Modeling Optimal Age-Specific Vaccination Strategies Against Pandemic Influenza

In the context of pandemic influenza, the prompt and effective implementation of control measures is of great concern for public health officials around the world. In particular, the role of vaccination should be considered as part of any pandemic preparedness plan. The timely production and efficient distribution of pandemic influenza vaccines are important factors to consider in mitigating the morbidity and mortality impact of an influenza pandemic, particularly for those individuals at highest risk of developing severe disease. In this paper, we use a mathematical model that incorporates age-structured transmission dynamics of influenza to evaluate optimal vaccination strategies in the epidemiological context of the Spring 2009 A (H1N1) pandemic in Mexico. We extend previous work on age-specific vaccination strategies to time-dependent optimal vaccination policies by solving an optimal control problem with the aim of minimizing the number of infected individuals over the course of a single pandemic wave. Optimal vaccination policies are computed and analyzed under different vaccination coverages (21%–77%) and different transmissibility levels (R₀\mathcal{R}_{0} in the range of 1.8–3). The results suggest that the optimal vaccination can be achieved by allocating most vaccines to young adults (20–39 yr) followed by school age children (6–12 yr) when the vaccination coverage does not exceed 30%. For higher R₀\mathcal{R}_{0} levels ($\mathcal{R}_{0}>=2.4$\mathcal{R}_{0}>=2.4), or a time delay in the implementation of vaccination (>90 days), a quick and substantial decrease in the pool of susceptibles would require the implementation of an intensive vaccination protocol within a shorter period of time. Our results indicate that optimal age-specific vaccination rates are significantly associated with R₀\mathcal{R}_{0}, the amount of vaccines available and the timing of vaccination.     

Antioxidant system in programmed cell death of sycamore (<Emphasis Type="Italic">Acer pseudoplatanus</Emphasis> L.) cultured cells

Reactive oxygen species (ROS) have pleiotropic effects in plants. ROS can lead to cellular damage and death or play key roles in control and regulation of biological processes, such as programmed cell death (PCD). This dual role of ROS, as toxic or signalling molecules, is possible because plant antioxidant system (AS) is able to achieve a tight control over ROS cellular levels, balancing properly their production and scavenging. AS response in plant PCD has been clearly described only in the hypersensitive response in incompatible plant–pathogen interactions and in the senescence process and has not been completely unravelled. In sycamore (Acer pseudoplatanus L.) cultured cells PCD can be induced by Fusicoccin (Fc), Tunicamycin (Tu), and Brefeldin A (Ba). These chemicals induce comparable PCD time course and extent, while H₂O₂ production is detectable only in Fc- and, to a lesser extent, in Ba-treated cells. In this paper the AS has been investigated during PCD of sycamore cells, measuring the effects of the three inducers on the cellular levels of non-enzymatic and enzymatic antioxidants. Results show that the AS behaviour is different in the PCD induced by the three chemicals. In Fc-treated cells AS is mainly devoted to decrease the concentration of toxic intracellular H₂O₂ levels. On the contrary, in cells treated with Tu and Ba, the cell redox state is shifted to a more reduced state and the enzymatic AS is partially down-regulated, allowing ROS to act as signalling molecules.     

Female reproductive behaviour,ovarian hormones and vaginal cytology of the induced ovulator, <Emphasis Type="Italic">Ctenomys talarum</Emphasis>

In the present study, we evaluated whether reproductive condition affects female reproductive behaviour in the induced ovulator Ctenomys talarum. We also explored the effect of the interaction with a male on the reproductive condition of females. To evaluate this, we arranged mating trials and evaluated female reproductive behaviour. Reproductive status of females was evaluated using a combined approach of vaginal smears, urinary progesterone and oestradiol, and ovarian histology. Behaviours denoting attraction (‘male sniff’ and ‘mount attempts’) and mutual courtship behaviours (‘spin’ and copula) were correlated with vaginal cytology before and oestradiol and progesterone levels in urine 12 h after male–female encounter. After 24 h of the interaction, oestradiol levels and vaginal epithelization increased while progesterone levels decreased in soliciting females. C. talarum females’ reproductive behaviour was related to its physiological reproductive state and vaginal cytology. The kind of male interaction, whether couples copulated or remained indifferent affected the later status of females. Females are induced ovulators by mating but male presence and interaction also affected other components of their reproductive physiology such as ovarian hormones and vaginal cytology.     

Headgroup Conformations of Phospholipids from Molecular Dynamics Simulation: Sampling Challenges and Comparison to Experiment

The preferred conformations of the glycerol region of a phospholipid have been explored using replica exchange molecular dynamics (MD) simulations and compared with the results of standard MD approaches and with experiment. We found that due to isomerization rates in key torsions that are slow on the timescale of atomistic MD simulations, standard MD is not able to produce accurate equilibrium conformer distributions from reasonable trajectory lengths (e.g., on the 100 ns) timescale. Replica exchange MD, however, results in quite efficient sampling due to the rapid increase in isomerization rate with temperature. The equilibrium distributions obtained from replica exchange MD have been compared with the results of experimental nuclear magnetic resonance observations. This comparison suggests that the sampling approach demonstrated here is a valuable tool that can be used in evaluating force fields for molecular simulation of lipids.     

Assessment of hybrid vigor between flightless lines to restore survival and reproductive characteristics in the ladybird beetle <Emphasis Type="Italic">Harmonia axyridis</Emphasis>

The effectiveness of hybrid vigor, which can counteract deleterious effects of inbreeding in flightless Harmonia axyridis Pallas (Coleoptera: Coccinellidae), was investigated. First, we performed the reciprocal cross between two isofemale lines and compared survival and reproductive characteristics between isofemale and hybrid lines under laboratory conditions. The survival of one of the hybrid lines was significantly higher than that of the two isofemale lines. Early fecundity tended to be higher in the two hybrid lines than in the two isofemale lines. Second, we compared the effectiveness of control of Aphis gossypii Glover (Homoptera: Aphididae) between isofemale and hybrid lines by release experiments in greenhouses. The number of A. gossypii was suppressed in treatments in which two hybrid lines were released compared with those in which two isofemale lines were released. These results suggest that hybrid vigor is effective as a method for assuring the quality of flightless H. axyridis.     

Phenology constrains opportunistic growth response in <Emphasis Type="Italic">Bromus tectorum</Emphasis> L.

Seasonal resource availability may act as a constraint on plant phenology and thereby influence the range of growth responses observed among populations of annual species, especially those occupying a wide range of environments. We compared a mesic and a xeric population of the non-native, annual grass, Bromus tectorum, to examine phenology in response to interspecific competition and water availability. Using a target-neighborhood approach, we assessed how phenological patterns of the two populations affected morphological and growth responses to enhanced resource availability represented by late-season soil moisture. The xeric population exhibited a highly constrained phenology and was unable to extend the growing season despite available soil resources. Because of the low phenotypic variation, allocation to reproduction was similar across resource conditions. In contrast, the mesic population flowered later and showed a more opportunistic phenology in response to late-season water availability. The mesic population was not able to maintain consistent reproductive allocation at low resource levels. The responses of the two populations to late-season water availability were not affected by the density of neighboring plants. We suggest that post-introduction selection pressure on B. tectorum in the xeric habitat has resulted in a more fixed phenology which limits opportunistic response to unpredictable, particularly late-season resource availability. Opportunistic and fixed responses represent contrasting strategies for optimizing fitness in temporally varying environments and, while both play important roles for ensuring reproductive success, these results suggest that local adaptation to temporal resource variation may reflect a balance between flexible and inflexible phenology.     

Development of a loop-mediated isothermal amplification assay for detection of <Emphasis Type="Italic">Cronobacter</Emphasis> spp. (<Emphasis Type="Italic">Enterobacter sakazakii</Emphasis>)

Contamination of Cronobacter spp. (Enterobacter sakazakii) in infant formulas and other food products is a severe problem. Here a loop-mediated isothermal amplification (LAMP) assay was developed for rapidly detecting Cronobacter spp. in powdered infant formula. Sequences of 16S/23S rDNA internal intergenic spacer of Cronobacter spp. were used as the target template to design LAMP primers. The detection outcome can be evaluated by the white precipitate or the fluorescence intensity under ultraviolet irradiation, both visible to naked eyes. The sensitivity and specificity of the LAMP assay was further analyzed in comparison with that of regular PCR and real time quantitative PCR. The results showed that all of Cronobacter spp. strains display positive reaction to the detections while all of the non-Cronobacter spp. strains were negative, and that the LAMP assay exhibits a high sensitivity of 9.1 fg/μL (The sensitivity of regular PCR and real time quantitative PCR is 91 and 9.1 pg/μL, respectively.). The amplified reaction could be accomplished in about 1 h, with the results visible to naked eyes. Hence, the LAMP assay developed by this study can provide a rapid and simple approach for the detection of Cronobacter spp. in infant formula.     

Spatial dimensions of dengue virus transmission across interepidemic and epidemic periods in Iquitos, Peru (1999-2003)

Background

Knowledge of spatial patterns of dengue virus (DENV) infection is important for understanding transmission dynamics and guiding effective disease prevention strategies. Because movement of infected humans and mosquito vectors plays a role in the spread and persistence of virus, spatial dimensions of transmission can range from small household foci to large community clusters. Current understanding is limited because past analyses emphasized clinically apparent illness and did not account for the potentially large proportion of inapparent infections. In this study we analyzed both clinically apparent and overall infections to determine the extent of clustering among human DENV infections.

Methodology/Principal Findings

We conducted spatial analyses at global and local scales, using acute case and seroconversion data from a prospective longitudinal cohort in Iquitos, Peru, from 1999–2003. Our study began during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned to epidemic DENV-3 transmission. Infection status was determined by seroconversion based on plaque neutralization testing of sequential blood samples taken at approximately six-month intervals, with date of infection assigned as the middate between paired samples. Each year was divided into three distinct seasonal periods of DENV transmission. Spatial heterogeneity was detected in baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence calculated by trimester from 2001–2003 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley''s K statistic) appeared at radii of ∼200–800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999–2003. The number of seroconversions per cluster ranged from 3–34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. No clustering was detected among clinically apparent infections.

Conclusions/Significance

Seroprevalence of previously circulating DENV serotypes can be a predictor of transmission risk for a different invading serotype and, thus, identify targets for strategically placed surveillance and intervention. Seroprevalence of a specific serotype is also important, but does not preclude other contributing factors, such as mosquito density, in determining where transmission of that virus will occur. Regardless of the epidemiological context or virus serotype, human movement appears to be an important factor in defining the spatial dimensions of DENV transmission and, thus, should be considered in the design and evaluation of surveillance and intervention strategies.