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Biomedical subjects

Weidong Gu

Publications and source records attributed to Weidong Gu.

At least 19 recordsLinked to original sources

Source reduction of mosquito larval habitats has unexpected consequences on malaria transmission.

Reduction of aquatic habitats through environmental management mitigates malaria transmission not only by reducing emergence of host-seeking mosquitoes, but also by increasing the amount of time required for vectors to locate oviposition sites. However, the consequence of source reduction on mosquito oviposition has largely been neglected in evaluations of environment-management programs. Here, by theoretically examining the relationship between the time spent for oviposition and the availability of aquatic habitats, we show that prolonged oviposition cycles induced by source reduction account for a great deal of reductions in the basic reproductive rate of malaria, especially when aquatic habitats are scarce and the mosquito's flight ability is limited. Neglecting this mechanism may lead to substantial underestimation of the impact of source reduction of aquatic habitats on malaria transmission. Our findings suggest that the prolonged duration of the gonotrophic cycle might be one of the important mechanisms underlying the effectiveness of environment-management interventions for malaria control.

Animals↗

Spatio-temporal analyses of West Nile virus transmission in Culex mosquitoes in northern Illinois, USA, 2004.

After a severe outbreak of West Nile virus (WNV) in Cook County, Illinois, in 2002, detections of WNV in mosquitoes were frequent across the state in the following years despite small numbers of human cases. We conducted a spatio-temporal analysis of Culex (subgenus Culex) mosquitoes collected in 2004 in three mosquito abatement districts (MAD) in Cook County by calculating monthly estimates of mosquito density, prevalence of infected mosquitoes, and exposure intensity, which in turn is a product of mosquito density and infection rates. Mosquito infections were detected early at three sites in late May and were widely detected throughout the three MADs in the summer with infection rates as high as 13 per 1000 in August. Exposure intensities were higher at sites adjacent to the Des Plaines River, especially in August and September. The aggregated pattern of WNV transmission along the river might be related to the existence of substantial forest preserves and wetlands that might produce ecological conditions favorable for mosquito proliferation and interactions between mosquitoes and birds.

Animals↗

Statistical estimation of degree days of mosquito development under fluctuating temperatures in the field.

Degree-days are important parameters for developing predictive models of mosquito populations. Conventional methods of estimation of degree-days are typically applied to observations under constant temperatures in the laboratory. These methods are difficult to apply in the field where temperatures fluctuate. For estimating degree-days of larval developments of mosquitoes in the field, we applied Dennis' stochastic phenological model to a semi-field observation of Culex restuans. A parametric bootstrap approach was introduced to estimate standard errors of the parameters. We found that the estimated degree-days varied with various assumptions about the temperature base. Given the latter, the model can satisfactorily estimate the degree-days of larval and pupal developments of Cx. resturans. This approach is especially useful to measure spatio-temporal variability in larval development among various types of aquatic habitats.

Animals↗

Mosquito species diversity and abundance in relation to land use in a riceland agroecosystem in Mwea, Kenya.

We conducted an entomological survey to determine the mosquito species diversity and abundance in relation to land use in the Mwea rice scheme, Kenya. Adult mosquitoes were collected by indoor spraying of houses and outdoors by CDC light traps in three villages representing planned (Mbuinjeru) and unplanned (Kiamachiri) rice agroecosystems and a non-irrigated agroecosystem (Murinduko). During the 12-month sampling period, a total of 98,708 mosquitoes belonging to five genera and 25 species were collected. The five most common species collected during this study were Anopheles arabiensis Patton (52.5%), Culex quinquefasciatus Say (36.7%), Anopheles pharoensis Theobald (5.2%), Anopheles coustani Laveran (1.4%), and Anopheles funestus Giles (1.3%). Anopheles arabiensis, Cx quinquefasciatus, and An. pharoensis were more abundant in rice agroecosystems than in the non-irrigated agroecosystem, and in planned than in the unplanned rice agroecosystems. In contrast, An. funestus was more abundant in the non-irrigated agroecosystem. The mosquito species diversity (H) and evenness (E(H)) in the non-irrigated agroecosystem (Shannon diversity Index, H = 1.507, EH = 0.503) was significantly higher than in the rice agroecosystems (H) = 0.968, E(H) = 0.313, unplanned; and H= 1.040, E(H) = 0.367 planned). Results of lag cross correlation analysis revealed a strong relationship between rainfall and the abundance of An. arabiensis, and C. quinquefasciatus in the non-irrigated agroecosystem but not in the rice agroecosystems. It is inferred from the data that different levels of habitat perturbations with regard to rice cultivation have different effects on mosquito diversity and abundance. This provides an understanding of how mosquito diversity is impacted by different habitat management and rice cropping strategies.

Agriculture↗

Modeling the impact of variable climatic factors on the crossover of Culex restauns and Culex pipiens (Diptera: culicidae), vectors of West Nile virus in Illinois.

The aim of this study was to model the impact of temperature on the timing of the seasonal shift in relative proportion of Culex restuans Theobald and Culex pipiens L. in Illinois. The temporal pattern of West Nile virus (WNV) and St. Louis encephalitis virus transmission in the midwest exhibits a late summer to early fall peak in activity, which parallels the temporal increase in the abundance of Cx. pipiens. The daily number of egg rafts oviposited by each species has been monitored at multiple surveillance sites in Urbana-Champaign in central Illinois for more than 13 years. The time when the two Culex species are in equal abundance (crossover) varies considerably from year to year. Our investigation of several thermal measures indicated that this variation was related in large part to climatic conditions with warmer (cooler) temperatures correlated to earlier (later) crossover dates. Models based on degree days and the number of days in which the daily maximum temperature exceeded an upper temperature threshold explained more than 60% of the variance in crossover dates. In contrast, models based on the number of days in which the daily minimum temperature exceeded a lower temperature threshold explained no more than 52% of the variance. An evaluation of these models demonstrated that they provide relatively simple and accurate estimates of crossover date from daily temperature data, a necessary component for developing an overall climatic index for the risk of WNV transmission in Illinois.

Animals↗

Habitat-based modeling of impacts of mosquito larval interventions on entomological inoculation rates, incidence, and prevalence of malaria.

Larval control of Anopheles mosquitoes has long been neglected in tropical Africa due to uncertainties about its impacts on incidence and prevalence of malaria. Population models of mosquitoes are a useful tool to provide qualitative and quantitative understandings of influences of larval interventions on malaria transmission. For these purposes, we develop a new modeling framework by conceiving a quantity of the total productivity in an area, which, in turn, can be partitioned into its constituent parts from individual habitats. Three scenarios of larval interventions were evaluated in relation to impacts on parasitological indicators of malaria transmission. Our results show that it is unnecessary to manage all aquatic habitats to obtain significant reductions in incidence and prevalence of malaria in situations of low and intermediate levels of transmission. We highlight that informed larval interventions featured by identifying and targeting prolific habitats can play a critical role in combating malaria in Africa.

Animals↗

Autologous vascular smooth muscle cell-based myocardial gene therapy to induce coronary collateral growth.

For therapeutic angiogenesis to achieve clinical relevance, it must be effective, with minimal side effects to other end organ systems. We developed a cardiac-specific gene delivery mechanism by transfecting autologous vascular smooth muscle cells (VSMC) with VEGF and administering these cells via intracoronary injection. We evaluated the efficacy of this protocol by its ability to stimulate angiogenesis in the presence of a subthreshold stimulus for collateralization. A modified canine repetitive coronary occlusion model was utilized in these experiments with left anterior descending coronary artery occlusions for 2 min every 2 h four times per day for 21 days. An intramyocardial catheter in the perfusion territory of the left anterior descending coronary artery measured proteins in the myocardial interstitial fluid. VSMC from jugular vein explants were isolated, amplified in culture for 3 wk, and transfected with a plasmid expressing VEGF-165 and/or enhanced green fluorescent protein. Cells were injected before commencement of occlusions. VEGF levels in myocardial interstitial fluid were significantly higher in VEGF-transfected animals than in sham (repetitive occlusions without cell transplantation) and control (repetitive occlusions with enhanced green fluorescent protein-transfected cells) animals at the onset of occlusions (P < 0.05). In the VEGF group, collateral flow was increased at day 7 and remained higher than in sham and control groups thereafter. We found that intracoronary administration of VEGF-transfected autologous VSMC effectively promotes collateral development. This approach may provide a way to confine delivery of a gene to a specified organ, thus minimizing complications related to gene transfection in nontargeted organ systems.

Alkaline Phosphatase↗

Short report: detection probability of arbovirus infection in mosquito populations.

An important component of arbovirus surveillance is monitoring the vector for presence of the pathogen. Intervention and preventive programs need early detection of arboviral activity in mosquito populations. In this report, we examine the factors affecting the probability of detection of mosquito infections. Since arbovirus infection rates in mosquito populations are very low, observations of zero-infected mosquito samples are common. Using statistical models, we describe methods to estimate the probability of detection and upper bounds of confidence intervals of mosquito infection rates as measures of confidence for observations of zero infection. Our results show that detection of low levels of mosquito infections requires large samples (greater than 1,600 individuals) for a high probability (0.8) of detection. Due to focal transmission of arboviruses, grouping samples over different sampling sites and times is often inappropriate for detection of mosquito infection. We emphasize sample size as a key determinant in detection of mosquito infections and recommend intensified entomologic surveys at sentinel sites to detect arboviral activity.

Animals↗

Reactive oxygen species are critical mediators of coronary collateral development in a canine model.

Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n = 8) or presence of N-acetylcysteine (NAC) (occlusion + NAC, n = 8). A sham group (n = 8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71 +/- 7%) in occlusion dogs after 21 days but remained unchanged (13 +/- 3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28 +/- 8%). Brief coronary artery occlusion and reperfusion caused ROS production (256 +/- 33% of baseline values), which was abolished with NAC (104 +/- 12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation.

Animals↗

Low recovery rates stabilize malaria endemicity in areas of low transmission in coastal Kenya.

The prevalence of Plasmodium falciparum malaria in African communities can be high and stable even in areas of relatively low transmission where people expose to only a few infectious bites per year. We show in this field study conducted in 30 sites along the coastal Kenya that prevalence in school children was consistently high, although there were many sites where transmission intensity measured by exposure to infectious bites was less than 10 per year. Statistical analyses revealed that prevalence was significantly correlated with the infectious exposure occurring 10-11 months previously, suggesting that long-lived infections were commonplace and one of the major contributors for the stability of malaria in these sites. Using mechanistic models of malaria transmission, we found that the association of high prevalence and low transmission could be due to low recovery rates. Therefore, significant reductions of malaria prevalence and burden require substantial reductions of the duration of acquired infections, even in areas that have quite low transmission intensities by the standards of sub-Saharan Africa. Infection control featured by active detection and drug treatment as well as vector control is critical to combat malaria in areas of relatively low transmission intensity.

Animals↗

Taking malaria transmission out of the bottle: implications of mosquito dispersal for vector-control interventions.

Most malaria transmission models assume enclosed systems of people, parasites, and vectors in which neither emigration nor immigration of mosquitoes is considered. This simplification has facilitated insightful analyses but has substantial limitations for evaluating control measures in the field. Here we show that mosquito dispersal can confound conventional approaches to evaluating malaria vector-control interventions, and explore this association with a model of two villages between which mosquito subpopulation exchange occurs. Exchange of mosquitoes between such subpopulations can readily explain the discrepancy between experimental efficacy measurements for insecticide-treated nets and their much lower apparent effectiveness when in use. Our results indicate that current approaches to assessing malaria interventions that confer community-level protection may be severely compromised by mosquito dispersal in many endemic settings. The true effectiveness of many vector-control methods may be much greater than previously appreciated and the application of such interventions should be consolidated into larger contiguous spatial units so that more effective local suppression of malaria can be achieved. Spatially explicit modelling formats that consider vector dispersal as a determinant of malaria transmission and control are needed urgently for rational planning and evaluation of efforts to roll back malaria.

Animals↗

Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast.

The seasonal dynamics and spatial distributions of Anopheles mosquitoes and Plasmodium falciparum parasites were studied for one year at 30 villages in Malindi, Kilifi, and Kwale Districts along the coast of Kenya. Anopheline mosquitoes were sampled inside houses at each site once every two months and malaria parasite prevalence in local school children was determined at the end of the entomologic survey. A total of 5,476 Anopheles gambiae s.l. and 3,461 An. funestus were collected. Species in the An. gambiae complex, identified by a polymerase chain reaction, included 81.9% An. gambiae s.s., 12.8% An. arabiensis, and 5.3% An. merus. Anopheles gambiae s.s. contributed most to the transmission of P. falciparum along the coast as a whole, while An. funestus accounted for more than 50% of all transmission in Kwale District. Large spatial heterogeneity of transmission intensity (< 1 up to 120 infective bites per person per year) resulted in correspondingly large and significantly related variations in parasite prevalence (range = 38-83%). Thirty-two percent of the sites (7 of 22 sites) with malaria prevalences ranging from 38% to 70% had annual entomologic inoculation rates (EIR) less than five infective bites per person per year. Anopheles gambiae s.l. and An. funestus densities in Kwale were not significantly influenced by rainfall. However, both were positively correlated with rainfall one and three months previously in Malindi and Kilifi Districts, respectively. These unexpected variations in the relationship between mosquito populations and rainfall suggest environmental heterogeneity in the predominant aquatic habitats in each district. One important conclusion is that the highly non-linear relationship between EIRs and prevalence indicates that the consistent pattern of high prevalence might be governed by substantial variation in transmission intensity measured by entomologic surveys. The field-based estimate of entomologic parameters on a district level does not provide a sensitive indicator of transmission intensity in this study.

Animals↗

Distribution of anopheline mosquitoes in Eritrea.

The spatial distribution of anopheline mosquito species was studied throughout Eritrea during the 1999-2001 malaria transmission seasons from October to December for the highlands and western lowlands and February to April for the coastal region. Of the 302 villages sampled, 59 were visited in both the first and second year. Overall, 13 anopheline species were identified, with the Anopheles gambiae complex predominating during the first year (75.6%, n = 861) and the second year (91.9%, n = 1,262). Intrazonal variation accounted for 90% of the total variation in mosquito distribution. Polymerase chain reaction results indicated that 99% (n = 1,309) of the An. gambiae s.l. specimens were An. arabiensis, indicating that this was the only member of the gambiae complex present. There was a high degree of aggregation of anophelines within zones and villages, with more than 80% of the total anophelines being collected from less than 20% of the villages and from only 10% of the houses sampled. At least 80% of the anopheline mosquitoes were collected from grass-thatched Agudo-type housing. Vector abundance showed an inverse relationship with elevation, with highest densities in the low-lying western lowlands. Multiple regression analysis of log-transformed mean density of An. arabiensis with rainfall and the normalized difference vegetation index (NDVI) (average NDVI, minimum NDVI, and maximum NDVI) showed that these independent variables were not significantly associated with mosquito densities (R2 = 0.058). Our study contributes to the basic understanding of the ecology and distribution of malaria vectors with respect to species composition and spatial heterogeneities both that could be used to guide vector control operations in Eritrea.

Animals↗

Isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo.

UNLABELLED: The administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction similar to those of ischemic preconditioning. A second window of preconditioning (SWOP) against myocardial infarction can also be elicited by brief episodes of ischemia when this occurs 24 h before prolonged coronary artery occlusion. Whether remote exposure to a volatile anesthetic also causes delayed myocardial protection is unknown. We tested the hypothesis that the administration of isoflurane 24 h before ischemia produces a SWOP against infarction. Barbiturate-anesthetized dogs (n = 25) were instrumented for measurement of hemodynamics, including aortic and left ventricular (LV) pressures and LV +dP/dt(max), and subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Two groups of dogs received 1.0 minimum alveolar anesthetic concentration isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Infarct size was 27% +/- 3% of the LV area at risk in the absence of pretreatment with isoflurane. Acute, but not remote, administration of isoflurane reduced infarct size (12% +/- 1% and 31% +/- 3%, respectively). No differences in hemodynamics or transmural myocardial perfusion during or after occlusion were observed between groups. The results indicate that isoflurane does not produce a SWOP when administered 24 h before prolonged myocardial ischemia in vivo. IMPLICATIONS: Isoflurane mimics the beneficial effects of ischemic preconditioning by protecting myocardium against infarction when it is administered shortly before a prolonged ischemic episode. However, unlike ischemic preconditioning, isoflurane does not produce a second window of protection 24 h after administration in dogs.

Anesthetics, Inhalation↗

Isoflurane-induced preconditioning is attenuated by diabetes.

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated K(+) channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 +/- 3% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 +/- 2 and 13 +/- 1% during 0.32 and 0.64% concentrations; n = 8 and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 +/- 3%; n = 8) but blocked the protective effects of 0.32% (27 +/- 2%; n = 7) and not 0.64% isoflurane (18 +/- 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning.

Anesthetics, Inhalation↗

An individual-based model of Plasmodium falciparum malaria transmission on the coast of Kenya.

Individual-based models provide powerful tools to model complex interactions characterized by individual variability. This paper presents an object-oriented design for individual-based modelling of Plasmodium falciparum malaria transmission. Two kinds of objects, human and mosquito, that exhibit variability among individuals for parameters such as recovery and survival rates are defined. The model tracks the dynamics of human hosts and adult female mosquitoes individually. Immunity, modelled as a function of exposure history, is represented by reduced susceptibility and increased recovery rate. The model was calibrated using epidemiological data collected at 30 sites along the coast of Kenya. The sites were grouped into low, intermediate and high transmission based on mean daily human-biting rates. Simulation results show that malaria transmission was stable even in low transmission areas where the human-biting rate is approximately 0.5 bite per day. The model was used to examine the effect of infection control programmes that aim at interrupting transmission by reducing human-vector contact rates and implementing active case detection and drug treatment of infections. With this intervention, local elimination of malaria is likely with a probability of extinction of approximately 0.8 in low transmission areas. However, a small amount of immigration (> 0.3%) by infected people into the community could prevent local extinction of the parasite. In intermediate and high transmission areas, reduction in prevalence is short-lived and the probability of local elimination is low, even at high coverage levels of the intervention.

Age Distribution↗