Implications of spatially heterogeneous vaccination coverage for the risk of congenital rubella syndrome in South Africa

Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Since vaccination at levels short of those necessary to achieve eradication may increase the average age of infection, and thus potentially the CRS burden, introduction of the vaccine has been limited to contexts where coverage is high. Recent work suggests that spatial heterogeneity in coverage should also be a focus of concern. Here, we use a detailed dataset from South Africa to explore the implications of heterogeneous vaccination for the burden of CRS, introducing realistic vaccination scenarios based on reported levels of measles vaccine coverage. Our results highlight the potential impact of country-wide reductions of incidence of rubella on the local CRS burdens in districts with small population sizes. However, simulations indicate that if rubella vaccination is introduced with coverage reflecting current estimates for measles coverage in South Africa, the burden of CRS is likely to be reduced overall over a 30 year time horizon by a factor of 3, despite the fact that this coverage is lower than the traditional 80 per cent rule of thumb for vaccine introduction, probably owing to a combination of relatively low birth and transmission rates. We conclude by discussing the likely impact of private-sector vaccination.     

Characterizing the dynamics of rubella relative to measles: the role of stochasticity

Rubella is a completely immunizing and mild infection in children. Understanding its behaviour is of considerable public health importance because of congenital rubella syndrome, which results from infection with rubella during early pregnancy and may entail a variety of birth defects. The recurrent dynamics of rubella are relatively poorly resolved, and appear to show considerable diversity globally. Here, we investigate the behaviour of a stochastic seasonally forced susceptible–infected–recovered model to characterize the determinants of these dynamics and illustrate patterns by comparison with measles. We perform a systematic analysis of spectra of stochastic fluctuations around stable attractors of the corresponding deterministic model and compare them with spectra from full stochastic simulations in large populations. This approach allows us to quantify the effects of demographic stochasticity and to give a coherent picture of measles and rubella dynamics, explaining essential differences in the recurrent patterns exhibited by these diseases. We discuss the implications of our findings in the context of vaccination and changing birth rates as well as the persistence of these two childhood infections.     

Introduction of rubella-containing-vaccine to Madagascar: implications for roll-out and local elimination

Few countries in Africa currently include rubella-containing vaccination (RCV) in their immunization schedule. The Global Alliance for Vaccines Initiative (GAVI) recently opened a funding window that has motivated more widespread roll-out of RCV. As countries plan RCV introductions, an understanding of the existing burden, spatial patterns of vaccine coverage, and the impact of patterns of local extinction and reintroduction for rubella will be critical to developing effective programmes. As one of the first countries proposing RCV introduction in part with GAVI funding, Madagascar provides a powerful and timely case study. We analyse serological data from measles surveillance systems to characterize the epidemiology of rubella in Madagascar. Combining these results with data on measles vaccination delivery, we develop an age-structured model to simulate rubella vaccination scenarios and evaluate the dynamics of rubella and the burden of congenital rubella syndrome (CRS) across Madagascar. We additionally evaluate the drivers of spatial heterogeneity in age of infection to identify focal locations where vaccine surveillance should be strengthened and where challenges to successful vaccination introduction are expected. Our analyses indicate that characteristics of rubella in Madagascar are in line with global observations, with an average age of infection near 7 years, and an impact of frequent local extinction with reintroductions causing localized epidemics. Modelling results indicate that introduction of RCV into the routine programme alone may initially decrease rubella incidence but then result in cumulative increases in the burden of CRS in some regions (and transient increases in this burden in many regions). Deployment of RCV with regular supplementary campaigns will mitigate these outcomes. Results suggest that introduction of RCV offers a potential for elimination of rubella in Madagascar, but also emphasize both that targeted vaccination is likely to be a lynchpin of this success, and the public health vigilance that this introduction will require.     

Evaluating strategies for spatial allocation of vaccines based on risk and centrality

When vaccinating a large population in response to an invading pathogen, it is often necessary to prioritize some individuals to be vaccinated first. One way to do this is to choose individuals to vaccinate based on their location. Methods for this prioritization include strategies that target those regions most at risk of importing the pathogen, and strategies that target regions with high centrality on the travel network. We use a simple infectious disease epidemic model to compare a risk-targeting strategy to two different centrality-targeting strategies based on betweenness centrality and random walk percolation centrality, respectively. We find that the relative effectiveness of these strategies in reducing the total number of infections varies with the basic reproduction number of the pathogen, travel rates, structure of the travel network and vaccine availability. We conclude that when a pathogen has high spreading capacity, or when vaccine availability is limited, centrality-targeting strategies should be considered as an alternative to the more commonly used risk-targeting strategies.     

Pedestrian signalization and the risk of pedestrian-motor vehicle collisions in Lima,Peru

Safe walking environments are essential for protecting pedestrians and promoting physical activity. In Peru, pedestrians comprise over three-quarters of road fatality victims. Pedestrian signalization plays an important role managing pedestrian and vehicle traffic and may help improve pedestrian safety. We examined the relationship between pedestrian-motor vehicle collisions and the presence of visible traffic signals, pedestrian signals, and signal timing to determine whether these countermeasures improved pedestrian safety. A matched case-control design was used where the units of study were crossing locations. We randomly sampled 97 control-matched collisions (weighted N = 1134) at intersections occurring from October, 2010 to January, 2011 in Lima. Each case-control pair was matched on proximity, street classification, and number of lanes. Sites were visited between February, 2011 and September, 2011. Each analysis accounted for sampling weight and matching and was adjusted for vehicle and pedestrian traffic flow, crossing width, and mean vehicle speed. Collisions were more common where a phased pedestrian signal (green or red-light signal) was present compared to no signalization (odds ratio [OR] 8.88, 95% Confidence Interval [CI] 1.32–59.6). A longer pedestrian-specific signal duration was associated with collision risk (OR 5.31, 95% CI 1.02–9.60 per 15-s interval). Collisions occurred more commonly in the presence of any signalization visible to pedestrians or pedestrian-specific signalization, though these associations were not statistically significant. Signalization efforts were not associated with lower risk for pedestrians; rather, they were associated with an increased risk of pedestrian-vehicle collisions.     

Effects of heterogeneity in infection-exposure history and immunity on the dynamics of a protozoan parasite

Infection systems where traits of the host, such as acquired immunity, interact with the infection process can show complex dynamic behaviour with counter-intuitive results. In this study, we consider the traits ‘immune status’ and ‘exposure history’, and our aim is to assess the influence of acquired individual heterogeneity in these traits. We have built an individual-based model of Eimeria acervulina infections, a protozoan parasite with an environmental stage that causes coccidiosis in chickens. With the model, we simulate outbreaks of the disease under varying initial contaminations. Heterogeneity in the traits arises stochastically through differences in the dose and frequency of parasites that individuals pick up from the environment. We find that the relationship between the initial contamination and the severity of an outbreak has a non-monotonous ‘wave-like’ pattern. This pattern can be explained by an increased heterogeneity in the host population caused by the infection process at the most severe outbreaks. We conclude that when dealing with these types of infection systems, models that are used to develop or evaluate control measures cannot neglect acquired heterogeneity in the host population traits that interact with the infection process.     

Shear-induced orientational dynamics and spatial heterogeneity in suspensions of motile phytoplankton

Fluid flow, ubiquitous in natural and man-made environments, has the potential to profoundly impact the transport of microorganisms, including phytoplankton in aquatic habitats and bioreactors. Yet, the effect of ambient flow on the swimming behaviour of phytoplankton has remained poorly understood, largely owing to the difficulty of observing cell–flow interactions at the microscale. Here, we present microfluidic experiments where we tracked individual cells for four species of motile phytoplankton exposed to a spatially non-uniform fluid shear rate, characteristic of many flows in natural and artificial environments. We observed that medium-to-high mean shear rates (1–25 s⁻¹) produce heterogeneous cell concentrations in the form of regions of accumulation and regions of depletion. The location of these regions relative to the flow depends on the cells'' propulsion mechanism, body shape and flagellar arrangement, as captured by an effective aspect ratio. Species having a large effective aspect ratio accumulated in the high-shear regions, owing to shear-induced alignment of the swimming orientation with the fluid streamlines. Species having an effective aspect ratio close to unity exhibited little preferential accumulation at low-to-moderate flow rates, but strongly accumulated in the low-shear regions under high flow conditions, potentially owing to an active, behavioural response of cells to shear. These observations demonstrate that ambient fluid flow can strongly affect the motility and spatial distribution of phytoplankton and highlight the rich dynamics emerging from the interaction between motility, morphology and flow.     

The importance of the generation interval in investigating dynamics and control of new SARS-CoV-2 variants

Inferring the relative strength (i.e. the ratio of reproduction numbers) and relative speed (i.e. the difference between growth rates) of new SARS-CoV-2 variants is critical to predicting and controlling the course of the current pandemic. Analyses of new variants have primarily focused on characterizing changes in the proportion of new variants, implicitly or explicitly assuming that the relative speed remains fixed over the course of an invasion. We use a generation-interval-based framework to challenge this assumption and illustrate how relative strength and speed change over time under two idealized interventions: a constant-strength intervention like idealized vaccination or social distancing, which reduces transmission rates by a constant proportion, and a constant-speed intervention like idealized contact tracing, which isolates infected individuals at a constant rate. In general, constant-strength interventions change the relative speed of a new variant, while constant-speed interventions change its relative strength. Differences in the generation-interval distributions between variants can exaggerate these changes and modify the effectiveness of interventions. Finally, neglecting differences in generation-interval distributions can bias estimates of relative strength.     

Iron storage indices and risk of bacterial infections in hemodialysis patients

Background: Infection is the second leading cause of death among hemodialysis (HD) patients. Because iron overload may be a risk factor for bacterial infection, concerns about excessive use of intravenous (IV) iron have arisen. In this retrospective analysis, we explored the relationship between target iron storage indices, as outlined in the Dialysis Outcomes Quality Initiative (DOQI) guidelines, and the incidence of bacterial infections. Methods: We reviewed the charts of 87 HD patients who received their first course of IV iron at our dialysis unit between 1997 and 2001. Transferrin saturation (TSAT) rate, ferritin level, and other clinical/laboratory measures were recorded at baseline. Patients were followed for up to 2 years for the outcomes of bacteremia and bacterial pneumonia and censored at death, end‐of‐study observation, or kidney transplantation. Cox proportional hazards regression was used to evaluate the relationship of bacterial infections to iron storage indices. Results: Thirty‐two patients had at least one episode of bacterial infections. In multivariate analyses, after adjusting for sex and venous catheter use, iron‐replete state (ferritin > 100 ng/mL and TSAT > 20%) was associated with a threefold higher risk of bacterial infections (95% CI 1.3–6.6; p = 0.01). Although diabetes mellitus and lower serum albumin had a nonsignificant trend toward an increased risk of bacterial infections, no such relationship was seen with the first 3‐month cumulative IV iron dose. Conclusions: This study suggests an increased risk for bacterial infections at modest levels of iron stores (ferritin > 100 ng/mL and TSAT > 20%) among HD patients initiating IV iron. Large prospective studies are needed to confirm these relationships.     

Management of coronary artery disease and acute coronary syndrome in the chronic kidney disease population—A review of the current literature

Coronary Artery Disease (CAD) is a large contributor to morbidity and mortality in the chronic kidney disease (CKD) and end‐stage renal disease (ESRD) population. Due to the fact that many large‐scale trials evaluating management for acute coronary syndromes (ACS) and CAD have excluded patients with CKD, there is a paucity of data investigating medical management of CAD and revascularization strategies of these patients. Further, while there have been many advances in the treatment for ACS and CAD, both medically and technologically, few studies have focused on the CKD population and many predate these advancements in management. Newer studies that include CKD patients have shown heterogeneity in various outcomes, making management decisions challenging. In this review, we summarize the epidemiologic significance of ACS and CAD in patients with CKD, discuss the diagnosis of ACS in this patient population, and review the therapeutic interventions in patients with CKD.     

Assessing the risk of bluetongue to UK livestock: uncertainty and sensitivity analyses of a temperature-dependent model for the basic reproduction number.

Since 1998 bluetongue virus (BTV), which causes bluetongue, a non-contagious, insect-borne infectious disease of ruminants, has expanded northwards in Europe in an unprecedented series of incursions, suggesting that there is a risk to the large and valuable British livestock industry. The basic reproduction number, R(0), provides a powerful tool with which to assess the level of risk posed by a disease. In this paper, we compute R(0) for BTV in a population comprising two host species, cattle and sheep. Estimates for each parameter which influences R(0) were obtained from the published literature, using those applicable to the UK situation wherever possible. Moreover, explicit temperature dependence was included for those parameters for which it had been quantified. Uncertainty and sensitivity analyses based on Latin hypercube sampling and partial rank correlation coefficients identified temperature, the probability of transmission from host to vector and the vector to host ratio as being most important in determining the magnitude of R(0). The importance of temperature reflects the fact that it influences many processes involved in the transmission of BTV and, in particular, the biting rate, the extrinsic incubation period and the vector mortality rate.     

Social license to operate in the mining industry: the case of Peru

ABSTRACT

Mining is an important industry in Peru, but local communities where mining takes place do not perceive its benefits. Mining corporations need to achieve legitimacy within these communities. The main objective of this study is to identify the factors that determine the provision of social licenses to operate in Peru’s mining regions. We conducted this research using a case study of two Peruvian mining companies. Our study concludes with the identification of four essential factors needed to achieve a social license to operate within these communities: a deep understanding of the socioeconomic environment, a strong commitment to the community, an active presence of Government, and effective communication between the actors involved in mining activities. The combination of these elements can result in improved trust levels between companies and society, enabling all agents to recognize the costs and benefits resulting from mining.     

Conceptualizing and communicating organizational risk dynamics in the thoroughness–efficiency space

Organizations that design and/or operate complex systems have to make trade-offs between multiple, interacting, and sometimes conflicting goals at both the individual and organizational levels. Identifying, communicating, and resolving the conflict or tension between multiple organizational goals is challenging. Furthermore, maintaining an appropriate level of safety in such complex environments is difficult for a number of reasons discussed in this paper. The objective of this paper is to propose a set of related concepts that can help conceptualize organizational risk and help managers to understand the implications of various performance and resource pressures and make appropriate trade-offs between efficiency and thoroughness that maintain system safety. The concepts here introduced include (1) the thoroughness–efficiency space for classifying organizational behavior, and the various resource/performance and regulatory pressures that can displace organizations from one quadrant to another within this space, (2) the thoroughness–efficiency barrier and safety threshold, and (3) the efficiency penalty that organizations should accept, and not trade against organizational thoroughness, in order to maintain safety. Unfortunately, many accidents share a conceptual sameness in the way they occur. That sameness can be related to the dynamics conceptualized in this paper and the violation of the safety threshold. This sameness is the sad story of the Bhopal accident, the Piper Alpha accident, and score of others. Finally, we highlight the importance of a positive safety culture as an essential complement to regulatory pressure in maintaining safety. We illustrate the “slippery slope of thoroughness” along which organizational behavior slides under the influence of performance pressure, and suggest that a positive safety culture can be conceived of as “pulling this slippery slope” up and preventing the violation of the safety threshold.     

Infection dynamics in ecosystems: on the interaction between red and grey squirrels,pox virus,pine martens and trees

Ecological and epidemiological processes and interactions influence each other, positively and negatively, directly and indirectly. The invasion potential of pathogens is influenced by the ecosystem context of their host species’ populations. This extends to the capacity of (multiple) host species to maintain their (common) pathogen and the way pathogen dynamics are influenced by changes in ecosystem composition. This paper exemplifies these interactions and consequences in a study of red and grey squirrel dynamics in the UK. Differences and changes in background habitat and trophic levels above and below the squirrel species lead to different dynamic behaviour in many subtle ways. The range of outcomes of the different interactions shows that one has to be careful when drawing conclusions about the mechanisms and processes involved in explaining observed phenomena concerning pathogens in their natural environment. The dynamic behaviour also shows that planning interventions, for example for conservation purposes, benefits from understanding the complexity of interactions beyond the particular pathogen and its threatened host species.     

Relationships of Fussell–Vesely and Birnbaum importance to structural importance in coherent systems

The notion of node criticality was introduced by Boland, Proschan and Tong to study the problem of optimal rearrangement of components in binary coherent systems. In this paper, we use this notion to study the importance of system components. We derive various relationships between the node criticality and the component importance measures due to Birnbaum, Fussell and Vesely, respectively. Some previous results due to Boland and Proschan, and Meng have been improved.     

Selective damping method for the weak‐Arlequin coupling of molecular dynamics and finite element method

An artificial damping force is introduced in the weak coupling between the molecular dynamics (MD) and finite element (FE) models, to reduce the reflection of the high‐frequency motion that cannot be transmitted from the MD domain to the FE domain. We take advantage of the orthogonal property of the decomposed velocity in the weak coupling method and apply the damping force only to the high‐frequency part, therefore minimizing its effect on the low‐frequency part, which can be transmitted into the FE domain. The effectiveness of the damping method will be demonstrated by 1D numerical examples with linear force field applied to the atomistic model. In addition, we emphasize the importance of using the Arlequin energy interpolation, which is usually ignored in the weak coupling literature. Non‐uniform rational basis spline functions have been used to interpolate the MD data for the weak coupling method, and the influence of changing the number and order of basis functions on the interpolation accuracy has been investigated numerically. For this work, we restrict our discussion to mechanical problems only, involving only mechanical energy terms (e.g., strain potential and kinetic energy). Copyright © 2013 John Wiley & Sons, Ltd.     

Role of two-way airflow owing to temperature difference in severe acute respiratory syndrome transmission: revisiting the largest nosocomial severe acute respiratory syndrome outbreak in Hong Kong

By revisiting the air distribution and bioaerosol dispersion in Ward 8A where the largest nosocomial severe acute respiratory syndrome (SARS) outbreak occurred in Hong Kong in 2003, we found an interesting phenomenon. Although all the cubicles were in ‘positive pressure’ towards the corridor, the virus-containing bioaerosols generated from the index patient''s cubicle were still transmitted to other cubicles, which cannot be explained in a traditional manner. A multi-zone model combining the two-way airflow effect was used to analyse this phenomenon. The multi-zone airflow model was evaluated by our experimental data. Comparing with the previous computational fluid dynamic simulation results, we found that the air exchange owing to the small temperature differences between cubicles played a major role in SARS transmission. Additionally, the validated multi-zone model combining the two-way airflow effect could simulate the pollutant transport with reasonable accuracy but much less computational time. A probable improvement in general ward design was also proposed.     

Simultaneous reconstruction of evolutionary history and epidemiological dynamics from viral sequences with the birth–death SIR model

The evolution of RNA viruses, such as human immunodeficiency virus (HIV), hepatitis C virus and influenza virus, occurs so rapidly that the viruses'' genomes contain information on past ecological dynamics. Hence, we develop a phylodynamic method that enables the joint estimation of epidemiological parameters and phylogenetic history. Based on a compartmental susceptible–infected–removed (SIR) model, this method provides separate information on incidence and prevalence of infections. Detailed information on the interaction of host population dynamics and evolutionary history can inform decisions on how to contain or entirely avoid disease outbreaks. We apply our birth–death SIR method to two viral datasets. First, five HIV type 1 clusters sampled in the UK between 1999 and 2003 are analysed. The estimated basic reproduction ratios range from 1.9 to 3.2 among the clusters. All clusters show a decline in the growth rate of the local epidemic in the middle or end of the 1990s. The analysis of a hepatitis C virus genotype 2c dataset shows that the local epidemic in the Córdoban city Cruz del Eje originated around 1906 (median), coinciding with an immigration wave from Europe to central Argentina that dates from 1880 to 1920. The estimated time of epidemic peak is around 1970.     

Studies of the strong coupling and weak coupling methods in FSI analysis

The weak coupling methods in fluid–structure interaction analysis are newly classified into three types; the weak coupling method for solving structures with interfaces, the weak coupling method for solving fluids with interfaces, and the weak coupling method for solving both fluids and structures with interfaces. The consistent added matrices of these weak coupling methods are derived from the condensation of the strong coupling formulation. Some approximations for the consistent added matrices, which can avoid the matrix coupling, are proposed. The reasons for convergence difficulty in the weak coupling methods are clarified. A number of numerical results are presented to investigate the convergence properties and computational efficiency of these methods. Copyright © 2004 John Wiley & Sons, Ltd.     

Extinction risk and eco-evolutionary dynamics in a variable environment with increasing frequency of extreme events

One of the most dramatic consequences of climate change will be the intensification and increased frequency of extreme events. I used numerical simulations to understand and predict the consequences of directional trend (i.e. mean state) and increased variability of a climate variable (e.g. temperature), increased probability of occurrence of point extreme events (e.g. floods), selection pressure and effect size of mutations on a quantitative trait determining individual fitness, as well as the their effects on the population and genetic dynamics of a population of moderate size. The interaction among climate trend, variability and probability of point extremes had a minor effect on risk of extinction, time to extinction and distribution of the trait after accounting for their independent effects. The survival chances of a population strongly and linearly decreased with increasing strength of selection, as well as with increasing climate trend and variability. Mutation amplitude had no effects on extinction risk, time to extinction or genetic adaptation to the new climate. Climate trend and strength of selection largely determined the shift of the mean phenotype in the population. The extinction or persistence of the populations in an ‘extinction window’ of 10 years was well predicted by a simple model including mean population size and mean genetic variance over a 10-year time frame preceding the ‘extinction window’, although genetic variance had a smaller role than population size in predicting contemporary risk of extinction.