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)

Resistance of P. falciparum to mefloquine emerged along the Thai-Cambodian border following the falciparum malaria outbreak in Bo Rai areas in late 1988. Efforts have been made since then to prevent or delay the spread of multi-drug resistant strains by restricting the use of mefloquine, limiting the distribution of the drug for presumptive treatment and chemoprophylaxis, encouraging personal protection, strengthening the case follow-up system, increasing physician awareness, and mass treatment with primaquine of gem miners crossing the borders.
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PMID:Current measures of containment of multi-drug resistant falciparum malaria in Thailand. 136 60

From July 1983 to March 1984 a randomized double blind prophylactic trial in Thai gem miners working across the border in Cambodia was conducted to determine the prophylactic efficacy of 3 drug regimens against P. falciparum and P. vivax malaria along the Thai-Cambodian border. Gem miners have a high incidence of malaria. Maximum duration of individual participation was 14 weeks. Of 334 participants in this study who were seen every 2 weeks, 145 received mefloquine 500 mg fortnightly, 112 received chloroquine 300 mg base weekly plus Fansidar (1000 mg sulfadoxine and 50 mg pyrimethamine) fortnightly and 77 received chloroquine as 300 mg base weekly. The significant reduction of vivax malaria in study subjects (compared to background incidence) implied good compliance with self administration of chloroquine in the intervening weeks between scheduled appointments. The attack rate in each prophylactic regimen was 2188 cases/1000/year with mefloquine, 8338 cases/1000/year with chloroquine-Fansidar and 10,207 cases/1000/year receiving chloroquine alone. There was a 79% prophylactic efficacy for mefloquine and 18% efficacy for the chloroquine plus Fansidar regimen compared to chloroquine. Using life table analysis, 56% of the mefloquine group, 6% of the chloroquine-Fansidar group and 4% of the chloroquine group were malaria free at the end of the 14 weeks study. The chloroquine plus sulfadoxine-pyrimethamine regimen prescribed for prophylaxis is no longer effective for multidrug resistant strains of P. falciparum in the study area. This study also seriously questions the efficacy of mefloquine prophylaxis.
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PMID:Comparison of mefloquine, chloroquine plus pyrimethamine-sulfadoxine (Fansidar), and chloroquine as malarial prophylaxis in eastern Thailand. 194 77

An in vivo study of the response of P. falciparum to the combination drug, MSP, was conducted among gem miners who contracted malaria from Cambodia in 1991-1992. High level resistance (RII, RIII responses) was observed in 22.5% of the 40 cases attending Mae Sot malaria clinic, west Thailand border, and in 28.1% of the 96 cases attending Bo Rai malaria clinic, east Thailand border. The observations on in vitro studies conducted prior to the MSP treatment and after recrudescence, together with the findings on adequate mefloquine blood levels strongly indicated the serious deterioration of mefloquine efficacy. The first line treatment for the malaria control program needs to be revised and the use of qinghaosu derivatives considered. Intensive measures to combat spreading of the highly resistant strains to other parts of the country should be taken into account.
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PMID:In vivo study of the response of Plasmodium falciparum to standard mefloquine/sulfadoxine/pyrimethamine (MSP) treatment among gem miners returning from Cambodia. 862 47

To determine whether the nonregulated use of antimalaria drugs on the Thai-Cambodian border promoted the recent loss of mefloquine sensitivity by Plasmodium falciparum parasites, we identified the drugs consumed there by gem miners. Of those drug concoctions that were self-administered, five contained chloroquine, one contained primaquine and bactrim and two merely contained analgesics. Local nonregulated healers prescribed orally administered concoctions containing chloroquine, quinine, tetracycline or primaquine for patients suffering mild illness. They administered parenteral chloroquine for severely ill patients and quinine when malaria was life-threatening. Certain of these healers prescribed fansimef, but only infrequently and after 1990. Because gem miners appear not to have had informed access to mefloquine before 1990, we conclude that the loss of antimalaria efficacy of this drug on the Thai-Cambodian border during the late 1980s was independent of its nonregulated use.
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PMID:Mefloquine insusceptibility of malaria in Thailand not promoted by nonregulated drug-use. 865 27

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechanics calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest activity toward D6 clone with IC50 = 155 nM.
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PMID:Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure determination and their antimalarial activity. 898 37

The study was conducted in eight adjacent villages in central Sri Lanka where there are many shallow pits dug by gem miners that fill with water. These become breeding places of the main malarial vector Anopheles culicifacies, and of the second most important vector Anopheles subpictus, but not of Anopheles varuna, the third most important vector. With the help of local volunteers, data on the adult populations of these three species was collected by various standard methods, and data on the incidence of malaria cases was collected by two clinics set up for the project and through the existing hospitals. Prevalence of malaria infection in symptom-less people was investigated by mass blood surveys. On the basis of a year's pre-intervention data the villages were stratified into four with high levels of malaria transmission and four with lower transmission. Within each stratum two villages were randomly assigned for mosquito control by treating all the gem pits, as well as river bed pools, with a granular formulation of the insect growth regulator pyriproxyfen at a target dose of 0.01 mg a.i./litre. The intervention caused significant reductions in the adult populations of An. culicifacies and An. subpictus. Similarly, incidence of malaria was reduced in the intervention villages to about 24% (95% c.l. 20-29%) of that in the controls. Prevalence of parasitaemia also declined significantly. It is concluded that in this situation where, with active community participation, the breeding sites of the main vectors could be located; vector control by a highly active and persistent insect growth regulator can be a very effective means of malaria control.
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PMID:Control of malaria vectors with the insect growth regulator pyriproxyfen in a gem-mining area in Sri Lanka. 1170 Jan 85

Hand-dug gem pits are important breeding sites for larvae of malaria vectors in Sri Lanka. Therefore, studies were carried out to help to select an effective, economic and convenient method that could be used to control malaria vector mosquito breeding in gem pits in a mining area. The effectiveness of four types of floating layers of polystyrene was compared in the laboratory and it was found that 2 mm expanded beads were the most effective for suffocating Anopheles larvae and pupae. The insect growth regulator, pyriproxyfen at dosages of 0.01 and 0.1 mg/l were tested in the laboratory and complete inhibition of emergence was found at both concentrations. A small-scale field trial was carried out for over a year to assess the efficacy of two concentrations of pyriproxyfen, 2 mm diameter expanded polystyrene beads, temephos, used engine oil and filling pits with soil. Pyriproxyfen only required re-application twice a year, whereas temephos or oil require 12 applications per year. Due to re-excavation by gem miners, polystyrene beads and filling of pits were not as permanent solutions as was expected. Calculations based on all available data showed that two annual treatments with pyriproxyfen at 0.01 mg/l would be the most cost-effective method with oil only slightly more expensive. However, the reduced required frequency for visiting every pit made the pyriproxyfen method the one of choice. The same low concentration of pyriproxyfen also effectively inhibited emergence of adults from river-bed pools.
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PMID:Laboratory and field comparisons of pyriproxyfen, polystyrene beads and other larvicidal methods against malaria vectors in Sri Lanka. 1183 98

The aspartic proteinases are a family of enzymes involved in a number of important biological processes. In animals the enzyme renin has a hypertensive action through its role in the renin-angiotensin system. The retroviral aspartic proteinases, such as the HIV proteinase, are essential for maturation of the virus particle and inhibitors have a proven therapeutic record in the treatment of AIDS. The lysosomal aspartic proteinase cathepsin D has been implicated in tumorigenesis and the stomach enzyme pepsin, which plays a major physiological role in hydrolysis of acid-denatured proteins, is responsible for much of the tissue damage in peptic ulcer disease. Since aspartic proteinases also play major roles in amyloid disease, malaria and common fungal infections such as candidiasis, inhibitors to these enzymes are much sought after as potential therapeutic agents. In all aspartic proteinases, the catalytic aspartate residues are involved in an intricate arrangement of hydrogen bonds involving a solvent molecule which is presumed to be water. The catalytic mechanism is thought to involve nucleophilic attack of the active site water molecule on the scissile bond carbonyl generating a tetrahedral gem-diol intermediate. The design of inhibitors generally involves the use of short oligopeptides containing a transition state analogue which mimic this tetrahedral intermediate. The application of structure-based drug design to members of the aspartic proteinase family is the main subject of this review.
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PMID:Aspartic proteinases in disease: a structural perspective. 1195 98

Functionally related homologues of known genes can be difficult to identify in divergent species. In this paper, we show how multi-character analysis can be used to elucidate the relationships among divergent members of gene superfamilies. We used probabilistic modelling in conjunction with protein structural predictions and gene-structure analyses on a whole-genome scale to find gene homologies that are missed by conventional similarity-search strategies and identified a variant gene superfamily in six species of malaria (Plasmodium interspersed repeats, pir). The superfamily includes rif in P.falciparum, vir in P.vivax, a novel family kir in P.knowlesi and the cir/bir/yir family in three rodent malarias. Our data indicate that this is the major multi-gene family in malaria parasites. Protein localization of products from pir members to the infected erythrocyte membrane in the rodent malaria parasite P.chabaudi, demonstrates phenotypic similarity to the products of pir in other malaria species. The results give critical insight into the evolutionary adaptation of malaria parasites to their host and provide important data for comparative immunology between malaria parasites obtained from laboratory models and their human counterparts.
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PMID:Plasmodium interspersed repeats: the major multigene superfamily of malaria parasites. 1550 85

Anopheline vectors of malaria were studied in the Kaluganga gem mining area in the dry zone of central Sri Lanka. Adult mosquitoes were collected using cattle-baited huts and nets, pyrethrum spray sheets, window exit traps and light traps and partial and full-night human landing collections over a period of 17 mo. The collections produced a total of 13,591 anophelines belonging to 14 species. Using ELISA for circumsporozoite proteins of Plasmodium vivax and P. falciparum, Anopheles culicifacies, An. subpictus and An. varuna were incriminated as malaria vectors. For these species, estimated entomological inoculation rates were 5.9, 5.7, and 6.7 infective bites per person per year, respectively. An. culicifacies and An. subpictus show endophagic behavior, while An. varuna were exophagic. Mosquito larval surveys indicated that the gem pits, when filled with water, contributed 60% of the larvae of the three vector species. Parasitological data were collected by two mobile malaria clinics and by hospitals. The incidence rates of fever per 1,000 person-years with P. vivax and P. falciparum were 122.8 and 26.1 respectively, with a significantly higher rate in males over 15 years of age than in females of that age. Changes in the environment due to gem mining may have caused the emergence of An. subpictus and An. varuna as significant malaria vectors. The conventional view of An. culicifacies being the main vector of malaria in Sri Lanka needs to be reconsidered when planning the vector control programs in this study area. Due to migration of malaria patients, there is a likelihood the disease could be spread to other parts of the island. Therefore, action should be taken to eliminate these pits as breeding sites.
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PMID:Vectors and malaria transmission in a gem mining area in Sri Lanka. 1570 86


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