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Cytoadherence and severe malaria

Craig AG, Khairul MF, Patil PR

Malays J Med Sci, 2012 Apr;19(2):5-18.
PMID: 22973133

Malaria is a disease that causes enormous human morbidity and mortality. One feature of mature Plasmodium falciparum-infected erythrocytes leading to the development of severe malaria is thought to be cytoadherence and blockage of the microvasculature. Therefore, an understanding of mechanisms that mediate parasite adhesion leading to malaria pathology is needed to yield new treatments for malaria. However, to date, cytoadherence-associated pathology is still under debate. Is cytoadherence needed to develop severe malaria? This review will discuss the available information on associations of cytoadherence with the development of severe malaria.

Matched MeSH terms: Plasmodium falciparum
Fulltext Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage of Plasmodium falciparum Asexual Maturation

Dahalan FA, Sidek HM, Murtey MD, Embi MN, Ibrahim J, Fei Tieng L, et al.

Biomed Res Int, 2016;2016:1645097.
PMID: 27525262 DOI: 10.1155/2016/1645097

Plasmodium falciparum mitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that the P. falciparum specific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages of P. falciparum and is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites' developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.

Matched MeSH terms: Plasmodium falciparum/enzymology*
Fulltext Anti-malarial Activities of Two Soil Actinomycete Isolates from Sabah via Inhibition of Glycogen Synthase Kinase 3β

Dahari DE, Salleh RM, Mahmud F, Chin LP, Embi N, Sidek HM

Trop Life Sci Res, 2016 Aug;27(2):53-71.
PMID: 27688851 MyJurnal DOI: 10.21315/tlsr2016.27.2.5

Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection. The present study aims to evaluate whether anti-malarial activities of H11809 and FH025 involve the inhibition of GSK3β. The acetone crude extracts of H11809 and FH025 each exerted strong inhibition on the growth of Plasmodium falciparum 3D7 in vitro with 50% inhibitory concentration (IC50) values of 0.57 ± 0.09 and 1.28 ± 0.11 µg/mL, respectively. The tested extracts exhibited Selectivity Index (SI) values exceeding 10 for the 3D7 strain. Both H11809 and FH025 showed dosage-dependent chemo-suppressive activities in vivo and improved animal survivability compared to non-treated infected mice. Western analysis revealed increased phosphorylation of serine (Ser 9) GSK3β (by 6.79 to 6.83-fold) in liver samples from infected mice treated with H11809 or FH025 compared to samples from non-infected or non-treated infected mice. A compound already identified in H11809 (data not shown), dibutyl phthalate (DBP) showed active anti-plasmodial activity against 3D7 (IC50 4.87 ± 1.26 µg/mL which is equivalent to 17.50 µM) and good chemo-suppressive activity in vivo (60.80% chemo-suppression at 300 mg/kg body weight [bw] dosage). DBP administration also resulted in increased phosphorylation of Ser 9 GSK3β compared to controls. Findings from the present study demonstrate that the potent anti-malarial activities of H11809 and FH025 were mediated via inhibition of host GSK3β. In addition, our study suggests that DBP is in part the bioactive component contributing to the anti-malarial activity displayed by H11809 acting through the inhibition of GSK3β.

Matched MeSH terms: Plasmodium falciparum
Fulltext Clinical and laboratory features of human Plasmodium knowlesi infection

Daneshvar C, Davis TM, Cox-Singh J, Rafa'ee MZ, Zakaria SK, Divis PC, et al.

Clin Infect Dis, 2009 Sep 15;49(6):852-60.
PMID: 19635025 DOI: 10.1086/605439

BACKGROUND: Plasmodium knowlesi is increasingly recognized as a cause of human malaria in Southeast Asia but there are no detailed prospective clinical studies of naturally acquired infections.
METHODS: In a systematic study of the presentation and course of patients with acute P. knowlesi infection, clinical and laboratory data were collected from previously untreated, nonpregnant adults admitted to the hospital with polymerase chain reaction-confirmed acute malaria at Kapit Hospital (Sarawak, Malaysia) from July 2006 through February 2008.
RESULTS: Of 152 patients recruited, 107 (70%) had P. knowlesi infection, 24 (16%) had Plasmodium falciparum infection, and 21 (14%) had Plasmodium vivax. Patients with P. knowlesi infection presented with a nonspecific febrile illness, had a baseline median parasitemia value at hospital admission of 1387 parasites/microL (interquartile range, 6-222,570 parasites/microL), and all were thrombocytopenic at hospital admission or on the following day. Most (93.5%) of the patients with P. knowlesi infection had uncomplicated malaria that responded to chloroquine and primaquine treatment. Based on World Health Organization criteria for falciparum malaria, 7 patients with P. knowlesi infection (6.5%) had severe infections at hospital admission. The most frequent complication was respiratory distress, which was present at hospital admission in 4 patients and developed after admission in an additional 3 patients. P. knowlesi parasitemia at hospital admission was an independent determinant of respiratory distress, as were serum creatinine level, serum bilirubin, and platelet count at admission (p < .002 for each). Two patients with knowlesi malaria died, representing a case fatality rate of 1.8% (95% confidence interval, 0.2%-6.6%).
CONCLUSIONS: Knowlesi malaria causes a wide spectrum of disease. Most cases are uncomplicated and respond promptly to treatment, but approximately 1 in 10 patients develop potentially fatal complications.

Matched MeSH terms: Plasmodium falciparum/isolation & purification
EXPERIMENTAL INOCULATION OF MALARIA BY MEANS OF ANOPHELES LUDLOWI

Darling ST

J. Exp. Med., 1920 Aug 31;32(3):313-29.
PMID: 19868447

Three persons were experimentally inoculated with malaria by means of Anopheles ludlowi reared from larvae and infected with a pure strain of subtertian plasmodium (Plasmodium falciparum), thus proving that there exists no mechanical impediment or obstacle to the free exit of sporozoites from the salivary ducts or proboscis. In the dissection of infected mosquitoes there were no evidences of degenerated zygotes. Sporozoites appeared promptly in the salivary glands (9 to 12 days). Inoculation occurred with ease either in an interrupted feeding or after mosquitoes had been fed twice previously. The period of incubation was 14 and 18 days. The clinical manifestations were more severe in the subject that had never been infected with malaria previously, while the splenic enlargement was most pronounced in the subject infected after a long interval of freedom from malaria. In a third subject already suffering from tertian malaria there was only the slightest evidence of physical illness elicited by the superimposed subtertian infection; his temperature, however, became duly elevated. The type of febrile reaction in the two uncomplicated cases was at first tertian, becoming quotidian later, and this phenomenon in a pure strain leads strongly to the supposition that Plasmodium falciparum possesses inherently both tertian (or subtertian) and quotidian tendencies, as well as its well known tendencies to cause fever of the irregularly remittent or continued type. The creation of a specific plasmodium to account for clinical forms of aestivo-autumnal or subtertian malaria having a quotidian periodidty is probably unwarranted. In consideration of the facility with which this species can be infected and man inoculated experimentally, the occurrence of naturally infected wild specimens, and the positive epidemiological evidence, there should no longer exist in the minds of sanitarians any doubt as to its being a malarial carrier. Operations against this species can therefore be recommended without reservation and should be carried out without delay.

Matched MeSH terms: Plasmodium falciparum
Fulltext Artemisinin combination therapy fails even in the absence of Plasmodium falciparum kelch13 gene polymorphism in Central India

Das S, Kar A, Manna S, Mandal S, Mandal S, Das S, et al.

Sci Rep, 2021 05 11;11(1):9946.
PMID: 33976269 DOI: 10.1038/s41598-021-89295-0

Artemisinin is the frontline fast-acting anti-malarial against P. falciparum. Emergence and spread of resistant parasite in eastern-India poses a threat to national malaria control programs. Therefore, the objective of our study is to evaluate the artesunate-sulfadoxine-pyrimethamine efficacy in Central India. 180 monoclonal P. falciparum-infected patients received standard ASSP therapy during August 2015-January 2017, soon after diagnosis and monitored over next 42-days. Artemisinin-resistance was assessed through in-vivo parasite clearance half-life (PC1/2), ex-vivo ring-stage survivability (RSA), and genome analysis of kelch13 and other candidate gene (pfcrt, pfmdr1, pfatpase 6, pfdhfr and pfdhps). Of 180 P. falciparum positive patients, 9.5% showed increased PC1/2 (> 5.5 h), among them eleven isolates (6.1%) showed reduced sensitivity to RSA. In 4.4% of cases, parasites were not cleared by 72 h and showed prolonged PC1/2(5.6 h) (P

Matched MeSH terms: Plasmodium falciparum/drug effects*; Plasmodium falciparum/genetics; Plasmodium falciparum/pathogenicity
A novel nano-anti-malarial induces redox damage and elicits cytokine response to the parasite

Das S, Tripathy S, Pramanik P, Saha B, Roy S

Cytokine, 2021 08;144:155555.
PMID: 33992538 DOI: 10.1016/j.cyto.2021.155555

Emergence and spread of resistant parasites to the newest chemotherapeutic anti-malarial agents are the biggest challenges against malaria control programs. Therefore, developing a novel effective treatment to reduce the overgrowing burden of multidrug resistant malaria is a pressing need. Herein, we have developed a biocompatible and biodegradable, non-toxic chitosan-tripolyphosphate-chloroquine (CS-TPP CQ) nanoparticle. CS-TPP CQ nanoparticles effectively kill the parasite through redox generation and induction of the pro- and anti-inflammatory cytokines in both sensitive and resistant parasite in vitro. The in vitro observations showed a strong inhibitory effect (p

Matched MeSH terms: Plasmodium falciparum/drug effects
Fulltext Genomic characterization of Plasmodium falciparum genes associated with anti-folate drug resistance and treatment outcomes in eastern India: A molecular surveillance study from 2008 to 2017

Das S, Tripathy S, Das A, Sharma MK, Nag A, Hati AK, et al.

Front Cell Infect Microbiol, 2022;12:865814.
PMID: 36583107 DOI: 10.3389/fcimb.2022.865814

INTRODUCTION: After being used vigorously for the previous two decades to treat P. falciparum, chloroquine and sulfadoxine-pyrimethamine were replaced in 2009 with an artemisinin-based combination therapy (artesunate-sulfadoxine-pyrimethamine) in an effort to combat multidrug-resistant parasites.
METHODS: We set out to assess the genetic variants of sulfadoxine-pyrimethamine resistance and the effectiveness of its treatment in eastern India prior to, during, and 6 to 8 years following the introduction of the new pharmacological regime. In 2008-2009, 318 P. falciparum-positive patients got the recommended doses of sulfadoxine-pyrimethamine. We used 379 additional isolates from 2015 to 2017 in addition to the 106 isolates from 2010. All 803 isolates from two study sites underwent in vitro sulfadoxine-pyrimethamine sensitivity testing and genomic characterisation of sulfadoxine-pyrimethamine resistance (pfdhfr and pfdhps).
RESULTS: In Kolkata and Purulia, we observed early treatment failure in 30.7 and 14.4% of patients, respectively, whereas recrudescence was found in 8.1 and 13.4% of patients, respectively, in 2008-2009. In 2017, the proportion of in vitro pyrimethamine and sulfadoxine resistance steadily grew in Kolkata and Purulia despite a single use of sulfadoxine-pyrimethamine. Treatment failures with sulfadoxine-pyrimethamine were linked to quintuple or quadruple pfdhfr- pfdhps mutations (AICII-AGKAT, AICII-AGKAA, AICII-SGKGT, AICII-AGKAA, AICNI-AGKAA) in 2008-2009 (p < 0.001). The subsequent spread of mutant-haplotypes with higher in vitro sulfadoxine-pyrimethamine resistance (p < 0.001), such as the sextuple (dhfr-AIRNI+dhps-AGEAA, dhfr-ANRNL+dhps-AGEAA) and septuple (dhfr-AIRNI+dhps-AGEAT), mutations were observed in 2015-2017.
DISCUSSION: This successive spread of mutations with high in vitro sulfadoxine-pyrimethamine resistance confirmed the progressive increase in antifolate resistance even after an 8-year withdrawal of sulfadoxine-pyrimethamine.

Matched MeSH terms: Plasmodium falciparum/genetics
The burden and epidemiology of polyparasitism among rural communities in Kano State, Nigeria

Dawaki S, Al-Mekhlafi HM, Ithoi I

Trans R Soc Trop Med Hyg, 2019 04 01;113(4):169-182.
PMID: 30551211 DOI: 10.1093/trstmh/try128

BACKGROUND: Parasitic infections constitute a major public health problem worldwide, particularly among underprivileged communities in developing countries including Nigeria. The present study aimed to determine the epidemiology of polyparasitism (multiple parasitic infections) among rural communities in Kano State, North Central Nigeria.
METHODS: A total of 551 individuals were screened for the presence of intestinal, urogenital and blood parasites by using different diagnostic techniques. Demographic, socioeconomic, household and behavioural characteristics were collected using a pre-tested questionnaire.
RESULTS: Overall, 84.0% (463/551) of the participants were found to be infected with at least one parasite species, with 51.2% (282/551) of them having polyparasitism. The most prevalent parasites were Plasmodium falciparum (60.6%) followed by Blastocystis sp. (29.2%) and hookworm (15.4%). No significant association was found between malaria and helminth infections (p>0.05). Univariate and multivariate analyses showed that the presence of other family members who had intestinal polyparasitism (adjusted odds ratio [AOR]=4.12; 95% CI=2.72, 6.24), walking barefoot outside (AOR=1.70; 95% CI=1.09, 2.63) and being male (AOR=1.74; 95% CI=1.14, 2.66) were the significant risk factors of intestinal polyparasitism among the population studied.
CONCLUSION: Polyparasitism is highly prevalent among rural communities in Kano State. Therefore, effective, sustainable and integrated control measures should be identified and implemented to significantly reduce the burden and consequences of these infections in rural Nigeria.

Matched MeSH terms: Plasmodium falciparum
The effects of diaphenylsulfone (DDS) against chloroquine-resistant Plasmodium falciparum

Degowin RL, Eppes RB, Carson PE, Powell RD

Bull World Health Organ, 1966;34(5):671-81.
PMID: 5328901

In view of the problems caused by the chloroquine-resistance of some strains of Plasmodium falciparum, the authors have investigated the effectiveness of diaphenylsulfone against two such resistant strains, from Malaya and Viet-Nam. They found that diaphenylsulfone given during acute attacks of malaria had a blood schizontocidal activity against the Malayan resistant strain but was not rapidly effective in terminating acute attacks in non-immune persons, and that, when the drug was given prophylactically in relatively small doses, it was substantially effective in preventing patency of mosquito-induced infection with the same strain. The protective effect of diaphenylsulfone is that of a clinical prophylactic or suppressive drug; it does not appear to be a true causal prophylactic. It was also found that the protective effect is vitiated by the concurrent administration of paraaminobenzoic acid.These studies indicate a need for further assessment of the antimalarial value of sulfones and sulfonamides, both alone and in combination with other drugs, for prevention and cure.

Matched MeSH terms: Plasmodium falciparum/drug effects
Fulltext Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

Dieye Y, Mbengue B, Dagamajalu S, Fall MM, Loke MF, Nguer CM, et al.

PeerJ, 2016;4:e1965.
PMID: 27168977 DOI: 10.7717/peerj.1965

Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

Matched MeSH terms: Plasmodium falciparum
Studies on the resistance of malaria to chloroquine and to a combination of chloroquine and pyrimethamine in Peninsular Malaysia

Dondero TJ, Parsons RE, Ponnampalam JT

Trans R Soc Trop Med Hyg, 1976;70(2):145-8.
PMID: 785725

In vivo chloroquine resistance surveys, which allowed for detection of late recrudescing RI resistance, were conducted in three regions of Peninsular Malaysia, which were previously not recognized as having appreciable drug resistance. Among the 485 Plasmodium falciparum infections tested resistance rates ranged locally from 20% to 67% in those with parasitaemias over 1,000 per mm3, and 5% to 59% in all parasitaemias. The region found to have the most serious resistance was western Pahang. In one study a combination of chloroquine and pyrimethamine proved no more efficacious than chloroquine alone. Most of the resistance encountered was the late recrudescing RI type. There was no apparent correlation between drug resistance and Anopheles balabacensis as this species was not found despite intensive collections in two of the three main regions. There was no evidence of resistance among the 222 P. vivax and 35 P. malariae infections also tested.

Matched MeSH terms: Plasmodium falciparum/drug effects*
Increased frequency of chloroquine resistant P. falciparum on a rubber estate in Peninsular Malaysia during two years of systematic chloroquine treatment

Dondero TJ, Parsons RE, O'Holohan DR

Southeast Asian J. Trop. Med. Public Health, 1975 Dec;6(4):488-94.
PMID: 775652

Chloroquine pressure was applied over a 22 month period on a somewhat isolated, malarious rubber estate by examination of residents at 4-week intervals and treatment of parasitaemias with chloroquine. During this time the monthly attack rate for P. falciparum rose four-fold to an average of nearly 18% per month, while that of P. vivax remained relatively constant at about 8%. Eight in vivo chloroquine resistance studies, which allowed both detection of late recrudescing R-I resistance and estimation of the risk of reinfection, showed an apparent rise in the drug resistance rate, from 12% to 20% prior to the study to the range of 40-50%. Virtually all resistance encountered was R-I in nature. There was no convincing evidence of chloroquine resistance among 148 tested P. vivax infections.

Matched MeSH terms: Plasmodium falciparum/drug effects
Fulltext Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets

Dooley NL, Chabikwa TG, Pava Z, Loughland JR, Hamelink J, Berry K, et al.

Nat Commun, 2023 Nov 15;14(1):7387.
PMID: 37968278 DOI: 10.1038/s41467-023-43181-7

Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.

Matched MeSH terms: Plasmodium falciparum/genetics
Evaluation of ethnopharmacologically selected Vitex negundo L. for In vitro antimalarial activity and secondary metabolite profiling

Dwivedi MK, Shukla R, Sharma NK, Manhas A, Srivastava K, Kumar N, et al.

J Ethnopharmacol, 2021 Jul 15;275:114076.
PMID: 33789139 DOI: 10.1016/j.jep.2021.114076

ETHANOPHARMACOLOGICAL RELEVANCE: Limited drugs, rise in drug resistance against frontline anti-malarial drugs, non-availability of efficacious vaccines and high cost of drug development hinders malaria intervention programs. Search for safe, effective and affordable plant based anti-malarial agents, thus becomes crucial and vital in the current scenario. The Vitex negundo L. is medicinal plant possessing a variety of pharmaceutically important compounds. The plant is used traditionally worldwide for the treatment of malaria including India and Malaysia by the indigenous tribes. In vitro studies have reported the anti-malarial use of the plant in traditional medicinal systems.
AIM OF THE STUDY: The aim of the current study is to evaluate the traditionally used medicinal plants for in vitro anti-malarial activity against human malaria parasite Plasmodium falciparum and profiling secondary metabolite using spectroscopic and chromatographic methods. Chemical profiling of active secondary metabolites in the extracts was undertaken using LC-MS.
MATERIALS AND METHODS: Based on the ethno-botanical data V. negundo L. was selected for in vitro anti-malarial activity against P. falciparum chloroquine-sensitive (3D7) and multidrug resistant (K1) strains using SYBR Green-I based fluorescence assay. Cytotoxicity of extracts was evaluated in VERO cell line using the MTT assay. Haemolysis assay was performed using human red blood cells. Secondary metabolites profiling was undertaken using chromatographic and spectroscopic analysis. Liquid chromatography analysis was performed using a C18, 150 X 2.1, 2.6 μm column with gradient mobile phase Solvent A: 95% (H2O: ACN), Solvent B: Acetonitrile, Solvent C: Methanol, Solvent D: 5 mM NH4 in 95:5 (H2O: ACN) at a constant flow rate of 0.250 ml/min. The LC-MS spectra were acquired in both positive and negative ion modes with electrospray ionization (ESI) source.
RESULTS: The anti-malarial active extract of V. negundo L. leaf exhibited potent anti-malarial activity with IC50 values of 7.21 μg/ml and 7.43 μg/ml against 3D7 and K1 strains, respectively with no evidence of significant cytotoxicity against mammalian cell line (VERO) and no toxicity as observed in haemolysis assay. The HPLC-LC-MS analysis of the extract led to identification of 73 compounds. We report for the first time the presence of Sabinene hydrate acetate, 5-Hydroxyoxindole, 2(3,4-dimethoxyphenyl)-6, 7-dimethoxychromen-4-one, Cyclotetracosa-1, 13-diene and 5, 7-Dimethoxyflavanone in the anti-malarial active extract of V. negundo L. leaf. Agnuside, Behenic acid and Globulol are some of the novel compounds with no reports of anti-malarial activity so far and require further evaluation in pure form for the development of potent anti-malarial compounds.
CONCLUSIONS: The result report and scientifically validate the traditional use of V. negundo L. for the treatment of malaria providing new avenues for anti-malarial drug development. Several novel and unknown compounds were identified that need to be further characterized for anti-malarial potential.

Matched MeSH terms: Plasmodium falciparum/drug effects
Malaria in China and the equatorial Pacific area from 1937 to 1943

Ebisawa I

Yale J Biol Med, 1973 Apr;46(2):94-101.
PMID: 4611054
Matched MeSH terms: Plasmodium falciparum
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: Plasmodium falciparum/drug effects; Plasmodium falciparum/isolation & purification
Prevalence of erythrocyte G6PD deficiency in Sabah

Fong T

Mod Med Asia, 1977 Sep;13(9):14-6.
PMID: 340882
Matched MeSH terms: Plasmodium falciparum
Conserved and variant epitopes of target antigens of transmission-blocking antibodies among isolates of Plasmodium falciparum from Malaysia

Foo A, Carter R, Lambros C, Graves P, Quakyi I, Targett GA, et al.

Am J Trop Med Hyg, 1991 Jun;44(6):623-31.
PMID: 1713424

Monoclonal antibodies (MAbs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of Plasmodium falciparum, Pfs 25, Pfs 230, and Pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of P. falciparum from Malaysia, using immunofluorescence microscopy (IFA). Among 45 Malaysian isolates, one epitope of Pfs 25, designated region I, showed evidence of variable reactivity with MAbs among different isolates; the Pfs 25 epitope, region II, was universally recognized by MAbs in all isolates. Two apparently distinct epitope regions of Pfs 230 were defined by MAbs, one of which was universally recognized by MAbs among the 45 isolates; the other was conserved in all but three isolates. The epitope regions of gamete-surface protein Pfs 48/45, designated regions I, IIa, IIb, IIc, III, and IV, were examined for reactivity by IFA in 33 isolates. Epitope regions I, IIb, III, and IV were conserved in all isolates; regions IIa and IIc existed in variant forms.

Matched MeSH terms: Plasmodium falciparum/immunology*
Fulltext Evaluation of three rapid diagnostic tests for the detection of human infections with Plasmodium knowlesi

Foster D, Cox-Singh J, Mohamad DS, Krishna S, Chin PP, Singh B

Malar J, 2014;13:60.
PMID: 24548805 DOI: 10.1186/1475-2875-13-60

Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, infects humans and can cause fatal malaria. It is difficult to diagnose by microscopy because of morphological similarity to Plasmodium malariae. Nested PCR assay is the most accurate method to distinguish P. knowlesi from other Plasmodium species but is not cost effective in resource-poor settings. Rapid diagnostic tests (RDTs) are recommended for settings where malaria is prevalent. In this study, the effectiveness of three RDTs in detecting P. knowlesi from fresh and frozen patient blood samples was evaluated.

Matched MeSH terms: Plasmodium falciparum/isolation & purification

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