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Query: UMLS:C0024530 (malaria)
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In 1976, epidemic organophosphate insecticide poisoning due to malathion occurred among 7500 field workers in the Pakistan malaria control programme. In July, the peak month of the epidemic, it is estimated that there were about 2800 cases. In field studies low red-cell cholinesterase activities were associated with the signs and symptoms of organophosphate insecticide intoxication. Toxicity was seen with 3 different formulations of the insecticide and was greatest with the products containing increased amounts of isomalathion, a toxic malathion degradation product. Poor work practices, which had developed when D.D.T. was the primary insecticide for malaria control, resulted in excessive skin contact with and percutaneous absorption of the pesticide. Airborne malathion concentrations were very low. Implementation of good work practices and proscription of use of the 2 pesticide formulations most contaminated with isomalathion halted the epidemic in September. An extensive training programme and surveillance system for pesticide toxicity preceded 1977 spraying operations.
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PMID:Epidemic malathion poisoning in Pakistan malaria workers. 7 8

Rhesus monkey erythrocytes when incubated in vitro under similar conditions to those used for the cultivation of Plasmodium knowlesi-infected erythrocytes in vitro, exhibit an increase both in their osmotic fragility and in the activity of their acetylthiocholinesterase. No effect was observed on the catabolism of glucose through the glycolytic pathway or through the primary dehydrogenases of the pentose phosphate pathway. The ATP content of normal monkey erythrocytes was also unchanged during incubation in vitro. These observations indicate that incubation of erythrocytes in vitro primarily causes membrane changes. Infection of normal erythrocytes by P. knowlesi was reduced markedly by preincubation in vitro at 37 degrees C for 24 and 48 h. These results suggest that the maintenance of integrity of the surface of the erythrocyte in vitro is a necessary prerequisite for an efficient culture system for the malaria parasite.
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PMID:The effect of incubation in vitro on the susceptibility of monkey erythrocytes to invasion by Plasmodium knowlesi. 82 5

Insecticide bioassays and biochemical microtitre assays were compared for detection of resistance to the organophosphate insecticides malathion and fenitrothion, using inbred laboratory strains of malaria vectors Anopheles albimanus Wiedemann, An.arabiensis Patton and An.stephensi Liston. With susceptible mosquitoes, the LT100 values determined from bioassays corresponded closely with times taken to abolish the activity of acetylcholinesterase activity in biochemical assays: approximately 2 h for malathion and 3 h for fenitrothion. Resistant strains of all three anophelines showed longer survival correlated with prolonged acetylcholinesterase activity. An.albimanus strains with insensitive acetylcholinesterase survived bioassays with discriminating doses of 1 h exposure to 5% malathion or 1% fenitrothion and were judged as resistant. It is concluded that enzyme-specific microassays provide a reliable means of detecting resistant individuals, with practical advantages over bioassays which do not reveal the resistance mechanism and require large numbers of healthy mosquitoes.
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PMID:A generalized approach to detection of organophosphate resistance in mosquitoes. 142 79

In Turkey, the mosquito Anopheles sacharovi has been under field selection pressure sequentially with DDT, dieldrin, malathion and pirimiphosmethyl over a period of 30 years for the purpose of malaria control. In 1984, the field population of An.sacharovi in the malarious Cukurova plain of Adana Province contained an altered acetylcholinesterase-based resistance gene giving broad spectrum resistance against organophosphorus and carbamate insecticides. The cross-resistance spectrum from this mechanism conferred resistance to malathion but not to the organophosphorus insecticide pirimiphos-methyl. Over the 6 years that pirimiphos-methyl has been applied for malaria vector control in this area, the frequency of the altered acetylcholinesterase resistance gene has declined, although in 1989 and 1990 it was still present at measurable frequencies in An.sacharovi from Cukurova. In addition to the acetylcholinesterase resistance mechanism there is evidence of an increased level of glutathione S-transferase in some of the An.sacharovi populations tested. This is known to be correlated with DDT resistance in other anophelines. In Turkish An.sacharovi, DDT resistance and elevated glutathione S-transferase occur in the same populations at similar frequencies. The continued prevalence of resistance to DDT and dieldrin, long after the 1971 cessation of DDT spraying for malaria control in Turkey, suggests that the DDT resistance gene has insufficient reduced fitness associated with it to have been lost from the field population during the past two decades. The implications of the slow decline in resistance gene frequencies in this field population are discussed in relation to mathematical models for managing resistance.
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PMID:Insecticide resistance gene frequencies in Anopheles sacharovi populations of the Cukurova plain, Adana Province, Turkey. 146 99

1. The acetylcholinesterase (AChE) gene from the important malaria vector Anopheles stephensi has been isolated by homology to the Drosophila acetylcholinesterase gene. 2. The complete sequence and intron-exon organization has been determined. The encoded protein has 69% identity to Drosophila AChE and 38 and 36% identity to Torpedo AChE and human butyrylcholinesterase, respectively.
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PMID:The acetylcholinesterase gene of Anopheles stephensi. 190 15

The phospholipid and fatty acid compositions of the host infected erythrocyte plasma membrane (IEPM) have been determined for erythrocytes infected with the human malaria parasite Plasmodium falciparum. IEPM were prepared by selective lysis of the host erythrocyte (but not of the parasite membranes) with 0.1% saponin, followed by differential centrifugation. The purity of the IEPM was determined by measuring the membrane-specific enzyme markers acetylcholinesterase, glutamate dehydrogenase and lactate dehydrogenase, and by immunoelectron microscopy using monoclonal antibodies specific for human erythrocyte glycophorin A (4E7) and for a 195 kDa parasite membrane glycoprotein (Pf6 3B10.1). Both approaches demonstrated that the host erythrocyte plasma membrane preparation was free from contamination by parasite membranes. During intra-erythrocytic development of the parasite, the phospholipid composition of the erythrocyte membrane was strikingly altered. IEPM contained more phosphatidylcholine (38.7% versus 31.7%) and phosphatidylinositol (2.1% versus 0.8%) and less sphingomyelin (14.6% versus 28.0%) than normal uninfected erythrocytes. Similar alterations in phospholipid composition were determined for erythrocyte membranes of parasitized cells isolated by an alternative method utilizing polycationic polyacrylamide microbeads (Affigel 731). The total fatty acid compositions of the major phospholipids in IEPM were determined by g.l.c. The percentage of polyunsaturated fatty acids in normal erythrocyte phospholipids (39.4%) was much higher than in phospholipids from purified parasites (23.3%) or IEPM (24.0%). The unsaturation index of phospholipids in IEPM was considerably lower than in uninfected erythrocytes (107.5 versus 161.0) and was very similar to that in purified parasites (107.5 versus 98.5). Large increases in palmitic acid (C16:0) (from 21.88% to 31.21%) and in oleic acid (C18:1) (from 14.64% to 24.60%), and major decreases in arachidonic acid (C20:4) (from 17.36% to 7.85%) and in docosahexaenoic acid (C22:6) (from 4.34% to 1.8%) occurred as a result of infection. The fatty acid profiles of individual phospholipid classes from IEPM resembled in many instances the fatty acid profiles of parasite phospholipids rather than those of uninfected erythrocytes. Analysis of IEPM from P. falciparum-infected erythrocytes (trophozoite stage) revealed that, during intra-erythrocytic maturation of the parasite, the host erythrocyte phospholipid composition was markedly refashioned. These alterations were not dependent on the method used to isolate the IEPM, with similar results obtained using either a saponin-lysis method or binding to Affigel beads. Since mature erythrocytes have negligible lipid synthesis and metabolism, these alterations must occur as a result of parasite-directed metabolism of erythrocyte lipids and/or trafficking of lipids between the parasite and erythrocyte membranes.
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PMID:Modification of host cell membrane lipid composition by the intra-erythrocytic human malaria parasite Plasmodium falciparum. 200 Dec 27

A programme emphasizing intensive training, use of protective equipment and uniforms, daily supervision of safety measures at work, and weekly monitoring of blood cholinesterase levels by the tintometric method was instituted to prevent toxicity in Haitian malaria workers during spraying with the organophosphate insecticides fenitrothion and malathion. The programme functioned well, depressed cholinesterase activity (</= 50% of normal) being detected rapidly prior to the development of serious symptoms. Evidence of fenitrothion overexposure appeared in spraymen early in the first spray cycle, and was associated with faulty protective clothing and a failure to observe strictly the recommended safety measures at work. After these deficiencies were corrected, insecticide application continued without serious incidents or interruption of the programme. No serious reduction of cholinesterase activity was seen in a more limited study of spraymen using malathion. It is strongly recommended that similar training and monitoring programmes should be instituted whenever organophosphate pesticides are used as residual sprays for malaria control. This is particularly important in areas where the more toxic compound, fenitrothion, is to be used.
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PMID:Safety measures associated with the use of organophosphate insecticides in the Haitian malaria control programme. 387 15

Measurement of blood cholinesterase activity and of the urinary metabolites of fenitrothion (p-nitrocresol) and malathion (monocarboxylic acid) was used to assess the exposure to these insecticides of workers in the Haitian malaria control programme and of residents in the sprayed houses. Cholinesterase activity was significantly reduced at the end of the working week in 3 out of 28 fenitrothion workers. Urinary levels of p-nitrocresol (PNC) in the spraymen ranged from 2.2 to 25.2 mg/l. In fenitrothion workers who had no direct contact with spraying (weighers and supervisors), the cholinesterase activity remained >/= 75% of the normal control value, and the urinary PNC levels were relatively low. Urinary malathion monocarboxylic acid (MCA) levels at the end of the working week ranged between 1.1 and 5.3 mg/l in workers using malathion and their blood cholinesterase activity remained essentially normal. In both groups of workers the cholinesterase levels improved and the urinary excretion of metabolites decreased after 2 days of rest from the spraying operations. In the residents of the sprayed houses, low concentrations of PNC and MCA were detected in the urine 1 day after spraying and measurable but reduced levels were still present after 7 days. In all these cases the cholinesterase activity remained >/= 75% of the normal control value.
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PMID:Assessment of exposure to organophosphate insecticides during spraying in Haiti: monitoring of urinary metabolites and blood cholinesterase levels. 387 16

Serum cholinesterase (CHE) and acetylcholinesterase (ACHE) in cerebrospinal fluid (CSF) were determined simultaneously in 30 patients with P. falciparum cerebral malaria. Nineteen patients (63%) had low serum CHE and mean value of this serum enzyme in 30 patients was significantly lower than that of non-infected group. CSF ACHE levels were found to be significantly lower than those of normal subjects reported earlier. Post-treatment in the hospital for one week, both serum CHE and CSF ACHE levels in 9 convalescent subjects increased significantly. These findings indicated that both serum CHE and CSF ACHE levels were depressed in patients with cerebral malaria and increased on recovery.
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PMID:Acetylcholinesterase activities in cerebrospinal fluid of patients with Plasmodium falciparum cerebral malaria. 391 1

During an operational field-trial which was conducted as a part of the WHO Programme for Testing and Evaluating New Insecticides, a study of the safety of o-isopropoxyphenylmethylcarbamate (OMS-33) was carried out. Clinical observations associated with biochemical studies were performed. Minor reactions to over-exposure to OMS-33 were recorded among some spraymen and a few inhabitants. Their incidence was, in operators, mainly associated with heavy skin contamination and insufficient washing during work, or, in inhabitants, with entering the house while it was being sprayed. No cumulative inhibitory effect could be demonstrated on whole-blood or plasma cholinesterase in operators during the 6-week exposure. A pronounced fall in whole-blood cholinesterase activity during the work and a distinct recovery after exposure ceased was established as a daily pattern of the enzyme's activity fluctuation, erythrocyte cholinesterase being much more sensitive to OMS-33 than plasma cholinesterase. In view of the very marked symptomless daily fluctuation in cholinesterase activity and the absence of cumulative inhibitory effect, the conclusion was reached that routine cholinesterase determination has little if any practical value as an early indication of serious exposure to OMS-33. Minor complaints, from which recovery is rapid, serve as an early indication of over-exposure.OMS-33 can be used safely in malaria eradication programmes provided proper attention is paid to the exercise of those measures of general and personal hygiene which should be practised in any spraying programme.
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PMID:A study of the safety of O-isopropoxyphenylmethylcarbamate in an operational field-trial in Iran. 530 52


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