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Journal of Physiological Anthropology Apr 2022Plasmodium knowlesi malaria infection in humans has been reported throughout southeast Asia. The communities at risk are those living in areas where Macaque monkeys and... (Review)
Review
Plasmodium knowlesi malaria infection in humans has been reported throughout southeast Asia. The communities at risk are those living in areas where Macaque monkeys and Anopheles mosquito are present. Zoonotic malaria control is challenging due to the presence of the reservoir host and the possibility of human-vector-human transmission. Current control measures, including insecticide-treated nets (ITNs) and indoor residual spraying (IRS), are insufficient to address this threat due to gaps in protection associated with outdoor and early evening vector biting and social and economic activities, such as agricultural and forest work. Understanding the challenges faced by affected communities in preventing mosquito bites is important for reducing disease transmission. This opinion paper discusses opportunities to improve P. knowlesi malaria control through understanding the challenges faced by communities at risk and increasing community engagement and ownership of control measures. The paper highlights this issue by describing how the concept of reimagining malaria can be adapted to zoonotic malaria control measures including identifying current gaps in vector control, understanding interactions between environmental, economic, and human behavioral factors, and increasing community participation in and ownership of control measures.
Topics: Animals; Anopheles; Humans; Insecticides; Malaria; Mosquito Vectors; Plasmodium knowlesi
PubMed: 35413881
DOI: 10.1186/s40101-022-00288-y -
Briefings in Functional Genomics Sep 2019Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained... (Review)
Review
Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host-parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host-parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.
Topics: Animals; Genomics; Host-Parasite Interactions; Humans; Plasmodium; Plasmodium cynomolgi; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Primates; Systems Biology
PubMed: 31241151
DOI: 10.1093/bfgp/elz013 -
Clinical Infectious Diseases : An... Oct 2019Plasmodium knowlesi causes severe and fatal malaria, and incidence in Southeast Asia is increasing. Factors associated with death are not clearly defined.
BACKGROUND
Plasmodium knowlesi causes severe and fatal malaria, and incidence in Southeast Asia is increasing. Factors associated with death are not clearly defined.
METHODS
All malaria deaths in Sabah, Malaysia, from 2015 to 2017 were identified from mandatory reporting to the Sabah Department of Health. Case notes were reviewed, and a systematic review of these and all previously reported fatal P. knowlesi cases was conducted. Case fatality rates (CFRs) during 2010-2017 were calculated using incidence data from the Sabah Department of Health.
RESULTS
Six malaria deaths occurred in Sabah during 2015-2017, all from P. knowlesi. Median age was 40 (range, 23-58) years; 4 cases (67%) were male. Three (50%) had significant cardiovascular comorbidities and 1 was pregnant. Delays in administering appropriate therapy contributed to 3 (50%) deaths. An additional 26 fatal cases were included in the systematic review. Among all 32 cases, 18 (56%) were male; median age was 56 (range, 23-84) years. Cardiovascular-metabolic disease, microscopic misdiagnosis, and delay in commencing intravenous treatment were identified in 11 of 32 (34%), 26 of 29 (90%), and 11 of 31 (36%) cases, respectively. The overall CFR during 2010-2017 was 2.5/1000: 6.0/1000 for women and 1.7/1000 for men (P = .01). Independent risk factors for death included female sex (odds ratio, 2.6; P = .04), and age ≥45 years (odds ratio, 4.7; P < .01).
CONCLUSIONS
Earlier presentation, more rapid diagnosis, and administration of intravenous artesunate may avoid fatal outcomes, particularly in females, older adults, and patients with cardiovascular comorbidities.
Topics: Administration, Intravenous; Adult; Age Factors; Aged; Aged, 80 and over; Antimalarials; Artemisinins; Comorbidity; Female; Humans; Incidence; Malaria; Malaysia; Male; Middle Aged; Plasmodium knowlesi; Pregnancy; Risk Factors; Sex Factors; Young Adult
PubMed: 30624597
DOI: 10.1093/cid/ciz011 -
Parasitology Jan 2018Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins,... (Review)
Review
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research.
Topics: Animals; Antigenic Variation; Disease Models, Animal; Macaca; Malaria; Plasmodium knowlesi; Protozoan Proteins; Systems Biology
PubMed: 28712361
DOI: 10.1017/S0031182017001135 -
Journal of Physiological Anthropology Nov 2020Malaria is a major public-health problem, with over 40% of the world's population (more than 3.3 billion people) at risk from the disease. Malaysia has committed to...
BACKGROUND
Malaria is a major public-health problem, with over 40% of the world's population (more than 3.3 billion people) at risk from the disease. Malaysia has committed to eliminate indigenous human malaria transmission by 2020. The objective of this descriptive study is to understand the epidemiology of malaria in Malaysia from 2000 through 2018 and to highlight the threat posed by zoonotic malaria to the National Malaria Elimination Strategic Plan.
METHODS
Malaria is a notifiable infection in Malaysia. The data used in this study were extracted from the Disease Control Division, Ministry of Health Malaysia, contributed by the hospitals and health clinics throughout Malaysia. The population data used in this study was extracted from the Department of Statistics Malaysia. Data analyses were performed using Microsoft Excel. Data used for mapping are available at EPSG:4326 WGS84 CRS (Coordinate Reference System). Shapefile was obtained from igismap. Mapping and plotting of the map were performed using QGIS.
RESULTS
Between 2000 and 2007, human malaria contributed 100% of reported malaria and 18-46 deaths per year in Malaysia. Between 2008 and 2017, indigenous malaria cases decreased from 6071 to 85 (98.6% reduction), while during the same period, zoonotic Plasmodium knowlesi cases increased from 376 to 3614 cases (an 861% increase). The year 2018 marked the first year that Malaysia did not report any indigenous cases of malaria caused by human malaria parasites. However, there was an increasing trend of P. knowlesi cases, with a total of 4131 cases reported in that year. Although the increased incidence of P. knowlesi cases can be attributed to various factors including improved diagnostic capacity, reduction in human malaria cases, and increase in awareness of P. knowlesi, more than 50% of P. knowlesi cases were associated with agriculture and plantation activities, with a large remainder proportion linked to forest-related activities.
CONCLUSIONS
Malaysia has entered the elimination phase of malaria control. Zoonotic malaria, however, is increasing exponentially and becoming a significant public health problem. Improved inter-sectoral collaboration is required in order to develop a more integrated effort to control zoonotic malaria. Local political commitment and the provision of technical support from the World Health Organization will help to create focused and concerted efforts towards ensuring the success of the National Malaria Elimination Strategic Plan.
Topics: Animals; Communicable Diseases, Emerging; Disease Eradication; Humans; Malaria; Malaysia; Plasmodium knowlesi; Zoonoses
PubMed: 33228775
DOI: 10.1186/s40101-020-00247-5 -
British Journal of Clinical Pharmacology Feb 2022The aim of this study was to assess the pharmacokinetic properties of artemether, lumefantrine and their active metabolites in Plasmodium knowlesi malaria.
AIMS
The aim of this study was to assess the pharmacokinetic properties of artemether, lumefantrine and their active metabolites in Plasmodium knowlesi malaria.
METHODS
Malaysian adults presenting with uncomplicated P. knowlesi infections received six doses of artemether (1.7 mg/kg) plus lumefantrine (10 mg/kg) over 3 days. Venous blood and dried blood spot (DBS) samples were taken at predetermined time-points over 28 days. Plasma and DBS artemether, dihydroartemisinin, lumefantrine and desbutyl-lumefantrine were measured using liquid chromatography-mass spectrometry. Multi-compartmental population pharmacokinetic models were developed using plasma with or without DBS drug concentrations.
RESULTS
Forty-one participants (mean age 45 years, 66% males) were recruited. Artemether-lumefantrine treatment was well tolerated and parasite clearance was prompt. Plasma and DBS lumefantrine concentrations were in close agreement and were used together in pharmacokinetic modelling, but only plasma concentrations of the other analytes were used because of poor correlation with DBS levels. The areas under the concentration-time curve (AUC ) for artemether, dihydroartemisinin and lumefantrine (medians 1626, 1881 and 625 098 μg.h/L, respectively) were similar to those reported in previous pharmacokinetic studies in adults and children. There was evidence of auto-induction of artemether metabolism (mean increase in clearance relative to bioavailability 25.2% for each subsequent dose). The lumefantrine terminal elimination half-life (median 9.5 days) was longer than reported in healthy volunteers and adults with falciparum malaria.
CONCLUSION
The disposition of artemether, dihydroartemisinin and lumefantrine in knowlesi malaria largely parallels that in other human malarias. DBS lumefantrine concentrations can be used in pharmacokinetic studies but DBS technology is currently unreliable for the other analytes.
Topics: Adult; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Ethanolamines; Female; Fluorenes; Humans; Lumefantrine; Malaria; Malaria, Falciparum; Male; Middle Aged; Plasmodium knowlesi
PubMed: 34296469
DOI: 10.1111/bcp.15001 -
The Korean Journal of Parasitology Oct 2015Malaria is a tropical disease caused by protozoans of the Plasmodium genus. Delayed diagnosis and misdiagnosis are strongly associated with higher mortality. In recent... (Review)
Review
Malaria is a tropical disease caused by protozoans of the Plasmodium genus. Delayed diagnosis and misdiagnosis are strongly associated with higher mortality. In recent years, a greater importance is attributed to Plasmodium knowlesi, a species found mainly in Southeast Asia. Routine parasitological diagnostics are associated with certain limitations and difficulties in unambiguous determination of the parasite species based only on microscopic image. Recently, molecular techniques have been increasingly used for predictive diagnosis. The aim of the study is to draw attention to the risk of travelling to knowlesi malaria endemic areas and to raise awareness among personnel involved in the therapeutic process.
Topics: Asia, Southeastern; Global Health; Humans; Malaria; Microscopy; Molecular Diagnostic Techniques; Plasmodium knowlesi; Public Health
PubMed: 26537037
DOI: 10.3347/kjp.2015.53.5.575 -
Clinical Infectious Diseases : An... Jul 2018Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only...
BACKGROUND
Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking.
METHODS
Over 3.5 years, we prospectively assessed patients of any age with molecularly-confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia.
RESULTS
Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538-8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization-defined anemia was present in 82% (95% confidence interval [CI], 67%-92%) of children vs 36% (95% CI, 31%-41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%-8.3%) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults).
CONCLUSIONS
Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.
Topics: Acute Kidney Injury; Age Factors; Antimalarials; Artemisinins; Artesunate; Child; Child, Preschool; Female; Humans; Infant; Kidney; Malaria; Malaysia; Male; Parasitemia; Plasmodium knowlesi; Prospective Studies; Severity of Illness Index
PubMed: 29873683
DOI: 10.1093/cid/ciy065 -
The Journal of Antimicrobial... Nov 2017The simian malaria parasite Plasmodium knowlesi is now a well-recognized pathogen of humans in South-East Asia. Clinical infections appear adequately treated with... (Comparative Study)
Comparative Study
BACKGROUND
The simian malaria parasite Plasmodium knowlesi is now a well-recognized pathogen of humans in South-East Asia. Clinical infections appear adequately treated with existing drug regimens, but the evidence base for this practice remains weak. The availability of P. knowlesi cultures adapted to continuous propagation in human erythrocytes enables specific studies of in vitro susceptibility of the species to antimalarial agents, and could provide a surrogate system for testing investigational compounds against Plasmodium vivax and other non-Plasmodium falciparum infections that cannot currently be propagated in vitro.
OBJECTIVES
We sought to optimize protocols for in vitro susceptibility testing of P. knowlesi and to contrast outputs with those obtained for P. falciparum under comparable test conditions.
METHODS
Growth monitoring of P. knowlesi in vitro was by DNA quantification using a SYBR Green fluorescent assay or by colorimetric detection of the lactate dehydrogenase enzyme. For comparison, P. falciparum was tested under conditions identical to those used for P. knowlesi.
RESULTS
The SYBR Green I assay proved the most robust format over one (27 h) or two (54 h) P. knowlesi life cycles. Unexpectedly, P. knowlesi displays significantly greater susceptibility to the dihydrofolate reductase inhibitors pyrimethamine, cycloguanil and trimethoprim than does P. falciparum, but is less susceptible to the selective agents blasticidin and DSM1 used in parasite transfections. Inhibitors of dihydroorotate dehydrogenase also demonstrate lower activity against P. knowlesi.
CONCLUSIONS
The fluorescent assay system validated here identified species-specific P. knowlesi drug susceptibility profiles and can be used for testing investigational compounds for activity against non-P. falciparum malaria.
Topics: Antimalarials; Benzothiazoles; Colorimetry; Diamines; Dihydroorotate Dehydrogenase; Erythrocytes; Fluorescence; Humans; L-Lactate Dehydrogenase; Malaria; Organic Chemicals; Oxidoreductases Acting on CH-CH Group Donors; Parasitic Sensitivity Tests; Plasmodium falciparum; Plasmodium knowlesi; Proguanil; Pyrimethamine; Quinolines; Sensitivity and Specificity; Triazines
PubMed: 28961865
DOI: 10.1093/jac/dkx279 -
Malaria Journal Jan 2010A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area...
A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed.
Topics: Animals; Cluster Analysis; Genotype; Humans; Malaria; Phylogeny; Plasmodium knowlesi; Plasmodium vivax; Polymerase Chain Reaction; Sequence Analysis, DNA; Vietnam
PubMed: 20082717
DOI: 10.1186/1475-2875-9-20