Gene/Protein Disease Symptom Drug Enzyme Compound
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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

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

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

An operational-scale trial, using residual fenitrothion, for control of malaria was carried out in Central Java, Indonesia, from 1980 to 1982. Two areas, each comprising about 70 km(2) and a population of about 50 000, were treated with fenitrothion (40% water dispersible powder) at a target dosage of 2 g/m(2) for 3 cycles at 6-monthly intervals. One area was treated with full coverage (i.e., the interiors of houses and cattle shelters were sprayed to a height of 3 m) for 2 cycles, followed by a third cycle with selective coverage (i.e., the interiors of houses were sprayed with one 75 cm horizontal swath between 10 cm and 85 cm from the floor while the cattle shelters were sprayed to a height of 3 m). The other area was treated for 3 cycles with only selective coverage. While both treatment methods reduced malaria rates and vector populations to very low levels, the full coverage treatment was more rapidly effective and also reduced the Plasmodium falciparum index. However, the selective coverage treatment was 68% less expensive than full coverage and greatly reduced the degree of cholinesterase depressions among the spraymen. The trial also showed that a dosage of 1 g/m(2) with full coverage was nearly as effective as the 2 g/m(2) dosage.
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PMID:Malaria control with residual fenitrothion in Central Java, Indonesia: an operational-scale trial using both full and selective coverage treatments. 639 17

The involvement of the brain, lungs and kidneys was studied in a lethal rat malaria. Lewis inbred rats were infected with Plasmodium berghei K173. The disease proved fatal within 10-14 days. Parasitaemia showed an increase of up to 43% parasitised red blood cells on Day 10 p.i. The haematocrit decreased from 50% to 12%. The systolic blood pressure dropped from 99 to 56 mmHg. The lactate dehydrogenase activity rose to 2,543 U/l. BUN and serum creatinine doubled during the course of the disease. The transaminases increased tenfold and the cholinesterase decreased from 943 U/l to 271 U/l. Morphologically the kidneys showed an immune complex glomerulo-nephritis with a normal tubulo-interstitial system. The brain, heart and lungs were normal by light microscopic examination. Marked anaemia and shock were the main causes of death in the above-mentioned specimen rat, showing that the course of the disease is significantly different from lethal infections in humans with Plasmodium falciparum who show severe pulmonary, renal and cerebral complications.
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PMID:Causes of death in lethal rat malaria. 661 21

Serum cholinesterase activities were determined in 87 patients of both sexes with P. falciparum malaria in comparison to those of 80 blood donors. Patients with acute P. falciparum malaria had significantly lower serum cholinesterase activity than those of the control group. After treatment, their serum cholinesterase levels returned to the normal level. Serum albumin concentration also showed the same pattern and had a direct relationship to those of serum cholinesterase levels. These findings indicated that malarial parasites had some effect on the liver cells which resulted in impaired hepatic synthesis of serum cholinesterase and albumin concentrations. This result therefore add new information that there was a disturbance of enzyme cholinesterase among many liver enzymes that have been shown to be altered during an acute malarial attack.
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PMID:Serum cholinesterase activity in patients with malaria infection. 701 93

Five reference laboratories were established in Pakistan for monitoring cholinesterase (ChE) activities of workers exposed to organophosphorus compounds. ChE activities were determined by the Michel and tintometric method. Observations of ChE activities were made during two malaria seasons. The first season showed that although a significant depression of cholinesterase occurred among some of the workers, the ChE activities of workers were within the normal range during the following season. The reason for the difference is discussed. Similar studies were undertaken in Haiti. Mean and standard deviations (SD) were calculated for comparison of the tintometric versus the Michel method. The data show a correlation between the methods. For further evaluation of the tintometric method, organophosphorus and oxon analog inhibition of cholinesterase were determined in vitro. The tabulated data show that the tintometric method is adequate for determining whether a worker is exposed to dangerous amounts of insecticides.
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PMID:Cholinesterase activities of workers exposed to organophosphorus insecticides in Pakistan and Haiti and an evaluation of the tintometric method. 707 53


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