Malaria/parasitology*
Fulltext Genetic polymorphism and natural selection in the C-terminal 42 kDa region of merozoite surface protein-1 (MSP-1) among Plasmodium knowlesi samples from Malaysia

Yap NJ, Vythilingam I, Hoh BP, Goh XT, Muslim A, Ngui R, et al.

Parasit Vectors, 2018 Dec 05;11(1):626.
PMID: 30518419 DOI: 10.1186/s13071-018-3234-5

BACKGROUND: The merozoite surface protein-1 (MSP-1) gene encodes for a leading malaria vaccine candidate antigen. However, its extensive polymorphic nature represents a major obstacle to the development of a protective vaccine. Previously, a pilot study was carried out to explore the sequence variation of the C-terminal 42 kDa fragment within P. knowlesi MSP-1 gene (PkMSP-142) based on 12 clinical samples; however, further study on an adequate sample size is vital in estimating the genetic diversity of the parasite population.
METHODS: In the present study, we included a larger sample size of P. knowlesi (83 samples) covering eight states of Malaysia to determine the genetic polymorphism, natural selection and haplotype groups of the gene fragment coding PkMSP-142. The region flanking PkMSP-142 was amplified by PCR and directly sequenced. Genetic diversity, haplotype diversity, population genetic differentiation and natural selection were determined in order to study the polymorphic characteristic of PkMSP-142.
RESULTS: A high level of genetic diversity (Hd = 0.970 ± 0.007; л = 0.01079 ± 0.00033) was observed among the 83 P. knowlesi samples, confirming the extensive genetic polymorphism exhibited among the P. knowlesi population found in Malaysia. A total of 18 distinct haplotypes with 17 amino acid changes were identified, whereby 15 were new haplotypes. High population differentiation values were observed within samples from Peninsular Malaysia and Malaysian Borneo. The 42 kDa fragments of P. knowlesi from Malaysian Borneo were found to be acting on balancing selection whilst purifying selection was suggested to act on isolates from Peninsular Malaysia. The separation of PkMSP-142 haplotypes into two main groups based on geographical separation has further supported the existence of two distinct P. knowlesi lineages.
CONCLUSIONS: A high level of genetic diversity was observed among PkMSP-142 in Malaysia, whereby most of the polymorphisms were found within the 33 kDa region. Taken together, these data will be useful in order to understand the nature of P. knowlesi population in Malaysia as well as the design and development of a MSP-142 based knowlesi malaria vaccine.

Matched MeSH terms: Malaria/parasitology*
Fulltext Genetic diversity, haplotypes and allele groups of Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Fong MY, Lau YL, Chang PY, Anthony CN

Parasit Vectors, 2014;7:161.
PMID: 24693997 DOI: 10.1186/1756-3305-7-161

The monkey malaria parasite Plasmodium knowlesi is now recognized as the fifth species of Plasmodium that can cause human malaria. Like the region II of the Duffy binding protein of P. vivax (PvDBPII), the region II of the P. knowlesi Duffy binding protein (PkDBPαII) plays an essential role in the parasite's invasion into the host's erythrocyte. Numerous polymorphism studies have been carried out on PvDBPII, but none has been reported on PkDBPαII. In this study, the genetic diversity, haplotyes and allele groups of PkDBPαII of P. knowlesi clinical isolates from Peninsular Malaysia were investigated.

Matched MeSH terms: Malaria/parasitology
Genetic diversity of the full length apical membrane antigen-1 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Ng YL, Fong MY, Lau YL

Trop Biomed, 2021 Jun 01;38(2):159-164.
PMID: 34172705 DOI: 10.47665/tb.38.2.052

The Plasmodium knowlesi apical membrane antigen-1 (PkAMA-1) plays an important role in the invasion of the parasite into its host erythrocyte, and it has been regarded as a potential vaccine candidate against human knowlesi malaria. This study investigates genetic diversity and natural selection of the full length PkAMA-1 of P. knowlesi clinical isolates from Peninsular Malaysia. Blood samples were collected from P. knowlesi malaria patients from Peninsular Malaysia. The PkAMA-1 gene was amplified from DNA samples using PCR, cloned into a plasmid vector and sequenced. Results showed that nucleotide diversity of the full length PkAMA-1 from Peninsular Malaysia isolates (π: 0.006) was almost similar to that of Sarawak (π: 0.005) and Sabah (π: 0.004) isolates reported in other studies. Deeper analysis revealed Domain I (π: 0.007) in the PkAMA-1 had the highest diversity as compared to Domain II (π: 0.004) and Domain III (π: 0.003). Z-test indicated negative (purifying) selection of the gene. Combined alignment analysis at the amino acid level for the Peninsular Malaysia and Sarawak PkAMA-1 sequences revealed 34 polymorphic sites. Thirty-one of these sites were dimorphic, and 3 were trimorphic. The amino acid sequences could be categorised into 31 haplotypes. In the haplotype network, PkAMA-1 from Peninsular Malaysia and Sarawak were separated into two groups.

Matched MeSH terms: Malaria/parasitology
Genetic diversity in the C-terminus of merozoite surface protein 1 among Plasmodium knowlesi isolates from Selangor and Sabah Borneo, Malaysia

Yap NJ, Goh XT, Koehler AV, William T, Yeo TW, Vythilingam I, et al.

Infect Genet Evol, 2017 10;54:39-46.
PMID: 28634105 DOI: 10.1016/j.meegid.2017.06.019

Plasmodium knowlesi, a malaria parasite of macaques, has emerged as an important parasite of humans. Despite the significance of P. knowlesi malaria in parts of Southeast Asia, very little is known about the genetic variation in this parasite. Our aim here was to explore sequence variation in a molecule called the 42kDa merozoite surface protein-1 (MSP-1), which is found on the surface of blood stages of Plasmodium spp. and plays a key role in erythrocyte invasion. Several studies of P. falciparum have reported that the C-terminus (a 42kDa fragment) of merozoite surface protein-1 (MSP-142; consisting of MSP-119 and MSP-133) is a potential candidate for a malaria vaccine. However, to date, no study has yet investigated the sequence diversity of the gene encoding P. knowlesi MSP-142 (comprising Pk-msp-119 and Pk-msp-133) among isolates in Malaysia. The present study explored this aspect. Twelve P. knowlesi isolates were collected from patients from hospitals in Selangor and Sabah Borneo, Malaysia, between 2012 and 2014. The Pk-msp-142 gene was amplified by PCR and directly sequenced. Haplotype diversity (Hd) and nucleotide diversity (л) were studied among the isolates. There was relatively high genetic variation among P. knowlesi isolates; overall Hd and л were 1±0.034 and 0.01132±0.00124, respectively. A total of nine different haplotypes related to amino acid alterations at 13 positions, and the Pk-MSP-119 sequence was found to be more conserved than Pk-msp-133. We have found evidence for negative selection in Pk-msp-42 as well as the 33kDa and 19kDa fragments by comparing the rate of non-synonymous versus synonymous substitutions. Future investigations should study large numbers of samples from disparate geographical locations to critically assess whether this molecule might be a potential vaccine target for P. knowlesi.

Matched MeSH terms: Malaria/parasitology*
Fulltext Genetic clustering and polymorphism of the merozoite surface protein-3 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

De Silva JR, Lau YL, Fong MY

Parasit Vectors, 2017 01 03;10(1):2.
PMID: 28049516 DOI: 10.1186/s13071-016-1935-1

BACKGROUND: The simian malaria parasite Plasmodium knowlesi has been reported to cause significant numbers of human infection in South East Asia. Its merozoite surface protein-3 (MSP3) is a protein that belongs to a multi-gene family of proteins first found in Plasmodium falciparum. Several studies have evaluated the potential of P. falciparum MSP3 as a potential vaccine candidate. However, to date no detailed studies have been carried out on P. knowlesi MSP3 gene (pkmsp3). The present study investigates the genetic diversity, and haplotypes groups of pkmsp3 in P. knowlesi clinical samples from Peninsular Malaysia.
METHODS: Blood samples were collected from P. knowlesi malaria patients within a period of 4 years (2008-2012). The pkmsp3 gene of the isolates was amplified via PCR, and subsequently cloned and sequenced. The full length pkmsp3 sequence was divided into Domain A and Domain B. Natural selection, genetic diversity, and haplotypes of pkmsp3 were analysed using MEGA6 and DnaSP ver. 5.10.00 programmes.
RESULTS: From 23 samples, 48 pkmsp3 sequences were successfully obtained. At the nucleotide level, 101 synonymous and 238 non-synonymous mutations were observed. Tests of neutrality were not significant for the full length, Domain A or Domain B sequences. However, the dN/dS ratio of Domain B indicates purifying selection for this domain. Analysis of the deduced amino acid sequences revealed 42 different haplotypes. Neighbour Joining phylogenetic tree and haplotype network analyses revealed that the haplotypes clustered into two distinct groups.
CONCLUSIONS: A moderate level of genetic diversity was observed in the pkmsp3 and only the C-terminal region (Domain B) appeared to be under purifying selection. The separation of the pkmsp3 into two haplotype groups provides further evidence of the existence of two distinct P. knowlesi types or lineages. Future studies should investigate the diversity of pkmsp3 among P. knowlesi isolates in North Borneo, where large numbers of human knowlesi malaria infection still occur.

Matched MeSH terms: Malaria/parasitology*
Genetic characterisation of the erythrocyte-binding protein (PkβII) of Plasmodium knowlesi isolates from Malaysia

Fong MY, Lau YL, Jelip J, Ooi CH, Cheong FW

J Genet, 2019 Sep;98.
PMID: 31544794

Plasmodium knowlesi contributes to the majority of human malaria incidences in Malaysia. Its uncontrollable passage among the natural monkey hosts can potentially lead to zoonotic outbreaks. The merozoite of this parasite invades host erythrocytes through interaction between its erythrocyte-binding proteins (EBPs) and their respective receptor on the erythrocytes. The regionII of P. knowlesi EBP, P. knowlesi beta (PkβII) protein is found to be mediating merozoite invasion into monkey erythrocytes by interacting with sialic acid receptors. Hence, the objective of this study was to investigate the genetic diversity, natural selection and haplotype grouping of PkβII of P. knowlesi isolates in Malaysia. Polymerase chain reaction amplifications of PkβII were performed on archived blood samples from Malaysia and 64 PkβII sequences were obtained. Sequence analysis revealed length polymorphism, and its amino acids at critical residues indicate the ability of PkβII to mediate P. knowlesi invasion into monkey erythrocytes. Low genetic diversity (π = 0.007) was observed in the PkβII of Malaysia Borneo compared to Peninsular Malaysia (π = 0.015). The PkβII was found to be under strong purifying selection to retain infectivity in monkeys and it plays a limited role in the zoonotic potential of P. knowlesi. Its haplotypes could be clustered into Peninsular Malaysia and Malaysia Borneo groups, indicating the existence of two distinct P. knowlesi parasites in Malaysia as reported in an earlier study.

Matched MeSH terms: Malaria/parasitology
Fulltext Genetic Diversity and Natural Selection of the Plasmodium knowlesi Circumsporozoite Protein Nonrepeat Regions

Fong MY, Ahmed MA, Wong SS, Lau YL, Sitam F

PLoS One, 2015;10(9):e0137734.
PMID: 26379157 DOI: 10.1371/journal.pone.0137734

Plasmodium knowlesi is a simian malaria parasite that has been identified to cause malaria in humans. To date, several thousand cases of human knowlesi malaria have been reported around Southeast Asia. Thus far, there is no detailed study on genetic diversity and natural selection of P. knowlesi circumsporozoite protein (CSP), a prominent surface antigen on the sporozoite of the parasite. In the present study, the genetic diversity and natural selection acting on the nonrepeat regions of the gene encoding P. knowlesi CSP were investigated, focusing on the T-cell epitope regions at the C-terminal of the protein.

Matched MeSH terms: Malaria/parasitology
Fulltext Gancidin W, a potential low-toxicity antimalarial agent isolated from an endophytic Streptomyces SUK10

Zin NM, Baba MS, Zainal-Abidin AH, Latip J, Mazlan NW, Edrada-Ebel R

Drug Des Devel Ther, 2017;11:351-363.
PMID: 28223778 DOI: 10.2147/DDDT.S121283

Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.

Matched MeSH terms: Malaria/parasitology*
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/parasitology*

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