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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aotus lemurinus griseimembra is considered one of the best nonhuman primate species for malarial studies because of its susceptibility to infection by Plasmodium falciparum asexual blood stages. However, reproducible transmission of infective P. falciparum sporozoites by mosquito inoculation has been difficult to achieve even in splenectomized monkeys. Characterization of an Aotus-P. falciparum cyclical transmission model has become a top priority as a result of the significant progress toward the development of preerythrocytic malaria vaccines. Herein, we describe a reproducible model developed using intact A. lemurinus griseimembra monkeys intravenously inoculated with sporozoites from a monkey-adapted P. falciparum (Santa Lucia) strain and a wild Falciparum-Cali-Colombia-4 (FCC-4) strain. Sporozoites were obtained by salivary gland dissection of laboratory-reared Anopheles albimanus mosquitoes. Parasitemia was monitored by thick-smear microscopy, parasite lactate dehydrogenase (pLDH) determination, and mosquito xenodiagnosis. The last method proved to be the most sensitive method for monitoring parasitemias. Infection with the Santa Lucia strain showed a mean prepatent period of 16 days (range 6-21 days), whereas infection with the wild FCC-4 strain resulted in a 24-day prepatent period. Mean peak parasite density was approximately 900 parasites/microliter for both parasite strains. The prepatent period, the peak of parasitemia, and the duration of patency were independent of the size of the sporozoite inoculum and the presence of spleen in the host. This model is being successfully used to test the protective efficacy of P. falciparum preerythrocytic vaccine candidates.
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PMID:Reproducible infection of intact Aotus lemurinus griseimembra monkeys by Plasmodium falciparum sporozoite inoculation. 1219 21

Alternative, non-microscopic methods for the diagnosis of malaria have recently become available. Among these, rapid dipstick methods stand out. One such test, OptiMAL(R), is based on the immunochromatographic detection of Plasmodium lactate dehydrogenase (pLDH) and has the capacity to detect and distinguish infections caused by P. falciparum and Plasmodium sp. This capacity is particularly important in countries where different species of Plasmodium co-exist. In this study we evaluated the performance of OptiMAL(R) in an urban referral center for malaria diagnosis. Two sets of patients were included: one (n = 112) having predetermined infections with P. falciparum or P. vivax and individuals with negative blood smears; and another consisting of all eligible consecutive patients (n = 80) consulting for diagnosis at the referral center during one month. The overall diagnostic efficiency of OptiMAL(R) for both sets of patients was 96.9%. Efficiency was higher for P. vivax (98.1%) than for P. falciparum (94.9%). These results corroborate the diagnostic utility of OptiMAL(R) in settings where P. vivax and P. falciparum co-exist and support its implementation where microscopic diagnosis is unavailable and in circumstances that exceed the capacity of the local microscopic diagnosis facility.
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PMID:Performance of OptiMAL(R) in the diagnosis of Plasmodium vivax and Plasmodium falciparum infections in a malaria referral center in Colombia. 1221 43

Malaria is the most important parasitic disease worldwide. With the advent of multidrug-resistant strains, it is highly important that the disease be diagnosed both early and accurately. For the diagnosis of malaria parasites, the thick blood film approach remains the gold standard. However, the use of that standard requires a microscope, stains, and a trained microscopist to interpret the films. The author describes the microscopical detection of the malaria parasite through the use of fluorochrome as well as the development of antigen detection tests to improve the laboratory diagnosis of malaria. Histidine-rich protein II (HRPII) is expressed by the asexual stages of Plasmodium falciparum. The detection of HRPII antigen appears to be a useful alternative diagnostic technique when microscopes are unavailable. However, a negative test result may indicate the presence of non-P falciparum malaria or that it is too early in the course of infection to detect parasites. One advantage of a parasite lactate dehydrogenase (pLDH) detection system is its ability to detect all 4 species of malaria and to diagnose both P. falciparum and P. vivax infections.
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PMID:Latest developments in the laboratory diagnosis of malaria. 1229 40

The parasite lactate dehydrogenase (pLDH) assay method, a recently developed in vitro enzymatic method for evaluating antimalarial compounds, was used to examine the antiplasmodial activities of the aqueous leaf, stem-bark and fruit extracts of some plants used for the treatment and/or prophylaxis of malaria in KwaZulu-Natal province of South Africa. The in vitro antiplasmodial assay was carried out using a chloroquine-sensitive strain of malarial parasite, Plasmodium falciparum D10. A preliminary phytochemical analysis of the plant extracts was carried out using UV spectral analysis and thin-layer chromatography (TLC) to separate the chemical constituents of the extracts. Their chemical components were subsequently identified by treating the TLC plates with various spray reagents. Of the 14 plant extracts investigated, only 10 were found to have IC50 values of 10-50 micrograms/ml. The two most active extracts were Psidium guajava stem-bark extract and Vangueria infausta leaf extract, both of which showed IC50 values of 10-20 micrograms/ml. Phytochemical analysis of these two active plant extracts revealed the presence of anthraquinones, flavonoids, seccoirridoids and terpenoids.
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PMID:Studies on the antiplasmodial properties of some South African medicinal plants used as antimalarial remedies in Zulu folk medicine. 1242 27

Conventional light microscopy has been the established method for malaria diagnosis. However, recently several nonmicroscopic rapid diagnostic tests have been developed for situations in which reliable microscopy may not be available. This study was conducted to evaluate the diagnostic performance of a recently introduced ICT Malaria Pf/Pv test. This assay detects Plasmodium falciparum histidine-rich protein 2 antigen (PfHRP-2) for P. falciparum diagnosis and pan-malarial antigen for P. vivax diagnosis. In this study we compared the performance of ICT Malaria Pf/Pv with microscopy of Giemsa-stained blood films and with an OptiMAL test that detects Plasmodium lactate dehydrogenase (pLDH) antigen. A total of 750 clinically suspected malaria patients were examined at local health centers in Kuwait. Both the antigen tests had a high degree of specificity (>98%) for detection of malaria infection. However, they were less sensitive than microscopy. Compared with microscopy the ICT Malaria PF/pf test failed to detect malaria infection in 93 (34%) of 271 malaria patients (11% of patients with P. falciparum and 37% of patients with P. vivax) and the OptiMAL test failed to detect malaria infection in 41 (15%) of 271 malaria patients (7% of patients with P. falciparum and 13% of patients with P. vivax). The sensitivities of the ICT Malaria Pf/Pv and OptiMAL tests for detection of P. falciparum infection were 81 and 87%, and those for detecting P. vivax were 58 to 79%, respectively. The sensitivity of the ICT Malaria Pf/Pv and OptiMAL tests decreased significantly to 23 and 44%, respectively, at parasite densities of <500/ micro l. Both of the tests also produced a number of false-positive results. Overall, the performance of the OptiMAL test was better than that of the ICT Malaria Pf/Pv test. However, our results raise particular concern over the sensitivity of the ICT Malaria Pf/Pv test for detection of P. vivax infection. Further developments appear necessary to improve the performance of the ICT Malaria Pf/Pv test.
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PMID:Comparison of two commercial assays with expert microscopy for confirmation of symptomatically diagnosed malaria. 1245 71

We determined the sensitivity and specificity of three rapid immunochromatographic malarial antigen detection test systems (RDTs) for the detection of Plasmodium falciparumand assessed the quality of follow-up results. ParaSight-F and ICT Malaria detect histidine-rich protein-2 (HRP-2), whereas OptiMal detects plasmodial lactate dehydrogenase (pLDH). ParaSight-F performed with 95.1% sensitivity and 97.1% specificity (554 patients tested of whom 144 had falciparum malaria). ICT Malaria performed with 95.7% sensitivity and 99.2% specificity (718 patients tested of whom 184 had falciparum malaria). OptiMal performed with 76.2% sensitivity and 99.7% specificity (539 patients tested of whom 130 had falciparum malaria). In follow-up investigations, HRP-2 did not appear to be a useful antigen due to its long half-life, whereas pLDH offers a reasonable correlation with the presence of viable parasites in those cases initially detected. We therefore conclude that a combination of both antigens might be the best option for creating a reliable RDT for the diagnosis of falciparum malaria.
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PMID:Comparison of three antigen detection tests for diagnosis and follow-up of falciparum malaria in travellers returning to Berlin, Germany. 1263 46

Ferriprotoporphyrin IX (FPIX) is a potentially toxic product of hemoglobin digestion by intra-erythrocytic malaria parasites. It is detoxified by biomineralization or through degradation by glutathione. Both processes are inhibited by the antimalarial drug chloroquine, leading to the accumulation of FPIX in the membranes of the infected cell and their consequent permeabilization. It is shown here that treatment of Plasmodium falciparum-infected erythrocytes with chloroquine also leads to the binding of FPIX to a subset of parasite proteins. Parasite enzymes such as aldolase, pyrimidine nucleaside monophosphate kinase and pyrimidine 5'-nucleotidase were inhibited by FPIX in vitro, but only the activity of 6-phosphogluconate dehydrogenase was reduced significantly in cells after drug treatment. Additional proteins were extracted from parasite cytosol by their ability to bind FPIX. Sequencing of these proteins identified heat shock proteins 90 and 70, enolase, elongation factor 1-alpha, phoshoglycerate kinase, glyceraldehyde 3-phosphate dehydrogenase, L-lactate dehydrogenase and gametocytogenesis onset-specific protein. The possible involvement of these proteins in the antimalarial mode of action of chloroquine is discussed. It is concluded that drug-induced binding of FPIX to parasite glycolytic enzymes could underlie the demonstrable inhibition of glycolysis by chloroquine. The inhibition of 6-phosphogluconate dehydrogenase could explain the reduction of the activity of the hexose monophosphate shunt by the drug. Inhibition of both processes is deleterious to parasite survival. Binding of FPIX to other proteins is probably inconsequential to the rapid killing of the parasite by chloroquine.
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PMID:The treatment of Plasmodium falciparum-infected erythrocytes with chloroquine leads to accumulation of ferriprotoporphyrin IX bound to particular parasite proteins and to the inhibition of the parasite's 6-phosphogluconate dehydrogenase. 1266 48

Malaria remains the most important parasitic disease, and tens of thousands of cases are imported into non-endemic countries annually. However, any single institution may see only a very few cases-this is probably the reason why laboratory and clinical misdiagnosis may not be uncommon. In the laboratory, unfamiliarity with microscopic diagnosis may be the main reason, considering the large number of laboratory staff who provide on-call services, often without expert help at hand, as well as the difficulty in detecting cases with low-level parasitemia. Staff should therefore be provided with continuing microscopic training to maintain proficiency. The complementary use of immunochromatographic rapid detection tests (RDTs) may be useful, especially during on-call hours, although, in order to ensure correct interpretation, their inherent limitations have to be well known. Diagnosis based on the polymerase chain reaction is still unsuitable for routine use, due to its long turnaround time, its cost, and its unavailability outside regular hours, although it may be helpful in selected cases. Once the alert clinician has considered the possibility of malaria, and suspicion continues to be high, malaria can be excluded by repeat smears or RDTs. However, the absence of clinical suspicion may not be infrequent, and may have more serious consequences. Depending on the local number of malaria cases seen, laboratory staff should have a low threshold for the decision to perform unsolicited malaria diagnostic tests on suspicious samples, especially if other laboratory tests are abnormal (e.g. thrombocytopenia, presence of atypical lymphocytes, or raised lactate dehydrogenase). The detection of intraleukocytic hemozoin during automated full blood counts is a promising new way to avoid misdiagnosis of clinically unsuspected malaria.
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PMID:Current strategies to avoid misdiagnosis of malaria. 1284 24

Resistance to antimalarial drugs is a public health problem worldwide. Molecular markers for drug-resistant malaria, such as pfcrt and pfmdr1 polymorphisms, could serve as useful surveillance tools. To evaluate this possibility, sequence polymorphisms in pfcrt (position 76) and pfmdr1 (positions 86, 184, 1034, 1042, and 1246) and in vitro drug sensitivities were measured for 65 Plasmodium falciparum isolates from Thailand, Myanmar, Vietnam, and Bangladesh. The pfcrt Thr76 polymorphism was present in 97% of samples, consistent with observations that chloroquine resistance is well established in this region. Polymorphisms in pfmdr1 clustered into four specific patterns: the wild type (category I), a Tyr86 polymorphism only (category II), a Phe184 polymorphism only (category III), and Phe184 in combination with Cys1034 and/or Asp1042 (category IV). Isolates in categories I and III were more sensitive to chloroquine and more resistant to mefloquine, artesunate, and artemisinin than isolates in categories II and IV (P </= 0.01). Mefloquine resistance was significantly more common in category I and III isolates than in category II and IV isolates, with a prevalence ratio of 14.95 (95% confidence interval, 3.88 to 57.56). These categories identified mefloquine resistance with a sensitivity and a specificity of 94 and 91%, respectively. The pfmdr1 gene copy number was measured by real-time PCR as a ratio of the amount of pfmdr1 DNA to the amount of lactate dehydrogenase (ldh) DNA. Eight samples had pfmdr1 DNA/ldh DNA ratios >/=3. The isolates in all 8 samples fell into categories I and III and were significantly more resistant to mefloquine, quinine, artemisinin, and artesunate and more sensitive to chloroquine than the isolates in the 57 samples with <3 copies of the gene (P </= 0.001). Thus, measurement of pfmdr1 mutations and gene copy number may be useful for surveillance of mefloquine-resistant malaria in Southeast Asia.
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PMID:Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1. 1287 99

Lactic dehydrogenase activity increased in direct proportion to the degree of parasitization in synchronous infections of duck erythrocytes. Deviations from this linearity could be accounted for on the basis of the developmental stage of the parasite. Erythrocyte-free P. lophurae showed activities which averaged 3 times that of uninfected erythrocytes, whereas infected erythrocytes had intermediate values. In addition, a patent infection was generally reflected by an increase in the lactic dehydrogenase activity in the plasma, but no direct correlation with parasitemia was established. Molecular heterogeneity of the enzyme was determined on the basis of kinetic data and electrophoretic isolation on a starch block. The uninfected red blood cell showed a major anodal and a minor cathodal peak of lactic dehydrogenase activity, and was further characterized by a kinetic constant representing a high pH optimum with low concentrations of substrate. Isolated P. lophurae had a single, cathodal peak of activity dissimilar from that of the uninfected erythrocyte, and a kinetic constant describing a low pH optimum with a high concentration of substrate. Infected erythrocytes showed a combination of these electrophoretic entities and an intermediate range of kinetic constants. The data indicate that the avian malaria parasite P. lophurae contains a lactic dehydrogenase qualitatively dissimilar from that of its host cell, and the increased enzymatic activity of infected erythrocytes is a result of the enzyme content of the growing parasite added to that of the red blood cell. It is suggested that the LDH of the parasite has a physiological advantage under those conditions which prevail inside the red blood cell.
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PMID:Molecular heterogeneity of lactic dehydrogenase in avian malaria (Plasmodium lophurae). 1391 22


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