Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet.

BACKGROUND: In endemic communities, zoonotic tungiasis, a severe skin disease caused by penetrating female sand fleas, is a public health hazard causing significant human and animal morbidity. No validated drugs are currently available for treatment of animal tungiasis. Due to the reservoir in domestic animals, integrated management of human and animal tungiasis is required to avert its negative effects. METHODS AND PRINCIPAL FINDINGS: A topical aerosol containing chlorfenvinphos 4.8%, dichlorphos 0.75% and gentian violet 0.145% licensed to treat tick infestations, myiasis and wound sepsis in animals in the study area, was tested for its potential tungicidal effects in a randomized controlled field trial against pig tungiasis in rural Uganda. Animals with at least one embedded flea were randomized in a treatment (n = 29) and a control (n = 26) group. One week after treatment, 58.6% of the treated pigs did not show any viable flea lesion whereas all control pigs had at least one viable lesion. After treatment the number of viable lesions (treated median = 0, overall range = 0-18 vs. control median = 11.5, range = 1-180) and the severity score for estimating acute pathology in pig tungiasis (treated median = 1, range = 0-3.5 vs. control median = 7, range = 0-25) were significantly lower in treated than in control pigs (p < 0.001). In the treatment group the median number of viable flea lesions decreased from 8.5 to 0 (p < 0.001). Similarly, the median acute severity score dropped from 6 to 1 (p < 0.001). Every pig in the treatment group showed a decrease in the number of viable fleas and tungiasis-associated acute morbidity while medians for both increased in the control group. CONCLUSIONS: The study demonstrates that a topical treatment based on chlorfenvinphos, dichlorphos and gentian violet is highly effective against pig tungiasis. Due to its simplicity, the new approach can be used for the treatment of individual animals as well as in mass campaigns.

[Serum immunoglobulin E concentration in workers producing chlorfenvinphos]. / Stezenie immunoglobulin E w surowicy pracowników zatrudnionych przy produkcji chlorfenwinfosu.

Organophosphorous pesticides exert sensitizing effects. Our investigations in workers of the chlorfenvinphos production department showed frequent incidence of the upper respiratory tract allergy as well as diminished specific airways conductance. The aim of the study is to assess serum immunoglobulin E concentration in the workers of the chemical plant department producing chlorfenvinphos. The study covered the entire staff of the department:--35 men aged 25-55 years, employed for 1-15 years. Chronic bronchitis was diagnosed in 13 (37.1%) workers; in none of the subjects examined bronchial asthma was found. Spirometry showed a lower Tiffeneau's index in 5 (14.3%) and impaired specific airways conductance in 11 (31.4%) workers. Air chlorfenvinphos concentration in the work environment did not exceed MAC level, the average concentration was 0.0008-0.0018 mg/m3, and the erythrocyte acetylcholinesterase activity was within normal range. Serum IgE concentration was evaluated with the enzyme immunoassay (Enzymun-Test IgE from Boehringer, Cat. No. 1289071), the results were compared with those of a control group of 30 healthy male inhabitants of the region, professionally not exposed to chemical noxes. Mean serum IgE concentration in the workers (109.6 +/- 120.0 IU/ml) was significantly (p < 0.01) higher as compared to the control group (51.1 +/- 36.4 IU/ml). In 14 (40.0%) workers the IgE concentration exceeded 100 IU/ml, whereas in the control group only in 4 (13.3%) people the IgE level was elevated. The results of our investigations provide support for an essential role of type I hypersensitivity reaction in the pathogenesis of inflammatory changes in the respiratory system caused by chlorfenvinphos.

Long-term effects of acute exposure to chlorphenvinphos on behavioural responsiveness to amphetamine and scopolamine in rats.

We investigated the effect of acute exposure to chlorphenvinphos (CVP) (2-chloro-1 (2,4-dichlorophenyl)-vinyl-diethyl-phosphate), an organophosphate anticholinesterase, on the amphetamine- and scopolamine-induced open-field locomotion in Wistar rats. CVP was administered at a single i.p. dose of 1.0 mg/kg (1/10 of LD50). In part of the rats cholinesterase (ChE) was determined. Three hours after CVP injection, the ChE activity decreased by about 27%. It returned to the preinjection level within 14 days after the exposure. In the behavioural part of the experiment, the animals were challenged with 1.0 mg/kg amphetamine or 0.75 mg/kg scopolamine three weeks after CVP exposure, i.e. after a period of time sufficient for cholinesterase recovery. It has been found that in the CVP-exposed rats, the behavioural responses to amphetamine or scopolamine challenge (the increase in locomotor activity) was significantly reduced compared to the controls. This suggests that acute exposure to CVP produced an increase in cholinergic activity which persisted long after ChE activity had returned to normal.

Impaired respiratory muscle function in chemical plant workers producing chlorfenvinphos.

All employees of a chemical plant division producing chlorfenvinphos were studied, i.e. 35 males aged 25-57 years (mean 42.1); their employment period ranged from 1-15 years (mean 9.0). Chronic bronchitis was diagnosed in 13 workers (37.1%). Mean air chlorfenvinphos concentrations in the work environment estimated with gas-liquid chromatography were from 0.0008-0.0018 mg/m3 (maximum allowable concentration according to Polish standards is 0. 01 mg/m3). The activity of erythrocyte acetylcholinesterase was similar to that observed in people who were not exposed to chemicals, however, a slightly lowered activity of plasma cholinesterase in the studied population was evidently the result of mild liver impairment. Spirometric investigations performed in the studied workers revealed slight alterations manifested by increased intrathoracic gas volume (ITGV) (the value of the index was 138.6% of the mean value, 24 workers with an abnormally high index), as well as by decreased specific airway conductance (sGaw); its mean value in the studied group was 58.5% of the mean standard (11 people showed an abnormal index). Substantial functional changes were found in the respiratory muscles. Maximal inspiratory pressures (MIP = 97. 2 +/- 28.3 cm H2O) as well as maximal expiratory pressures (MEP = 113.9 +/- 44.2 cm H2O) in the studied group were significantly lower (p < 0.01) as compared to those observed in the control group (MIP = 120.7 +/- 31.7; MEP = 154.4 +/- 40.2 cm H2O) of 22 males having similar cigarette smoking habit, without occupational exposure to chemicals. It was also found that the people who had worked for more than 10 years under conditions of exposure to chlorfenvinphos showed significantly lower (p < 0.05) values of maximal inspiratory pressure (87.2 +/- 28.06 cm H2O, n = 17) compared to the workers whose period of employment was shorter than 10 years (106.6 +/- 26.8 cm H2O, n = 18). The two groups were comparable with regard to age and smoking habits. The values of maximal expiratory pressures were similar in both groups. No essential disturbances in neuro-muscular transmission were observed; only in 3 workers (8.5%) the electrostimulating myasthenic test showed some disturbances in neuro-muscular transmission. It seems that respiratory muscles impairment in humans exposed to chlorfenvinphos results from changes in the metabolism and structure of muscles, and partly from lung hyperinflation.

[Changes in rats liver in late period of intoxication with chlorphenvinphos in a single dose]. / Zmiany w watrobie szczura w póznym okresie zatrucia chlorfenwinfosem w dawce jednorazowej.

The present investigation was undertaken to study the effect of chlorphenvinphos on the activity of liver enzymes in acute poisoning with this compound. The investigation was carried out on male Wistar rats. The animals received oil--control group and oil solution of chlorphenvinphos in dose 0.5 or 0.1 LD50--the examined group, intragastrically. Material for examination was collected in the 48 h after intoxication. Activity of GOT and GPT in a serum, cytosolic and mitochondrial fractions of liver; BGR and AcP in a serum and lysosomal fraction of liver, ChE in a serum and concentration of lactate in the cytosolic fraction of liver were assayed. It can be concluded that in the 48 h after intoxication with chlorphenvinphos, activity of ChE was normalized in the case of lower dose and has such tendency in the case of higher dose. The changes of other assayed parameters in the serum and liver homogenate indicates that in this period of study, the liver is in point of no return.

Biochemical evaluation of the liver function in workers employed at the production of chlorfenvinphos.

In order to assess the liver damage caused by chlorfenvinphos, all the workers employed at the production of this compound were examined twice, 9 years apart. Serum concentration of bilirubin, protein components and the activity of some selected enzymes--red blood cell acetylcholinesterase (AChE), serum alkaline phosphatase (AP), gamma-glutamyltranspeptydase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and malic dehydrogenase (MDH) were determined in 41 males on the first examination. On the second examination serum bilirubin concentration and the activity of AChE, ChE, AP and ALT were determined in 35 males. As compared to the results obtained in control groups the first study showed that a lower concentration of serum proteins was accompanied by decreased globulin alpha 1 and beta percentage along with an increased globulin gamma percentage; bilirubin concentration and the activity of ALT, AST, and MDH were higher, whereas the activity of AP, GGT and AChE was lower. The results of the second study were similar--lowered activity of ChE and AP, and increased ALT activity. The results of the investigation provide support for a very slight impairment of the liver parenchyma.

Release of interleukin-1 beta from peripheral blood monocytes and its concentration in the blood serum of the workers employed at the production of chlorfenvinphos.

Our earlier investigations of people exposed to chlorfenvinphos revealed obstructive impairment of pulmonary function and changes in collagen metabolism. In order to evaluate the role of interleukin-1 beta in the development of these changes the serum interleukin-1 beta concentration and the ability of spontaneous and LPS stimulated production of interleukin-1 beta by monocytes were determined in 25 males aged 33-54 years and employed at the department producing chlorfenvinphos (its air concentration did not exceed permissible levels). Higher spontaneous production of interleukin-1 beta was found; the remaining parameters did not differ significantly as compared to the control group of 23 healthy males.

Biological indicators for the assessment of human exposure to organophosphorous compounds.

UNLABELLED: The aim of the present study is to review selected biological effects of organophosphorous compounds used as pesticides and to discuss their significance in terms of occupational exposure. The results of a long-term study of the red cells and plasma ChE in group of workers engaged in the production of pesticides are also presented. Cholinesterase activity in plasma and red blood cells was determined spectrophotometrically by the Ellman modified method. Occupational exposure to pesticides was analysed by the Durham and Wolf method. CONCLUSIONS: 1. Cholinesterase activity in blood serum of the workers employed at the production of organophosphorous compounds is statistically significantly lower, compared to the control group and the lower accepted standard limit. 2. Cholinesterase activity in plasma seems to be a more sensitive indicator of exposure, compared to the activity of enzyme contained in erythrocytes after a long-lasting exposure to low levels of organophosphorous compounds. 3. Changes in cholinesterase activity according to the level of exposure show a better correlation if the exposure is expressed in % of the toxic dose/day than in mg/day. Toxicological properties of organophosphorous compounds are of the great importance for this correlation.

[Evaluation of respiratory tract function in workers employed in the production of Enolophos]. / Ocena stanu ukladu oddechowego u pracowników zatrudnionych przy produkcji Enolofosu.

An analysis of the respiratory function of workers of a chemical factory producing Enolophos was carried out. All workers were included in the study-41 men (age range 23-59 years, mean working duration 4.9 years). In 48.8% chronic bronchitis was diagnosed. Spirometric analysis was carried out using an electronical spirometer with a steady volume plethysmograph. The following along with other pulmonary mechanics parameters were assessed: compliance, airway resistance. An increase of the FEV1%VC index was seen in 34.2% and RV/TLC in 40%. Compliance was increased in 30%. Airway resistance was increased especially in subjects with chronic bronchitis and a decrease in FEV1, FEV1%VC, FEF50, FEF25 rates. In patients with decreased erythrocyte acetylcholinesterase activity only increased airway resistance was seen. The duration of working in this factory did not affect respiratory function. The results demonstrate a harmful effect of Enolophos to the lungs and airways.