Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While various infectious agents have been reported to induce hemophagocytic syndrome (HPS), protozoan malaria-associated HPS has not been documented. We describe a patient with Plasmodium falciparum malaria complicated by HPS. A 24-year old man with a history of recent travel in tropical areas was hospitalized with high fever and hepatosplenomegaly. Blood smear showed many of the erythrocytes infected with the ring form of P. falciparum. Laboratory data disclosed bicytopenia with coagulopathy, a high serum level of LDH, hyperferritinemia and hypercytokinemia. Bone marrow smear demonstrated proliferation of mature histiocytes with vivid hemophagocytosis. He was free from other active, disseminated viral, bacterial and fungal infections which have been reported to induce HPS. He recovered rapidly from HPS after resolution of the original malarial infection.
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PMID:Hemophagocytic syndrome induced by Plasmodium falciparum malaria infection. 892 89

Blood samples were collected from 61 P. vivax infected fresh and recurrent malaria patients and liver function parameters studied. Plasma albumin, A/G ratio were found decreased significantly (p < 0.001) when compared to controls. Among the group of recurrent malaria patients with more than five attacks lowest values were found and the decrease was directly correlated with the number of attacks. The enzyme activities of plasma LDH, SGPT and thymol turbidity were found increased significantly with the increase in the number of attacks (p < 0.001). The increase was more pronounced in more than 5 attack (R3) group. The levels of total, conjugated and free bilirubin and the enzyme activities of SGOT, alkaline phosphatase were also found increased significantly in all the recurrent malarial groups, when compared to controls, without any correlation between the number of attacks. The isoenzyme pattern of plasma LDH was not altered in either fresh or recurrent malarial attack groups when compared to controls.
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PMID:Liver function tests in recurrent P. vivax malaria. 905 46

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

Malaria is relatively rare in Japan. Of 13 patients referred to our laboratory for malarial screening in the past 4 years, malarial parasites were detected in 8. Conventional screening procedures commonly detect hepatic dysfunction, thrombocytopenia, elevated LDH activity, and increased CRP levels in malaria patients. More notably, the 8 malaria patients identified by our laboratory also demonstrated reactive lymphocytosis. In the absence of additional clinical information, reactive lymphocytosis alone may be enough to warrant laboratory blood smear tests on the suspicion of malaria. Conventional microscopic methods have often proved inconclusive in identifying malarial parasite species or detecting mixed infections. However, by combining the methods of DNA analysis with those of microscopy, we were able to conclusively diagnose all cases of suspected malaria. As a test of their skills, 9 laboratory technicians relatively inexperienced with malarial parasites were asked to screen 6 samples: 3 containing malarial parasites, and 3 that were malaria-free. Although none of the technicians were able to accurately identify the samples without additional clinical information, 4 accurately identified all malarial samples when that information was provided. Experience is a crucial determinant of ability to detect malarial parasites by microscopic methods alone. Nonetheless, the findings of our study suggested the diagnostic accuracy of laboratory screening procedures for malaria can be significantly improved if combined with minimal clinical data and the techniques of DNA analysis.
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PMID:[Diagnosis of malaria by allele-specific PCR]. 1035 38

Malaria particularly falciparum malaria is a major public health problem in India. Its correct and early diagnosis is very important for prompt treatment as a preventive and control measure. Microscopy is the traditional method for laboratory diagnosis of malaria, which is used widely. However, it is time consuming, needs expertism and the detection limit is 10-20 parasites/ml blood in thick film and 100 parasites/ml blood in thin film. Quantitative buffy coat technique (QBC) is highly sensitive method but expensive equipment is needed for this test. The serological methods involving antibody detection give information regarding exposure to malaria but do not differentiate between present and past infections. Genetic probes and PCR are highly sensitive methods but require expensive equipments. Parasite antigen detection tests are useful in field and PHC level for rapid diagnosis of P falciparum malaria.LDH based test for diagnosing malaria is sensitive but can not differentiate between species. For monitoring of drug resistance or follow-up of patients, methods which can quantify parasitaemia are needed. Simply microscopy is the best solution at present.
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PMID:Laboratory diagnosis of malaria. 1201 50

The frequency and spectrum of adverse events associated with the antimalarial therapeutic regimen of mefloquine (MQ) (750 and 500 mg at an interval of 6 h) was assessed in 22 healthy volunteers who were monitored for 21 days following drug administration. An unexpected high frequency of side effects of any grade were reported by all 22 subjects. The most commonly reported symptoms were vertigo (96%), followed by nausea (82%) and headache (73%). Participants suffering from severe (grade 3) vertigo (73%) required bed rest and specific medication for 1 to 4 days. More females than males reported severe adverse reactions. The majority (77.3%) of the participants (f: 8/12, m: 9/10) showed symptom resolution within 3 weeks (510 h) after drug administration. Biochemical and haematological findings stayed within the normal range of values, but showed nevertheless a significant rise of Na, Cl, Ca, bilirubin, GGT and LDH. The unexpectedly high frequency and severity of adverse reactions after normal therapeutic dosage of MQ in healthy subjects may influence future recommendations regarding the use of MQ for stand-by treatment of suspected malaria in travellers.
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PMID:Unexpected frequency, duration and spectrum of adverse events after therapeutic dose of mefloquine in healthy adults. 1180 Dec 24

Platelet counts and automated detection of platelet clumps were evaluated by optical analysis with the Abbott CD4000 analyser (Abbott Diagnostics, Santa Clara, CA, USA) in this South African study of 828 samples referred for malaria investigations. Based on microscopy (Micro) and rapid tests (RT) for HRP2 protein and parasite-associated LDH, malaria negative samples (n = 417) were defined as Micro-, RT-. Convalescent cases (n = 64) were Micro-, RT+ and had a recent record of positive microscopy. Malaria positive cases were subdivided into Micro+ (n = 315) and Micro-, RT+, PCR+ (polymerase chain reaction) (n = 32) subgroups. The mean platelet count for Micro+ cases (89.7 x 10(9)/l) was significantly lower than both the malaria negative (mean 212.6 x 10(9)/l) and convalescent malaria (mean 152.8 x 10(9)/l) groups; 89% of microscopy positive cases were thrombocytopenic (< 150 x 10(9)/l) and 30% had severe thrombocytopenia (< 50 x 10(9)/l). For comparison, 32% of the 417 malaria negative samples were thrombocytopenic and 6% of these were severe. Two thirds of samples with parasitaemia above 10% had platelet counts of < 50 x 10(9)/l while the counts were largely independent of parasite numbers when the parasitaemia was below 10%. Thirty percent of samples with microscopically detectable parasites had a PltClmp flag compared to 13% of the malaria negative group but, when the actual platelet count was taken into account, it became apparent that appearance of the flag was primarily associated with thrombocytopenia per se rather than malaria status. In most samples with a PltClmp flag, the CD4000 optical platelet clump 'signature' was indicative of small platelet aggregates and giant platelets. Morphological examination confirmed the presence of varying numbers of small platelet aggregates (3-12 individual platelets), often together with increased giant platelets, in many samples with a PltClmp flag. The observations suggest that while patients with malaria may be predisposed to the development of thrombocytopenia, a reduced platelet count in some patients may also be due in part to pseudo-thrombocytopenia.
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PMID:Thrombocytopenia in patients with malaria: automated analysis of optical platelet counts and platelet clumps with the Cell Dyn CD4000 analyser. 1235 91

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

Prompt diagnosis and early institution of therapy is an important determinant of outcome in severe falciparum malaria. Thick smears are the gold standard for diagnosis; in situations where reliable microscopy is not available, tests based on HRP-2 antigen/parasite LDH are useful. As there is widespread resistance to chloroquine in P falciparum in India, the choice for specific antimalarial therapy is between quinine and artermisinin derivatives. Randomized controlled trials have not revealed any significant benefit of the artemisinin derivatives over quinine in quinine sensitive areas. Also, if quinine is administered in the recommended way, the side effects are no greater than artemisinins. However, as the artemisinin derivatives are easier to administer, their use in severe malaria in India is increasing. It is vital that we use these drugs in a rational and judicious manner to prevent development of drug resistance. Supportive care, early diagnosis and management of complications are as essential as antimalarial therapy. The role of exchange blood transfusion in the management of severe malaria is still controversial. It may be considered in the presence of high parasites counts (>10%) with multiorgan dysfunction if adequate quantities of safe blood are available.
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PMID:Management of severe malaria. 1497 92

Malate dehydrogenase (MDH) may be important in carbohydrate and energy metabolism in malarial parasites. The cDNA corresponding to the MDH gene, identified on chromosome 6 of the Plasmodium falciparum genome, was amplified by RT-PCR, cloned and overexpressed in Escherichia coli. The recombinant Pf MDH was purified to homogeneity and biochemically characterized as an NAD(+)(H)-specific MDH, which catalysed reversible interconversion of malate to oxaloacetate. Pf MDH could not use NADP/NADPH as a cofactor, but used acetylpyridine adenine dinucleoide, an analogue of NAD. The enzyme exhibited strict substrate and cofactor specificity. The highest levels of Pf MDH transcripts were detected in trophozoites while the Pf MDH protein level remained high in trophozoites as well as schizonts. A highly refined model of Pf MDH revealed distinct structural characteristics of substrate and cofactor binding sites and important amino acid residues lining these pockets. The active site amino acid residues involved in substrate binding were conserved in Pf MDH but the N-terminal glycine motif, which is involved in nucleotide binding, was similar to the GXGXXG signature sequence found in Pf LDH and also in alpha-proteobacterial MDHs. Oxamic acid did not inhibit Pf MDH, while gossypol, which interacts at the nucleotide binding site of oxidoreductases and shows antimalarial activity, inhibited Pf MDH also. Treatment of a synchronized culture of P. falciparum trophozoites with gossypol caused induction in expression of Pf MDH, while expression of Pf LDH was reduced and expression of malate:quinone oxidoreductase remained unchanged. Pf MDH may complement Pf LDH function of NAD/NADH coupling in malaria parasites. Thus, dual inhibitors of Pf MDH and Pf LDH may be required to target this pathway and to develop potential new antimalarial drugs.
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PMID:An alpha-proteobacterial type malate dehydrogenase may complement LDH function in Plasmodium falciparum. Cloning and biochemical characterization of the enzyme. 1531 84


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