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The CNS toxicity of the insect repellent, diethyltoluamide (DEET), has been documented by several publications on severely affected adults and children. We report a 4-year-old boy with mental retardation, impaired sensorimotor coordination, and craniofacial dysmorphology, whose mother applied DEET daily throughout her whole pregnancy in addition to the prophylactic use of chloroquine.
Selected pharmaceuticals, among them analgesics, ss-blockers and anti-depressants as well as caffeine, the anti-bacterial triclosan and the insect repellent N,N-diethyl-3-toluamide (DEET) were determined in different sewage samples (sewage treatment plants, hospital effluents) from Tromsø/Norway and in seawater from Tromsø-Sound, into which the sewage is discharged. While caffeine, triclosan, ibuprofen and its major metabolites hydroxy- and carboxy-ibuprofen were present in all sewage samples, additional pharmaceuticals were observed in sewage containing hospital effluents. Concentrations were in the range of 20-293 microg/l (caffeine), 0.2-2.4 microg/l (triclosan) and 0.1-20 microg/l (sum ibuprofen + metabolites). In seawater, only caffeine (7-87 ng/l), DEET (0.4-13 ng/l) and ibuprofen + metabolites (sum concentration < LOQ-7.7 ng/l) were detected. Ibuprofen and its metabolites hydroxy- and carboxy-ibuprofen were quantified individually by use of the respective reference compounds. Relative amounts of the three compounds were determined in different types of water showing characteristic patterns, with hydroxy-ibuprofen being the major component in sewage whereas carboxy-ibuprofen was dominant in seawater samples. The patterns which were compared to those observed in similar samples from Germany indicated different transformation behaviour under limnic and marine conditions.
Malaria prevention has benefited from many diverse disciplines of research, including epidemiologic monitoring, development of laboratory techniques, assessment of insect repellents, or pharmaceutical innovations. Strategies in all these sectors have been explored in recent years, resulting in improved options to prevent travelers' malaria. The addition of atovaquone-proguanil for malaria chemoprophylaxis and the recommendation of primaquine as primary prophylaxis have been significant advances. Tafenoquine seems promising. Standby treatment recommendations have been refined. Many areas still need better strategies. Problematic areas include chemoprophylaxis for long-term travelers, expatriates, and pregnant women; optimal criteria for terminal prophylaxis; and the prevention of malaria in populations that are least likely to seek pretravel evaluations, such as those visiting friends and relatives in their home countries (VFRs). Finally, research in travel and tropical medicine should continue to focus on additional strategies to confront the ever-widening challenge of drug-resistant malaria.
Field ethnobotanical survey was undertaken for the period of 2002-2003 in the Tyrrhenian part of the Basilicata region of southern Italy. Data of 56 species of plants belonging to 29 families where gathered through interviews; among the species, 47 are used in human therapy, 6 as insect repellents, 15 in veterinary medicine, 1 for its ichthyotoxic properties and 3 for magic therapeutic purposes. The most important findings in ethnomedicine relate to Nasturtium officinale (renal colic, liver diseases), Foeniculum vulgare subsp. piperitum (mouth ulcers), Leopoldia comosa (toothache, headache), Micromeria graeca subsp. graeca (coughs) and Ceterach officinarum (malaria), while in the ethnoveterinary field, we have Pteridium aquilinum (wolf bites) and Spartium junceum (fractures of animal limbs).
Gulf War syndrome (GWS) is a perplexing multi-symptom condition comprising a constellation of signs and symptoms consistently described in the literature. These include muscle fatigue and tiredness, malaise, myalgia, impaired cognition, ataxia, diarrhoea, bladder dysfunction, sweating disturbances, headaches, fever, arthralgia, skin rashes, and gastrointestinal and sleep disturbances. Excessive chemical sensitivity and odour intolerance is reported. Epidemiological analysis suggests association with pyridostigmine bromide (PB) use as nerve gas prophylaxis, insect repellent, certain vaccination regimes, a variety of possible chemical exposures and physical and psychological stress. Pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) are potent vasoactive (vasodilatory) neuropeptides (VNs) having pleiotropic functions as immunomodulators, neuroregulators and hormones. VNs also have neurotrophic and anti-apoptotic roles. VNs act on G protein-coupled receptors (GPCRs) to activate adenylate cyclase, an important step in cyclic AMP metabolism. Autoimmune dysfunction of these VNs or their receptors is postulated to give rise to fatigue-related conditions such as chronic fatigue syndrome (CFS). Complex mechanisms involving heat shock proteins (hsps) and cytosine-guanine dinucleotide (CpG) DNA fragments may also be associated with autoimmunity to VNs or their GPCRs in contributing to fatigue-related conditions. Dysfunction of certain VNs may be the missing link in explaining the nebulous nexus between PB and GWS. This paper explores a possible link between exposures to PB and other chemical, physical and psychological stressors in producing a fatigue-related illness possibly related to autoimmune dysfunction of certain VNs. Treatment options involving restoration of VN function are considered in the context of analogues with other neurotransmitter fatigue-related conditions such as myasthenia gravis (MG). While evidence associating these conditions is thin, vasoactive neuropeptide neurotransmitters of the VIP/PACAP family have acetylcholine co-transmission functions via specific GPCRs. Autoimmune reactions to these receptors may have parallels with muscarinic (e.g., Sjogren's syndrome) and nicotinic (e.g., MG) acetylcholine neurotransmission. Hence theoretically, treatment options such as thymectomy, corticosteroids, plasma exchange, anti-idiotype antibodies and receptor genomic expression reactivation/suppression may be considered. Paradoxically pyridostigmine may prove to have a role in therapy although VN treatment/replacement may be associated with tachyphylaxis.
Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. Our previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 h ranged from 54.9 +/- 4.7 for the no sunscreen control to 86.9 +/- 2.5 for padimate-o. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D.
A questionnaire survey of malaria chemoprophylaxis knowledge, attitudes, and practices of 90 expatriates on a Mali mine yielded 68 (75.5%) responses. A total of 49 (72%) subjects took perennial chemoprophylaxis, 6 (9%) were children <5 years. Out of 68, 13 (19%) took chemoprophylaxis during the high transmission season only and 10 (15%) never took chemoprophylaxis. Reasons advanced for not taking chemoprophylaxis were concern over adverse effects, presumed immunity from long term residence in Africa, and on site access to quality medical care. Chemoprophylactics used were: atovaquone-proguanil 1 (2%); chloroquine and proguanil 15 (30%); doxycycline 16 (33%); mefloquine 17 (35%). Thirteen out of 49 (27%) subjects admitted to missing chemoprophylaxis doses and 15/68 (22%) had suffered malaria while on chemoprophylaxis. Fifteen out of 49 (31%) low season chemoprophylaxis users and 4/19 (21%) non-users contracted low season malaria (chi(2), p=0.63). A total of 46 (68%) used insect repellants, 50 (74%) used insecticide sprays or coils in rooms, 9 (13%) slept under insecticide treated nets. Malaria control in expatriates requires improvement; additional strategies for consideration that require reduced compliance requirements by expatriates are suggested, including residual spraying, seasonal chemoprophylaxis use, and emergency stand by medication.
The biodegradation of selected non-adsorbing persistent polar pollutants (P(3)) during wastewater (WW) treatment was studied by comparing a lab-scale membrane bioreactor (MBR) running in parallel to activated sludge treatment (AST). The investigated P(3) are relevant representatives or metabolites from the compound classes: pesticides, pharmaceuticals, insect repellents, flame retardants and anionic surfactants. Analyses of all these P(3) at low ng L(-1) levels with sufficient standard deviations was performed in WW influents and effluents. Non-degradable micropollutants, such as EDTA and carbamazepine were not eliminated at all during WW treatment by any technique. However, the MBR showed significant better removals compared to AST for the investigated poorly biodegradable P(3), such as diclofenac, mecoprop and sulfophenylcarboxylates. An application of such an in terms of sludge retention time optimised MBR may lead to a reduction of these P(3) in the watercycle.
After observing an apparent increase in severe falciparum malaria among travellers returning from The Gambia to the United Kingdom (UK) in the last quarter of 2000, we conducted a case-control study to investigate risk factors for malaria. The study participants had visited The Gambia between 1 September and 31 December 2000, travelling with the largest UK tour operator serving this destination. The main outcome measures were risk factors associated with malaria. Forty-six cases and 557 controls were studied. Eighty-seven percent of all participants reported antimalarial use (41% chloroquine/proguanil, 31% mefloquine). On univariate analysis the strongest risk factors for disease were: early calendar period of visit, longer duration of stay, non-use of antimalarial prophylaxis, non-use of mefloquine, lack of room air-conditioning, less use of insect repellent, prior visit to another malarial area and accommodation in 'hotel X'. After adjustment in multivariate analysis, use of mefloquine remained strongly protective (odds ratios, OR 0.13 [95% confidence intervals, 95% CI 0.04-0.40]), and the strongest independent risk factors for malaria were early calendar period (OR 5.19 [2.35-11.45] for 1 September to 9 November 2000 versus 10 November to 31 December 2000), prior visit to another malarial area (OR 3.27 [1.41-7.56]), main accommodation in 'hotel X' (OR 3.24 [1.51-6.97]) and duration of stay (OR 2.05 per extra week [1.42-2.95]). Neither any use, nor > 90% adherence to chloroquine/proguanil were protective (adjusted OR for any use 0.57 [0.27-1.21], P = 0.14). We concluded mefloquine use was strongly protective against malaria (87% protective efficacy), whereas chloroquine/proguanil, which is no longer recommended but remains widely used, was less than half as effective (43% protective efficacy). Waning efficacy of chloroquine/proguanil may have contributed to the observed increase in malaria among travellers to The Gambia in 2000. Local factors may also influence the risk of malaria. Malaria could be prevented among travellers to West Africa if current national guidelines on antimalarial prophylaxis were better implemented.
Several malariometric studies have examined the impact on human-vector contact of house construction, demographics, bed net and insect repellent use. However, few studies have documented the significance of these proximate determinants on the risks of clinical disease. We undertook a matched case-control study of the risks of both mild clinical malaria and severe life-threatening malaria according to a range of putative factors which would influence the frequency of child-vector encounters in Kilifi district on the Kenyan coast. Among 394 severe disease cases, 380 age-matched mild disease cases, and their respective location and age-matched community controls, we were unable to demonstrate any statistically significant effect upon disease outcome of house construction, presence of domestic animals, or bed net use. Higher population density within a 250 m radius of the homes conferred significant protection from the risks of developing severe malaria compared to community controls. The risks of developing severe malaria compared to the community controls and the transition from mild to severe disease were statistically significantly lower in those who reported use of mosquito coils, local repellents or aerosol insecticides. We concluded that it is likely that the impact of household features on disease outcome is dependent upon both the density of infecting mosquitoes and acquired immunity within a given locality.
To investigate complaints of Gulf War veterans, epidemiologic, case-control and animal modeling studies were performed. Looking for OPIDP variants, our epidemiologic project studied 249 Naval Reserve construction battalion (CB24) men. Extensive surveys were drawn for symptoms and exposures. An existing test (PAI) was used for neuropsychologic. Using FACTOR, LOGISTIC and FREQ in 6.07 SAS, symptom clusters were sought with high eigenvalues from orthogonally rotated two-stage factor analysis. After factor loadings and Kaiser measure for sampling adequacy (0.82), three major and three minor symptom clusters were identified. Internally consistent by Cronbach's coefficient, these were labeled syndromes: (1) impaired cognition; (2) confusion-ataxia; (3) arthro-myo-neuropathy; (4) phobia-apraxia; (5) fever-adenopathy; and (6) weakness-incontinence. Syndrome variants identified 63 patients (63/249, 25%) with 91 syndromes. With pyridostigmine bromide as the drug in these drug-chemical exposures, syndrome chemicals were: (1) pesticide-containing flea and tick collars (P < 0.001); (2) alarms from chemical weapons attacks (P < 0.001), being in a sector later found to have nerve agent exposure (P < 0.04); and (3) insect repellent (DEET) (P < 0.001). From CB24, 23 cases, 10 deployed and 10 non-deployed controls were studied. Auditory evoked potentials showed dysfunction (P < 0.02), nystagmic velocity on rotation testing, asymmetry on saccadic velocity (P < 0.04), somatosensory evoked potentials both sides (right P < 0.03, left P < 0.005) and synstagmic velocity after caloric stimulation bilaterally (P-range, 0.02-0.04). Brain dysfunction was shown on the Halstead Impairment Index (P < 0.01), General Neuropsychological Deficit Scale (P < 0.03) and Trail Making part B (P < 0.03). Butylcholinesterase phenotypes did not trend for inherent abnormalities. Parallel hen studies at Duke University established similar drug-chemical delayed neurotoxicity. These investigations lend credibility that sublethal exposures to drug-chemical combinations caused delayed-onset neurotoxic variants.
The textile roots of yeast microencapsulation technology was introduced as were the wide range of applications in food and other business sectors. In microencapsulation in general the number of commercial applications in the textile industry continues to grow particularly in the textile industries of Western Europe, Japan and North America. The move by the more developed countries into textiles with new properties and added value, into medical textile and technical textiles for example has encouraged the industry to use microencapsulation processes as a means of imparting finishes and properties on textiles which were not possible or cost-effective using other technology. Textile manufacturers are demonstrating increasing interest in the application of durable fragrances to textile as well as skin softeners. Other potential applications include, insect repellents, dyes, vitamins, antimicrobials, phase change materials and in specific medical applications, antibiotics, hormones and other drugs. Examples of each technology are described. A short summary of a new microencapsulation technology with roots in the textile industry, yeast based microencapsulation, is also described.
Travel is associated with a number of neurological disorders that can be divided into two categories: (1) Neurological infections including encephalitides, neurotuberculosis, neurobrucellosis, cysticercosis and trichinosis. Some of these disorders can be prevented by vaccinations, such as Japanese B encephalitis and rabies, some by the use of insect repellents and some by avoiding raw milk products and undercooked meat. (2) Non-infective neurological disorders, such as acute mountain sickness and high altitude cerebral oedema, problems occurring during air travel such as syncope, seizures, strokes, nerve compression, barotrauma and vertigo, motion sickness and foodborne neurotoxic disorders such as ciguatera, shellfish poisoning and intoxication by cassava. This group of diseases and disorders could be prevented if the traveller knows about them, applies simple physiological rules, takes some specific medications and knows how to avoid intoxications in certain geographical areas. Meningococcal meningitis, malaria and jet lag syndrome are extensively discussed in other articles of this issue. The discussion in this paper will be limited to the other disorders.
In the United States, plague poses a threat to humans from the infected animals in the endemic areas of the Western states. Plague may also be used in the near future as an agent of warfare or terrorism. Although the presentation of bubonic plague may be less of a problem, the septicemic and pneumonic forms present challenges to early diagnosis and prompt treatment. The major threat of plague as an agent of terrorism will probably be through the inhalational route. which could result in many cases of the pneumonic form, requiring early recognition and initiation of appropriate therapy. In a mass-casualty scenario, the clinician should be aware of the potential agents of biowarfare and be familiar with the treatment and prophylaxis recommendations outlined by the CDC. It is also prudent to employ universal precautions and respiratory isolation when treating patients with any unknown exposure. In endemic areas, personal protective measures such as use of insecticides, insect repellants, and prompt prophylaxis in cases of exposure to plague are recommended for reducing the incidence of infection. The author also recommends review of CDC website on bioterrorism (http://www.bt.cdc.gov) to keep informed of plague updates.
The ability to estimate low-dose human exposure to commonly used pesticides often is requested in epidemiologic studies. Therefore, fast and robust methods are necessary that can measure many analytes in the same sample. We have developed a method for high-throughput analysis of 19 markers of commonly used pesticides in human urine. The analytes were seven specific metabolites of organophosphorus pesticides, five metabolites of synthetic pyrethroids, six herbicides or their metabolites, and one insect repellant. Human urine (2 mL) was spiked with stable isotopically labeled analogues of the analytes, enzymatically hydrolyzed, extracted using solid-phase extraction, concentrated, and analyzed using high-performance liquid chromatography-tandem mass spectrometry. The sample was divided into two portions and analyzed on two different mass spectrometers, one using atmospheric pressure chemical ionization (APCI) and the other using turbo ion spray atmospheric pressure ionization (TIS). All analytes except the pyrethroid metabolites were analyzed using APCI. The detection limits for all analytes ranged from 0.1 to 1.5 ng/mL of urine, with the majority (17) below 0.5 ng/mL. The analytical precision for the different analytes, estimated as both the within-day and between-day variation, was 3-14 and 4-19%, respectively. The extraction recoveries of the analytes ranged from 68 to 114%. The throughput, including calibration standards and quality control samples, is approximately 50 samples a day. However, the analysis time with the TIS application is much shorter, and if only pyrethroid metabolite data are of interest, the throughput can be increased to 100-150 samples/day.
beta-Cyclodextrin (beta-CD) can be easily grafted onto cellulosic textiles through covalent bonds. In such a way beta-CD empty cavities provide an efficient tool for entrapping different kinds of hydrophobic molecules on the surface of the fabric and releasing them slowly in time. The capability of cyclodextrins to include hydrophobic molecules such as fragrances, antimicrobial agents, and other chemicals can be then exploited to produce new grafted textiles with peculiar and useful performances. In this work we report the inclusion of two different products, the pyrethroid insecticide permethrin (PERM) and the insect repellent N,N-diethyl-m-toluamide (DEET), into beta-CD molecules grafted on cotton fabric. UV-vis spectrophotometry and thermal analysis confirmed the presence of the guest molecules on the fabric surface. Bioassays were carried out on two mosquito species of medical importance, Aedes aegypti and Anopheles stephensi; knock down effect and mortality were measured using standard World Health Organization (WHO) cone tests. Repellency and irritancy (blood feeding inhibition) were also measured using cage tests and a baited tunnel device. PERM-treated fabrics kept the insecticidal/irritant efficacy even for a long time after the treatment, whereas DEET activity lasted more shortly.
To provide the first nationwide reconnaissance of the occurrence of pharmaceuticals, hormones, and other organic wastewater contaminants (OWCs) in water resources, the U.S. Geological Survey used five newly developed analytical methods to measure concentrations of 95 OWCs in water samples from a network of 139 streams across 30 states during 1999 and 2000. The selection of sampling sites was biased toward streams susceptible to contamination (i.e. downstream of intense urbanization and livestock production). OWCs were prevalent during this study, being found in 80% of the streams sampled. The compounds detected represent a wide range of residential, industrial, and agricultural origins and uses with 82 of the 95 OWCs being found during this study. The most frequently detected compounds were coprostanol (fecal steroid), cholesterol (plant and animal steroid), N,N-diethyltoluamide (insect repellant), caffeine (stimulant), triclosan (antimicrobial disinfectant), tri(2-chloroethyl)phosphate (fire retardant), and 4-nonylphenol (nonionic detergent metabolite). Measured concentrations for this study were generally low and rarely exceeded drinking-water guidelines, drinking-water health advisories, or aquatic-life criteria. Many compounds, however, do not have such guidelines established. The detection of multiple OWCs was common for this study, with a median of seven and as many as 38 OWCs being found in a given water sample. Little is known about the potential interactive effects (such as synergistic or antagonistic toxicity) that may occur from complex mixtures of OWCs in the environment. In addition, results of this study demonstrate the importance of obtaining data on metabolites to fully understand not only the fate and transport of OWCs in the hydrologic system but also their ultimate overall effect on human health and the environment.
A highly sensitive analytical method for the simultaneous determination of 39 gaseous and particulate polycyclic aromatic hydrocarbons (PAHs) was used to determine the PAH composition of indoor and outdoor air in Shimizu, Japan. In both indoor and outdoor air, gaseous PAH concentrations were higher in summer than in winter, whereas particulate PAH concentrations were higher in winter than in summer. Correlation analysis indicated that indoor PAH compositions, especially the gaseous PAH composition, differed significantly from outdoor PAH compositions. Gaseous PAH concentrations indoors were significantly affected by insect repellents and heating sources. Particulate PAH concentrations indoors were significantly affected by cigarette smoking, the age and type (wood) of the house, and outdoor PAH concentrations. Inhalation risk associated with carcinogenic PAHs was estimated by using toxic equivalency factors based on the potency of benzo[a]pyrene (BaP). The carcinogenicity of the indoor PAH mixture was dominated by naphthalene followed by BaP and dibenz[a,h]anthracene.