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PubMed2002

The prevention of malaria.

Long before the advent of modern chemoprophylaxis drugs, many practitioners successfully prevented the debilitating and fatal outcomes associated with infection by the Plasmodium parasites that cause malaria. Today, with effective insect repellents and several excellent medications available for chemoprophylaxis, there has never been a better array of quality products to prevent mosquito bites and infection and to suppress parasites once in the blood stream; however, there are thousands of imported cases into nonendemic countries and scores of deaths and near-fatal outcomes every year in returning travelers, soldiers, immigrants, and refugees. In this article, the author focuses on practical uses of currently available prevention tools.

Animals↗
PubMed1992

Epidemiologic investigation of an outbreak of cutaneous leishmaniasis in a defined geographic focus of transmission.

An outbreak of cutaneous leishmaniasis occurred in a unit of 608 Puerto Rican national guardsmen conducting jungle warfare training in the Panama Canal Area in July 1984. An epidemiologic investigation of reported nonhealing, ulcerating skin lesions was conducted among 540 (89%) unit members in November and December 1984. Fifteen (88%) of 17 individuals with chronic, ulcerating skin lesions were confirmed as cases of cutaneous leishmaniasis by culture or histopathology. Twelve cases yielded positive Leishmania cultures, identified as L. braziliensis panamensis by cellulose acetate electrophoresis. Evaluation of different diagnostic techniques revealed that direct examination of tissues by Giemsa-stained histological examination was the most sensitive test (87% sensitivity), with an indirect immunofluorescent antibody test being rather insensitive (67%). All but one of the confirmed cases operated in small units that trained and slept overnight at a mortar firing site for a period of three days, yielding a site-specific attack rate of 22% (14 of 64). This contrasted with a much lower attack rate of 0.2% (1 of 476), experienced by unit members who trained at other locations during the same time frame (P less than 0.001). The median incubation period calculated from day of arrival at the mortar firing site was 17 days (range 2-78) for the 15 confirmed cases. Available personal protection methods, such as the use of insect repellents, were not appropriately implemented by unit personnel and thus, were not found to effectively protect against Leishmania infection. This is the largest reported outbreak of cutaneous leishmaniasis in military personnel associated with a single geographic focus of infection and contrasts with the usual sporadic disease experience in Panama.

Adult↗
PubMed2004

Does anything beat DEET?

In comparison trials, DEET is more effective than any other insect repellent. Despite some reports of serious adverse events, when comparing the thousands of other reports of exposure and millions of past users, DEET has a good safety record. The appropriate and safest concentration to use on children remains unclear, however. Due to potential absorption through the skin, prudence would dictate that the lowest effective concentration for the time period of exposure be used. Because research has shown that solvents with less skin permeation may be used as an alternative to the ethanol used in some commercial DEET preparations, manufacturers could develop products that are less likely to be absorbed. Pediatricians should be familiar with the duration of action of various formulations of DEET and the efficacy (and in some cases lack of efficacy) of other products in order to advise patients on safe but effective methods of insect control.

Animals↗
PubMed2005

Human pharmaceuticals, hormones, and personal care product ingredients in runoff from agricultural fields irrigated with treated wastewater.

Irrigation of crops with treated wastewater has the potential to introduce effluent-derived organic microcontaminants into surface waters through agricultural runoff. To determine whether compounds indicative of the presence of treated effluent in irrigation water could be identified in agricultural runoff, surface runoff samples collected from effluent-irrigated and rain-fed cultivated fields were analyzed for a broad spectrum of organic compounds. A variety of compounds was identified that appeared to be associated with irrigation with treated wastewater. These compounds included human pharmaceuticals (e.g., carbamazepine, gemfibrozil, carisoprodol), personal care product ingredients (e.g., insect repellent, polycyclic musks), and alkyl phosphate flame retardant chemicals. Most of these compounds appear not to have been previously reported in agricultural runoff. These compounds were present at concentrations below the few published aquatic toxicology data available; however, their potential to elicit more subtle effects in aquatic organisms cannot be excluded. None of these compounds were detected by broad-spectrum analysis in samples from the same fields during runoff-producing rain events.

Agriculture↗
PubMed2003

Longitudinal evaluation of an educational intervention for preventing tick bites in an area with endemic lyme disease in Baltimore County, Maryland.

The authors attempted to determine whether a targeted educational intervention in an area with endemic Lyme disease could increase knowledge, positive attitudes, and reported behaviors related to tick bite prevention and consequently decrease tick bites, as measured by a biomarker of tick bites. Between April and September of 1999, 317 subjects in Baltimore County, Maryland, were randomized to receive either tick-related or general health-related educational materials bimonthly through the mail. At each of three clinic visits, participants completed a self-administered questionnaire and provided a serum sample. Anti-recombinant tick calreticulin antibody (ARTCA), measured in ng/ micro l, was used as a biomarker of tick bites. Linear and logistic regression analyses were used to determine 1) whether the educational intervention was associated with a change in knowledge, attitudes, and behaviors (KAB) and 2) whether change in KAB predicted change in ARTCA levels. Proportions of desired responses increased significantly among intervention subjects versus the comparison group on KAB measures related to examining the body for ticks and insect repellent use. Levels of ARTCA were low among all study subjects. Only six of 37 models exhibited a significant relation between change in a KAB variable and change in ARTCA levels over time. The behavioral intervention was associated with an increase in the KAB measures in the intervention group, but this change was not associated with change in ARTCA levels.

Adolescent↗
PubMed2002

Risk factors for tick exposure and suboptimal adherence to preventive recommendations.

BACKGROUND: Tickborne diseases are the most common vectorborne illnesses in the United States. Understanding risk factors for tick bites and adherence to preventive measures are important in preventing morbidity associated with tickborne disease. METHODS: A random-digit-dialing telephone survey was administered to 1820 residents of 11 counties in Tennessee. RESULTS: Of respondents, 16.4% reported a tick bite within the previous year. Only 29% consistently used insect repellant in high-risk situations, and only 54% always checked their bodies for ticks after leaving potentially infested areas. Nearly one fourth of dog owners removed ticks from their pets with bare hands. Dog ownership, rural residence, and exposure to a farm were associated with increased risk of tick bites. CONCLUSIONS: We identified several groups that were at increased risk of tick bites and might benefit from targeted prevention messages.

Adolescent↗
PubMed2000

Repeated coadministrations of pyridostigmine bromide, DEET, and permethrin alter locomotor behavior of rats.

Interactions of pyridostigmine bromide (PB), permethrin (PERM), and the insect repellent DEET (DEET) have been suggested as possible causes of Gulf War Syndrome (GWS) in humans. Open field locomotor studies have long been used in behavioral toxicology. Using male and female Sprague-Dawley rats, video-computer analyses, and the isobolographic method we have determined the effects on locomotor speed and thigmotaxis following repeated administration of single-, double-, or triple-drug or vehicle controls in an open field. The effects were measured 24 hours after 7 daily drug administrations. Single-drug administrations caused no significant effects. Double-drug administrations resulted in significant effects in the following cases: males given PB + DEET had a significantly slower locomotion rate; males given DEET + PERM had a significantly faster locomotion rate; females given PB + DEET had a significantly slower locomotion rate; and females given PB + PERM spent significantly more time in the center zone (less thigmotaxis). Triple-drug administration caused no significant effect. These results in comparison with behavioral studies in chickens and insects show certain similarities. The implications of the lasting effects on animal models are relevant to GWS in humans.

Animals↗
PubMed2002

Assessment of dengue risk in relief workers in Puerto Rico after Hurricane Georges, 1998.

Health risk assessment is important in the safe deployment of workers to tropical areas. We monitored dengue incidence in 204 of 222 North American relief workers visiting Puerto Rico after Hurricane Georges and during a dengue epidemic in 1998. We recorded information regarding participants' living conditions and any illness they experienced from arrival to 2 weeks after their departure. Virus isolation, polymerase chain reaction, and serological tests for anti-dengue immunoglobulin (Ig) M and IgG antibodies were used to diagnose dengue infection by means of departure and follow-up serum specimens. Among respondents, 82% (164 of 199) reported mosquito bites, 97% (156 of 161) reported having insect repellent available, and 41% (79 of 195) reported using repellent every day. Twelve participants reported a mild denguelike illness. No participants had laboratory evidence of dengue infection after 1.8 person-years of assessable exposure to areas with dengue transmission (upper 95% confidence limit of 1.67 cases per person-year). The risk of acquiring dengue among relief workers in this study appears low, possibly as a result of protective factors. Travelers to dengue-endemic areas should continue to be advised to protect themselves against mosquito bites.

Adult↗
PubMedDate not supplied

Analysis of diethyltoluamide (DEET) following intentional oral ingestion of Muscol.

N,N-Diethyl-m-toluamide (DEET) is an effective component of several insect repellent products. A 19-year-old woman was admitted to the emergency department following ingestion of 15-25 mL 95% diethyltoluamide (Muscol). Serum and urine toxicology screening tests were negative except for detection of DEET. DEET was qualitatively identified and quantitated by gas chromatography-mass spectrometry. Concentrations of DEET based on selected ion monitoring (ion at m/z 119) were 63.0, 17.2, 1.9, and less than 0.2 mg/L in serum specimens collected at 2, 5, 24, and 48 h following ingestion, respectively. Serial monitoring of DEET concentrations and the cardiac abnormalities observed in this case following oral ingestion were not reported previously.

Adult↗
PubMed2004

An outbreak of Plasmodium vivax malaria in Far North Queensland, 2002.

OBJECTIVE: To describe an outbreak of Plasmodium vivax malaria in Far North Queensland in 2002. DESIGN: Epidemiological and entomological investigations; molecular analyses of the infecting parasites. MAIN OUTCOME MEASURES: Case characteristics, adult and larval mosquito counts at the outbreak location, haplotyping of parasites in blood samples from different cases determined through sequencing of AMA1 and MSP1 genes. RESULTS: A man with imported P. vivax malaria stayed at a camping ground 95 km north of Cairns in late September 2002. This led to an outbreak of P. vivax malaria in 10 adults who stayed at the camping ground in October. Large numbers of Anopheles farauti sensu lato larvae were present in stagnant pools in a creek at the camping ground, and many adult mosquitoes were collected nearby. Not only had most of the infected patients been exposed to mosquitoes at night, they were also less likely than other campers to have used insect repellents appropriately (odds ratio, 0.01; P < 0.001). Two different haplotypes of P. vivax, only one of which was detected in the imported case, were involved in the outbreak. CONCLUSIONS: Although local transmission of malaria is rare in Far North Queensland, the risk is probably higher in the dry season (September to December). Campers need to be aware of the increased risk of mosquito-borne diseases. Sexual recombination of multiple gametocytes in mosquitoes infected by the imported case may have resulted in the two haplotypes of P. vivax involved in the outbreak.

Adult↗
PubMedDate not supplied

Hydroxylation of 3-acetyl-2-(2,6-dimethyl-5-heptenyl)oxazolidine by rat liver microsomes. Identification of some isomeric metabolites.

The metabolism of nonradiolabeled, stereoisomeric mixtures of 3-acetyl-2-(2,6-dimethyl-5-heptenyl)oxazolidine (I), a new citronelial-based insect repellent, by induced and uninduced rat liver microsomes has been examined in a NADPH-generating system at a substrate concentration of 1.67 mM. By comparison of retention times and mass spectra of the metabolites with the products from oxidation of I with selenium dioxide, the allylic methyl carbons of the isobutenyl group were identified as the major sites of oxidative metabolism, with two samples of I prepared from different sources of (+/-)-citronelial. Both diastereomeric and E-Z isomeric forms of the metabolites were separated by high resolution capillary gas chromatography with Carbowax 20M-terephthalic acid. Diastereomeric mixtures of unmetabolized I, E alcohol (II), Z alcohol (III), and E aldehyde (IV) were detected in postsincubate extracts. From integration of peak areas, the mean ratio of II to III was 70:30 in 47 extracts.

Alcohols↗
PubMed2003

Chemical sensitivity in symptomatic Cambodia veterans.

Following their participation in a United Nations peacekeeping operation in Cambodia (1992-1993), Dutch veterans complained of symptoms similar to those reported by Gulf War veterans. The authors conducted a matched case-control study to evaluate 76 symptomatic and 32 matched asymptomatic Cambodia veterans on the basis of data collected by postal questionnaire. The number of symptomatic veterans who reported having used insect repellants that contained N,N,-diethyl-meta-toluamide (DEET) during the mission in Cambodia was significantly higher, compared with asymptomatic veterans. The percentage of veterans who reported feeling ill following brief exposures to chemicals such as paint or pesticides was equal in both groups, but the percentage was low compared with the results of other studies of Multiple Chemical Sensitivity Syndrome. The current study was limited by self-report and time delay (potential recall bias) between deployment to Cambodia and the time of survey. Nevertheless, the study results did not support the hypothesis that symptoms in the total group of Cambodia veterans could be related to Multiple Chemical Sensitivity Syndrome.

Adult↗
PubMed1999

Development and evaluation of LIPODEET, a new long-acting formulation of N, N-diethyl-m-toluamide (DEET) for the prevention of schistosomiasis.

N, N-diethyl-m-toluamide (DEET) is a common and fairly safe active ingredient in many insect repellents. Our recent studies showed that when applied to the skin, DEET has a potent anti-parasitic effect against Schistosoma mansoni. However, the beneficial effects of DEET lasted only for a few minutes, presumably due to its rapid absorption through the skin. In this study, we evaluated different carrier formulations that prolong the activity of DEET in the skin. Among the various formulations analyzed, DEET incorporated into liposomes (LIPODEET) appeared to prolong the activity of DEET for more than 48 hr after a single application. Furthermore, LIPODEET was found to be minimally absorbed through the skin and loss due to washing off was limited. These findings thus suggest LIPODEET is a safe and long-acting formulation of DEET that is quite effective against schistosomiasis.

Animals↗
PubMed2001

Effect of selected pesticides and their ozonation by-products on gap junctional intercellular communication using rat liver epithelial cell lines.

The non-genotoxic effects of two commonly used pesticides, 1,1-bis (p-chlorophenyl)-2,2,2-trichloroethane (DDT) and malathion, and one widely used commercial insect repellent N,N-diethy-m-toluamide (DEET) on gap junction intercellular communication (GJIC) were determined using a rat liver epithelial cell line. Malathion and DDT reversibly inhibited GJIC in a treatment time- and dose-dependent manner at non-cytotoxic doses, whereas, DEET did not inhibit GJIC. Malathion was very reactive with ozone, while DEET and DDT did not react to any appreciable extent with ozone. The mixtures of ozonation products from malathion and DEET did not inhibit GJIC. The mixtures of ozonation by-products formed from DDT inhibited GJIC, but to a lesser extent than did DDT, itself. These results suggest that ozone can effectively remove malathion from solution without forming GJIC-toxic products, but is less effective in eliminating DEET and DDT from solution.

Animals↗
PubMed2006

Reaction mechanism and kinetic modeling of DEET degradation by flow-through anodic fenton treatment (FAFT).

The previously developed batch anodic Fenton treatment (AFT) technology has been successfully applied to degrade various pesticides in aqueous solution. The goal of this work is the development of a flow-through AFT system (FAFT) which is critical to bringing this technology into practical general use in the field. For this purpose, the degradation of DEET (N,N-diethyl-3-methylbenzamide), an insect repellent, and nine model amides was studied. Oxidation products of these compounds in FAFT were identified by GC/MS, and the results revealed that various -OH additions (most likely on the aromatic ring), quinone/keto product formation, and dimerization/bimolecular disproportionation are the major reaction pathways. This proposed overall reaction mechanism was then combined with the basic Fenton's mechanism to model the kinetics of various active species in FAFT including DEET, Fe2+, H2O2, and total iron under different reaction conditions. In addition, both initial and steady-state hydroxyl radical concentrations were measured in FAFT using benzoic acid as a chemical probe; the measured *OH concentrations were best-fitted exponentially. On the basis of the obtained [*OH] trend and the mass balance of the FAFT system, a simple FAFT model was developed to fit all of the degradation data of DEET and the model amides.

DEET↗
PubMed2006

A single oral dose of ethanol can alter transdermal absorption of topically applied chemicals in rats.

Topical ethanol is used as a dermal penetration enhancer in some commercial products. Previous studies have demonstrated that chronic ethanol consumption can also disrupt skin barrier function, leading to increased transdermal penetration. This observation becomes much more relevant if a single drinking episode induces similar changes. The purpose of this study was thus to examine the transdermal penetration of three model chemicals after acute ethanol consumption. Wistar rats were gavaged with either 10, 6, 4.3, 3, 1.5 g/kg ethanol or saline and allowed to recover for 2 or 24 h. Blood and skin ethanol levels were determined and in vitro penetration experiments performed. The herbicide paraquat, industrial solvent N,N-dimethylformamide (DMF), and insect repellent N,N-diethyl-m-toluamide (DEET) were used as is model chemicals. Absorption was determined and directly compared between ethanol- and saline-treated skin by calculating enhancement ratios. Blood ethanol levels range from 0.25 to 0.015% at 2 h with skin levels at 12-18% of blood values. Ethanol enhances the absorption of paraquat, DMF, and DEET in a dose-dependent fashion. Paraquat and DEET showed no appreciable reduction in enhancement between 2 and 24 h postgavage for the 10-g/kg dose, but DMF did. Enhancement ratios were higher at 24 h for 10 than for 6 g/kg animals, demonstrating a dose-response relationship for recovery time. These studies imply that increased absorption of topical chemical occurs after alcohol ingestion. Both acute and chronic ethanol consumption can compromise the dermal barrier.

Administration, Cutaneous↗
PubMed1996

U.S. military overseas medical research laboratories.

Many infectious disease threats to U.S. military operations are uncommon in the United States. The advanced development and testing of countermeasures, such as vaccines, drugs, or insect repellents, requires the capability to study militarily important infectious diseases where they occur. With formal agreements between the U.S. and each host country, the U.S. military operates seven overseas medical research laboratories (labs). Six labs conduct infectious disease research and are distributed over three continents: Africa (labs in Egypt and Kenya), Asia (labs in Indonesia and Thailand), and South America (labs in Brazil and Peru). One other lab is located in Germany and conducts psychosocial research related to military personnel and their families. In addition to product development, these labs play vital roles supporting overseas deployments, providing technical training, and promoting international relations. Also, these labs are well positioned to become part of a developing global surveillance and response system to help address the threat posed by emerging infectious diseases. This article will present an overview of this unique medical research capability, describe the history and some of the activities of each lab, and discuss the importance of maintaining these labs in the 21st century.

Communicable Diseases↗
PubMed2006

Initial evaluation of N,N-diethyl-m-toluamide and permethrin absorption in human volunteers under stress conditions.

OBJECTIVES: This was a pilot study to determine (1) whether it is feasible to effectively blind human subjects to the presence of the insect repellents N,N-diethyl-m-toluamide (DEET) and permethrin; (2) whether DEET affects the absorption of permethrin; and (3) whether combat videotape viewing and mental arithmetic are stressful. METHODS: Ten volunteers were exposed to DEET, permethrin, and stress (1-hour combat videotape plus mental arithmetic) in a double-blind, randomized, placebo-controlled trial. Outcome measurements included hemodynamics, plasma DEET and permethrin levels, and questionnaires to assess blinding. RESULTS: Highly sensitive serologic assays readily detected DEET but not permethrin. Staff members and subjects were effectively blinded to both. The videotape-math combination was stressful by both self-report and hemodynamic measures. CONCLUSIONS: It is possible to blind subjects with respect to DEET and permethrin. Permethrin on clothing does not enter the bloodstream at appreciable levels. Combat videotapes and mental arithmetic can be stressful.

Adult↗