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Query: UMLS:C0024530 (malaria)
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Swift diagnosis of Plasmodium falciparum malaria in areas where the disease is not endemic is frequently complicated by the lack of experience on the side of involved laboratory personal. Diagnostic tools based on the dipstick principle for the detection of plasmodial histidine-rich protein 2 (HRP-2) and parasite-specific lactate dehydrogenase (pLDH), respectively, have become available for the qualitative detection of P. falciparum malaria. In order to evaluate two of the currently available assays, specimens from 231 patients were screened during a prospective multicenter study. Among the screened specimens, samples from 53 patients (22.9%) were positive for P. falciparum malaria by microscopy and/or PCR. While the test kit based on the detection of HRP-2 performed with a sensitivity of 92.5% and a specificity of 98.3%, the kit for the detection of pLDH showed a sensitivity of 88.5% and a specificity of 99.4%. Dipstick tests have the potential of enhancing speed and accuracy of the diagnosis of P. falciparum malaria, especially if nonspecialized laboratories are involved.
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PMID:Sensitivity and specificity of dipstick tests for rapid diagnosis of malaria in nonimmune travelers. 998 39

We have developed two diagnostic assays based on the specific detection of Plasmodium lactate dehydrogenase (pLDH) activity. These assays exploit a panel of monoclonal antibodies that capture the parasite enzyme and allow for the quantitation and speciation of human malaria infections. An immunocapture pLDH activity assay (ICpLDH) allows for the rapid purification and measurement of pLDH from infected blood using the NAD analog APAD, which reacts specifically with Plasmodium LDH isoforms. An immunochromatographic test (the OptiMAL assay) was also formatted and allowed the detection of parasite infections of approximately 200 parasites/microl of blood. By using a combination of antibodies, both tests can not only detect but differentiate between P. falciparum and non-P. falciparum malaria. Both assays show a sensitivity comparable with other commercial nonmicroscopic tests; importantly, we found very few instances of false-positive samples, especially with samples from patients recently cleared of malaria infection. Furthermore, we find that when one uses the quantitative ICpLDH assay, the levels of pLDH activity closely mirror the levels of parasitemia in both initial diagnosis and while following patient therapy. We conclude that diagnostic tests based on the detection of pLDH are both sensitive and practical for the detection, speciation, and quantitation of all human Plasmodium infections and can also be used to indicate drug-resistant infections.
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PMID:Immunocapture diagnostic assays for malaria using Plasmodium lactate dehydrogenase (pLDH). 998 33

Microscopic examination of blood smears remains the gold standard for malaria diagnosis, but is labor-intensive and requires skilled operators. Rapid dipstick technology provides a potential alternative. A study was conducted in The Gambia to compare the performance of OptiMAL, an immunochromatographic antigen detection assay for the diagnosis of malaria using parasite lactate dehydrogenase, against standard microscopy in patients with suspected malaria. For initial diagnosis of Plasmodium falciparum, irrespective of stage, this assay had a sensitivity of 91.3%, a specificity of 92%, a positive predictive value of 87.2%, and a negative predictive value of 94.7%. The sensitivity of the test decreased markedly at parasitemias < 0.01%. This assay can be used for the diagnosis of malaria in areas where microscopy is not available and for urgent malaria diagnosis at night and at weekends, when routine laboratories are closed and when relatively inexperienced microscopists may be on duty.
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PMID:Comparison of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (OptiMAL) with microscopy for the detection of malaria parasites in human blood samples. 1046 63

Interactive effects of gossypol and chloroquine as determined by activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and liver lactate dehydrogenase (LDH), alkaline phosphatase (ALK-pase), glucose-6-phosphatase (G-6-pase) and cholesterol level were investigated in rats. Administration of gossypol for eight weeks, at a concentration of 20 mg per kg body wt. per day with or without chloroquine had no effect on the serum enzymes and glucose-6-phosphatase activities. When chloroquine at a concentration of 5 mg per kg body wt. thrice a week was administered alone, there was a marked decrease in total protein content and ALK-pose activities, while a significant increase in LDH activity was observed. Administration of either gossypol or chloroquine decreased the level of cholesterol. A greater decrease was recorded when both were given together. It is suggested that gossypol can be employed as a male contraceptive among malaria-infected populations.
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PMID:Experimental analysis of gossypol and chloroquine interaction in serum and in liver of rat. 1035 61

The OptiMAL test (Flow Inc., Portland, Oreg.), which detects a malaria parasite lactate dehydrogenase (pLDH) antigen, has not been evaluated for its sensitivity in the diagnosis of malaria infection in various epidemiological settings. Using microscopy and a PCR as reference standards, we performed a comparison of these assays with the OptiMAL test for the detection of Plasmodium falciparum and Plasmodium vivax infection in 550 immigrants who had come from areas where malaria is endemic to reside in Kuwait, where malaria is not endemic. As determined by microscopy, 125 (23%) patients had malaria, and of these, 84 (67%) were infected with P. vivax and 36 were infected with P. falciparum; in 5 cases the parasite species could not be determined due to a paucity of the parasites. The PCR detected malaria infection in 145 (26%) patients; 102 (70%) of the patients had P. vivax infection and 43 had P. falciparum infection. Of the five cases undetermined by microscopy, the PCR detected P. falciparum infection in two cases, P. vivax infection in two cases, and mixed (P. falciparum plus P. vivax) infection in one case. Correspondingly, the OptiMAL test detected malaria infection in 95 patients (17%); of these, 70 (74%) had P. vivax infection and 25 were infected with P. falciparum. In this study, 61 (49%) of the 125 malaria cases, as confirmed by microscopy, had a degree of parasitemia of <100 parasites per microl, and 23 (18%) of the cases had a degree of <50 parasites per microl. Our results show that the sensitivity of the OptiMAL test is high (97%) at a high level of parasitemia (>100 parasites/microl) but drops to 59% when the level is <100 parasites/microl and to 39% when it is <50 parasites/microl. In addition, the OptiMAL test failed to identify four patients whose blood smears contained P. falciparum gametocytes only. We conclude that the sensitivity and specificity of the OptiMAL test are comparable to those of microscopy in detecting malaria infection at a parasitemia level of >100 parasites/microl; however, the test failed to identify more than half of the patients with a parasitemia level of <50 parasites/microl. Thus, the OptiMAL test should be used with great caution, and it should not replace conventional microscopy in the diagnosis of malaria infection.
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PMID:Comparison of the OptiMAL test with PCR for diagnosis of malaria in immigrants. 1052 67

A simple, efficient, sensitive, reproducible and high throughput assay for measuring the cytoadhesion of Plasmodium falciparum-infected red blood cells (human malaria) is described. The assay format uses 96-well microplates, with the number of P. falciparum parasitized erythrocytes bound determined by measuring Plasmodium specific lactic dehydrogenase activity colorimetrically (absorbance at 655 nm) using the 3-acetylpyridine analog of nicotinamide adenine dinucleotide, nitro blue tetrazolium and diaphorase. The results of the described microplate assay were found to be comparable to those using microscopic analysis but much less time consuming.
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PMID:A high capacity in vitro assay for measuring the cytoadherence of Plasmodium falciparum-infected erythrocytes. 1055 1

Recently introduced rapid nonmicroscopic immunocapture assays for the diagnosis of malaria infection are being evaluated for their sensitivity and specificity in various epidemiological settings. A Plasmodium falciparum histidine-rich protein 2 (PfHRP-2)-based assay (ICT) and a Plasmodium-specific lactate dehydrogenase test (OptiMAL) were evaluated for their specificities in different groups of patients who tested negative for malaria infection by microscopy. The patients were selected from different disease groups: rheumatoid arthritis, hepatitis C, toxoplasmosis, schistosomiasis, and hydatid disease. One hundred thirty-three of the 225 patients were positive for rheumatoid factor. Thirty-five of the 133 (26%) rheumatoid factor-positive patients gave a false-positive reaction with the ICT assay, but only 4 of these gave false-positive reactions with the OptiMAL test. Thirty-three of the 35 false-positive specimens became negative when repeat tested with the ICT assay after absorbing out the rheumatoid factor activity. Our study shows that the PfHRP-2-based ICT assay gave a false-positive reaction in 26% of the patients who had rheumatoid factors, but were negative for malaria by microscopy.
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PMID:Plasmodium falciparum histidine-rich protein 2-based immunocapture diagnostic assay for malaria: cross-reactivity with rheumatoid factors. 1069 18

Field trips to herbalists' practices in an area about 200 miles around Nairobi (Kenya) enabled us to make a list of medicinal plant species preferentially used to treat malaria. Ajuga remota and Caesalpinia volkensii were further investigated as being the most frequently used species. Aqueous decoctions, ethanol macerates, and petroleum ether, methanol and water Soxhlet extracts of these plants were further tested for their in vitro antimalarial properties in a chloroquine sensitive (FCA/20GHA) and resistant (W2) strain of Plasmodium falciparum. The activity was assessed by the parasite lactate dehydrogenase (pLDH) assay method. There was a concentration-dependent inhibition by the vegetal extracts of both plants. The IC(50) of the most active A. remota extract (ethanol macerate) was 55 and 57 microg/ml against FCA/20GHA and W2, respectively. For C. volkensii, it was the Soxhlet-water extract which was most active against FCA/20GHA with an IC(50) of 404 microg/ml while the petroleum ether extract exhibited the most activity against W2 with an IC(50) of 250 microg/ml. Further phytochemical work is being done in order to identify the active principles.
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PMID:Antimalarial activity of Ajuga remota Benth (Labiatae) and Caesalpinia volkensii Harms (Caesalpiniaceae): in vitro confirmation of ethnopharmacological use. 1116 32

Haemolysis is the major cause of anaemia in acute Plasmodium falciparum malaria, destroying both parasitized and non-parasitized erythrocytes. Oxidative stress on erythrocytes is considered an important mechanism of haemolysis. Since non-parasitized erythrocytes are also destroyed, the extracellular environment of the erythrocyte may be a contributor to the oxidative stress. To examine the influence of extracellular factors on oxidative stress and haemolysis, baseline values of erythrocyte thio-barbituric acid-reactive substance (ETBAR) and haemolytic indices such as plasma haemoglobin and lactate dehydrogenase (LDH) were estimated in 19 children in Orissa (India) with acute P. falciparum malaria (haemoglobin level < or = 70 g/L). The indices were measured after incubating cross-matched isogroup adult control erythrocytes with patient's plasma, and patient's erythrocytes with adult control plasma both in presence of and in absence of t-butyl hydroperoxide (t-BHP). The procedure was repeated in the blood of 19 age- and sex-matched non-malarial children. Baseline plasma LDH, haemoglobin and ETBAR concentrations were significantly greater in malaria patients than non-malarial children (P < 0.001 for all). Post-incubation values of ETBAR and plasma haemoglobin were significantly higher (P < 0.05) when adult control erythrocytes were incubated with patient plasma, and plasma haemoglobin was significantly higher (P < 0.05) in incubates of patient erythrocytes with adult control plasma, than their respective pre-incubation values when incubated in absence of t-BHP. These differences were not noticed in the incubates of non-malarial children with healthy adult control samples. When incubated in presence of t-BHP all the post-incubation values in the patients were significantly higher than their respective pre-incubation values and post-incubation values without t-BHP (P < 0.001). In non-malarial control samples, only ETBAR concentration was higher than their respective pre-incubation and post-incubation values without t-BHP (P < 0.01). All the values for post-incubation samples with t-BHP were significantly higher in patients than controls (P < 0.001). In post-incubation samples of control erythrocytes and patient plasma in presence of t-BHP, ETBAR correlated inversely with pre-incubation haptoglobin values (P < 0.001). Thus, plasma of acute malaria patients appears to contain pro-oxidants, which may contribute to extracellular oxidative stress on both parasitized and non-parasitized erythrocytes.
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PMID:Presence of pro-oxidants in plasma of patients suffering from falciparum malaria. 1119 57

Malaria is one of the most important parasitic diseases especially in tropical areas. Over 300 million people are affected and the condition causes 1-3 million deaths each year. It is transmitted by the bite of infected Anopheles mosquitoes. Although Korea was declared to be free of Malaria by the WHO in 1979, malaria re-emergence has been apparent since 1993 amongst soldiers located near the De-Militarized Zone (DMZ) in the northern part of the country. Conventional microscopic examination of thin and thick blood films demonstrates the presence of the parasite and thus this method has been used to confirm the diagnosis of malaria, but it is a labor-intensive procedure and relies upon subjective interpretation. To overcome these limitations, fast and reliable methods for malaria detection have been recently introduced. In this study, we compared three kinds of antibody detection kits and one biochemical test kit that determines the presence of Plasmodium lactate dehydrogenase (pLDH) with conventional peripheral blood smears. The antibody detection methods examined were, two rapid test pack format methods and a single microplate format enzyme-linked immunosorbent assay (ELISA) kit, as manufactured by Korean companies. The sensitivities of the three commercial antibody detection kits in the early stage of malaria were 70.8%, 77.4%, and 63.6%, their corresponding specificities 90.5%, 91.8%, and 80.9%, and their accuracies 87.6%, 87.0%, and 76.7%. The sensitivity and specificity of the pLDH assay were 100% apiece and the results were in 100% concordance with the microscopy of thick blood films. Thus, the pLDH assay may be used as an alternative for conventional microscopic blood film examination, especially in emergency situations when prompt treatment is necessary.
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PMID:Evaluation of diagnostic methods of re-emerging malaria in Korean patients. 1129 5


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