Pyrethroid Insecticide Resistance Mechanisms in the Adult Phlebotomus papatasi (Diptera: Psychodidae).

Phlebotomus papatasi is one of the most medically important sand fly species in the Old World, serving as a vector of Leishmania parasites and phleboviruses. Chemical control is still considered the most effective method for rapidly reducing populations of flying insects involved in vector-borne disease transmission, but is increasingly threatened by insecticide resistance in the target insect posing significant problems for entomologists responsible for control programs. This study was conducted to determine pyrethroid resistance mechanisms and the biological, physiological, and molecular impacts of resistance in Ph. papatasi, and to compare their resistance mechanisms against those reported for mosquitoes and other intensely studied dipterans. Field-collected Ph. papatasi from Aswan, Egypt, were subjected to sublethal doses of permethrin and reared as a resistant strain under laboratory conditions through 16 generations. Biological parameter observations of resistant Ph. papatasi revealed an association of resistance with productivity cost. Physiological analysis revealed that concentrations of oxidase and esterase enzymes increased in early generations of the resistant colony, and then subsided through the F16 generation to levels similar to those in a susceptible colony. The activity levels of acetylcholinesterase were higher in field-collected Ph. papatasi than in susceptible colony flies, but decreased significantly despite subsequent exposure to permethrin. The molecular search for gene mutations in the resistant strain of Ph. papatasi failed to identify any mutations common in pyrethroid-resistant mosquitoes. Our study revealed that the mechanism of pyrethroid resistance in sand flies is different than that in mosquitoes, at least at the genetic level.

Childhood exposures to Rn-222 and background gamma radiation in the uranium provinces of south Kazakhstan and northern Kyrgyzstan.

The project was undertaken in southern Kazakhstan and Kyrgyzstan. It was speculated that the radiation doses in these areas would be sufficiently high and dispersed to facilitate a case-control study where the radiation doses to leukaemia subjects/their siblings could be compared with those received by control children. As a precursor a pilot project was undertaken to confirm radiation exposures in the region. This was undertaken in association with regional childhood cancer treatment centres. Children from families affected by childhood leukaemia were monitored for 1 month for external γ-radiation dose and for exposure to radon gas. 28 children from families in Kazakhstan and from 31 families in Kyrgyzstan were monitored. The median measured radon in air concentration recorded in Kazakhstan was 123 Bq m(-3) and in Kyrgyzstan was 177 Bq m(-3). These represent 24-h average indoor/outdoor values. In the case of the γ-doses the mean annual dose was 1.2 mGy for Kazakhstan and 2.1 mGy for Kyrgyzstan. Overall, the results suggest that the populations studied receive similar annual radiation doses to those received by populations living in other areas with enhanced natural radioactivity and that further study of Kazakh and Kyrgyz populations would not facilitate a successful case-control study for childhood leukaemia.

Comparison of three carbon dioxide sources on phlebotomine sand fly capture in Egypt.

Lighted Centers for Disease Control and Prevention (CDC) light traps were baited with carbon dioxide (CO2) produced from three different sources to compare the efficacy of each in collecting phlebotomine sand flies in Bahrif village, Aswan Governorate, Egypt. Treatments consisted of compressed CO2 gas released at a rate of 250 ml/min, 1.5 kg of dry ice (replaced daily) sublimating from an insulated plastic container, CO2 gas produced from a prototype FASTGAS (FG) CO2 generator system (APTIV Inc., Portland, OR), and a CDC light trap without a CO2 source. Carbon dioxide was released above each treatment trap's catch opening. Traps were placed in a 4 x 4 Latin square designed study with three replications completed after four consecutive nights in August 2007. During the study, 1,842 phlebotomine sand flies were collected from two genera and five species. Traps collected 1,739 (94.4%) Phlebotomus papatasi (Scopoli), 19 (1.0%) Phlebotomus sergenti, 64 (3.5%) Sergentomyia schwetzi, 16 (0.9%) Sergentomyia palestinensis, and four (0.2%) Sergentomyia tiberiadis. Overall treatment results were dry ice (541) > FG (504) > compressed gas (454) > no CO2 (343). Total catches of P. papatasi were not significantly different between treatments, although CO2-baited traps collected 23-34% more sand flies than the unbaited (control) trap. Results indicate that the traps baited with a prototype CO2 generator were as attractive as traps supplied with CO2 sources traditionally used in sand fly surveillance efforts. Field-deployable CO2 generators are particularly advantageous in remote areas where dry ice or compressed gas is difficult to obtain.

Efficacy of commercial mosquito traps in capturing phlebotomine sand flies (Diptera: Psychodidae) in Egypt.

Four types of commercial mosquito control traps, the Mosquito Magnet Pro (MMP), the Sentinel 360 (S360), the BG-Sentinel (BGS), and the Mega-Catch Ultra (MCU), were compared with a standard Centers for Disease Control and Prevention (CDC) light trap for efficacy in collecting phlebotomine sand flies (Diptera: Psychodidae) in a small farming village in the Nile River Valley 10 km north of Aswan, Egypt. Each trap was baited with either carbon dioxide (CO2) from combustion of butane gas (MMP), dry ice (CDC and BGS traps), light (MCU and S360), or dry ice and light (CDC). Traps were rotated through five sites in a5 x 5 Latin square design, repeated four times during the height of the sand fly season (June, August, and September 2007) at a site where 94% of sand flies in past collections were Phlebotomus papatasi (Scopoli). A total of 6,440 sand flies was collected, of which 6,037 (93.7%) were P. papatasi. Of the CO2-baited traps, the BGS trap collected twice as many P. papatasi as the MMP and CDC light traps, and at least three times more P. papatasi than the light-only MCU and S360 traps (P < 0.05). Mean numbers (+/- SE) of P. papatasi captured per trap night were as follows: BGS 142.1 (+/- 45.8) > MMP 56.8 (+/- 9.0) > CDC 52.3 (+/- 6.1) > MCU 38.2 (+/- 6.4) > S360 12.6 (+/- 1.8). Results indicate that several types of commercial traps are suitable substitutes for the CDC light trap in sand fly surveillance programs.

Determining the relative toxicity and RBE of internal emitters in animals.

It is almost impossible to conduct a perfect study of the relative toxicity of the radiations produced by different radionuclides. This is because the results of such studies are commonly confounded by spatial and temporal differences in the distributions of dose produced by the radionuclides employed. In addition, the results of a study designed to overcome these problems (using matched radionuclides incorporated within fused clay particles) revealed additional characteristics of an ideal study. These included the use of sufficient numbers of animals to give the study statistical power; the derivation of all causes of death and of survival for the analysis; the use of relative risk, rather than crude incidence data, to determine toxicity ratios; the cautious use of relative biological effectiveness values derived from fitted curves; and the preferred use of relative toxicity values derived directly from the data.

Evaluation of six mosquito traps for collection of Aedes albopictus and associated mosquito species in a suburban setting in north central Florida.

We compared 6 adult mosquito traps for effectiveness in collecting Aedes albopictus from suburban backyards with the goal of finding a more suitable surveillance replacement for the Centers for Disease Control and Prevention (CDC) light trap. Trap selection included 2 commercial propane traps (Mosquito Magnet Professional trap and Mosquito Magnet Liberty trap), 2 Aedes-specific traps (Fay-Prince Omnidirectional trap and Wilton trap), 1 experimental trap (Mosquito Magnet-X trap), and a standard surveillance CDC light trap that served as a control. Traps that did not generate carbon dioxide were provided with bottled CO2 at a flow rate of 500 ml/min. Those traps designed for use with chemical attractants (Mosquito Magnet traps) were baited with Lurex (L-lactic acid) and octenol (1-octen-3-ol) commercial baits, known attractants to Ae. albopictus. Three repetitions of a 6 x 6 Latin square test yielded a total of 37,237 mosquitoes, of which 5,280 (14.2%) were Ae. albopictus. Significantly more (P < 0.05) Ae. albopictus were collected from the experimental and commercial traps (4,244/5,280; 80.3%) than from the CDC light trap and Aedes-specific traps. The Mosquito Magnet Liberty collected the most Ae. albopictus (1,591), accounting for 30.1% of the total take, followed closely by the Mosquito Magnet-X (1,468) and the Mosquito Magnet Pro (1,185). The omnidirectional Fay-Prince trap performed better than the CDC or Wilton trap. Twenty-seven mosquito species were collected during these trials, 9 species in large enough numbers for meaningful analysis. Aedes albopictus was the second most common mosquito trapped. The results of these trials indicate that propane-powered commercial traps would serve as useful substitutes in lieu of CDC traps in Ae. albopictus surveillance efforts. Trap features advantageous for collecting Ae. albopictus and other mosquito species are discussed.

New models for evaluation of radiation-induced lifetime cancer risk and its uncertainty employed in the UNSCEAR 2006 report.

Generalized relative and absolute risk models are fitted to the latest Japanese atomic bomb survivor solid cancer and leukemia mortality data (through 2000), with the latest (DS02) dosimetry, by classical (regression calibration) and Bayesian techniques, taking account of errors in dose estimates and other uncertainties. Linear-quadratic and linear-quadratic-exponential models are fitted and used to assess risks for contemporary populations of China, Japan, Puerto Rico, the U.S. and the UK. Many of these models are the same as or very similar to models used in the UNSCEAR 2006 report. For a test dose of 0.1 Sv, the solid cancer mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 5.4% Sv(-1) [90% Bayesian credible interval (BCI) 3.1, 8.0]. At 0.1 Sv, leukemia mortality for a UK population using the generalized linear-quadratic relative risk model is estimated as 0.50% Sv(-1) (90% BCI 0.11, 0.97). Risk estimates varied little between populations; at 0.1 Sv the central estimates ranged from 3.7 to 5.4% Sv(-1) for solid cancers and from 0.4 to 0.6% Sv(-1) for leukemia. Analyses using regression calibration techniques yield central estimates of risk very similar to those for the Bayesian approach. The central estimates of population risk were similar for the generalized absolute risk model and the relative risk model. Linear-quadratic-exponential models predict lower risks (at least at low test doses) and appear to fit as well, although for other (theoretical) reasons we favor the simpler linear-quadratic models.

Meta-analysis of standardized incidence and mortality rates of childhood leukaemia in proximity to nuclear facilities.

The meta-analysis combined and statistically analysed studies of childhood leukaemia and nuclear facilities. Focus was on studies that calculated standardized rates for individual facilities. Due to variability between study designs, eight separate analyses were performed stratified by age and zone. One hundred and thirty-six sites were used in at least one analysis. Unadjusted, fixed effects and random effects models were used. Meta-rates greater than one were found in all models at all stratification levels often achieving statistical significance. Caution must be used when interpreting these results. The meta-analysis was able to show an increase in childhood leukaemia near nuclear facilities, but does not support a hypothesis to explain the excess. Each type of model utilized has limitations. Fixed effects models give greater weight to larger studies; however, population density may be a risk factor. Random effects models give greater weight to smaller studies that may be more likely to be affected by publication bias. A limitation of the overall study design is that standardized rates must be available for individual sites which led to exclusion of studies that only calculated rates for multiple sites and those that presented other statistical methods. Further, dose-response studies do not support excess rates found near nuclear facilities. However, it cannot be ignored that the majority of studies have found elevated rates, although not usually statistically significant.

Evaluation of carbon dioxide, 1-octen-3-ol, and lactic acid as baits in Mosquito Magnet Pro traps for Aedes albopictus in north central Florida.

The impact of the attractants l-octen-3-ol (octenol) and L-lactic acid (LurexTM) on collection of Aedes albopictus in suburban backyards was assessed in Mosquito Magnet Pro traps. These carbon dioxide-producing traps were additionally baited with commercial formulated lures with octenol, lactic acid, octenol + lactic acid, or no attractant (control) and evaluated in 4 residential sites. Three repetitions of the study resulted in the total collection of 1,321 Ae. albopictus. Significantly more Ae. albopictus were captured in traps baited with octenol + lactic acid than in traps baited only with octenol. Lactic acid-baited and control trap captures were not significantly different from octenol + lactic acid- or octenol-baited trap totals. Octenol- + lactic acid-baited traps collected 36.2% and 52.0% more Ae. albopictus than lactic acid-baited and control traps, respectively. Male Ae. albopictus accounted for 26.7% of the total capture. Other mosquito species collected in sufficient numbers for analysis included Cx. nigripalpus, Ochlerotatus infirmatus, Psorophoraferox, and Cx. erraticus. Larger numbers of these species were collected in traps that were unbaited or baited with only octenol than in traps baited with lactic acid or octenol + lactic acid.

Residential mobility and risk of childhood acute lymphoblastic leukaemia: an ecological study.

We conducted an ecological analysis of childhood acute lymphoblastic leukaemia-incidence data from children or=$5000 as potential predictors. Incidence was lower among black boys (rate ratio (RR)=0.5) and black girls (RR=0.4) than among other children of the same sex; no other significant racial differences were detected. Incidence was elevated among males (but not females) residing in counties where >or=50% of the population relocated (RR=1.5) and among females (but not males) residing in counties where <6% of the households had incomes <$5000 (RR=1.5). These sex differences in risk factors were unexpected.

Response of phlebotomine sand flies to light-emitting diode-modified light traps in southern Egypt.

Centers For Disease Control and Prevention (CDC) light traps were modified for use with light-emitting diodes (LED) and compared against a control trap (incandescent light) to determine the effectiveness of blue, green, and red lights against standard incandescent light routinely used for sand fly surveillance. Light traps were baited with dry ice and rotated through a 4 x 4 Latin square design during May, June, and July, 2006. Trapping over 12 trap nights yielded a total of 2,298 sand flies in the village of Bahrif, 6 km north of Aswan on the east bank of the Nile River in southern Egypt. Phlebotomus papatasi comprised 94.4% of trap collections with five other species collected in small numbers. Over half (55.13%) of all sand flies were collected from red light traps and significantly more sand flies (P < 0.05) were collected from red light traps than from blue, green, or incandescent light traps. Red light traps collected more than twice as many sand flies as control (incandescent) traps and > 4 x more than blue and green light traps. Results indicate that LED red light is a more effective substitute for standard incandescent light when surveying in areas where P. papatasi is the predominant sand fly species. Each LED uses approximately 15% of the energy that a standard CDC lamp consumes, extending battery life and effective operating time of traps. Our prototype LED-modified traps performed well in this hot, arid environment with no trap failures.

Relative toxicity of chronic irradiation by 45Ca beta particles and 242Cm alpha particles with respect to the production of lung tumors in CBA/Ca mice.

Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to beta particles from (45)Ca-labeled fused aluminosilicate particles (FAP), to alpha particles from (242)Cm-labeled FAP, or to carrier control FAP. Another group of mice inhaled no FAP and were designated as untreated cage controls. The FAP in combination with these radionuclides was used to achieve the same spatial and temporal distribution of alpha- and beta-particle dose within the irradiated mice. Some mice were killed to determine the clearance of radiolabeled FAP from their lungs, and the remainder were allocated to a life-span study. All animals were subjected to a detailed necropsy. To facilitate the identification of small tumors, the lungs were rendered transparent in methyl salicylate and examined under back illumination for the presence of lesions. Lung nodules and other microscopic lesions were excised for histological examination. The median survival of mice in all groups was approximately 910 days. The control animals lived longer than those that were irradiated, but it was difficult to determine a dose-response relationship for survival among the exposed mice. Benign adenomas and, less frequently, malignant adenocarcinomas were identified in all animal groups. The prevalence of these tumors was approximately 28.8% in the control mice, which is consistent with the results of other studies using the same strain of mouse. After exposure to radionuclide-labeled FAP, there was a significant dose-related increase in the prevalence of lung tumors in (242)Cm- (peak prevalence 55%) and (45)Ca-exposed (peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received (242)Cm-labeled FAP was approximately twice that in the mice that inhaled (45)Ca-labeled FAP within the range of doses employed (0.55-4.69 Gy). Using the ratio of the slope of the linear component of the dose-response curves, the toxicity of the alpha particles relative to the beta particles was 1.5 (90% CI: 0.7, 9.0) for all adenomas and 9.4 (90% CI: 5.0, 23.0) for the less frequent adenocarcinomas. The relative toxicity for adenocarcinomas was found to decrease with increasing dose.

Residential radon exposure and lung cancer risk: commentary on Cohen's county-based study.

The large United States county-based study () in which an inverse relationship has been suggested between residential low-dose radon levels and lung cancer mortality has been reviewed. While this study has been used to evaluate the validity of the linear nonthreshold theory, the grouped nature of its data limits the usefulness of this application. Our assessment of the study's approach, including a reanalysis of its data, also indicates that the likelihood of strong, undetected confounding effects by cigarette smoking, coupled with approximations of data values and uncertainties in accuracy of data sources regarding levels of radon exposure and intensity of smoking, compromises the study's analytic power. The most clear data for estimating lung cancer risk from low levels of radon exposure continue to rest with higher-dose studies of miner populations in which projections to zero dose are consistent with estimates arising from most case-control studies regarding residential exposure.

Stable chromosome aberrations and ionizing radiation in airline pilots.

INTRODUCTION: The purpose of this study was to determine the frequency of translocations and insertions in the blood of long-term pilots in relation to estimated cumulative radiation dose received while flying, and to compare that to the frequency in a group of similarly aged men without a history of frequent airline travel. METHODS: Healthy, non-smoking male pilots aged 40-60 yr were recruited from a single airline. Non-pilot controls were recruited from healthy, non-smoking professional males in the same age range and without a history of frequent flying. Eligibility was determined based on screening surveys. Career pilot radiation doses were calculated individually using airline flight profiles, personal flight history, and the CARI computer program. Translocation frequency was determined using fluorescence in situ hybridization. RESULTS: Blood samples for chromosome analysis were provided by 19 individuals. The mean number of metaphases counted per subject was 2802 in the pilots and 3000 in the controls. The mean number of translocations per cell (genome equivalent) was significantly higher among the pilots (mean +/- SE; 0.0031 +/- 0.0008) than among the controls (0.0010 +/- 0.0003) (p = 0.03, Mann-Whitney U test). However, within the 26 to 72 millisievert range encountered in this study, observed values among the pilots did not follow the dose-response pattern expected based on available models for chronic low dose radiation exposure. CONCLUSIONS: There was a statistically significant higher number of translocations per cell among pilots than among controls, although the expected dose-response relationship for radiation was not observed among the pilots.

Breast dose variability in a bi-racial population undergoing screening mammography.

This study evaluated individual and population dose variability during screening mammography, among 570 white and black women in South Carolina, USA. Aspects of dosimetry that were considered include compressed breast thickness (CBT), number of films per screening session, and dose in previous or subsequent sessions. Breast dose was log-normally distributed in the population, with a geometric mean of 6.6 mGy per session. Doses were significantly higher for black women, for women with high CBT or who receive more than two views per breast, and for the mediolateral oblique, compared to the craniocaudal, view. No relationship was observed between age and dose. Total dose per breast varied by a factor of 20 across the study population, but the individual's dose varied little among repeat screening sessions, especially after adjusting for the number of films received per session. These results may inform assessments of the projected risks of inducing breast cancer from screening mammography.

Mammography dose in relation to body mass index, race, and menopausal status.

Mammography dose increases with compressed breast thickness (CBT), but few studies have examined other correlates of dose. The purpose of this study was to evaluate the relation between factors such as race, age, body mass index (BMI), CBT, and menopausal status and mammography screening dose, measured for 509 women in a US population. A multiple linear regression model was developed for dose, based on consideration of these factors as well as examination characteristics. BMI and number of films during examination were positively related to dose. After adjusting for these factors, high CBT also leads to higher dose. Whites receive lower doses than black women but differences are slight after controlling for the effects of CBT and BMI, which were significantly higher among black women. Pre-menopausal women receive higher doses, after adjusting for all other factors, than post-menopausal women. Jointly, these factors account for approximately 75% to 80% of the variability in dose among this study population. Because rates of overweight are increasing in the US, average doses from mammography may be increasing as well.

Health among commercial airline pilots.

BACKGROUND: The airline pilot works within a complex exposure environment that may present physiological challenges to long-term health. METHODS: This study investigated self-reported disease outcomes among a large group of active and retired commercial airline pilots in the United States and Canada. A survey methodology was used, including the collection of historical information. RESULTS: Of 10,678 surveys mailed, 6609 were returned (6533 men, 63 women). Given the limitations of survey methodology, increased disease rates among pilots were suggested for melanoma, motor neuron disease, and cataracts. However, rates for other diseases were in general lower than those for the U.S. population. CONCLUSIONS: Further study has been initiated to verify and follow reported cases, to expand the study to a larger group, and to collect more in-depth information on flight histories, occupational exposures, and lifestyle factors.

Biologically-based risk estimation for radiation-induced chronic myeloid leukemia.

Radiation cancer risks are typically determined by the use of simple statistical descriptions of epidemiological data. It is important in risk assessment in general, however, to attempt to incorporate as much biological information into the risk models as possible. We illustrate this by presenting a biologically-based linear-quadratic-exponential (LQE) incidence rate model for radiation-induced chronic myeloid leukemia (CML). The model consists of a linear-quadratic dose-response for the induction of BCR-ABL, a waiting time distribution between BCR-ABL formation and detection of CML, and an exponential cell-killing term that multiplies both the background and induced incidence rates. Using data exclusive of the A-bomb survivor cohort, Bayesian priors are defined for each of the nine parameters in this LQE model. The priors are based on chromosomal translocations in lymphocytes, hematopoietic stem cell survival experiments, CML waiting times in women irradiated for benign disease, the background CML incidence rate in the U.S. population, and genomic DNA target sizes of BCR and ABL. Fixing three of the LQE model parameters to the means of their priors, maximum likelihood estimates of the remaining six parameters were obtained using A-bomb survivor incidence data for Hiroshima males. The likelihood estimates and the corresponding six prior distributions, both approximated as multivariate normal, were then used to form Bayesian posteriors for the six parameters not fixed. With these posteriors the LQE model yields Qgamma*=0.0042 Gy(-1) where Qgamma* is the upper 95% confidence bound of the lifetime CML risk per person-gray in the limit of low doses of gamma-rays. This value is slightly less than Qgamma*=0.0049 Gy(-1) obtained from likelihood estimates of the LQE parameters, and substantially less than Qgamma*=0.0158 Gy(-1) obtained for a simple statistical model linear in dose for kermas less than 4 Gy.

Geographic patterns of pulmonary disease in south carolina.

PURPOSE: The purpose of this study is to assess the patterns of geographic variation of the following pulmonary diseases: tuberculosis (TB), lung cancer (LC), berylliosis (BR), sarcoidosis (SR), and asthma (AS).METHODS: Hospitalization rates for the five diseases were calculated for the 46 South Carolina (SC) counties from 1985-1995. Variation in rates was assessed by county, region, and urban/rural status using analysis of variance. SC was divided into 4 regions, according to proximity to the coastline and to physiographic characteristics. Region 1 comprised counties in the western-most part of the state, and region 4 comprised the counties closest to the coastline. SC was also divided into 5 population density settings: extreme rural (<15,000), rural (15,000-30,000), middle-size (30,000-50,000), middle-urban (50,000-100,000) and urban (>100,000). Statistical analyses were performed with SAS Version 8.RESULTS:Table 1The rates of SR, TB, and BR were significantly higher in the coastal region. In contrast, no coastal pattern was detected by population density.CONCLUSIONS: The consistent association of SR, TB, and BR with geographical region, as opposed to the inconsistent association with population density, suggests that environmental factors may be involved in these pulmonary diseases. These results demonstrate the need for further analysis of the relationship between socio-economic, behavioral, and environmental factors and the development of these diseases.