The Plasmodium falciparum Merozoite Surface Protein 1(Pf MSP1), a predominant antigen on the surface of the asexual blood stage of the parasite, plays a role in erythrocyte invasion. It elicits immune responses during exposure to natural P. falciparum infections, hence, it is a potential vaccine candidate. However, its extensive sequence diversity causes antigenic variability. Parasites that express variants other than that targeted by immune protection mounted as a result of a vaccine variant, evade the resultant host immune protection. This compromises the efficacy of allele-specific vaccines formulated to protect against a single variant. Due to this, Pf MSP1 has been extensively studied, including in Kenya. However, the extent of Pf MSP1 diversity in children with multiple infections are unknown in Kilifi which is a moderate to high malaria transmission zone. Parasite genomic DNA was extracted from 421 blood samples in 33 children aged below 5 years who had at least 9 multiple infections. ...

The roles of allelic and conserved epitopes in vaccine-induced immunity to the C-terminal 42-kDa fragment of the Plasmodium falciparum merozoite surface protein 1 (MSP1) were investigated. The C-terminal fragment of MSP1 was expressed as a baculovirus recombinant protein, BVp42. Rabbits were immunized with BVp42, and antibodies were tested for reactivity to MSP1s of the homologous and heterologous allelic forms, represented by the FUP, FVO, FC27, and Honduras parasite isolates, by enzyme-linked immunosorbent assay and indirect immunofluorescence antibody assay. Despite the fact that allelic sequences accounted for approximately 50% of the BVp42 molecule, anti-BVp42 antibodies cross-reacted extensively with parasites carrying heterologous MSP1 alleles. Enzyme-linked immunosorbent inhibition assays confirmed that an overwhelming majority of the anti-BVp42 antibodies were cross-reactive, suggesting that determinants within conserved block 17 are dominant B-cell epitopes in the anti-BVp42 response. ...

Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A alleles have been suggested to play a role in the outcome of P. falciparum malaria infection in a Malian study. Herein, we investigated the association between HLA-A alleles and the outcome of malaria infection in children in Ibadan southwest Nigeria. HLA-A genotyping was performed on 393 children samples (DNA) using the sequence-based method. We compared genotype and allele frequencies data obtained from these Nigerian children; 176 with asymptomatic malaria infection (controls), 124 with uncomplicated malaria and 93 children with severe malaria (51 severe malarial anaemia and 42 cerebral malaria). We found a high frequency of HLA-A*36:01 (13.5%) in the entire studied population ...

Plasmodium falciparum malaria remains a global public health threat. Leading malaria vaccine candidates confer only partial short-lived protection at best. An understanding of the mechanisms by which humans acquire malaria immunity through repeated P. falciparum infections may aid the development of a malaria vaccine. This pilor study is designed to initiate the epidemiological groundwork for a future prospective cohort study of acquired malaria immunity in Kalifabougou, Mali, a rural village of approximately 5 000 individuals who are exposed to seasonal P. falciparum transmission each year from July through December. This study will estimate the age-stratified point prevalence of P. falciparum infection before the malaria season and at the peak of the 6-month malaria season, and it will estimate the age-stratified incidence of symptomatic p. falciparum infection during the 6-month malaria season. The spatial distribution of asymptomatic P. falciparum infections and incident malaria cases within ...

Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Lung injury was demonstrated in malaria patients with PE. The

Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Lung injury was demonstrated in malaria patients with PE. The

The malaria genome encodes over 5,000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage Plasmodium falciparum malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC). However, many other antigens could also elicit neutralizing antibodies against the merozoite, and most of these have never been compared directly to RH5. The objective of this study was to compare a range of blood-stage antigens to RH5, to identify any antigens that outperform or synergize with anti-RH5 antibodies. We selected 55 gene products, covering 15 candidate antigens that have been described in the literature and 40 genes selected on the basis of bioinformatics functional prediction. We were able to make 20

Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The in vitro antimalarial susceptibility of pyronaridine was assessed in multidrug-resistant P. vivax (n = 99) and P. falciparum (n = 90) isolates from Papua, Indonesia, using a schizont maturation assay. The median 50% inhibitory concentration (IC(50)) of pyronaridine was 1.92 nM (range, 0.24 to 13.8 nM) against P. falciparum and 2.58 nM (range, 0.13 to 43.6 nM) against P. vivax, with in vitro susceptibility correlating significantly with chloroquine, amodiaquine, and piperaquine (r(s) [Spearmans rank correlation coefficient] = 0.45 to 0.62; P | 0.001). P. falciparum parasites initially at trophozoite stage had higher IC(50)s of pyronaridine than those exposed at the ring stage (8.9 nM

Substantial evidence indicates that antibodies to Plasmodium falciparum merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one ...

TY - JOUR. T1 - Safety, immunogenicity, and efficacy of a Plasmodium falciparum vaccine comprising a circumsporozoite protein repeat region peptide conjugated to Pseudomonas aeruginosa toxin A. AU - Fries, L. F.. AU - Gordon, D. M.. AU - Schneider, I.. AU - Beier, J. C.. AU - Long, G. W.. AU - Gross, M.. AU - Que, J. U.. AU - Cryz, S. J.. AU - Sadoff, J. C.. N1 - Copyright: Copyright 2004 Elsevier B.V., All rights reserved.. PY - 1992. Y1 - 1992. N2 - Twenty-one malaria-naive volunteers were immunized with a vaccine consisting of a 22-kDa recombinant peptide (R32LR), derived from the repeat region of Plasmodium falciparum circumsporozoite (CS) protein, covalently coupled to detoxified Pseudomonas aeruginosa toxin A. Nineteen volunteers received a second dose of vaccine at 8 weeks, and eighteen received a third dose at 8 to 12 months. The vaccine was well tolerated, with only one volunteer developing local discomfort and induration at the site of injection which limited function for 48 h. The ...

Thesis (Ph.D.)--Georgetown University, 2009.; Includes bibliographical references.; Text (Electronic thesis) in PDF format. Malaria caused by the Apicomplexan parasite Plasmodium falciparum is an alarming health problem due to increasing incidence of deaths and growing resistance to antimalarial drugs such as chloroquine. Chloroquine resistance in P. falciparum is primarily determined by PfCRT (P. falciparum chloroquine resistance transporter), a transmembrane protein localized to the digestive vacuolar membrane of the parasite. Bioinformatic studies by Fidock et al. (2000) and Martin & Kirk (2004) suggested that PfCRT belongs to the drug/metabolite transporter superfamily but its mode of action has not yet been fully established. In order to elucidate the role of PfCRT in chloroquine resistance, chloroquine binding and transport were analyzed using membrane preparations from yeast Pichia pastoris expressing PfCRT, as well as proteoliposomes harboring purified protein.; Chloroquine binding was ...

TY - JOUR. T1 - Murine model for assessment of Plasmodium falciparum transmission-blocking vaccine using transgenic Plasmodium berghei parasites expressing the target antigen Pfs25. AU - Mlambo, Godfree. AU - Maciel, Jorge. AU - Kumar, Nirbhay. PY - 2008/5. Y1 - 2008/5. N2 - Currently, there is no animal model for Plasmodium falciparum challenge to evaluate malaria transmission-blocking vaccines based on the well-established Pfs25 target antigen. The biological activity of transmission-blocking antibodies is typically assessed using an assay known as the membrane feeding assay (MFA). It is an in vitro method that involves mixing antibodies with cultured P. falciparum gametocytes and feeding them to mosquitoes through an artificial membrane followed by assessment of infection in the mosquitoes. We genetically modified Plasmodium berghei to express Pfs25 and demonstrated that the transgenic parasites (TrPfs25Pb) are susceptible to anti-Pfs25 antibodies during mosquito-stage development. The ...

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Malaria causes a worldwide annual mortality of about a million people.Rapidly evolving drug-resistant species of the parasite have created a pressing need for the identification of new drug targets and vaccine candidates. By developing fractionation protocols to enrich parasites from low-parasitemia patient samples, we have carried out the first ever proteomics analysis of clinical isolates of early stages of Plasmodium falciparum (Pf) and P. vivax. Patient-derived malarial parasites were directly processed and analyzed using shotgun proteomics approach using high-sensitivity MS for protein identification. Our study revealed about 100 parasite-coded gene products that included many known drug targets such as Pf hypoxanthine guanine phosphoribosyl transferase, Pf L-lactate dehydrogenase, and Plasmepsins. In addition,our study reports the expression of several parasite proteins in clinical ring stages that have never been reported in the ring stages of the laboratory-cultivated parasite strain. ...

Chloroquine-resistant Plasmodium falciparum at the Tanganyika Planting Company sugar estate, Moshi, Tanzania / by T. K. Mutabingwa, V. A. E. G. Kilimali and W. L. ...

Chronic Plasmodium falciparum malaria infections in a Sudanese village, in an area of seasonal and unstable malaria transmission, were monitored and genetically characterized to study the in¯uence of persistent infection on the immunology and epidemiology of low endemicity malaria. During the October±December malaria season of 1996, 51 individuals out of a population of 420 had con®rmed and treated P. falciparum malaria in the village of Daraweesh in eastern Sudan. In a cross-sectional survey carried out in December 1996, an additional 6 individuals were found to harbour a microscopically negative but polymerase chain reaction (PCR)-positive P. falciparum infection. On 1 January 1997, a cohort of 43 individuals aged from 9 to 53, recruited from this group of recently malaria-infected individuals agreed to donate fortnightly blood samples for the next 9 months, the ®rst 6 of which constitute the long Sudanese dry season when transmission falls to undetectable levels. Each blood sample was ...

Study Rationale: Evidence suggests that if PPAR-RXR agonists (such as rosiglitazone) are used as adjunctive therapy in P. falciparum malaria infections they may increase phagocytic clearance of P. falciparum malaria, modulate deleterious inflammatory responses and decrease sequestration of malaria parasites in vital organs. They may therefore represent a novel immunomodulatory treatment approach for P. falciparum malaria.. Study Objectives: 1) To examine the in vivo effect of rosiglitazone on the rapidity of clearance of P. falciparum parasitemia and fever in patients with non-severe P. falciparum infections 2) To assess the safety and tolerability of adjunctive rosiglitazone treatment in non-severe cases of P. falciparum infection.. Primary Outcomes: Time to clearance of P. falciparum parasitemia. Study Design: Randomized double blind placebo-controlled trial.. Intervention: Standard antimalarial treatment (atovaquone/proguanil) to all patients combined with adjuvant rosiglitazone treatment ...

Resistance-conferring PfCRT isoforms (which harbor mutation K76T and are distinguished by 3-8 additional mutations) are believed to confer resistance to the 4-amino quinoline drug chloroquine (CQ) by transporting CQ away from the drugs digestive vacuole (DV) - localized heme target. One theory then is that variable CQ transport catalyzed by different mutant PfCRTs are responsible for the range of CQ sensitivities now found for P. falciparum around the globe. Alternatively, additional mutations in drug- selected parasites may complement PfCRT in conferring a range of resistance phenotypes. In this thesis, I further optimize a convenient method for screening for CQ transport mediated by PfCRT, involving heterologous expression in Saccharomyces cerevisiae. I use this method and other techniques to quantify activity for all currently known naturally occurring PfCRT isoforms. My results show that chlorquine resistance (CQR) in isolates expressing certain PfCRT isoforms likely depends upon additional ...

BioAssay record AID 723630 submitted by ChEMBL: Antiplasmodial activity against erythrocyte form of chloroquine-resistant Plasmodium falciparum Dd2 by parasite lactate dehydrogenase assay.

TY - JOUR. T1 - Characterization of PfPuf2, member of the Puf family RNA-binding proteins from the malaria parasite Plasmodium falciparum. AU - Fan, Qi. AU - Li, Jinfang. AU - Kariuki, Michael. AU - Cui, Liwang. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 2004/11. Y1 - 2004/11. N2 - Puf proteins are a family of evolutionarily conserved translational regulators in eukaryotes. The malaria parasite has two Puf proteins (PfPuf1 and PfPuf2) that share 25% homology in the RNA binding domain. Here we confirmed the preferential expression of PfPuf2 in gametocyte stages using Northern analysis. The transcriptional initiation site of this gene, mapped using RNA ligase-mediated rapid amplification of cDNA end and primer extension, is located ∼300 bp upstream from the translational start codon. The 3′ end of PfPuf2 is located ∼250 bp downstream from the stop codon. The total length of the RNA is approximately 2.1 kb, consistent with the mRNA size determined by Northern ...

Studies were conducted to determine how malaria parasites are cleared from the blood after antimalarial treatment. Neither artesunate nor quinine decreased parasitized red cell deformability or increased antibody binding. In acute falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased significantly (P=.002) within 24 h of starting artesunate but rose much more slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased significantly (P=. 001) within hours of starting artesunate but not with quinine treatment (P=.43). RESA-RBCs were not produced after drug treatment of malaria parasite cultures in vitro. Rapid malaria parasite clearance after treatment with artemisinin derivatives results mainly from the extraction of drug-affected parasites from host erythrocytes-presumably by the spleen. This explains

Plasmodium falciparum malaria merozoites require erythrocyte sialic acid for optimal invasion of human erythrocytes. Since mouse erythrocytes have the form of sialic acid found on human erythrocytes (N-acetyl neuraminic acid), mouse erythrocytes were tested for invasion in vitro. The Camp and 7G8 strains of P. falciparum invaded mouse erythrocytes at 17-45% of the invasion rate of human erythrocytes. Newly invaded mouse erythrocytes morphologically resembled parasitized human erythrocytes as shown on Giemsa-stained blood films and by electron microscopy. The rim of parasitized mouse erythrocytes contained the P. falciparum 155-kD protein, which is on the rim of ring-infected human erythrocytes. Camp but not 7G8 invaded rat erythrocytes, indicating receptor heterogeneity. These data suggest that it may be possible to adapt the asexual erythrocytic stage of P. falciparum to rodents. The development of a rodent model of P. falciparum malaria could facilitate vaccine development. ...

TY - JOUR. T1 - In vivo transcriptional profiling of Plasmodium falciparum. AU - Daily, Johanna P.. AU - Le Roch, Karine G.. AU - Sarr, Ousmane. AU - Fang, Xuemin. AU - Zhou, Yingyao. AU - Ndir, Omar. AU - Mboup, Soulyemane. AU - Sultan, Ali. AU - Winzeler, Elizabeth A.. AU - Wirth, Dyann F.. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2004/8/5. Y1 - 2004/8/5. N2 - Background: Both host and pathogen factors contribute to disease outcome in Plasmodium falciparum infection. The feasibility of studying the P. falciparum in vivo transcriptome to understand parasite transcriptional response while it resides in the human host is presented. Methods: A custom made oligonucleotide array with probes based on the P. falciparum 3D7 laboratory strain chromosome 2 sequence was used to detect in vivo P. falciparum transcripts. This study analyzed transcripts from total RNA derived from small blood samples of P. falciparum infected patients and compared the in vivo expression ...

Background: The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major repetitive epitope (Asn-Pro-Asn-Ala)n, (NPNA)n. In individuals immunized by the bites of. irradiated Anopheles mosquitoes carrying P. falciparum sporozoites in their salivary glands, the antirepeat. response dominates and is thought by many to play a role in protective immunity.. Methods: The antibody repertoire from a protected individual immunized by the bites of irradiated P. falciparum infected Anopheles stephensi was recapitulated in a phage display library. Following affinity based selection against (NPNA)3 antibody fragments that recognized the PfCSP repeat epitope were rescued.. Results: Analysis of selected antibody fragments implied the response was restricted to a single antibody fragment consisting of VH3 and VkI families for heavy and light chain respectively with moderate affinity for the ...

Differences between Plasmodium vivax and Plasmodium falciparum. Plasmodium vivax and Plasmodium falciparum Differences. Plasmodium vivax vs falciparum.

BioAssay record AID 157870 submitted by ChEMBL: Growth inhibition of chloroquine-resistant Plasmodium falciparum K1 by [3H]hypoxanthine uptake.

Link to Pubmed [PMID] - 25522250. PLoS Pathog. 2014 Dec;10(12):e1004520. All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify cAMP as a key regulator that triggers the timely secretion of microneme proteins enabling receptor-engagement and invasion. We demonstrate that exposure of merozoites to a low K+ environment, typical of blood plasma, activates a bicarbonate-sensitive cytoplasmic adenylyl cyclase to raise cytosolic cAMP levels and activate protein kinase A, which regulates microneme secretion. We also show that cAMP regulates merozoite cytosolic Ca2+ levels via induction of an Epac pathway and demonstrate that increases in both cAMP and Ca2+ are essential to trigger microneme secretion. Our identification of the different ...

Isolation of Non-Parenchymal Cells from the Mouse Liver -- Measurement of the T Cell Response to Pre-Erythrocytic Vaccination in Mice -- Characterization of Liver CD8 T cell Subsets that are Associated with Protection against Pre-Erythrocytic Plasmodium Parasites -- Flow Cytometry-Based Assessment of Antibody Function against Malaria Pre-Erythrocytic Infection -- Assessment of Parasite Liver Stage Burden in Human-Liver Chimeric Mice -- Measurement of Antibody-Mediated Reduction of Plasmodium Yoelii Liver Burden by Bioluminescent Imaging -- Detection of Plasmodium Berghei and Plasmodium Yoelii Liver-Stage Parasite Burden by Quantitative Real Time PCR -- Membrane Feeding Assay to Determine the Infectiousness of Plasmodium Vivax Gametocytes -- The Standard Membrane Feeding Assay: Advances Using Bioluminescence -- Agglutination Assays of the Plasmodium Falciparum Infected Erythrocyte -- Antibody-Dependent Cell-Mediated Inhibition (ADCI) of Plasmodium Falciparum: One and Two-Step ADCI Assays -- A ...

Fetal hemoglobin modifies the disease manifestation of severe Plasmodium falciparum malaria in adult patients with sickle cell anemia.

BACKGROUND: Artemisinin-based combination therapies are the recommended first-line treatments of falciparum malaria in all countries with endemic disease. There are recent concerns that the efficacy of such therapies has declined on the Thai-Cambodian border, historically a site of emerging antimalarial-drug resistance. METHODS: In two open-label, randomized trials, we compared the efficacies of two treatments for uncomplicated falciparum malaria in Pailin, western Cambodia, and Wang Pha, northwestern Thailand: oral artesunate given at a dose of 2 mg per kilogram of body weight per day, for 7 days, and artesunate given at a dose of 4 mg per kilogram per day, for 3 days, followed by mefloquine at two doses totaling 25 mg per kilogram. We assessed in vitro and in vivo Plasmodium falciparum susceptibility, artesunate pharmacokinetics, and molecular markers of resistance. RESULTS: We studied 40 patients in each of the two locations. The overall median parasite clearance times were 84 hours (interquartile

A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 microg, 20 microg or 80 microg of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study ...

Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogeneous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P | 0.01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes

Genotyping of the chloroquine-resistance biomarker pfcrt (Plasmodium falciparum chloroquine resistance transporter gene) suggests that, in the absence of chloroquine pressure, Plasmodium falciparum parasites in Malawi have reverted to chloroquine sensitivity. However, malaria infections in Africa are commonly polyclonal, and standard PCRs cannot detect minority genotypes if present in <20% of the parasites in an individual host. We have developed a multiple site-specific heteroduplex tracking assay (MSS-HTA) that can detect pfcrt 76T mutant parasites consisting of as little as 1% of the parasite population. In clinical samples, no pfcrt 76T was detected in 87 pregnant Malawian women by standard PCR. However, 22 (25%) contained minority-variant resistant genotypes detected by the MSS-HTA. These results were confirmed by subcloning and sequencing. This finding suggests that the chloroquine-resistant genotype remains common in Malawians and that PCR-undetectable drug-resistant genotypes may be

Treatment failures to the first- and second-lines antimalarial drugs chloroquine and sulfadoxine-pyrimethamine have increased in the Purworejo district on the island of Java, Indonesia. A molecular epidemiologic study was conducted to determine the frequency distribution of mutant alleles of the genes associated with the resistance among the isolates of Plasmodium falciparum from the area. Analyses using a polymerase chain reaction and restriction fragment length polymorphism showed that nearly all of the 111 samples carried mutant alleles in genes associated with chloroquine resistance: P. falciparum multi-drug resistance 1 (pfmdr1) 86Y (92%), 1042D (4.5%), and P. falciparum chloroquine resistance transporter (pfcrt) 76T (99.1%). Mutant alleles of the in the dihydrofolate reductase (dhfr) gene were also high (84.7%), either as 108N and 108T or paired with 59R, and 16V, respectively. Mutant alleles in the dihydropteroate synthase gene were the least common, either as a single 437G mutation (35.3%) or

The catalytic activity and ability to confer resistance to antifolates of Plasmodium falciparum dihydrofolate reductase (pfDHFR) through single and double mutations at Asp-54 and Phe-223 were investigated. A single Asp54Glu (D54E) mutation in the pfDHFR domain greatly decreased the catalytic activity of the enzyme and affected both the K, values for the substrate dihydrofolate and the K-i values for pyrimethamine, cycloguanil and WR99210. The Phe223Ser (F223S) single mutant had unperturbed kinetics but had very poor affinity with the first two antifolates. The ability to confer high resistance to the antifolates of F223S enzyme was, however, abolished in the D54E + F223S double mutant enzyme. When D54E mutation was present together with the A16V + S108T double mutation, the effects on the Km values for the substrate dihydrofolate and the binding affinity of antifolates were much more pronounced. The severely impaired kinetics and poor activity observed in A16V+S108T+D54E enzyme could, however, ...

No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC(50) values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte

There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping |9000 individuals across three African populations. Using population- and family-based tests, we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: case-control allelic odds ratio (OR), 1.2; 95% confidence interval (CI), 1.09-1.32; P = 0.0003; family-studies allelic OR, 1.19; 95% CI, 1.08-1.32; P = 0.001; pooled across all studies allelic OR, 1.18; 95% CI, 1.11-1.26; P = 2 x 10(-7). We

BACKGROUND: The efficient allocation of financial resources for malaria control and the optimal distribution of appropriate interventions require accurate information on the geographic distribution of malaria risk and of the human populations it affects. Low population densities in rural areas and high population densities in urban areas can influence malaria transmission substantially. Here, the Malaria Atlas Project (MAP) global database of Plasmodium falciparum parasite rate (PfPR) surveys, medical intelligence and contemporary population surfaces are utilized to explore these relationships and other issues involved in combining malaria risk maps with those of human population distribution in order to define populations at risk more accurately. METHODS: First, an existing population surface was examined to determine if it was sufficiently detailed to be used reliably as a mask to identify areas of very low and very high population density as malaria free regions. Second, the potential of

TY - JOUR. T1 - Phylogenetic Analysis and Protein Modeling of Plasmodium falciparum Aspartate Transcarbamoylase (ATCase). AU - Depamede, Sulaiman. AU - Menz, Ian. PY - 2011. Y1 - 2011. N2 - Unlike most mammalian cells, Plasmodium sp., are unable to utilize preformed pyrimidine bases and nucleosides hence they are reliant solely on de novo pathway. Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) catalyzes the first committed step in de novo pyrimidine biosynthesis pathway, is a potential target for novel anti-parasitic including antimalarial drugs. P. falciparum ATCase has not been studied extensively. To reveal whether it has a regulatory subunit or no and how its evolution, phylogenetic analysis and protein modeling of ATCase P. falciparum were studied. The structural model can be used to identify the possible differences between active sites of mammalian and Plasmodium enzyme. This is important in a relation with antimalarial drug development. Analogous sequences from P. falciparum were ...

Background Sickle cell trait (HbAS) confers partial protection against malaria by reducing the adhesion of Plasmodium falciparum-infected erythrocytes to host receptors, but little is known about its potential protection against placental malaria. Methods Using flow cytometry, we assessed the recognition of HbAA and HbAS VAR2CSA-expressing infected erythrocytes, by plasma from 159 Beninese pregnant women with either HbAA (normal) or HbAS. Using multivariate linear models adjusted for gravidity, parasite infection at delivery, glucose-6-phosphate dehydrogenase deficiency, and α-thalassemia carriage, we observed significantly reduced cell surface antibody binding of HbAS-infected erythrocytes by plasma from HbAS compared with HbAA women (P , 10-3). Results The difference in cell surface antibody binding was only observed when infected erythrocytes and plasma were associated according to the same hemoglobin genotype. Similar levels of VAR2CSA-specific antibody were measured by enzyme-linked ...

Fishes, amphibia and reptiles, the ectothermic vertebrates, are hosts for a variety of intraerythrocytic parasites including protists, prokaryotes, viruses and structures of uncertain status. These parasites may experience host temperature fluctuations, host reproductive strategies, population genetics, host habitat and migratory behaviour quite unlike those of endothermic hosts. Few blood infections of fishes, amphibia and reptiles have proven pathogenicity, in contrast to the many intraerythrocytic parasites of mammals and some birds which harm their hosts. Although not given the attention afforded to intraerythrocytic parasites of endotherms, those of ectotherms have been studied for more than a century. This review reports on the diversity, general biology and phylogeny of intraerythrocytic parasites of ectotherms. The existence of taxonomic confusion is emphasized and the main taxonomic features of most of the 23 better characterized genera, particularly the kinetoplastid and apicomplexan ...

blockquote class=wp-embedded-content,,a href=https://acreme.org.au/publication/investigating-the-efficacy-of-triple-artemisinin-based-combination-therapies-tacts-for-treating-plasmodium-falciparum-malaria-patients-using-mathematical-modelling/,Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling,/a,,/blockquote, ,script type=text/javascript, ,!--//--,,![CDATA[//,,!-- /*! This file is auto-generated */ !function(c,d){use strict;var e=!1,n=!1;if(d.querySelector)if(c.addEventListener)e=!0;if(c.wp=c.wp,,{},!c.wp.receiveEmbedMessage)if(c.wp.receiveEmbedMessage=function(e){var t=e.data;if(t)if(t.secret,,t.message,,t.value)if(!/[^a-zA-Z0-9]/.test(t.secret)){for(var ...

Background. Rapid diagnostic tests (RDTs) account for more than two-thirds of malaria diagnoses in Africa. Deletions of the Plasmodium falciparum hrp2 (pfhrp2) gene cause false-negative RDT results and have never been investigated on a national level. Spread of pfhrp2-deleted P. falciparum mutants, resistant to detection by HRP2-based RDTs, would represent a serious threat to malaria elimination efforts. Methods. Using a nationally representative cross-sectional study of 7,137 children under five years of age from the Democratic Republic of Congo (DRC), we tested 783 subjects with RDT-/PCR+ results using PCR assays to detect and confirm deletions of the pfhrp2 gene. Spatial and population genetic analyses were employed to examine the distribution and evolution of these parasites. Results. We identified 149 pfhrp2-deleted parasites, representing 6.4% of all P. falciparum infections country-wide (95% confidence interval 5.1-8.0%). Bayesian spatial analyses identified statistically significant ...

Although Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate, extensive allelic diversity may compromise its vaccine potential. We have previously shown that naturally acquired antibodies to AMA1 were associated with protection from clinical malaria in this Kenyan population. To assess the impact of allelic diversity on naturally acquired immunity, we first sequenced the ectodomain-encoding region of P. falciparum ama1 from subjects with asymptomatic, mild, and severe malaria and measured allele frequency distributions. We then measured antibodies to three allelic AMA1 proteins (AMA1_3D7, AMA1_FVO, and AMA1_HB3) and used competition enzyme-linked immunosorbent assays (ELISAs) to analyze allele-specific antibodies. Seventy-eight unique haplotypes were identified from 129 alleles sampled. No clustering of allelic haplotypes with disease severity or year of sampling was observed. Differences in nucleotide frequencies in clinical (severe plus mild malaria) versus

The surface-accessible ectodomain region of the Plasmodium falciparum apical membrane antigen 1 (AMA1) is a malaria vaccine candidate. The amino acid sequence may be under selection from naturally acquired immune responses, and previous analyses with a small number of allele sequences indicate a non-neutral pattern of nucleotide variation. To investigate whether there is selection to maintain polymorphism within a population, and to identify the parts of the ectodomain under strongest selection, a sample of 51 alleles from a single endemic population was studied. Analyses using Fu and Lis D and F tests, Tajimas D test, and the McDonald-Kreitman test (with the chimpanzee parasite P. reichenowi as outgroup) show significant departure from neutrality and indicate the selective maintenance of alleles within the population. There is also evidence of a very high recombination rate throughout the sequence, as estimated by the recombination parameter, C, and by the rapid decline in linkage disequilibrium with

Chanda, P; Hawela, M; Mharakurwa, S; Shinondo, C; Roper, C; Pota, H; (2007) Frequency of Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase markers in six Districts in Zambia. Medical Journal of Zambia, 34. pp. 58-61. ...

BACKGROUND: Single low doses of primaquine, when added to artemisinin-based combination therapy, might prevent transmission of Plasmodium falciparum malaria to mosquitoes. We aimed to establish the activity and safety of four low doses of primaquine combined with dihydroartemisinin-piperaquine in male patients in Mali. METHODS: In this phase 2, single-blind, dose-ranging, adaptive randomised trial, we enrolled boys and men with uncomplicated P falciparum malaria at the Malaria Research and Training Centre (MRTC) field site in Ouelessebougou, Mali. All participants were confirmed positive carriers of gametocytes through microscopy and had normal function of glucose-6-phosphate dehydrogenase (G6PD) on colorimetric quantification. In the first phase, participants were randomly assigned (1:1:1) to one of three primaquine doses: 0 mg/kg (control), 0·125 mg/kg, and 0·5 mg/kg. Randomisation was done with a computer-generated randomisation list (in block sizes of six) and concealed with sealed, opaque

Vol 9: Diversifying Selection on the Thrombospondin-Related Adhesive Protein (TRAP) Gene of Plasmodium falciparum in Thailand.. This article is from PLoS ONE, volume 9.AbstractSporozoites of Plasmodium falciparum are transmitted to human hosts by A. Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Plasmodium falciparum infecting hemoglobin (Hb)H and/or Hb Constant Spring erythrocytes has higher resistance to artemisinin in vitro than when infecting normal erythrocytes. This is due to low drug accumulation of infected erythrocytes resulting from competition with uninfected variant erythrocytes, which have a higher accumulation capacity than genetically normal cells. Drug accumulation of the parasite was shown to be saturable and dependent on metabolic energy. The 50% inhibitory concentrations (IC50s) for the parasite in HbH/Hb Constant Spring erythrocytes were decreased when normal erythrocytes were added to the infected cells, and correspondingly, the IC50s in normal erythrocytes were increased when HbH/Hb Constant Spring erythrocytes were added to the infected cells. The changes of IC50 corresponded to the variation in drug accumulation of mixtures of normal and variant erythrocytes of different compositions. The IC50s for the parasite in variant erythrocytes were also greatly ...

Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.,br/, ...

The antimicrobial biocide triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol] potently inhibits the growth of Plasmodium falciparum in vitro and, in a mouse model, Plasmodium berghei in vivo. Inhibition of [C-14]acetate and [C-14]malonyl-CoA incorporation into fatty acids in vivo and in vitro, respectively, by triclosan implicate FabI as its target. Here we demonstrate that the enoyl-ACP reductase purified from P. falciparum is triclosan sensitive. Also, we present the evidence for the existence of FabI gene in P, falciparum. We establish the existence of the de novo fatty acid biosynthetic pathway in this parasite, and identify a key enzyme of this pathway for the development of new antimalarials.. ...

Despite the growing recognition that Plasmodium falciparum malaria constitutes a major threat to child survival, the indirect consequences of disease and infection on general human development have been less well described. This review suggests that malaria in childhood is likely to have effects on general cognitive and behavioral development, which range from subtle to profound. Nevertheless, our understanding of the numbers of affected children, and the persistence of and recovery from impairment remains ill defined. Only through large long-term studies will we be able to establish the wider consequences of malaria on communities in areas of the world where malaria is endemic.

TY - JOUR. T1 - Purine import into malaria parasites as a target for antimalarial drug development. AU - Frame, I. J.. AU - Deniskin, Roman. AU - Arora, Avish. AU - Akabas, Myles H.. N1 - Publisher Copyright: © 2014 New York Academy of Sciences. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 2015/4/1. Y1 - 2015/4/1. N2 - Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes. Purines are imported from the host erythrocyte by equilibrative nucleoside transporters (ENTs). They are processed via purine salvage pathway enzymes to form the required purine nucleotides. The Plasmodium falciparum genome encodes four putative ENTs (PfENT1-4). Genetic, biochemical, and physiologic evidence suggest that PfENT1 is the primary purine transporter supplying the purine salvage pathway. Protein mass spectrometry shows that PfENT1 is ...

Malaria remains a major public health problem in most tropical countries. It occasionally presents with both typical and atypical signs and symptoms. Gastrointestinal manifestations are common in malaria endemic areas but intestinal obstruction as a complication is extremely rare. We present the case of a 42-year-old black African man who presented with signs and symptoms of intestinal obstruction and was diagnosed as having Plasmodium falciparum malaria. He was successfully treated with both parenteral and orally administered antimalarial medication and the intestinal obstruction subsequently resolved. With intestinal obstruction being an important cause of morbidity and mortality, we report this case to highlight this rare complication of malaria and therefore increase physicians awareness and prompt diagnosis and management.

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4

My research focuses on understanding of the molecular signal and machinery involved in egress Plasmodium falciparum merozoites from host erythrocytes, involving multidisciplinary approach such as live cell imaging, molecular biology, cell biology and protein chemistry. P. falciparum causes the most virulent form of malaria in humans leading to tremendous morbidity and mortality. All the clinical symptoms of malaria are attributed to the blood stage of the parasite life cycle. To complete its life cycle in blood stage, P. falciparum merozoites invade erythrocytes, replicate, and then exit by a process known as egress. The egress of P. falciparum merozoites from the host erythrocytes is an essential yet poorly understood process. Live video microscopy has played a special role in studies on egress and invasion. Real-time light microscopic visualization of in vitro blood-stage egress in live parasites has been performed in the simian parasite Plasmodium knowlesi and in P. falciparum. In both cases ...

Early this morning, the New England Journal of Medicine released a piece warning of potential artemisinin-resistant malaria near the Cambodia-Thailand border. Artemisinin is a drug used in combination therapies against malaria. Since the 1990s, when artemisinin-based combination therapies (ACTs) were introduced, there have been significant reductions in malaria cases around the world. Countries began to consider malaria eradication instead of malaria control. In 2006, the World Health Organization (WHO) recommended artemisinin-based therapies as the first line of control against uncomplicated Plasmodium falciparum (a protozoan parasite causing a specific type of malaria) malaria cases in countries where the disease is endemic.. Studies from 2008 and 2009 document the reduced susceptibility to the anti-malarial drug in Plasmodium falciparum, the most lethal among the malaria-causing parasites.. The studies show that some P. falciparum parasites are taking a longer time to die than previously ...

TY - JOUR. T1 - Platelets kill circulating parasites of all major Plasmodium species in human malaria. AU - Kho, Steven. AU - Barber, Bridget E.. AU - Johar, Edison. AU - Andries, Benediktus. AU - Poespoprodjo, Jeanne R.. AU - Kenangalem, Enny. AU - Piera, Kim A.. AU - Ehmann, Anna. AU - Price, Ric N.. AU - William, Timothy. AU - Woodberry, Tonia. AU - Foote, Simon. AU - Minigo, Gabriela. AU - Yeo, Tsin W.. AU - Grigg, Matthew J.. AU - Anstey, Nicholas M.. AU - McMorran, Brendan J.. PY - 2018/9/20. Y1 - 2018/9/20. N2 - Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi. Blood samples from 376 participants were collected from malaria-endemic areas of ...

Merrill T. Fine structure of the heart of the owl monkey (Aotus trivirgatus) infected with human malaria (Plasmodium falciparum). J Am Osteopath Assoc 1972;72(2):180. doi: .. Download citation file:. ...

315. A+chur, R. N., Valiyaveettil, M., Alkhalil, A., Ockenhouse, C. F., Gowda, C. D. Chondroitin sulfate proteoglycan-mediated adherence of plasmodium falciparum-infected erythrocytes to human placenta. Glycobiology 2000; 10:166. 316. Achur, R. N., Valiyaveettil, M., Alkhalil, A., Ockenhouse, C. F., Gowda, C. D. Identification of chondroitin sulfate proteoglycans that mediate the adherence of Plasmodium falciparum-infected erythrocytes to human placenta and structural requirements for adherence. Am J Trop Med Hyg 2000; 62(3 Suppl):207. 317. Alger, J., Salgado, L. J., Fernandez, E., Andrade, H., Pang, L., Saravia, N. G., Krogstad, D. J. Recurrent malaria infection in an endemic area on the northern coast of Honduras. Am J Trop Med Hyg 2000; 62(3 Suppl):401. 318. Alkhalil, A., Achur, R. N., Ockenhouse, C. F., Gowda, D. C. Adherence of malaria parasite-infected erythrocytes to human placenta. FASEB J 2000; 14(8):A1395. 319. Atkins, J. L., Bentley, T. B., Nelson, L. D., Pearce, F. J. Evaluation of ...

The emergence and spread of multidrug resistant (MDR) malaria caused by |i|Plasmodium falciparum|/i| or |i|Plasmodium vivax|/i| have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease |i|in vitro|/i| and |i|in vivo|/i| susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in |i|Anopheles|/i| vectors is proposed to monitor infection pockets in transmission control areas

1. EylesDE. HooCC. WarrenM. SandoshamAA. 1963 Plasmodium falciparum resistant to chloroquine in Cambodia. Am J Trop Med Hyg 12 840 843. 2. VerdragerJ. 1986 Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia. J Trop Med Hyg 89 277 289. 3. HurwitzES. JohnsonD. CampbellCC. 1981 Resistance of Plasmodium falciparum malaria to sulfadoxine-pyrimethamine (Fansidar) in a refugee camp in Thailand. Lancet 1 1068 1070. 4. WongsrichanalaiC. MeshnickSR. 2008 Declining artesunate-mefloquine efficacy against falciparum malaria on the Cambodia-Thailand border. Emerg Infect Dis 14 716 719. 5. WHO 2002 Development of South-Asia surveillance network for malaria drug resistance. Report on informal consultative meeting. World Health Organization, Geneva, Switzerland. 6. HurlyMG. 1959 Potentiation of pyrimethamine by sulphadiazine in human malaria. Trans R Soc Trop Med Hyg 53 412 413. 7. ChulayJD. WatkinsWM. SixsmithDG. 1984 Synergistic antimalarial ...

Resistance to many antimalaria drugs developed on the Cambodia-Thailand border long before developing elsewhere. Because antimalaria resistance is now a global problem, artemisinin-based combination therapies (ACTs) are the first-line therapies in most malaria-endemic countries. However, recent clinical and molecular studies suggest the emergence of ACT-resistant Plasmodium falciparum infections in the Cambodia-Thailand border area, where standard ACT is artesunate and mefloquine. These ACT failures might be caused by high-level mefloquine resistance because mefloquine was used for monotherapy long before the introduction of ACT. This observation raises 2 questions. First, how can existing P. falciparum-resistant strains be controlled? Second, how can the evolution of new ACT- resistant strains be avoided elsewhere, e.g., in Africa? Enforcement of rational drug use and improved diagnostic capacity are among the measures needed to avoid and contain ACT resistance ...

Background Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based...

Abstract in English:. PROBLEM: There has been a constant increase in the level of therapeutic failure of the sulfadoxine-pyrimethamine (SP) combination for treating uncomplicated Plasmodium falciparum malaria. OBJECTIVE: To use high-performance liquid chromatography to quantify blood levels of SP in patients with good clinical response and in patients who did not respond to treatment. METHODS: This experimental study was carried out in 2002 in Turbo and Zaragoza, two municipalities in the department of Antioquia in Colombia. There were 79 patients (45 in Turbo and 34 in Zaragoza), including both men and women, who ranged in age from 1 year to 60 years. All the patients had uncomplicated Plasmodium falciparum malaria, with a parasite density of 500 to 50 000 parasites/L. The patients were each randomly assigned to a treatment group. The treatment groups were not blinded; the physician who provided the medication also evaluated the therapeutic response. The treatment consisted of a single ...

The parasite Plasmodium falciparum is perceived as the only culprit of deadly malaria. But P. falciparum is not the only one of its kind. Plasmodium vivax also causes malaria that can be fatal. In a recent paper in Molecular & Cellular Proteomics, researchers have developed a workflow that delves into the transcriptomic and proteomic information of the mosquito, Anopheles albimanus, which is a vector of this equally devastating parasite to better understand parasite transmission biology and identify potential vaccine targets.. A lot is known about P. falciparum and its interactions with its main African vector, the mosquito Anopheles gambiae that transmits the parasite (An. gambiaes genome was sequenced 10 years ago). The transmission of the parasite from its vector into humans has been the cause of malaria cases in Africa. Just in 2008, there were 243 million cases of malarial fever and about 863,000 deaths from the disease in Africa, mostly in children younger than the age of 2.. But research ...

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Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regressio

The National Institute of Malariology, Parasitology, and Entomology conducted this study as part of routine surveillance on drug efficacy following the 2009 World Health Organization protocol (2). After obtaining written consent, patients (age of inclusion, 2-60 years) were enrolled and given dihydroartemisinin/piperaquine (Pharbaco, Hanoi, Vietnam) at a target dosage of 2.4 mg/kg for dihydroartemisinin and 18 mg/kg for piperaquine once a day for 3 days. Patients with treatment failures were subsequently given quinine hydrochlorate (30 mg/kg/d) and doxycycline (3 mg/kg/d) for 7 days. Primary endpoint was adequate clinical and parasitologic response (ACPR) on day 42; PCR genotyping, comparing day 0 and day of failure samples, was used to distinguish recrudescence from reinfection with another strain (2). Dried blood spots were collected on day 0 and analyzed for mutations in the K13 propeller domain (3), Pfmdr1 copy number (4), and Pfplasmepsin2 (PfPM2) copy number (5), which are markers ...

Ian Howie-Willis. Abstract. During the 25 years following World War II, malaria re-emerged as a major threat to Australian military personnel deployed to malarious regions in South-East Asia. By 1952, malariologists in Britain knew that drug-resistant strains of the malaria parasites Plasmodium falciparum and Plasmodium vivax had emerged in Malaya.[i] Successive contingents of Australian soldiers serving in Malaya from the mid-1950s to the early 1960s and then in Vietnam from the early 1970s encountered drug-resistant malaria. They suffered a series of malaria outbreaks and epidemics.. Drug-resistant malaria was an issue causing severe tensions between the Royal Australian Army Medical Corps (RAAMC) medical officers serving in the field in South-East Asia and their superiors in the Army Medical Directorate (AMD) in Melbourne and later Canberra. The Directorate had adopted an orthodoxy which required that the anti-malarial drug Paludrine (also called Proguanil) be taken prophylactically in ...