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)

In studying the relationship between genetic abnormalities of red blood cells and malaria endemicity in the Vanuatu archipelago in the southwestern Pacific, we have found that of 1,442 males tested, 98 (6.8%) were G6PD deficient. The prevalence of GdPD deficiency varied widely (0%-39%), both from one island to another and in different parts of the same island, and generally correlated positively with the degree of malaria transmission. The properties of G6PD from GdPD-deficient subjects were analyzed in a subset of 53 samples. In all cases the residual red-blood-cell activity was < 10%. There were three phenotypic patterns. PCR amplification and sequencing of the entire coding region of the G6PD gene showed that the first of these patterns corresponded to G6PD Union (nucleotide 1360C-->T; amino acid 454Arg-->Cys), previously encountered elsewhere. Analysis of samples exhibiting the second pattern revealed two new mutants: G6PD Vanua Lava (nucleotide 383T-->C; amino acid 128Leu-->Pro) and G6PD Namoru (nucleotide 208T-->C; amino acid 70Tyr-->His); in three samples, the underlying mutation has not yet been identified. Analysis of the sample exhibiting the third pattern revealed another new mutant: G6PD Naone (nucleotide 497G-->A; amino acid 166Arg-->His). Of the four mutations, G6PD Union and G6PD Vanua Lava have a polymorphic frequency in more than one island; and G6PD Vanua Lava has also been detected in a sample from Papua New Guinea. G6PD deficiency is of clinical importance in Vanuatu because it is a cause of neonatal jaundice and is responsible for numerous episodes of drug-induced acute hemolytic anemia.
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PMID:Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (southwestern Pacific). 782 90

Two field studies in Kenya and an experimental challenge study in the USA were done to assess the accuracy of a dipstick antigen-capture assay based on qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) in peripheral blood for diagnosis of P falciparum infection. In these studies, the assay was 96.5-100% sensitive for detection of greater than 60 P falciparum asexual parasites/microL blood, 70-81% sensitive for 11-60 parasites/microL blood, and 11-67% sensitive for 10 parasites or less/microL blood. Specificity was 95% (95% CI 85-105%; n = 20) among naive American volunteers, 98% (96-101%; n = 112) among volunteers exposed to the bite of P falciparum-infected mosquitoes, and 88% (84-92%; n = 285) among Kenyans living in an area with holoendemic malaria. Our results also indicated that PfHRP-2 antigen was not detectable in blood 6 days after initiation of curative chemotherapy, and suggest that such circulating antigens rarely lead to false-positive tests. The dipstick assay's sensitivity, specificity, simplicity, and speed may make it an important tool in the battle against malaria.
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PMID:Diagnosis of malaria by detection of Plasmodium falciparum HRP-2 antigen with a rapid dipstick antigen-capture assay. 791 Dec

A mixture of Plasmodium falciparum exoantigens inducing lymphocyte activation and cytokine production was shown to contain the malaria vaccine candidate, the serine-stretch protein. This protein was shown serologically to correspond to Ag2, an exoantigen recognized by antibodies linked with protection against malaria. The glycophorin-binding protein, the histidine-rich protein II, the S-antigen, the heat shock protein 70, the ring-infected erythrocyte surface antigen, and the apical membrane antigen-1 were also shown serologically to be present in the mixture of exoantigens.
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PMID:Serine-stretch protein (SERP) of Plasmodium falciparum corresponds to the exoantigen Ag2, a target of antibodies associated with protection against malaria. 816 1

Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of hemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, its rate decreasing with increasing pH, and increasing in presence of protease. Although the pH- and proteolysis-dependent release of iron paralleled Hb denaturation, released iron accounted for only a few percent of degraded Hb. Superoxide dismutase, catalase, and various scavengers of oxidative radicals had no effect on either process, consistent with the involvement of Fe(IV) intermediates in iron release from heme. Histidine and imidazole inhibited iron release, probably by binding directly to heme. Ascorbate enhanced iron release considerably but marginally enhanced the denaturation of Hb, suggesting that redox cycling of lysate free iron accelerated further release from heme. These processes could account for the endogenous supply of iron to the malarial parasite.
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PMID:Hemoglobin denaturation and iron release in acidified red blood cell lysate--a possible source of iron for intraerythrocytic malaria parasites. 822 82

George Carmichael Low, like so many early pioneers of Tropical Medicine, had his origin(s) in Scotland. Following a distinguished undergraduate (and early postgraduate) career, he joined Dr Patrick Manson at the newly established London School of Tropical Medicine in 1899. His first major contribution to the specialty (in 1900) was to demonstrate filariae in the proboscis sheath of mosquitoes which had been infected with Filaria bancrofti in Australia, using a technique recently learned in Heidelberg and Vienna. Shortly afterwards, he led an expedition to the Roman Campagna; this established beyond doubt mosquito-transmission of Plasmodium vivax infection to Homo sapiens. In 1901-1902, Low undertook a demanding tour of the Caribbean where he made important contributions to the understanding of the filariases, and assisted in malaria eradication. In 1902 he led a small team (the Royal Society's first sleeping sickness expedition) to investigate the 'negro lethargy' which had emerged in epidemic proportions on the northern shores of Lake Victoria in East Africa. This expedition narrowly failed to establish the aetiological agent (Trypanosoma sp.) of this disease. Following his return to London, Low became superintendent of the Albert Dock Hospital and from then onwards devoted most of his career to the London School of Tropical Medicine and the Hospital for Tropical Diseases (where he became senior physician). He wrote extensively, in addition to his clinical, teaching and administrative commitments. Perhaps Low's major contribution, however, was in establishing the Society (later Royal) of Tropical Medicine and Hygiene in 1907, with Mr (later Sir) James Cantlie.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Royal Society of Tropical Medicine and Hygiene meeting at Manson House, London, 10 December 1992. George Carmichael Low FRCP: twelfth president of the Society and underrated pioneer of tropical medicine. 824 57

A rapid manual test for Plasmodium falciparum, the ParaSight-F test, has been used on a series of patients in a holoendemic malaria area of coastal Tanzania. The test, which is an antigen capture test detecting trophozoite-derived histidine rich protein-II, is simple to perform and provides a definitive answer in about 10 min. It requires no special equipment and is read using a single drop of blood. When compared with 272 thick blood films examined microscopically by 2 observers and confirmed by the QBC malaria test, the ParaSight-F test had 88.9% sensitivity and 87.5% specificity. Detectable antigenaemia in a group of 40 people declined following treatment with Fansidar and by 10 d after treatment all but 4 individuals were antigen free. The remaining 4, although clear of peripheral parasitaemia, remained antigenaemic for 14 d. The test shows great promise for rapid effective diagnosis of P. falciparum in clinics and village health centres where there is no facility for microscopy. Because of its accuracy and rapid action it may even obviate the need for microscopical examination of blood films to diagnose P. falciparum malaria.
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PMID:The rapid manual ParaSight-F test. A new diagnostic tool for Plasmodium falciparum infection. 829 63

We field-tested a specific antigen-detection enzyme-linked immunosorbent assay (ELISA) based on the histidine-rich protein of Plasmodium falciparum, in a district hospital in Thailand. The test was simple to perform, takes less than 3 h to complete, can deal with batches of sera, be read visually, and was 98.05% sensitive and 96.22% specific. However, 3 of 154 microscopically identified P. falciparum cases gave false negative ELISA results. One of these patients had been admitted to hospital for P. falciparum malaria 3 months previously and all 3 came from hyperendemic villages and were thought to have had previous episodes of malaria, possibly resulting in high titres of circulating blocking antibody. The test was more sensitive when whole blood was frozen and thawed before testing. This test is promising but requires further refinement to eliminate false negatives before it can be used safely for screening acutely ill patients for falciparum malaria. The sensitivity of this ELISA appears to be sufficiently high to consider it as a tool for blood donor screening in regions with a high prevalence of P. falciparum carriers with low parasitaemia. There is at present no satisfactory routine screening method for large numbers of blood donors for malaria.
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PMID:Field study of an antigen-detection ELISA specific for Plasmodium falciparum malaria. 846 89

The knob associated histidine-rich protein (KAHRP) gene was cloned and sequenced from two Indian isolates of Plasmodium falciparum, Pf3-92 and Pf29-92. These isolates showed major sequence differences in the C-terminal repeat domain of KAHRP. However, the biologically important domains such as spectrin-actin binding region remained highly conserved. The PCR amplification of a variable C-terminal repeat domain from the clinical isolates of P. falciparum, from Rajasthan epidemic, showed the presence of multiple alleles of KAHRP gene. The presence of multiple alleles indicates the existence of several P. falciparum strains in India. This should be taken into account for future malaria control strategies such as molecular therapy and vaccines.
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PMID:Allelic forms of the knob associated histidine-rich protein gene of Plasmodium falciparum. 860 25

Three genes encoding serine proteases (Sp6A, Sp6T and Sp8T) were isolated from the malaria mosquito An. gambiae. The proteins that are conceptually translated from these genes contain all amino acids that have been described for this class of proteolytic enzymes, namely the His, Asp and Ser residues at the active site, and the six cysteine residues that form the three disulphide bridges in invertebrate serine proteases. The genes are expressed at low levels and the transcripts were detected only by PCR. Analysis of the nucleotide sequences of the three genes and their pattern of expression indicate that none of the genes code for digestive enzymes, but rather that the proteins have features of the tethered type of serine proteases.
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PMID:Isolation and characterization of three serine protease genes in the mosquito Anopheles gambiae. 863 May 36

The rapid manual ParaSight-F test for Plasmodium falciparum is an antigen capture test detecting trophozoite-derived histidine rich protein II, is simple and provides a definitive diagnosis within 10 min. Compared with 913 thick blood film examinations, the ParaSight-F test had 93.4% sensitivity and 98.2% specificity. Compared with 520 blood samples within the same study examined with the aid of the polymerase chain reaction, the ParaSight-F test had 91.6% sensitivity and 99.4% specificity. The ParaSight-F test could be a valuable diagnostic tool for falciparum malaria in any situation requiring rapid diagnosis in the absence of microscopical examination.
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PMID:A field trial of the ParaSight-F test for the diagnosis of Plasmodium falciparum infection. 875 63


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