Translating the message

The "one gene = one protein" model for understanding the genome is well-known. But, as with most biological "rules", it has its exceptions. The viral family that brings polio, the common cold and foot-and-mouth disease translates its entire genome into one long "polyprotein". The study of this translation strategy is bringing to light new targets for fighting disease and new techniques for the biotech industry.     

Quantifying the Impact of Expanded Age Group Campaigns for Polio Eradication

A priority of the Global Polio Eradication Initiative (GPEI) 2013–2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5–14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage—representing less than one tenth of additional vaccinations required for the six SIA EAG scenario—increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.     

Circulating Vaccine Derived Polio Viruses and their Impact on Global Polio Eradication

Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed regarding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts. B.G. Wagner’s research is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) Doctoral Scholarship. D.J.D. Earn’s research is supported by the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC) and the J.S. McDonnell Foundation.     

Unraveling the Transmission Ecology of Polio

Sustained and coordinated vaccination efforts have brought polio eradication within reach. Anticipating the eradication of wild poliovirus (WPV) and the subsequent challenges in preventing its re-emergence, we look to the past to identify why polio rose to epidemic levels in the mid-20th century, and how WPV persisted over large geographic scales. We analyzed an extensive epidemiological dataset, spanning the 1930s to the 1950s and spatially replicated across each state in the United States, to glean insight into the drivers of polio’s historical expansion and the ecological mode of its persistence prior to vaccine introduction. We document a latitudinal gradient in polio’s seasonality. Additionally, we fitted and validated mechanistic transmission models to data from each US state independently. The fitted models revealed that: (1) polio persistence was the product of a dynamic mosaic of source and sink populations; (2) geographic heterogeneity of seasonal transmission conditions account for the latitudinal structure of polio epidemics; (3) contrary to the prevailing “disease of development” hypothesis, our analyses demonstrate that polio’s historical expansion was straightforwardly explained by demographic trends rather than improvements in sanitation and hygiene; and (4) the absence of clinical disease is not a reliable indicator of polio transmission, because widespread polio transmission was likely in the multiyear absence of clinical disease. As the world edges closer to global polio eradication and continues the strategic withdrawal of the Oral Polio Vaccine (OPV), the regular identification of, and rapid response to, these silent chains of transmission is of the utmost importance.     

Reactions of fish to microorganisms in wastewater.

Fish were inoculated with various microorganisms present in wastewater. A threshold concentration was determined over which these microorganisms were recovered from the muscles. The threshold concentrations were different for bacteria, bacteriophages, and polio 1 LSc virus. The threshold values were lower when fish were inoculated than when they were immersed in water containing these organisms. Depuration experiments were efficient when the fish did not contain high concentrations of bacteria in their muscles. As the threshold concentrations are an expression of the capability of the immune system of the fish, these values can be useful for the design and management of fishponds in which treated wastewater is used.     

Reactions of fish to microorganisms in wastewater

Fish were inoculated with various microorganisms present in wastewater. A threshold concentration was determined over which these microorganisms were recovered from the muscles. The threshold concentrations were different for bacteria, bacteriophages, and polio 1 LSc virus. The threshold values were lower when fish were inoculated than when they were immersed in water containing these organisms. Depuration experiments were efficient when the fish did not contain high concentrations of bacteria in their muscles. As the threshold concentrations are an expression of the capability of the immune system of the fish, these values can be useful for the design and management of fishponds in which treated wastewater is used.     

Crippling Violence: Conflict and Incident Polio in Afghanistan

Background

Designing effective public health campaigns in areas of armed conflict requires a nuanced understanding of how violence impacts the epidemiology of the disease in question.

Methods

We examine the geographical relationship between violence (represented by the location of detonated Improvised Explosive Devices) and polio incidence by generating maps of IEDs and polio incidence during 2010, and by comparing the mean number of IED detonations in polio high-risk districts with non polio high-risk districts during 2004–2009.

Results

We demonstrate a geographic relationship between IED violence and incident polio. Districts that have high-risk for polio have highly statistically significantly greater mean numbers of IEDs than non polio high-risk districts (p-values 0.0010–0.0404).

Conclusions

The geographic relationship between armed conflict and polio incidence provides valuable insights as to how to plan a vaccination campaign in violent contexts, and allows us to anticipate incident polio in the regions of armed conflict. Such information permits vaccination planners to engage interested armed combatants to co-develop strategies to mitigate the effects of violence on polio.     

A network with tunable clustering, degree correlation and degree distribution, and an epidemic thereon

A random network model which allows for tunable, quite general forms of clustering, degree correlation and degree distribution is defined. The model is an extension of the configuration model, in which stubs (half-edges) are paired to form a network. Clustering is obtained by forming small completely connected subgroups, and positive (negative) degree correlation is obtained by connecting a fraction of the stubs with stubs of similar (dissimilar) degree. An SIR (Susceptible $\rightarrow $ Infective $\rightarrow $ Recovered) epidemic model is defined on this network. Asymptotic properties of both the network and the epidemic, as the population size tends to infinity, are derived: the degree distribution, degree correlation and clustering coefficient, as well as a reproduction number $R_*$ , the probability of a major outbreak and the relative size of such an outbreak. The theory is illustrated by Monte Carlo simulations and numerical examples. The main findings are that (1) clustering tends to decrease the spread of disease, (2) the effect of degree correlation is appreciably greater when the disease is close to threshold than when it is well above threshold and (3) disease spread broadly increases with degree correlation $\rho $ when $R_*$ is just above its threshold value of one and decreases with $\rho $ when $R_*$ is well above one.     

Spatial patterns in a discrete-time SIS patch model

How do spatial heterogeneity, habitat connectivity, and different movement rates among subpopulations combine to influence the observed spatial patterns of an infectious disease? To find out, we formulated and analyzed a discrete-time SIS patch model. Patch differences in local disease transmission and recovery rates characterize whether patches are low-risk or high-risk, and these differences collectively determine whether the spatial domain, or habitat, is low-risk or high-risk. In low-risk habitats, the disease persists only when the mobility of infected individuals lies below some threshold value, but for high-risk habitats, the disease always persists. When the disease does persist, then there exists an endemic equilibrium (EE) which is unique and positive everywhere. This EE tends to a spatially inhomogeneous disease-free equilibrium (DFE) as the mobility of susceptible individuals tends to zero. The limiting DFE is nonempty on all low-risk patches and it is empty on at least one high-risk patch. Sufficient conditions for the limiting DFE to be empty on other high-risk patches are given in terms of disease transmission and recovery rates, habitat connectivity, and the infected movement rate. These conditions are also illustrated using numerical examples.     

A vision of a world without polio: the OPV cessation strategy.

Once the eradication of wild poliovirus has been confirmed, the public health benefits of routine immunization with OPV will no longer outweigh the burden of disease either due to paralysis caused by OPV (vaccine associated paralytic polio), or by outbreaks caused by circulating vaccine-derived polioviruses. The eventual cessation of OPV use in routine immunization programmes worldwide will become necessary to assure a lasting eradication of polio. As the world moves towards polio eradication and its certification, preparations are therefore being intensified for OPV cessation, and the risk management framework for safe OPV cessation is being put in place. The framework includes bio-containment of all known poliovirus and potentially infected substances, development of an international stockpile of oral polio vaccine, ensuring a mechanism for continued global surveillance and response for polio after eradication has been certified, and national policies if countries decide to continue vaccinating with inactivated polio vaccine (IPV). It is ironic that the vaccine on which the world has depended for polio eradication will itself become a risk to eradication once the transmission of wild poliovirus has been interrupted. Final preparations for the eventual global and simultaneous cessation of OPV will require the same level of international cooperation and coordination that has brought the world to the verge of polio eradication.     

Endemic disease in environments with spatially heterogeneous host populations

The main interest in epidemic models stems from their use in uncovering certain qualitative features of epidemic processes. A deterministic model of a general epidemic in a population with an arbitrary number of separate population centers is presented. The mixing within each center is assumed to be homogeneous, and the usual threshold theorem holds for each population. The mixing between centers is nonhomogeneous. This model is used to identify the necessary and sufficient conditions under which a disease will become endemic in the general population when each population center is below the threshold required for establishment of the disease and does not mix with other centers. These conditions depend critically on the concavity of the infection rate function with respect to the length of exposure time. The application of these results to host-vector models is discussed.     

Variable initial depolarization in Stein's neuronal model with synaptic reversal potentials

The effect of a variable initial value is examined in Stein's stochastic neuronal model with synaptic reversal potentials under the conditions of a constant threshold and a constant input. The moments of the interspike interval distribution are presented as the functions of the initial depolarization which ranges from inhibitory reversal potential to the threshold potential. Normal, exponential and transformed Gamma distributions are tested for the initial value of depolarization. The coefficient of variation is shown to be greater than one when the initial depolarization is sufficiently above the resting level. An interpretation of this result in the terms of spatial facilitation is offered. The effect of a random initial value is found to be most pronounced for the neurons depolarized to a near threshold level.     

Prospects for malaria eradication in sub-Saharan Africa

Background

A characteristic of Plasmodium falciparum infections is the gradual acquisition of clinical immunity resulting from repeated exposures to the parasite. While the molecular basis of protection against clinical malaria remains unresolved, its effects on epidemiological patterns are well recognized. Accumulating epidemiological data constitute a valuable resource that must be intensively explored and interpreted as to effectively inform control planning.

Methodology/Principal Finding

Here we apply a mathematical model to clinical data from eight endemic regions in sub-Saharan Africa. The model provides a quantitative framework within which differences in age distribution of clinical disease are assessed in terms of the parameters underlying transmission. The shorter infectious periods estimated for clinical infections induce a regime of bistability of endemic and malaria-free states in regions of mesoendemic transmission. The two epidemiological states are separated by a threshold that provides a convenient measure for intervention design. Scenarios of eradication and resurgence are simulated.

Conclusions/Significance

In regions that support mesoendemic transmission, intervention success depends critically on reducing prevalence below a threshold which separates endemic and malaria-free regimes.     

Characteristics of Patients at First Visit to a Polio Clinic in Sweden

Aim

Describe polio patients visiting a polio clinic in Sweden, a country where vaccination was introduced in 1957.

Design

A consecutive cohort study.

Patients

Prior polio patients.

Methods

All patients (n = 865) visiting the polio clinic at Sahlgrenska University Hospital, Gothenburg Sweden, between 1994 and 2012 were included in this study. Data at first visit regarding patient characteristics, polio classification, data of electromyography, origin, assistive devices and gait speed as well as muscle strength were collected for these patients. Twenty-three patients were excluded because no polio diagnosis could be established. A total of 842 patients with confirmed polio remained in the study.

Results

More than twenty percent of the patients were from countries outside the Nordic region and considerably younger than those from the Nordic region. The majority of the emigrants were from Asia and Africa followed by Europe (outside the Nordic region). Of all patients included ninety-seven percent (n = 817) had polio in the lower extremity and almost 53% (n = 444) had polio in the upper extremity while 28% (n = 238) had polio in the trunk, according to clinical classification of polio. Compared with a sample of the normal population, the polio patients walked 61–71% slower, and were 53–77% weaker in muscle strength of the knee and foot as well as grip strength.

Conclusion

The younger patients with polio emigrating from countries with different cultures may lead to a challenge for the multi professional teams working with post-polio rehabilitation and are of importance when planning for the care of polio patients the coming years.     

Threshold Conditions for a Non-Autonomous Epidemic System Describing the Population Dynamics of Dengue

A non-autonomous dynamical system, in which the seasonal variation of a mosquito vector population is modeled, is proposed to investigate dengue overwintering. A time-dependent threshold, R(t), is deduced such that when its yearly average, denoted by , is less than 1, the disease does not invade the populations and when is greater than 1 it does. By not invading the population we mean that the number of infected individuals always decrease in subsequent seasons of transmission. Using the same threshold, all the qualitative features of the resulting epidemic can be understood. Our model suggests that trans-ovarial infection in the mosquitoes facilitates dengue overwintering. We also explain the delay between the peak in the mosquitoes population and the peak in dengue cases. An erratum to this article can be found at     

Use of Mobile Information Technology during Planning,Implementation and Evaluation of a Polio Campaign in South Sudan

Background

Use of mobile information technology may aid collection of real-time, standardised data to inform and improve decision-making for polio programming and response. We utilised Android-based smartphones to collect data electronically from more than 8,000 households during a national round of polio immunisation in South Sudan. The results of the household surveys are presented here, together with discussion of the application of mobile information technology for polio campaign planning, implementation and evaluation in a real-time setting.

Methods

Electronic questionnaires were programmed onto Android-based smartphones for mapping, supervision and survey activities during a national round of polio immunisation. National census data were used to determine the sampling frame for each activity and select the payam (district). Individual supervisors, in consultation with the local district health team, selected villages and households within each payam. Data visualisation tools were utilised for analysis and reporting.

Results

Implementation of mobile information technology and local management was feasible during a national round of polio immunisation in South Sudan. Red Cross visits during the polio campaign were equitable according to household wealth index and households who received a Red Cross visit had significantly higher odds of being aware of the polio campaign than those who did not. Nearly 95% of children under five were reported to have received polio immunisation (according to maternal recall) during the immunisation round, which varied by state, county and payam. A total of 11 payams surveyed were identified with less than 90% reported immunisation coverage and the least poor households had significantly higher odds of being vaccinated than the most poor. More than 95% of households were aware of the immunisation round and households had significantly higher odds of being vaccinated if they had prior awareness of the campaign taking place.

Conclusion

Pre-campaign community education and household awareness of polio is important to increase campaign participation and subsequent immunisation coverage in South Sudan. More emphasis should be placed on ensuring immunisation is equitable according to geographic area and household socio-economic index in future rounds. We demonstrate the utility of mobile information technology for household mapping, supervision and survey activities during a national round of polio immunisation and encourage future studies to compare the effectiveness of electronic data collection and its application in polio planning and programming.     

Mononucleotide and dinucleotide frequencies, and codon usage in poliovirion RNA.

The polio type 1 (Mahoney) RNA sequence (1) has been analyzed in terms of the distribution of its mononucleotides, dinucleotides and trinucleotides (codons). The distribution of adenosine in the sequence is nonuniform, being lower at the 5' end and higher at the 3' end. The dinucleotide CG is relatively rare and the dinucleotides UG and CA are relatively more common than expected. Codon usage is decidedly nonrandom. Codons containing CG are avoided and those ending in adenosine are favored. The asymmetric use of mononucleotides, dinucleotides and codons in polio RNA is unexplained at the present time although the lowered CG frequency may be the result of a DNA origin for polio RNA.     

EFFECTS OF HEALTH-RELATED CLAIMS ON THE DIFFERENTIAL THRESHOLD OF CONSUMERS' SWEETNESS SENSATION

Health concerns play an important role in people's consumption of food products and judgments of food taste. Previous studies on the effects of food labeling suggest that consumers' sensory evaluations are influenced by health concerns. The current study examined whether health-related claims would affect sweetness sensations. Differential thresholds for sensitivity to sweetness were measured separately under three conditions: without health-related claims, with a label suggesting a health advantage and with a health warning label. Results indicated that thresholds under both health-related labeling conditions were lower than those under the condition with no health-related claim, suggesting that consumers exposed to health-related labels were more sensitive to sweetness. The threshold for the health advantage label lay between those for no health-related claims (which yielded the highest threshold) and the health warning (which yielded the lowest). These findings are discussed in terms of health concerns, and suggestions for future research are explored.

PRACTICAL APPLICATIONS

The insights gained in this study give researchers and marketers information about how to measure consumers' differential threshold of sweetness threshold with the psychophysical method. It provides information about the effects of health-related claims on the differential threshold of sweetness sensation. The findings and explanations are beneficial for product development researchers and marketer to predict consumers' change of differential threshold when employing health-related claims to influence sweetness sensation of food products with varying levels of sweetener changes.     

Analysis of a tuberculosis model with a case study in Uganda

We consider a four-compartment tuberculosis model including exogenous reinfection. We derive sufficient conditions, in terms of the parameters of the system, which guarantee the occurrence of backward bifurcation. We also discuss the global stability of the endemic state by using a generalization of the Poincaré–Bendixson criterion. An application is given for the case of Internally Displaced People's Camps in North Uganda. The study suggests how important it is to provide qualitative indications on the threshold value of the population density in the area occupied by the camps, in order to possibly eradicate the disease.     

Population dynamics of live-attenuated virus vaccines

Viruses contained in live-attenuated virus vaccines (LAVV) can be transmitted between individuals, resulting in secondary or contact vaccinations. This fact has been exploited successfully in the use of the Oral Polio Vaccine (OPV) to better control wild-type polio viruses. In this work we analyze general LAVV vaccination models for infections that confer lifelong immunity. We consider both standard (continuous) vaccination strategies and pulse vaccination programs (where mass vaccination is carried out at regular intervals). For continuous vaccination, we provide a complete global analysis of a very general compartmental ordinary differential equation LAVV model. We find that the threshold vaccination level required for the eradication of wild-type virus depends on the basic reproduction numbers of both the wild-type and vaccine viruses, but is otherwise independent of the distributions of the durations in each of the sequence of stages of disease progression (e.g., latent, infectious, etc.). Furthermore, even for vaccine viruses with reproduction numbers below one, which would naturally fade from the population upon cessation of vaccination, there can be a significant reduction in the threshold vaccination level. The dependence of the threshold vaccination level on the virus reproduction numbers largely generalizes to the pulse vaccination model. For shorter pulsing periods there is negligible difference in threshold vaccination level as compared to continuous vaccination campaigns. Thus, we conclude that current policy in many countries to employ annual pulsed OPV vaccination does not significantly diminish the benefits of contact vaccination.