Giovanni Lo Iacono

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

Background Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Methodology/Principal Findings Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to . Conclusions/Significance This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection.

Where are the horses? With the sheep or cows? Uncertain host location, vector-feeding preferences and the risk of African horse sickness transmission in Great Britain

Understanding the influence of non-susceptible hosts on vector-borne disease transmission is an important epidemiological problem. However, investigation of its impact can be complicated by uncertainty in the location of the hosts. Estimating the risk of transmission of African horse sickness (AHS) in Great Britain (GB), a virus transmitted by Culicoides biting midges, provides an insightful example because: (i) the patterns of risk are expected to be influenced by the presence of non-susceptible vertebrate hosts (cattle and sheep) and (ii) incomplete information on the spatial distribution of horses is available because the GB National Equine Database records owner, rather than horse, locations. Here, we combine land-use data with available horse owner distributions and, using a Bayesian approach, infer a realistic distribution for the location of horses. We estimate the risk of an outbreak of AHS in GB, using the basic reproduction number (R0), and demonstrate that mapping owner addresses as a proxy for horse location significantly underestimates the risk. We clarify the role of non-susceptible vertebrate hosts by showing that the risk of disease in the presence of many hosts (susceptible and non-susceptible) can be ultimately reduced to two fundamental factors: first, the abundance of vectors and how this depends on host density, and, second, the differential feeding preference of vectors among animal species.

Durable Resistance to Crop Pathogens: An Epidemiological Framework to Predict Risk under Uncertainty

Increasing the durability of crop resistance to plant pathogens is one of the key goals of virulence management. Despite the recognition of the importance of demographic and environmental stochasticity on the dynamics of an epidemic, their effects on the evolution of the pathogen and durability of resistance has not received attention. We formulated a stochastic epidemiological model, based on the Kramer-Moyal expansion of the Master Equation, to investigate how random fluctuations affect the dynamics of an epidemic and how these effects feed through to the evolution of the pathogen and durability of resistance. We focused on two hypotheses: firstly, a previous deterministic model has suggested that the effect of cropping ratio (the proportion of land area occupied by the resistant crop) on the durability of crop resistance is negligible. Increasing the cropping ratio increases the area of uninfected host, but the resistance is more rapidly broken; these two effects counteract each other. We tested the hypothesis that similar counteracting effects would occur when we take account of demographic stochasticity, but found that the durability does depend on the cropping ratio. Secondly, we tested whether a superimposed external source of stochasticity (for example due to environmental variation or to intermittent fungicide application) interacts with the intrinsic demographic fluctuations and how such interaction affects the durability of resistance. We show that in the pathosystem considered here, in general large stochastic fluctuations in epidemics enhance extinction of the pathogen. This is more likely to occur at large cropping ratios and for particular frequencies of the periodic external perturbation (stochastic resonance). The results suggest possible disease control practises by exploiting the natural sources of stochasticity.

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: ‘spillover’, i.e. transmission of pathogens from animals to humans, and ‘stuttering transmission’, i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.

Moving interdisciplinary science forward: integrating participatory modelling with mathematical modelling of zoonotic disease in Africa.

This review outlines the benefits of using multiple approaches to improve model design and facilitate multidisciplinary research into infectious diseases, as well as showing and proposing practical examples of effective integration. It looks particularly at the benefits of using participatory research in conjunction with traditional modelling methods to potentially improve disease research, control and management. Integrated approaches can lead to more realistic mathematical models which in turn can assist with making policy decisions that reduce disease and benefit local people. The emergence, risk, spread and control of diseases are affected by many complex bio-physical, environmental and socio-economic factors. These include climate and environmental change, land-use variation, changes in population and people’s behaviour. The evidence base for this scoping review comes from the work of a consortium, with the aim of integrating modelling approaches traditionally used in epidemiological, ecological and development research. A total of five examples of the impacts of participatory research on the choice of model structure are presented. Example 1 focused on using participatory research as a tool to structure a model. Example 2 looks at identifying the most relevant parameters of the system. Example 3 concentrates on identifying the most relevant regime of the system (e.g., temporal stability or otherwise), Example 4 examines the feedbacks from mathematical models to guide participatory research and Example 5 goes beyond the so-far described two-way interplay between participatory and mathematical approaches to look at the integration of multiple methods and frameworks. This scoping review describes examples of best practice in the use of participatory methods, illustrating their potential to overcome disciplinary hurdles and promote multidisciplinary collaboration, with the aim of making models and their predictions more useful for decision-making and policy formulation.

Challenges in developing methods for quantifying the effects of weather and climate on water-associated diseases: A systematic review

Infectious diseases attributable to unsafe water supply, sanitation and hygiene (e.g. Cholera, Leptospirosis, Giardiasis) remain an important cause of morbidity and mortality, especially in low-income countries. Climate and weather factors are known to affect the transmission and distribution of infectious diseases and statistical and mathematical modelling are continuously developing to investigate the impact of weather and climate on water-associated diseases. There have been little critical analyses of the methodological approaches. Our objective is to review and summarize statistical and modelling methods used to investigate the effects of weather and climate on infectious diseases associated with water, in order to identify limitations and knowledge gaps in developing of new methods. We conducted a systematic review of English-language papers published from 2000 to 2015. Search terms included concepts related to water-associated diseases, weather and climate, statistical, epidemiological and modelling methods. We found 102 full text papers that met our criteria and were included in the analysis. The most commonly used methods were grouped in two clusters: process-based models (PBM) and time series and spatial epidemiology (TS-SE). In general, PBM methods were employed when the bio-physical mechanism of the pathogen under study was relatively well known (e.g. Vibrio cholerae); TS-SE tended to be used when the specific environmental mechanisms were unclear (e.g. Campylobacter). Important data and methodological challenges emerged, with implications for surveillance and control of water-associated infections. The most common limitations comprised: non-inclusion of key factors (e.g. biological mechanism, demographic heterogeneity, human behavior), reporting bias, poor data quality, and collinearity in exposures. Furthermore, the methods often did not distinguish among the multiple sources of time-lags (e.g. patient physiology, reporting bias, healthcare access) between environmental drivers/exposures and disease detection. Key areas of future research include: disentangling the complex effects of weather/climate on each exposure-health outcome pathway (e.g. person-to-person vs environment-to-person), and linking weather data to individual cases longitudinally.

A Comparison of Different Searching Strategies to Locate Sources of Odor in Turbulent Flows

Four different searching strategies to locate the source of odor in turbulent flows have been computationally tested. These algorithms can be separated into two classes. One is based on the rate of odor patches encountered by the searcher, the other employs the variation of odor concentrations as well as the rate of odor patches experienced by the searcher. The concentration of odor has been simulated by using a stochastic model for the time-evolution of concentrations along the path of a moving observer in an inhomogeneous plume. For each algorithm, we released the searchers at a crosswind location away from the plume centerline; we then calculated the ensemble average position relative to the plume centerline and the distribution of the searchers along the crosswind direction at the source. Compared with strategies using rate of odor patches only, the algorithms that also employ the variation of concentrations are seen to be more effective in locating the source; that is, the average path of all searchers is more biased toward the plume centerline and their crosswind distribution is more skewed toward the source. The findings of this work can be used as guidelines to discriminate successful strategies that can be tested in future experiments.Four different searching strategies to locate the source of odor in turbulent flows have been computationally tested. These algorithms can be separated into two classes. One is based on the rate of odor patches encountered by the searcher, the other employs the variation of odor concentrations as well as the rate of odor patches experienced by the searcher. The concentration of odor has been simulated by using a stochastic model for the time-evolution of concentrations along the path of a moving observer in an inhomogeneous plume. For each algorithm, we released the searchers at a crosswind location away from the plume centerline; we then calculated the ensemble average position relative to the plume centerline and the distribution of the searchers along the crosswind direction at the source. Compared with strategies using rate of odor patches only, the algorithms that also employ the variation of concentrations are seen to be more effective in locating the source; that is, the average path of all searchers is more biased toward the plume centerline and their crosswind distribution is more skewed toward the source. The findings of this work can be used as guidelines to discriminate successful strategies that can be tested in future experiments.

Particle Deposition Onto Rough Surfaces

Predictions for the number of particles depositing from fully developed turbulence onto a fully roughened kk-type surface are obtained from the results of large-eddy simulations for a ribbed-channel flow. Simulation data are found to provide only partial support for the “mass-sink hypothesis,” i.e., the notion that all particles entering a mass sink, a volume of fluid extending vertically from the deposition surface, are captured and eventually deposited. The equality of the number of particles entering the mass sink and the number of particles depositing is attained, and a qualitative agreement with the empirical model of Wood (1981, “A Simple Method for the Calculation of Turbulent Deposition to Smooth and Rough Surfaces ,” J. Aerosol Sci., 12(3), pp. 275–290) for the height of this mass sink is obtained. However, a significant proportion of particles escapes from the mass sink and the equality of numbers is attained only because many particles deposit onto rib surfaces above the mass sink, without first entering the mass sink.

A pilot project to encourage scientific debate in schools. Comics written and peer reviewed by young learners

Comprehension of the nature and practice of science and its social context are important aspects of communicating and learning science. However there is still very little understanding amongt the non-scientific community of the need for debate in driving scientific knowledge forward and the role of critical scrutiny in quality control. Peer review is an essential part of this process. We initiated and developed a pilot project to provide an opportunity for students to explore the idea that science is a dynamic process rather than a static body of facts. Students from two different schools experienced the process of peer-review by producing and reviewing comics related to the science done at Rothamsted Research. As authors, students showed a large degree of creativity and understanding of the science while as referees they showed good critical skills. Students had at first hand an insight into how science works.

Environmental limits of Rift Valley fever revealed using ecoepidemiological mechanistic models

Significance Vector-borne diseases represent complex infection transmission systems; previous epidemiological models have been unable to formally capture the relationship between the ecological limits of vector species and the dynamics of pathogen transmission. By making this advance for the key disease, Rift Valley fever, we are able to show how seasonally varying availability of water bodies and ambient temperatures dictate when the mosquito vector populations will persist and importantly, those sets of conditions resulting in stable oscillations of disease transmission. Importantly, under the latter scenario, short-term health control measures will likely fail, as the system quickly returns to the original configuration after the intervention stops. Our model, therefore, offers an important tool to better understand vector-borne diseases and design effective eradication programs. Vector-borne diseases (VBDs) of humans and domestic animals are a significant component of the global burden of disease and a key driver of poverty. The transmission cycles of VBDs are often strongly mediated by the ecological requirements of the vectors, resulting in complex transmission dynamics, including intermittent epidemics and an unclear link between environmental conditions and disease persistence. An important broader concern is the extent to which theoretical models are reliable at forecasting VBDs; infection dynamics can be complex, and the resulting systems are highly unstable. Here, we examine these problems in detail using a case study of Rift Valley fever (RVF), a high-burden disease endemic to Africa. We develop an ecoepidemiological, compartmental, mathematical model coupled to the dynamics of ambient temperature and water availability and apply it to a realistic setting using empirical environmental data from Kenya. Importantly, we identify the range of seasonally varying ambient temperatures and water-body availability that leads to either the extinction of mosquito populations and/or RVF (nonpersistent regimens) or the establishment of long-term mosquito populations and consequently, the endemicity of the RVF infection (persistent regimens). Instabilities arise when the range of the environmental variables overlaps with the threshold of persistence. The model captures the intermittent nature of RVF occurrence, which is explained as low-level circulation under the threshold of detection, with intermittent emergence sometimes after long periods. Using the approach developed here opens up the ability to improve predictions of the emergence and behaviors of epidemics of many other important VBDs.