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PubMed1999

Oral ivermectin in the treatment of scabies.

One hundred and twenty scabietic patients attending the outpatient clinic of the Department of Dermatology, Mansoura University Hospital, voluntarily participated in this uncontrolled, open label study to evaluate ivermectin 20 microg/kg as a scabietic after they had given their consent. The scabietic subjects included in this study were otherwise healthy, mentally competent, aged more than 18 years, and used no topical antiscabietic treatment in the week before ivermectin treatment, or during the 4-week study period. Patients were also required to show clinical evidence of scabies, and the microscopically demonstrated presence of Sarcoptes scabiei, their eggs, or their fecal pellets (scybala). A thorough history was taken, and a physical examination was conducted that included measurement of the pulse, blood pressure, temperature, and weight. For each participant, the distribution of scabies lesions was plotted on a body diagram, and the severity of disease was recorded as mild (10 or fewer lesions), moderate (11-49 lesions), or severe (50 or more lesions). Skin scrapings were examined for mites, eggs, or scybala. Urinalysis, stool analysis, a complete blood count, prothrombin time, and serum chemistry studies (serum creatinine, alanine aminotransferase (ALT), and total bilirubin) were performed before treatment, and 2 and 4 weeks after the drug was given. Ivermectin was administered as scored 6-mg tablets with water, and the dose was designed to provide 200 micrograms/kg (ivermectin was provided by Delta Pharma, Tenth of Ramadan City, Egypt). The patients were instructed to have recently worn clothing, sheets, and towels washed in a hot cycle the day after treatment. The patients were interviewed 3 days after treatment about any symptoms or subjective evidence of adverse reactions. Follow-up examinations were carried out 2 and 4 weeks after intake of ivermectin, and all examination procedures and laboratory investigations were repeated. Cure criteria included absence of nocturnal itching as well as dermatologic evidence of scabies, and negative skin scraping. Patients showing evidence of active scabies or having new lesions during the follow-up visits were given a second dose of ivermectin. All members of the household and immediate family were treated with either topical 5% permethrin cream or 1% gamma benzene hexachloride to reduce the chance of reinfestation.

Administration, Oral↗
PubMed2003

Efficacy of mosquito nets treated with a pyrethroid-organophosphorous mixture against Kdr- and Kdr+ malaria vectors (Anopheles gambiae).

In order to prevent the resistance of Anopheles gambiae s.l. to pyrethroids from spreading too quickly and to lengthen the effectiveness of insecticide impregnated mosquito nets, it has recently been suggested to use mixtures of insecticides that have different modes of action. This study presents the results obtained with tulle mosquito nets treated with bifenthrin (a pyrethroid) and chlorpyrifos-methyl (an organophosphorous) both separately and in mixture on two strains of An. gambiae, one sensitive to all insecticides, and the other resistant to pyrethroids. The values of KDt50 and KDt95 and the mortality induced with the mixture of bifenthrin (25 mg/m2) and chlorpyrifos-methyl (4.5 mg/m2) show a significant synergistic effect on the strain of An. gambiae susceptible to insecticides. However, the tested combination does not induce any synergistic effect on the VKPR strain selected with permethrin, but only enhances the effectiveness of the two insecticides taken separately.

Animals↗
PubMed2000

Outbreak of scabies in Norwegian nursing homes and home care patients: control and prevention.

Over a period of five months (October 1998-February 1999), an outbreak of scabies affected 19 persons associated with a nursing home in Oslo, Norway. Scabies was diagnosed in 13 patients; six long-term patients, five short-term patients also cared for at home, and two home care patients associated with the same institution. Six healthcare workers who had assisted with infected patients in their own homes were also diagnosed with scabies. Two separate index cases were found. Both had had pruritus for several months, diagnosed as eczema, and were repeatedly treated at dermatology outpatient clinics before the diagnosis was made. Both index cases were cared for at home and in the nursing home (short-term). Repeated treatments with permethrin were tried before effective treatment with benzyl benzoate. Altogether 370 persons (patients, staff, relatives) were treated. In June-July 1999, scabies was diagnosed in two other nursing homes; six patients or staff, and 156 persons were treated. Patients with scabies were contact isolated and disinfection and cleaning was performed. Simultaneous treatment and washing or disinfection of clothing, bedding and environment of all potentially affected individuals is imperative to control an outbreak of scabies.

Adult↗
PubMed2004

[Interdisciplinary diagnostics in the outpatient treatment department of an environmental medical centre - report on experience with 400 patients].

The medical diagnostics of 400 patients of an interdisciplinary environmental medical centre is presented. The basic diagnostics included a special environmental medical history using a questionnaire, physical examination, allergological examinations and human biomonitoring. The latter was carried out in order to quantify the internal exposure to environmental pollutants. The main focus was on the differential diagnostics which was supported by special medical divisions of the hospital. Allergic illnesses as well as results of human biomonitoring exceeding the reference ranges were found frequently. Unfortunately a link between external exposure, internal dose and symptoms can hardly be established in environmental medicine. However, in several cases we found a considerably increased internal exposure which allowed to identify the sources of exposure (for example, usage of dichlorobenzene, permethrin, pentachlorophenol). Eliminating the sources obviously improved the health status of some of the patients concerned.

Adolescent↗
PubMed2005

Enantioselectivity in environmental safety of current chiral insecticides.

Chiral pesticides currently constitute about 25% of all pesticides used, and this ratio is increasing as more complex structures are introduced. Chirality occurs widely in synthetic pyrethroids and organophosphates, which are the mainstay of modern insecticides. Despite the great public concerns associated with the use of insecticides, the environmental significance of chirality in currently used insecticides is poorly understood. In this study, we resolved enantiomers of a number of synthetic pyrethroid and organophosphate insecticides on chiral selective columns and evaluated the occurrence of enantioselectivity in aquatic toxicity and biodegradation. Dramatic differences between enantiomers were observed in their acute toxicity to the freshwater invertebrates Ceriodaphnia dubia and Daphnia magna, suggesting that the aquatic toxicity is primarily attributable to a specific enantiomer in the racemate. In field sediments, the (-)enantiomer of cis-bifenthrin or cis-permethrin was preferentially degraded, resulting in relative enrichment of the (+)enantiomer. Enantioselective degradation was also observed during incubation of sediments under laboratory conditions. Enantioselectivity in these processes is expected to result in ecotoxicological effects that cannot be predicted from our existing knowledge and must be considered in future risk assessment and regulatory decisions.

Animals↗
PubMed2004

Identification, expression, and purification of a pyrethroid-hydrolyzing carboxylesterase from mouse liver microsomes.

Carboxylesterases are enzymes that catalyze the hydrolysis of a wide range of ester-containing endogenous and xenobiotic compounds. Although the use of pyrethroids is increasing, the specific enzymes involved in the hydrolysis of these insecticides have yet to be identified. A pyrethroid-hydrolyzing enzyme was partially purified from mouse liver microsomes using a fluorescent reporter similar in structure to cypermethrin (Shan, G., and Hammock, B. D. (2001) Anal. Biochem. 299, 54-62 and Wheelock, C. E., Wheelock, A. M., Zhang, R., Stok, J. E., Morisseau, C., Le Valley, S. E., Green, C. E., and Hammock, B. D. (2003) Anal. Biochem. 315, 208-222) and subsequently identified as a carboxylesterase (NCBI accession number BAC36707). The expressed sequence tag was then cloned, expressed in baculovirus, and purified to homogeneity. Kinetic constants for a large number of both type I and type II pyrethroid or pyrethroid-like substrates were determined. This esterase possesses similar kinetic constants for cypermethrin and its fluorescent-surrogate (k(cat) = 0.12 +/- 0.03 versus 0.11 +/- 0.01 s(-1)). Compared with their cis- counterparts, trans-permethrin and cypermethrin were hydrolyzed 22- and 4-fold faster, respectively. Of the four fenvalerate isomers the (2R)(alphaR)-isomer was hydrolyzed at least 1 order of magnitude faster than any other isomer. However, it is unlikely that this enzyme accounts for the total pyrethroid hydrolysis in the microsomes because both isoelectrofocusing and native PAGE indicate the presence of a second region of cypermethrin-metabolizing enzymes. A second carboxylesterase gene (NCBI accession number NM_133960), isolated during a cDNA mouse liver library screening, was also found to hydrolyze pyrethroids. Both these enzymes could be used as preliminary tools in establishing the relative toxicity of new pyrethroids.

Animals↗
PubMed2003

Pyrethroids used indoors--biological monitoring of exposure to pyrethroids following an indoor pest control operation.

A prospective epidemiological study with respect to pyrethroid exposure was carried out combining clinical examination, indoor monitoring and biological monitoring. The results of the biological monitoring are presented. Biological monitoring was performed in 57 persons before (T1) as well as 1 day (T2), 3 days (T3), 4-6 months (T4), and 10-12 months (T5) following a pest control operation (PCO) with pyrethroid containing products such as cyfluthrin, cypermethrin, deltamethrin or permethrin. Pyrethroids in blood were measured by GC-ECD. The respective metabolities cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (DBCA), 3-phenoxybenzoic acid (3-PBA) and fluorophenoxybenzoic acid (FPBA) were measured in urine using GC/MS. For all cases the concentrations of pyrethroids in blood were found to be below the detection limit of 5 micrograms/l before and after the PCO. With a detection limit of 0.2 microgram/l of the investigated metabolites, the percentage of positive samples were 7% for cis-DCCA, 3.5% for trans-DCCA and 5.3% for 3-PBA before PCO. One day after PCO (T2) the percentage of positive samples increased remarkably for cis-DCCA (21.5%), trans-DCCA (32.1%) and 3-PBA (25%) showing significantly increased internal doses as compared to pre-existing values. This holds also true for T3, whereas at T4 and T5 the significant increase was no more present. FPBA and DBCA concentrations were below the respective detection limit before PCO and also in most cases after PCO. In 72% of the subjects the route of pyrethroid uptake (measured by determining the DCCA isomeric ratio) was oral/inhalative and in 28% it was dermal. Based on the biological monitoring data it could be shown that appropriately performed pest control operations lead to a significant increase of pyrethroid metabolite concentration in the early phase (1 and 3 days) after pyrethroid application as compared to the pre-exposure values. However, evaluated metabolite concentrations 4-6 months after PCO did not exceed values of published background levels.

Adult↗
PubMed1989

Sporozoite antibodies and malaria in children in a rural area of The Gambia.

Sporozoite antibody levels were measured in a group of children aged one to nine years resident in a rural area of The Gambia, using an ELISA to the repeat peptide (NANP)40. The prevalence and titre of antibodies varied with age but not with sex or ethnic group. Significant variations in prevalence were recorded within a group of adjacent villages. Children who were seropositive at the beginning of the dry season had higher spleen and parasite rates both at this time and at the end of the subsequent rainy season than did seronegative children, suggesting that they were exposed more frequently to infection. However, seropositive children had fewer episodes of fever accompanied by high levels of parasitaemia than did seronegative children, suggesting that they had a greater degree of clinical immunity. No differences were found in seroprevalence rates or in mean antibody titres between children who slept under conventional or Permethrin treated bed nets and those who did not, even though bed nets significantly reduced the number of bites by vector mosquitoes.

Age Factors↗
PubMed1993

Plasmodium falciparum sporozoite and entomological inoculation rates at the Ahero rice irrigation scheme and the Miwani sugar-belt in western Kenya.

Anopheles arabiensis and An. funestus were collected by pyrethrum spray sheet collections in houses and by human-bait catches at a village in western Kenya adjacent to the Ahero rice irrigation scheme; and using the same methods, An. gambiae s.l. and An. funestus were collected at Miwani, a village in the sugar-cane belt. Plasmodium falciparum sporozoite rates were determined by ELISA. At Ahero the mean sporozoite rates were 1.1% and 4.3% in An. arabiensis and An. funestus, respectively, while at Miwani the rates were 6.0% in An. gambiae s.l. and 4.3% in An. funestus. Entomolgoical inoculation rates (EIR) were derived from both human-bait collections (IR-HBC) and by the proportion of human blood-fed females caught resting indoors (IR-HBF). The IR-HBF appeared to be a more realistic index of EIR. At Ahero and Miwani people were exposed to an average of 416 and 91 infective bites/person/year, respectively. The main vectors were An. funestus at Ahero and An. gambiae s.l. at Miwani. In view of the intense and perennial malaria transmission at Ahero, vector control by insecticides should be considered, while at Miwani, where transmission is seasonal, permethrin-impregnated bed nets could be an alternative to indoor spraying. These measures must be augmented with availability of effective antimalarials.

Animals↗
PubMed1995

Entomological evaluation of the Gambia's National Impregnated Bednet Programme.

Entomological studies were conducted in paired study villages in three of the five study areas used for the epidemiological assessment of the Gambia's National Impregnated Bednet Programme. Baseline data collected in 1991 were compared with post-intervention data from 1992, when one of each village pair (from areas II, III and V) was included in the treatment programme in which villagers' nets were dipped in permethrin. In a longitudinal study, indoor-resting densities of Anopheles gambiae s.l. in the treated villages were significantly reduced, when compared with their paired untreated village, in areas II (t = 3.32, 13 degrees of freedom, P = 0.006) and III (t = 3.71, 13 degrees of freedom, P = 0.003). However, this was not associated with higher outdoor-biting rates in the evenings in the treated villages than in the controls. The reduction in vector population was most evident in area II, where the treated village was relatively isolated and 74% of the population slept under a treated net. Anopheles gambiae s.l. were also collected during two fortnightly periods in area V, where the sporozoite rates in 1991 had been relatively high (7.65% and 6.07%). There was no significant decrease in the sporozoite rate in the treated village in area V in 1992, despite the fact that this village was over 5 km from its nearest neighbouring village. However, the proportion of villagers sleeping under a treated net in this village was < 50%. No clear evidence for an epidemiologically significant 'mass killing effect', resulting from the village-wide use of treated nets, emerges in this or any other study undertaken in The Gambia. However, such an effect is indicated by results from Salikene, where the village mosquito population was relatively isolated and where the majority of the population slept under a treated net. This situation is unlikely to be repeated in most Gambian villages in the primary-health-care scheme, since treated and untreated villages are generally interspersed and the mosquito populations move freely between them. We must therefore conclude that, on a national scale, the nets provide an exceptionally high level of personal rather than community protection. The mechanisms underlying the personal protection are, however, still unclear.

Animals↗
PubMed1996

Self-protection from malaria vectors in Pakistan: an evaluation of popular existing methods and appropriate new techniques in Afghan refugee communities.

Experimental huts were used to measure the impact of several techniques for self-protection from malaria vectors in Pakistan. An electric fan, pyrethrum coils, untreated curtains, pyrethroid-vaporizing mats and permethrin-impregnated curtains reduced the total catches of blood-fed Anopheles stephensi by 27%, 36%, 47%, 56% and 65%, respectively. The most marked effect of all the interventions was in reducing the numbers of mosquitoes entering the huts, although all the techniques, except for the untreated curtain, also reduced the proportion of mosquitoes inside the hut which fed. Although the trends seen were similar for both anopheline (all An. stephensi) and culicine mosquitoes, they were more pronounced in the culicines. Social surveys were conducted on current self-protection practices. The social and economic constraints associated with each of the various techniques are discussed. All the strategies were shown to offer a degree of protection and their use should be encouraged. Impregnated curtains seem especially promising. Pyrethroid-impregnated bednets have been widely promoted in eastern Afghanistan since 1991 and have the advantage of providing protection when people sleep outside during the summer. However, surveys show that some owners stop using their nets in late autumn, despite the continued risk of malaria. People should be encouraged to use their bednets as impregnated curtains rather than putting them into storage.

Afghanistan↗
PubMed2005

Evaluation of estrogenic activities of pesticides using an in vitro reporter gene assay.

The estrogenic activities of 32 pesticides in agricultural products were evaluated using the E-CALUX assay system developed by Xenobiotic Detection Systems Inc (North Carolina, USA). This system utilizes human ovarian carcinoma cells (BG1) stably transfected with an estrogen-responsive luciferase reporter gene plasmid. It was found that tolclofos-methyl, prothiofos, diazinon, Thiabenclazole (TBZ) and pyriproxyfen had estrogenic activity. Several pesticides are often present in agricultural products. Therefore the estrogenicity of the mixtures of two kinds of pesticides was evaluated. The activity of diazinon/tolclofos-methyl, pyriproxyfen/prothiofos and TBZ/o-phenylphenol (OPP) was increased up to 1.2-5.3 fold. On the other hand, chlorfluazuron, imazalil and chlorfenapyr had anti-estrogenic activity. Further, to evaluate the change in the estrogenic activity of pesticide metabolites, an experimental system was established using a rat S9 mixture. Metabolites of permethrin and OPP had no estrogenic activity, but they had weak activity after the metabolism. On the other hand, the metabolites of TBZ exhibited less estrogenic activity than the original compounds.

Agriculture↗
PubMed2003

Percutaneous absorption of topical N,N-diethyl-m-toluamide (DEET): effects of exposure variables and coadministered toxicants.

Exposure to N,N-diethyl-m-toluamide (DEET) commonly occurs in the general population and has been implicated as a contributory factor to the Gulf War Illness. The focus of the present studies was to determine the effect of coexposure factors, potentially encountered in a military environment, that could modulate transdermal flux of topically applied DEET. Factors investigated were vehicle, dose, coexposure to permethrin, low-level sulfur mustard, occlusion, and simultaneous systemic exposure to pyridostigmine bromide and the nerve agent stimulant diisopropylfluorophosphate (DFP). Studies were conducted using the isolated perfused porcine skin flap (IPPSF), with a few mechanistically oriented studies conducted using in vitro porcine skin and silastic membrane diffusion cells. DEET was quantitated using high-performance liquid chromatography. The vehicle-control transdermal DEET flux in the IPPSF was approximately 2 micrograms/cm2/h for both 7.5 and 75% DEET concentrations, a value similar to that reported in humans. DEET absorption was enhanced by coinfusion of pyridostigmine bromide and DFP, by the presence of sulfur mustard, or by dosing under complete occlusion. The greatest increase in baseline flux was fivefold. In vitro diffusion cell studies indicated that silastic membranes had two orders of magnitude greater permeability than porcine skin, and showed vehicle effects on flux that were not detected in the IPPSF. These results suggest that coexposure to a number of chemicals that potentially could be encountered in a military environment may modulate the percutaneous absorption of topically applied DEET beyond that seen for normal vehicles at typically applied concentrations.

Administration, Cutaneous↗
PubMed1987

Comparison of the penetration of 14 pesticides through the skin of young and adult rats.

In vivo percutaneous absorption of 14 pesticides was studied in young (33-d-old) and adult (82-d-old) female Fischer 344 rats, at three different dose levels. Carbon-14-labeled pesticides in acetone were applied to previously clipped middorsal skin. The treatment area was 2-3% of the body surface area. Penetration of the pesticides during a 72-h period ranged from approximately 1%-90%, depending on compound, dose, and age of animal. No clear age-related pattern of dermal absorption among compounds was found. Only chlordecone, folpet, and permethrin did not show significant age-dependent differences in skin penetration. Atrazine, carbaryl, chlorpyrifos, and hexachloro-biphenyl had greater absorption in the young, while carbofuran, captan, dinoseb, DSMA, MSMA nicotine, and parathion displayed greater absorption in the adult. The majority of the compounds showed dose-dependent penetration. The dose-response curves for penetration were not parallel for 8 of the 14 compounds studied.

Age Factors↗
PubMed2004

Health effects of diazinon on a family.

There is increasing evidence of permanent sequalae from acute organophosphate poisoning. We report on accidental diazinon overexposure with acute organophosphate poisoning through cutaneous absorption and inhalation followed by persistent neurological effects. In addition, we observed skeletal and endocrine effects likely attributable to the diazinon poisoning. A family of seven was exposed to diazinon in June 1999 over a two-day period. The pesticide company mistakenly used diazinon to heavily spray the inside of the home instead of permethrin. The applicator applied the pesticide over the entire surface of the floor, carpeting, furniture, and clothing in closets to eradicate an infestation of fleas. Acute symptoms in the family members included headaches, nausea, skin irritation, runny nose, and vomiting. The family was first evaluated at 3 months and then 3 years after the acute poisoning. There were persisting neurological symptoms of memory loss, decreased concentration, irritability, and personality changes of varying degrees in all family members. Objective neurological findings of impaired balance, reaction time, color vision, slotted pegboards and trials making were present in the three older children who could be tested. Neuropsychological evaluation revealed evidence of organic brain dysfunction in all seven family members. Bone growth difficulties are present in four of five children. One child has delayed menarche.

Adult↗
PubMed2005

Human metabolism and metabolic interactions of deployment-related chemicals.

It has been suggested that chemicals and, more specifically, chemical interactions, are involved as causative agents in deployment-related illnesses. Unfortunately, this hypothesis has proven difficult to test, because toxicological investigations of deployment-related chemicals are usually carried out on surrogate animals and are difficult to extrapolate to humans. Other parts of the problem, such as the definition of variation within human populations and the development of methods for designating groups or individuals at significantly greater risk, cannot be carried out on surrogate animals, and the data must be derived from humans. The relatively recent availability of human cell.fractions, such as microsomes, cytosol, etc., human cells such as primary hepatocytes, recombinant human enzymes, and their isoforms and polymorphic variants has enabled a significant start to be made in developing the human data needed. These initial studies have examined the human metabolism by cytochrome P450, other phase I enzymes, and their isoforms and, in some cases, their polymorphic variants of compounds such as chlorpyrifos, carbaryl, DEET, permethrin, and pyridostigmine bromide, and, to a lesser extent, other chemicals from the same chemical and use classes, including solvents, jet fuel components, and sulfur mustard metabolites. A number of interactions at the metabolic level have been described both with respect to other xenobiotics and to endogenous metabolites. Probably the most dramatic have been seen in the ability of chlorpyrifos to inhibit not only the metabolism of other xenobiotics such as carbaryl and DEET but also to inhibit the metabolism of steroid hormones.

Drug Interactions↗
PubMed2006

Characteristics of pesticide pyrotechnic smoke devices.

Pesticide smoke generating products are widely used by amateurs and professionals but there is little published information available about their burn and deposition characteristics to enable the risks associated with using these devices to be assessed. This paper investigates their burn characteristics, deposition patterns, pesticide air concentrations and potential exposure to operators. Thirteen firings were carried out in different spaces with different ventilation conditions. Three types of devices were investigated: dicloran, permethrin and red dye. Pesticide air concentrations increased after firing, reaching a maximum determined by the room volume in approximately 10 min and decreasing exponentially as a result of ventilation and deposition. Ejected pesticide was present in the aerosol phase but there were only occasional traces of vapour. Settlement of pesticide was affected by surface orientation, height, sampling material and the pesticide-to-space volume ratio. The manufacturer's recommended treatment period for dicloran of 4 h followed by half an hour of ventilation may be insufficient to reduce pesticide to safe levels for re-entry under very calm conditions.

Air Pollutants↗
PubMed1996

Monitoring community response to malaria control using insecticide-impregnated bed nets, curtains and residual spray at Nsukka, Nigeria.

A project testing the efficacy of insecticide (permethrin)-impregnated bed nets, compared with impregnated door and window curtains, residual house spraying, and a control group was implemented in 12 village clusters in the Nsukka Local Government Area of Enugu State, Nigeria, using epidemiologic and entomologic indicators. The appropriate materials and services were given free to all families. During the first year of study, three monitoring exercises were carried out in a random selection of homes where children under 5 years of age resided. Information was collected on perceived effectiveness of the interventions, condition of nets and curtains, reasons for not sleeping under nets, and recall of steps required in caring for nets and curtains. Bed nets were perceived as more effective in reducing mosquito bites compared with the two other interventions. At the last monitoring period, which occurred a few weeks before a re-impregnation exercise, respondents also perceived bed nets to be most effective in preventing malaria. These findings coincided with epidemiologic evidence. Curtains, especially those at doors, were more likely to be torn and dirty than bed nets. Although holes would not reduce the effectiveness of the insecticide, they could reduce the 'beauty' of the curtains, a perceived benefit that initially attracted villagers to both curtains and nets. Bed net owners reported significantly less frequent use of other mosquito control measures in their homes than did members of the other groups. Finally, bed net users demonstrated increased knowledge of use and care steps than did those with curtains. These findings suggested a high level of social acceptability of bed nets, and point to the need to test their acceptability further under conditions where people would pay for nets and communities would manage distribution and re-impregnation systems.

Bedding and Linens↗