Mechanistic models for West Nile virus transmission: a systematic review of features, aims and parametrization.

Mathematical models within the Ross-Macdonald framework increasingly play a role in our understanding of vector-borne disease dynamics and as tools for assessing scenarios to respond to emerging threats. These threats are typically characterized by a high degree of heterogeneity, introducing a range of possible complexities in models and challenges to maintain the link with empirical evidence. We systematically identified and analysed a total of 77 published papers presenting compartmental West Nile virus (WNV) models that use parameter values derived from empirical studies. Using a set of 15 criteria, we measured the dissimilarity compared with the Ross-Macdonald framework. We also retrieved the purpose and type of models and traced the empirical sources of their parameters. Our review highlights the increasing refinements in WNV models. Models for prediction included the highest number of refinements. We found uneven distributions of refinements and of evidence for parameter values. We identified several challenges in parametrizing such increasingly complex models. For parameters common to most models, we also synthesize the empirical evidence for their values and ranges. The study highlights the potential to improve the quality of WNV models and their applicability for policy by establishing closer collaboration between mathematical modelling and empirical work.

Effectiveness of Systemic Insecticide Dog Treatment for the Control of Chagas Disease in the Tropics.

Chagas disease, caused by Trypanosoma cruzi and transmitted by triatomines, can lead to severe cardiac issues and mortality in many mammals. Recent studies have shown that systemic insecticide treatment of dogs is highly effective in killing triatomines. Here, we assessed the impact of dog treatment on T. cruzi transmission. We developed a mathematical model of T. cruzi transmission among triatomines, dogs, humans, and rodents. We used the model to evaluate the impact of dog treatment regimens on T. cruzi transmission dynamics to determine their effectiveness in reducing T. cruzi infection among hosts. We show that a 3-month treatment regimen may reduce T. cruzi incidence among humans by 59-80% in a high transmission setting, and 26-82% in a low transmission setting. An annual treatment may reduce incidence among humans by 49-74% in a high transmission setting, and by 11-76% in a low transmission setting. However, dog treatment may substantially increase T. cruzi prevalence among dogs if dog consumption of dead triatomines increases. Our model indicates that dog treatment may reduce T. cruzi infections among humans, but it may increase infections in dogs. Therefore, a holistic approach targeting different hosts is necessary for Chagas elimination.

A 'Portfolio of Model Approximations' approach to understanding invasion success with vector-borne disease.

The central challenge of mathematical modeling of real-world systems is to strike an appropriate balance between insightful abstraction and detailed accuracy. Models in mathematical epidemiology frequently tend to either extreme, focusing on analytically provable boundaries in simplified, mass-action approximations, or else relying on calculated numerical solutions and computational simulation experiments to capture nuance and details specific to a particular host-disease system. We propose that there is value in an approach striking a slightly different compromise in which a detailed but analytically difficult system is modeled with careful detail, but then abstraction is applied to the results of numerical solutions to that system, rather than to the biological system itself. In this 'Portfolio of Model Approximations' approach, multiple levels of approximation are used to analyze the model at different scales of complexity. While this method has the potential to introduce error in the translation from model to model, it also has the potential to produce generalizable insight for the set of all similar systems, rather than isolated, tailored results that must be started anew for each next question. In this paper, we demonstrate this process and its value with a case study from evolutionary epidemiology. We consider a modified Susceptible-Infected-Recovered model for a vector-borne pathogen affecting two annually reproducing hosts. From observing patterns in simulations of the system and exploiting basic epidemiological properties, we construct two approximations of the model at different levels of complexity that can be treated as hypotheses about the behavior of the model. We compare the predictions of the approximations to the simulated results and discuss the trade-offs between accuracy and abstraction. We discuss the implications for this particular model, and in the context of mathematical biology in general.

Further description of the Kerguelen sandpaper skate Bathyraja irrasa (Rajiformes: Arhynchobatidae) based on additional specimens, including egg cases and embryos.

Adult specimens, additional juvenile specimens, egg cases and embryos were used to provide a more detailed anatomical description of the Kerguelen sandpaper skate Bathyraja irrasa, a species of skate endemic to the Kerguelen Plateau and listed as Vulnerable by the IUCN Red List of Threatened Species. The morphological and meristic data reveal a relatively high level of intraspecific variation, mostly related to size. Egg cases are described for the first time and were shown to vary in colour and fouling depending on the length of time spent in the marine environment. Embryos removed from egg cases represent all stages of embryonic development in this species and include the largest embryo recorded for this species, i.e., 230 mm total length (LT ), which increases the range of size at hatching of B. irrasa to 178-230 mm LT . A number of morphometric and meristic characters varied ontogenetically in B. irrasa, in particular relative tail length, number of tail thorns in the median row and the size of orbits. This study highlights the importance of describing intraspecific variation in species and the importance of egg cases to taxonomic and biological research on oviparous species.

Vector-Borne Disease Models with Active and Inactive Vectors: A Simple Way to Consider Biting Behavior.

Vector-borne diseases are a serious public health problem, mosquitoes being one of the most important vectors. To analyze the dynamics of this type of disease, Ross-Macdonald models are commonly used. In its simplest formulation and the most common in scientific literature, it is assumed that all mosquitoes are biting at a given rate. To improve this general assumption, we developed a vector-borne disease model with active and inactive vectors as a simple way to incorporate the more general characteristics of mosquito feeding behavior into disease dynamics. Our objective is to obtain an estimate of the Ross-Macdonald biting rate from the feeding parameters that reproduce the same dynamics as the model with active and inactive vectors. Two different cases were analyzed: a SIS-SI model and a SIR-SI model with a single epidemic. Different methods to estimate the biting rate in the Ross-Macdonald model were proposed and analyzed. To compare the results of the models, different epidemiological indicators were considered. When the biting rate is estimated considering that both models have the same basic reproduction number, very similar disease dynamics are obtained. This method is a simple way to incorporate the mosquito feeding behavior into the standard Ross-Macdonald model.

Differentiating Radiation-Induced Necrosis from Tumor Progression After Stereotactic Radiosurgery for Brain Metastases, Using Evaluation of Blood Flow with Arterial Spin Labeling (ASL): The Importance of Setting a Baseline.

OBJECTIVE: This study evaluated the usefulness of arterial spin labeling (ASL) for assessment of tumor blood flow (TBF) and cerebral blood flow (CBF) before Gamma Knife surgery (GKS) for intracranial metastases, in order to analyze the variability of perfusion characteristics at baseline and to reveal how these data may impact differentiation of radiation-induced effects from tumor progression during follow-up. METHODS: Radiological data from 87 patients with intracranial metastases of solid cancers, who underwent TBF/CBF analysis by means of ASL at the Hawaii Advanced Imaging Institute between 2015 and 2018 both before and after GKS, were reviewed retrospectively. Only cases with a largest tumor diameter of ≥10 mm were included in the study cohort (N = 53). RESULTS: In comparison with CBF in the healthy contralateral cerebral cortex, TBF before GKS was greater in 32 cases (60%), lesser in 7 cases (13%), and equivalent in 14 cases (27%). There was significant variability in TBF both within and between histologically different groups of tumors. CONCLUSION: Since, at baseline, approximately 40% of intracranial metastases have TBF that is lesser or equivalent to CBF, increased blood flow in the contrast-enhancing lesion after GKS may have insufficient sensitivity for identification of tumor progression. Availability of baseline TBF data may significantly facilitate differential diagnosis in such cases.

The role of improved housing and living environments in malaria control and elimination.

Malaria risk and endemicity is often associated with the nature of human habitation and living environment. The disappearance of malaria from regions where it had been endemic for centuries, such as coastal areas of southern England, has been attributed, at least in part, to improvement in the quality of housing. Moreover, indigenous malaria transmission ceased throughout England without the necessity to eliminate the vector mosquitoes. The principles of malaria transmission, as formulated following the thinking of the pioneers of malaria epidemiology, Ronald Ross and George Macdonald, show how this may happen. Malaria ceases to be sustainable where its reproduction number, R0, the number of new cases generated on average for each existing case of malaria, falls below 1. In the terms of a Ross/Macdonald analysis the reduced contact between humans and blood-feeding mosquitoes that is achieved through housing that is secure against mosquito entry can have a powerful effect in reducing malaria R0. The island of Sri Lanka, where malaria had been endemic probably for centuries previously, has reported no indigenous cases of malaria since 2012. The disappearance of malaria from Sri Lanka followed an effective attack upon malaria transmission by the Sri Lanka Anti Malaria Campaign. The targeted and enhanced efforts of this campaign launched in 1999, drove the malaria R0 below 1 for most of the period up to 2012, leading to a nearly continuous decline in malaria cases until their extinction. The decades leading up to the launch of these efforts were ones of general improvement of living environment and notably in the quality of housing stock. Studies in the late 1980s had shown that quality of housing in a highly malarious district of Sri Lanka was a strong determinant of malaria risk. Through its effects on malaria R0, improved housing is likely to have facilitated the malaria control and cessation of indigenous malaria transmission in Sri Lanka and that it will help reduce the risk of the re-introduction of malaria to the island.

Ross-Macdonald models: Which one should we use?

Ross-Macdonald models are the building blocks of most vector-borne disease models. Even for the same disease, different authors use different model formulations, but a study of the dynamical consequences of assuming different hypotheses is missing. In this work we present different formulations of the basic Ross-Macdonald model together with a careful discussion of the assumptions behind each model. The most general model presented is an agent based model for which arbitrary distributions for latency and infectious periods for both, host and vectors, is considered. At population level we also developed a deterministic Volterra integral equations model for which also arbitrary distributions in the waiting times are included. We compare the model solutions using different distributions for the infectious and latency periods using statistics, like the epidemic peak, or epidemic final size, to characterize the epidemic curves. The basic reproduction number (R0) for each formulation is computed and compared with empirical estimations obtained with the agent based models. The importance of considering realistic distributions for the latent and infectious periods is highlighted and discussed. We also show that seasonality is a key driver of vector-borne disease dynamics shaping the epidemic curve and its duration.

A hybrid model for the effects of treatment and demography on malaria superinfection.

As standard mathematical models for the transmission of vector-borne pathogens with weak or no apparent sterilizing immunity, Susceptible-Infected-Susceptible (SIS) systems such as the Ross-Macdonald equations are a useful starting point for modeling the impacts of interventions on prevalence for diseases that cannot superinfect their hosts. In particular, they are parameterizable from quantities we can estimate such as the force of infection (FOI), the rate of natural recovery from a single infection, the treatment rate, and the rate of demographic turnover. However, malaria parasites can superinfect their host which has the effect of increasing the duration of infection before total recovery. Queueing theory has been applied to capture this behavior, but a problem with current queueing models is the exclusion of factors such as demographic turnover and treatment. These factors in particular can affect the entire shape of the distribution of the multiplicity of infection (MOI) generated by the superinfection process, its transient dynamics, and the population mean recovery rate. Here we show the distribution of MOI can be described by an alternative hyper-Poisson distribution. We then couple our resulting equations to a simple vector transmission model, extending previous Ross-Macdonald theory.

Not the Sum of Its Parts: A Critical Review of the MacDonald Triad.

The MacDonald triad posits that animal cruelty, fire setting, and bed wetting in childhood is indicative of later aggressive and violent behavior in adults. Researchers refer to this phenomenon as a precursor to later antisocial behaviors including serial and sexual murder; while practitioners cite the triad in clinical formulations and risk assessments. However, there is yet to be a critical review and consolidation of the literature that establishes whether there is empirical support. This article explores the validity of the triad. We conducted a narrative review of the relevant studies examining the MacDonald triad and its individual constituents. There is evidence that any one of the triad behaviors could predict future violent offending, but it is very rare to find all three behaviors together as predictors. Thus, the empirical research on the MacDonald triad does not fully substantiate its premise. Rather, it would appear that the triad, or its individual constituents, is better used as an indicator of dysfunctional home environments, or poor coping skills in children. Future research is needed with robust and rigorous methodologies (e.g., adequate control groups, longitudinal designs) to fully establish the MacDonald triad's validity. Finally, further consideration is needed as to whether the triad behaviors are more indicative of other problematic outcomes (e.g., maladaptive coping to life stressors).

State and parameter estimation for a class of schistosomiasis models.

We develop a general framework to estimate the proportion of infected snails and snail-human transmission parameter of a class of models that describes the evolution of schistosomiasis. To do so, we consider simultaneously the dynamics of schistosomiasis, captured by the homogeneous version of the classical MacDonald's model, and the measurable output: the number of female schistosomes per single host. The proposed method consists of designing an auxiliary dynamical system, called observer, whose solutions converge exponentially to those of the system capturing the schistosomiasis model. Moreover, we derive an estimation of the snail-human transmission rate, an unknown but key parameter in the dynamics of schistosomiasis. These estimations are central in two of the strategies of controlling schistosomiasis, namely the use of molluscicides and mass drug administration. To further investigate control strategies on a larger scale, we consider a heterogeneous model which consists of an arbitrary number of human groups or patches and an arbitrary number of fresh-water sources, natural habitats of snails. Provided that the data of infected humans' worm burden in each patch or group is available, we provide a method of estimating the proportion of infected snails in each snail natural habitat, thereby providing a map on where to implement control strategy to mitigate or eliminate Schistosomiasis.

Synergy and timing: a concurrent mass medical campaign predicted to augment indoor residual spraying for malaria.

BACKGROUND: Control programmes for high burden countries are tasked with charting effective multi-year strategies for malaria control within significant resource constraints. Synergies between different control tools, in which more than additive benefit accrues from interventions used together, are of interest because they may be used to obtain savings or to maximize health impact per expenditure. One commonly used intervention in sub-Saharan Africa is indoor residual spraying (IRS), typically deployed through a mass campaign. While possible synergies between IRS and long-lasting insecticide-treated nets (LLINs) have been investigated in multiple transmission settings, coordinated synergy between IRS and other mass medical distribution campaigns have not attracted much attention. Recently, a strong timing-dependent synergy between an IRS campaign and a mass drug administration (MDA) was theoretically quantified. These synergistic benefits likely differ across settings depending on transmission intensity and its overall seasonal pattern. METHODS: High coverage interventions are modelled in different transmission environments using two methods: a Ross-Macdonald model variant and openmalaria simulations. The impact of each intervention strategy was measured through its ability to prevent host infections over time, and the effects were compared to the baseline case of deploying interventions in isolation. RESULTS: By modelling IRS and MDA together and varying their deployment times, a strong synergy was found when the administered interventions overlapped. The added benefit of co-timed interventions was robust to differences in the models. In the Ross-Macdonald model, the impact compared was roughly double the sequential interventions in most transmission settings. Openmalaria simulations of this medical control augmentation of an IRS campaign show an even stronger response with the same timing relationship. CONCLUSIONS: The strong synergies found for these control tools between the complementary interventions demonstrate a general feature of effective concurrent campaign-style vector and medical interventions. A mass treatment campaign is normally short-lived, especially in higher transmission settings. When co-timed, the rapid clearing of the host parasite reservoir via chemotherapy is protected from resurgence by the longer duration of the vector control. An effective synchronous treatment campaign has the potential to greatly augment the impact of indoor residual spraying. Mass screening and treatment (MSAT) with highly sensitive rapid diagnostic tests may demonstrate a comparable trend while mass LLIN campaigns may similarly coordinate with MDA/MSAT.

Infrastructure-building for Public Health : The World Health Organization and Tuberculosis Control in South Korea, 1945-1963.

This paper examines WHO's involvement in South Korea within the context of the changing organization of public health infrastructure in Korea during the years spanning from the end of the Japanese occupation, through the periods of American military occupation and the Korean War, and to the early years of the Park Chung Hee regime in the early 1960s, in order to demonstrate how tuberculosis came to be addressed as a public health problem. WHO launched several survey missions and relief efforts before and during the Korean War and subsequently became deeply involved in shaping government policy for public health through a number of technical assistance programs, including a program for tuberculosis control in the early 1960s. This paper argues that the principal concern for WHO was to start rebuilding the public health infrastructure beyond simply abolishing the remnants of colonial practices or showcasing the superiority of American practices vis-à-vis those practiced under a Communist rule. WHO consistently sought to address infrastructural problems by strengthening the government's role by linking the central and regional health units, and this was especially visible in its tuberculosis program, where it attempted to take back the responsibilities and functions previously assumed by voluntary organizations like the Korea National Tuberculosis Administration (KNTA). This interest in public health infrastructure was fueled by WHO's discovery of a cost-effective, drug-based, and communityoriented horizontal approach to tuberculosis control, with a hope that these practices would replace the traditional, costly, disease-specific, and seclusion-oriented vertical approach that relied on sanatoria. These policy imperatives were met with the unanticipated regime change from a civilian to a military government in 1961, which created an environment favorable for the expansion of the public health network. Technology and politics were intricately intertwined in the emergence of a new infrastructure for public health in Korea, as this case of tuberculosis control illustrates.

Robust viability analysis of a controlled epidemiological model.

Managing infectious diseases is a world public health issue, plagued by uncertainties. In this paper, we analyze the problem of viable control of a dengue outbreak under uncertainty. For this purpose, we develop a controlled Ross-Macdonald model with mosquito vector control by fumigation, and with uncertainties affecting the dynamics; both controls and uncertainties are supposed to change only once a day, then remain stationary during the day. The robust viability kernel is the set of all initial states such that there exists at least a strategy of insecticide spraying which guarantees that the number of infected individuals remains below a threshold, for all times, and whatever the sequences of uncertainties. Having chosen three nested subsets of uncertainties - a deterministic one (without uncertainty), a medium one and a large one - we can measure the incidence of the uncertainties on the size of the kernel, in particular on its reduction with respect to the deterministic case. The numerical results show that the viability kernel without uncertainties is highly sensitive to the variability of parameters - here the biting rate, the probability of infection to mosquitoes and humans, and the proportion of female mosquitoes per person. So, a robust viability analysis is a possible tool to reveal the importance of uncertainties regarding epidemics control.

Identifying key factors of the transmission dynamics of drug-resistant malaria.

Development of resistance to malaria treatments remains a great threat to continued malaria burden reduction and elimination. Quantifying the impact of key factors which increase the emergence and spread of drug resistance can guide intervention strategies. Whilst modelling provides a framework to understand these factors, we show that a simple of model with a sensitive-resistant dichotomy leads to incorrectly focusing on reducing the treatment rate as a means to prevent resistance. Instead we present a model that considers the development of resistance within hosts as a scale, and we then quantify the number of resistant infections that would arise from a single sensitive infection. By including just one step before full resistance, the model highlights that disrupting this development is more effective than reducing treatment rate. This result is compounded when the model includes the more realistic scenario of several intermediary steps. An additional comparison to transmission probabilities, where resistant infections are less likely to be transmitted (cost of resistance), confirms that preventing the establishment of resistance is more effective than controlling the spread. Our work strongly advocates for further studies into within-host models of resistance, including the potential of combination therapies to disrupt emergence.

Infrastructure-building for Public Health: The World Health Organization and Tuberculosis Control in South Korea, 1945–1963 / 의사학

This paper examines WHO's involvement in South Korea within the context of the changing organization of public health infrastructure in Korea during the years spanning from the end of the Japanese occupation, through the periods of American military occupation and the Korean War, and to the early years of the Park Chung Hee regime in the early 1960s, in order to demonstrate how tuberculosis came to be addressed as a public health problem. WHO launched several survey missions and relief efforts before and during the Korean War and subsequently became deeply involved in shaping government policy for public health through a number of technical assistance programs, including a program for tuberculosis control in the early 1960s. This paper argues that the principal concern for WHO was to start rebuilding the public health infrastructure beyond simply abolishing the remnants of colonial practices or showcasing the superiority of American practices vis-à-vis those practiced under a Communist rule. WHO consistently sought to address infrastructural problems by strengthening the government's role by linking the central and regional health units, and this was especially visible in its tuberculosis program, where it attempted to take back the responsibilities and functions previously assumed by voluntary organizations like the Korea National Tuberculosis Administration (KNTA). This interest in public health infrastructure was fueled by WHO's discovery of a cost-effective, drug-based, and community-oriented horizontal approach to tuberculosis control, with a hope that these practices would replace the traditional, costly, disease-specific, and seclusion-oriented vertical approach that relied on sanatoria. These policy imperatives were met with the unanticipated regime change from a civilian to a military government in 1961, which created an environment favorable for the expansion of the public health network. Technology and politics were intricately intertwined in the emergence of a new infrastructure for public health in Korea, as this case of tuberculosis control illustrates.

Knowledge, Attitudes, and Practices Among Nurses in Pakistan Towards Diabetic Foot.

Introduction Diabetic foot ulcers are a pressing complication of diabetes mellitus. Wound care requires a significant proportion of healthcare resources. It is imperative, therefore, for healthcare professionals to possess sound knowledge of the disease along with a positive attitude to ensure better clinical practice. Our literature search revealed a scarcity of data pertaining to diabetic foot ulcers. Therefore, this study aims to evaluate the knowledge and attitudes of nurses regarding diabetic foot care. Methods A cross-sectional study design was employed, a pre-validated and pre-tested questionnaire was used to collect data from a sample size of 250 nurses working at two tertiary care hospitals in Karachi, Pakistan. The study was conducted over a period of three months (January to March 2018) and included all nurses who possessed at least one year of clinical experience in diabetic ulcer care. The statistical software employed was SPSS version 19 (IBM Corp., Armonk, NY, US). Non-parametric tests and descriptive statistics were used for data analysis and statistical significance was assumed at a p-value of less than 0.5. Results Only 54% of the nurses in our study possessed adequate knowledge of diabetic foot ulcers. The mean score of knowledge was 74.9 (±9.5). Macdonald's standard criteria for learning outcomes was used to gauge the knowledge levels of our study population. Nurses performed best in the domain of ulcer care with 65.3% of the participants possessing good knowledge of the topic. The overall attitude of nurses towards patients with diabetic ulcers was positive.  Conclusion This study highlights important gaps in nurses' knowledge and sheds light on the lack of evidence-based practice. Poor knowledge can compromise healthcare standards, even with the presence of positive attitudes. Hence, a comprehensive revision of nursing curricula across local tertiary hospitals for allowing nurses to update their knowledge is warranted.

Mathematical modeling of climate change and malaria transmission dynamics: a historical review.

Malaria, one of the greatest historical killers of mankind, continues to claim around half a million lives annually, with almost all deaths occurring in children under the age of five living in tropical Africa. The range of this disease is limited by climate to the warmer regions of the globe, and so anthropogenic global warming (and climate change more broadly) now threatens to alter the geographic area for potential malaria transmission, as both the Plasmodium malaria parasite and Anopheles mosquito vector have highly temperature-dependent lifecycles, while the aquatic immature Anopheles habitats are also strongly dependent upon rainfall and local hydrodynamics. A wide variety of process-based (or mechanistic) mathematical models have thus been proposed for the complex, highly nonlinear weather-driven Anopheles lifecycle and malaria transmission dynamics, but have reached somewhat disparate conclusions as to optimum temperatures for transmission, and the possible effect of increasing temperatures upon (potential) malaria distribution, with some projecting a large increase in the area at risk for malaria, but others predicting primarily a shift in the disease's geographic range. More generally, both global and local environmental changes drove the initial emergence of P. falciparum as a major human pathogen in tropical Africa some 10,000 years ago, and the disease has a long and deep history through the present. It is the goal of this paper to review major aspects of malaria biology, methods for formalizing these into mathematical forms, uncertainties and controversies in proper modeling methodology, and to provide a timeline of some major modeling efforts from the classical works of Sir Ronald Ross and George Macdonald through recent climate-focused modeling studies. Finally, we attempt to place such mathematical work within a broader historical context for the "million-murdering Death" of malaria.

Medical and entomological malarial interventions, a comparison and synergy of two control measures using a Ross/Macdonald model variant and openmalaria simulation.

Using an established Ross/Macdonald model variant for mosquito-born parasite transmission, we extend the formalism to simply incorporate time-dependent control measures. In particular, two interventions are considered, mass drug administration (MDA) and indoor residual spraying (IRS), whose individual intensities during their respective campaigns are set to the same intervention-reduced reproductive number R0. The impacts of these interventions, measured as each campaign's ability over time to reduce infections in a community, are found based on the transmission setting, coverage, and their associated durations. These impacts are compared for both interventions and their joint deployment. Synchronous campaigns of IRS deployed with MDA have a cooperative, synergistic effect whose impact exceeds that when the campaigns are deployed in isolation. Simulations with openmalaria, with its more complex model of transmission, are separately performed and show a similar impact enhancement with these interventions. A new, associated analysis yields simple scaling relationships that estimate the dynamical resurgence time, post-intervention, to infection proliferation in a community.