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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 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
Demographic, clinical and laboratory features of leptospirosis-malaria co-infections in Peninsular Malaysia

Rao M, Atiqah N, Dasiman M, Amran F

J Med Microbiol, 2020 Mar;69(3):451-456.
PMID: 31846413 DOI: 10.1099/jmm.0.001127

Introduction. Co-infection of leptospirosis-malaria is not uncommon due to their overlapping geographical distribution in the tropics.Aim. This study aimed to describe and compare the demographic, clinical and laboratory features of leptospirosis-malaria co-infection (LMCI) against leptospirosis mono-infection (LMI) in Peninsular Malaysia.Methodology. Data of patients admitted to various hospitals in Peninsular Malaysia from 2011 to 2014 diagnosed with leptospirosis in our laboratory were obtained from their admission records. Co-infections with malaria were identified via blood film for malaria parasites (BFMP). Description with inferential statistics analysis and multiple logistic regressions were used to distinguish features between dual and mono-infections.Results. Of 111 leptospirosis-positive patients, 26 (23.4 %) tested positive for malaria. Co-infections were predominant among male patients with a mean age of 33 years and were prevalent among immigrant populations who had settled in high-density suburban areas. Chills and rigor with splenomegaly were the only significant distinguishing clinical features of LMCI while leukocytosis and raised transaminases were significant laboratory parameters. Only chills and rigor demonstrated a predictive value for LMCI from analysis of multiple logistic regressions. No death was attributed to co-infection in this study, in contrast to LMI (11.8 %, n=10).Conclusion. The significant prevalence of LMCI found in this study with overlapping demographic, clinical and laboratory parameters makes diagnosis of co-infection challenging. It is essential to evaluate co-infection in endemic areas. Strengthened awareness of LMCI, comprehensive diagnostic services and further prospective studies are warranted.

Matched MeSH terms: Malaria/parasitology
Fulltext Severe Plasmodium knowlesi infection with multiorgan involvement in north east peninsular Malaysia

Azidah AK, Mohd Faizal MA, Lili HY, Zeehaida M

Trop Biomed, 2014 Mar;31(1):31-5.
PMID: 24862042 MyJurnal

Plasmodium knowlesi has been recently identified as the "fifth human malaria species" following the discovery in Malaysian Borneo of a large focus of this simian malaria parasite in humans. Even though it shares microscopic similarities with Plasmodium malariae, it may cause severe illness with risk of fatality. We describe a case of P. knowlesi infection causing multi-organ failure in a patient who was successfully managed due to early recognition of the infection. Clinicians in this region should be more aware of the infection as it is not as rare as previously thought. This case write up highlight the case of severe malaria infection which presented with multi organ involvement which is caused by P. knowlesi.

Matched MeSH terms: Malaria/parasitology
Fulltext Case series of naturally acquired Plasmodium knowlesi infection in a tertiary teaching hospital

Azira NM, Zairi NZ, Amry AR, Zeehaida M

Trop Biomed, 2012 Sep;29(3):398-404.
PMID: 23018503 MyJurnal

Plasmodium knowlesi is a simian malaria parasite and is recently recognized as the fifth malaria parasite infecting humans. Manifestation of the infection may resemble other infection particularly dengue fever leading to inappropriate management and delay in treatment. We reported three cases of naturally acquired P. knowlesi in Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. Clinical manifestations were quite similar in those cases. Microscopically, the diagnosis might be challenging. These cases were confirmed by polymerase chain reaction method which serves as a gold standard.

Matched MeSH terms: Malaria/parasitology
Fulltext Sequence analysis on the mitochondrial COXI gene of recent clinical isolates of Plasmodium knowlesi in Klang Valley, peninsular Malaysia

Fong MY, Lau YL, Chin LC, Al-Mekhlafi AM

Trop Biomed, 2011 Aug;28(2):457-63.
PMID: 22041769

The cytochrome oxidase subunit I (COXI) gene sequences of three recent (2007-2008) clinical Plasmodium knowlesi isolates from Klang Valley, peninsular Malaysia, were determined and compared with those of older (1960's) peninsular Malaysia, recent isolates from Sarawak (on Borneo Island), and an isolate from Thailand. Multiple alignment of the sequences showed that the three clinical isolates were more similar to the older peninsular Malaysia isolates than to those from Sarawak and Thailand. Phylogenetic tree based on the COXI sequences revealed three distinct clusters of P. knowlesi. The first cluster consisted of isolates from peninsular Malaysia, the second consisted of Sarawak isolates and the third composed of the Thailand isolate. The findings of this study highlight the usefulness of mitochondrial COXI gene as a suitable marker for phylogeographic studies of P. knowlesi.

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*
Fulltext Diagnostic challenges and case management of the first imported case of Plasmodium knowlesi in Sri Lanka

Dewanee Ranaweera A, Danansuriya MN, Pahalagedera K, de A W Gunasekera WM, Dharmawardena P, Mak KW, et al.

Malar J, 2017 03 21;16(1):126.
PMID: 28327145 DOI: 10.1186/s12936-017-1776-1

BACKGROUND: Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed.
CASE PRESENTATION: An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider. Microscopy findings were suspicious of P. knowlesi infection as the smears showed parasite stages similar to both Plasmodium malariae and Plasmodium falciparum. Nested PCR at AMC confirmed Plasmodium genus, but not the species. In the absence of species confirmation, the patient was treated as a case of P. falciparum. The presence of P. knowlesi was later confirmed by a semi-nested PCR assay performed at the Environmental Health Institute, National Environmental Agency in Singapore. The parasite strain was also characterized by sequencing the circumsporozoite gene. Extensive case investigation including parasitological and entomological surveillance was carried out.
CONCLUSIONS: Plasmodium knowlesi should be suspected in patients returning from countries in the South Asian region where the parasite is prevalent and when blood smear results are inconclusive.

Matched MeSH terms: Malaria/parasitology
Fulltext Defining the ecological and evolutionary drivers of Plasmodium knowlesi transmission within a multi-scale framework

Davidson G, Chua TH, Cook A, Speldewinde P, Weinstein P

Malar J, 2019 Mar 08;18(1):66.
PMID: 30849978 DOI: 10.1186/s12936-019-2693-2

Plasmodium knowlesi is a zoonotic malaria parasite normally residing in long-tailed and pig-tailed macaques (Macaca fascicularis and Macaca nemestrina, respectively) found throughout Southeast Asia. Recently, knowlesi malaria has become the predominant malaria affecting humans in Malaysian Borneo, being responsible for approximately 70% of reported cases. Largely as a result of anthropogenic land use changes in Borneo, vectors which transmit the parasite, along with macaque hosts, are both now frequently found in disturbed forest habitats, or at the forest fringes, thus having more frequent contact with humans. Having access to human hosts provides the parasite with the opportunity to further its adaption to the human immune system. The ecological drivers of the transmission and spread of P. knowlesi are operating over many different spatial (and, therefore, temporal) scales, from the molecular to the continental. Strategies to prevent and manage zoonoses, such as P. knowlesi malaria require interdisciplinary research exploring the impact of land use change and biodiversity loss on the evolving relationship between parasite, reservoir hosts, vectors, and humans over multiple spatial scales.

Matched MeSH terms: Malaria/parasitology
Effect of Brugia pahangi co-infection with Plasmodium berghei ANKA in gerbils (Meriones unguiculatus)

Junaid OQ, Vythilingam I, Khaw LT, Sivanandam S, Mahmud R

Parasitol Res, 2020 Apr;119(4):1301-1315.
PMID: 32179986 DOI: 10.1007/s00436-020-06632-4

Malaria and lymphatic filariasis (LF) are two leading and common mosquito-borne parasitic diseases worldwide. These two diseases are co-endemic in many tropical and sub-tropical regions and are known to share vectors. The interactions between malaria and filarial parasites are poorly understood. Thus, this study aimed at establishing the interactions that occur between Brugia pahangi and Plasmodium berghei ANKA (PbA) co-infection in gerbils. Briefly, the gerbils were matched according to age, sex, and weight and grouped into filarial-only infection, PbA-only infection, co-infection, and control group. The parasitemia, survival and clinical assessment of the gerbils were monitored for a period of 30 days post Plasmodium infection. The immune responses of gerbils to both mono and co-infection were monitored. Findings show that co-infected gerbils have higher survival rate than PbA-infected gerbils. Food and water consumption were significantly reduced in both PbA-infected and co-infected gerbils, although loss of body weight, hypothermia, and anemia were less severe in co-infected gerbils. Plasmodium-infected gerbils also suffered hypoglycemia, which was not observed in co-infected gerbils. Furthermore, gerbil cytokine responses to co-infection were significantly higher than PbA-only-infected gerbils, which is being suggested as a factor for their increased longevity. Co-infected gerbils had significantly elicited interleukin-4, interferon-gamma, and tumor necrotic factor at early stage of infection than PbA-infected gerbils. Findings from this study suggest that B. pahangi infection protect against severe anemia and hypoglycemia, which are manifestations of PbA infection.

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 Local human movement patterns and land use impact exposure to zoonotic malaria in Malaysian Borneo

Fornace KM, Alexander N, Abidin TR, Brock PM, Chua TH, Vythilingam I, et al.

Elife, 2019 10 22;8.
PMID: 31638575 DOI: 10.7554/eLife.47602

Human movement into insect vector and wildlife reservoir habitats determines zoonotic disease risks; however, few data are available to quantify the impact of land use on pathogen transmission. Here, we utilise GPS tracking devices and novel applications of ecological methods to develop fine-scale models of human space use relative to land cover to assess exposure to the zoonotic malaria Plasmodium knowlesi in Malaysian Borneo. Combining data with spatially explicit models of mosquito biting rates, we demonstrate the role of individual heterogeneities in local space use in disease exposure. At a community level, our data indicate that areas close to both secondary forest and houses have the highest probability of human P. knowlesi exposure, providing quantitative evidence for the importance of ecotones. Despite higher biting rates in forests, incorporating human movement and space use into exposure estimates illustrates the importance of intensified interactions between pathogens, insect vectors and people around habitat edges.

Matched MeSH terms: Malaria/parasitology
Fulltext Eurycoma longifolia extract-artemisinin combination: parasitemia suppression of Plasmodium yoelii-infected mice

Mohd Ridzuan MA, Sow A, Noor Rain A, Mohd Ilham A, Zakiah I

Trop Biomed, 2007 Jun;24(1):111-8.
PMID: 17568384 MyJurnal

Eurycoma longifolia, locally known as 'Tongkat Ali' is a popular local medicinal plant that possess a lot of medicinal properties as claimed traditionally, especially in the treatment of malaria. The claims have been proven scientifically on isolated compounds from the plant. The present study is to investigate the anti malaria properties of Eurycoma longifolia standardized extract (root) (TA164) alone and in combination with artemisinin in vivo. Combination treatment of the standardized extract (TA164) with artemisinin suppressed P. yoelii infection in the experimental mice. The 4 day suppressive test showed that TA164 suppressed the parasitemia of P. yoelii-infected mice as dose dependent manner (10, 30 and 60 mg/kg BW) by oral and subcutaneous treatment. By oral administration, combination of TA164 at 10, 30 and 60 mg/kg BW each with artemisinin respectively showed a significant increase in the parasitemia suppression to 63, 67 and 80 percent as compared to artemisinin single treatment (31%). Using subcutaneous administration, at 10 mg/kg BW of TA164 in combination with 1.7 mg/kg BW of artemisinin gave a suppression of 80% of infection. This study showed that combination treatment of TA164 with artemisinin gives a promising potential anti malaria candidate using both oral and subcutaneous route, the later being the most potent.

Matched MeSH terms: Malaria/parasitology
Fulltext Natural Human Infections With Plasmodium cynomolgi and Other Malaria Species in an Elimination Setting in Sabah, Malaysia

Grignard L, Shah S, Chua TH, William T, Drakeley CJ, Fornace KM

J Infect Dis, 2019 11 06;220(12):1946-1949.
PMID: 31418017 DOI: 10.1093/infdis/jiz397

To determine the presence and species composition of malaria infections, we screened a subset of samples collected during a cross-sectional survey in Northern Sabah, Malaysia using highly sensitive molecular techniques. Results identified 54 asymptomatic submicroscopic malaria infections, including a large cluster of Plasmodium falciparum and 3 P. knowlesi infections. We additionally identified 2 monoinfections with the zoonotic malaria Plasmodium cynomolgi, both in individuals reporting no history of forest activities or contact with macaques. Results highlight the need for improved surveillance strategies to detect these infections and determine public health impacts.

Matched MeSH terms: Malaria/parasitology
Fulltext Plasmodium knowlesi malaria during pregnancy

Barber BE, Bird E, Wilkes CS, William T, Grigg MJ, Paramaswaran U, et al.

J Infect Dis, 2015 Apr 1;211(7):1104-10.
PMID: 25301955 DOI: 10.1093/infdis/jiu562

BACKGROUND: Plasmodium knowlesi is the commonest cause of malaria in Malaysia, but little is known regarding infection during pregnancy.
METHODS: To investigate comparative risk and consequences of knowlesi malaria during pregnancy, we reviewed (1) Sabah Health Department malaria-notification records created during 2012-2013, (2) prospectively collected data from all females with polymerase chain reaction (PCR)-confirmed malaria who were admitted to a Sabah tertiary care referral hospital during 2011-2014, and (3) malaria microscopy and clinical data recorded at a Sabah tertiary care women and children's hospital during 2010-2014.
RESULTS: During 2012-2013, 774 females with microscopy-diagnosed malaria were notified, including 252 (33%), 172 (20%), 333 (43%), and 17 (2%) with Plasmodium falciparum infection, Plasmodium vivax infection, Plasmodium malariae/Plasmodium knowlesi infection, and mixed infection, respectively. Among females aged 15-45 years, pregnancy was reported in 18 of 124 (14.5%), 9 of 93 (9.7%), and 4 of 151 (2.6%) P. falciparum, P. vivax, and P. malariae/P. knowlesi notifications respectively (P = .002). Three females with knowlesi malaria were confirmed as pregnant: 2 had moderate anemia, and 1 delivered a preterm low-birth-weight infant. There were 17, 7, and 0 pregnant women with falciparum, vivax, and knowlesi malaria, respectively, identified from the 2 referral hospitals.
CONCLUSIONS: Although P. knowlesi is the commonest malaria species among females in Sabah, P. knowlesi infection is relatively rare during pregnancy. It may however be associated with adverse maternal and pregnancy outcomes.
KEYWORDS: Plasmodium knowlesi; malaria; maternal anemia; pregnancy; preterm delivery

Matched MeSH terms: Malaria/parasitology
Fulltext Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria

Barber BE, Grigg MJ, William T, Piera KA, Boyle MJ, Yeo TW, et al.

J Infect Dis, 2017 06 15;215(12):1908-1917.
PMID: 28863470 DOI: 10.1093/infdis/jix193

Background: In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood.
Methods: In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age.
Results: Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P < .0001). In knowlesi malaria, IL-6, angiopoietin-2, and microvascular dysfunction were increased in severe compared to nonsevere disease, and all correlated with age, independent of parasitemia. In falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria.
Conclusions: Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

Matched MeSH terms: Malaria/parasitology*
Fulltext Orangutans not infected with Plasmodium vivax or P. cynomolgi, Indonesia

Singh B, Simon Divis PC

Emerg Infect Dis, 2009 Oct;15(10):1657-8.
PMID: 19861067 DOI: 10.3201/eid1510.090364

After orangutans in Indonesia were reported as infected with Plasmodium cynomolgi and P. vivax, we conducted phylogenetic analyses of small subunit ribosomal RNA gene sequences of Plasmodium spp. We found that these orangutans are not hosts of P. cynomolgi and P. vivax. Analysis of >or=1 genes is needed to identify Plasmodium spp. infecting orangutans.

Matched MeSH terms: Malaria/parasitology
Fulltext Intravascular haemolysis with haemoglobinuria in a splenectomized patient with severe Plasmodium knowlesi malaria

Barber BE, Grigg MJ, William T, Yeo TW, Anstey NM

Malar J, 2016 Sep 09;15:462.
PMID: 27613607 DOI: 10.1186/s12936-016-1514-0

BACKGROUND: Haemoglobinuria is an uncommon complication of severe malaria, reflecting acute intravascular haemolysis and potentially leading to acute kidney injury. It can occur early in the course of infection as a consequence of a high parasite burden, or may occur following commencement of anti-malarial treatment. Treatment with quinine has been described as a risk factor; however the syndrome may also occur following treatment with intravenous artesunate. In Malaysia, Plasmodium knowlesi is the most common cause of severe malaria, often associated with high parasitaemia. Asplenic patients may be at additional increased risk of intravascular haemolysis.
CASE PRESENTATION: A 61 years old asplenic man was admitted to a tertiary referral hospital in Sabah, Malaysia, with severe knowlesi malaria characterized by hyperparasitaemia (7.9 %), jaundice, respiratory distress, metabolic acidosis, and acute kidney injury. He was commenced on intravenous artesunate, but1 day later developed haemoglobinuria, associated with a 22 % reduction in admission haemoglobin. Additional investigations, including a cell-free haemoglobin of 10.2 × 10(5) ng/mL and an undetectable haptoglobin, confirmed intravascular haemolysis. The patient continued on intravenous artesunate for a total of 48 h prior to substitution with artemether-lumefantrine, and made a good recovery with resolution of his haemoglobinuria and improvement of his kidney function by day 3.
CONCLUSIONS: An asplenic patient with hyperparasitaemic severe knowlesi malaria developed haemoglobinuria after treatment with intravenous artesunate. There are plausible mechanisms for increased haemolysis with hyperparasitaemia, and following both splenectomy and artesunate. Although in this case the patient made a rapid recovery, knowlesi malaria patients with this unusual complication should be closely monitored for potential deterioration.

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 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*

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