Zoonotic Transmission of Waterborne Disease: A Mathematical Model

Waterborne parasites that infect both humans and animals are common causes of diarrheal illness, but the relative importance of transmission between humans and animals and vice versa remains poorly understood. Transmission of infection from animals to humans via environmental reser12 voirs, such as water sources, has attracted attention as a potential source of endemic and epidemic infections, but existing mathematical models of water borne disease transmission have limitations for studying this phenomenon, as they only consider contamination of environmental reservoirs by humans. This paper develops a mathematical model that represents the transmission of waterborne parasites within and between both animal and human populations. It also improves upon existing models by including animal contamination of water sources explicitly. Linear stability analysis and simulation results, using realistic parameter values to describe Giardia transmission in rural Australia, show that endemic infection of an animal host with zoonotic protozoa can result in endemic infection in human hosts, even 22 in the absence of person to-person transmission. These results imply that zoonotic transmission via environmental reservoirs is important

Climate Change and Highland Malaria: Fresh Air for a Hot Debate

In recent decades, malaria has become established in zones at the margin of its previous distribution, especially in the highlands of East Africa. Studies in this region have sparked a heated debate over the importance of climate change in the territorial expansion of malaria, where positions range from its neglect to the reification of correlations as causes. Here, we review studies supporting and rebutting the role of climatic change as a driving force for highland invasion by malaria. We assessed the conclusions from both sides of the argument and found that evidence for the role of climate in these dynamics is robust. However, we also argue that over-emphasizing the importance of climate is misleading for setting a research agenda, even one which attempts to understand climate change impacts on emerging malaria patterns. We review alternative drivers for the emergence of this disease and highlight the problems still calling for research if the multidimensional nature of malaria is to be adequately tackled. We also contextualize highland malaria as an ongoing evolutionary process. Finally, we present Schmalhausen's law, which explains the lack of resilience in stressed systems, as a biological principle that unifies the importance of climatic and other environmental factors in driving malaria patterns across different spatio-temporal scales

The influence of HIV-1 genomic target region selection and sequence length on the accuracy of inferred phylogenies and clustering outcomes.

Masters Degree. University of KwaZulu-Natal, Durban.To improve the methodology of HIV-1 cluster analysis, we addressed how analysis of HIV-1 clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering, tree certainty, subtype diversity ratio (SDR), subtype diversity variance (SDV) and Shimodaira-Hasegawa (SH)-like support values were compared between 2881 HIV-1 full genome sequences and sub-genomic regions of which 2567 were retrieved from the LANL HIV Database and 314 were sequenced from blood samples from a cohort in KwaZulu-Natal. Sliding window analysis was based on 99 windows of 1000 bp, 45 windows of 2000 bp and 27 windows of 3000 bp. Clusters were enumerated for each window sequence length, and the optimal sequence length for cluster identification was probed. Potential associations between the extent of HIV clustering and sequence length were also evaluated. The phylogeny based on the full-genome sequences showed the best tree accuracy; it ranked highest with regards to both tree certainty and SH-like support. Product 4, a region associated with env, had the best tree accuracy among the sub-genomic regions. Among the HIV-1 structural genes, env had the best tree certainty, SH-like support, SDR score and the best SDV score overall. The hierarchy of cluster phylotype enumeration mirrored the tree accuracy analysis, with the full genome phylogeny showing the highest extent of clustering, and the product 4 region being second best. Among the structural genes, the highest number of phylotypes was enumerated from the pol phylogeny, followed by env. The extent of HIV-1 clustering was slightly higher for sliding windows of 3 000 bp than 2000 bp and 1000 bp, thus 3000 bp was found to be the optimal length for phylogenetic cluster analysis. We found a moderate association between the length of sequences used and proportion of HIV sequences in clusters; the influence of viral sequence length may have been diminished by the substantial number of taxa. Full-genome sequences could provide the most informative HIV cluster analysis. Selected sub-genomic regions with the best combination of high extent of HIV clustering and high tree accuracy, such as env, could also be considered as a second choice

Modelling the Effects of Mass Drug Administration on the Molecular Epidemiology of Schistosomes

As national governments scale up mass drug administration (MDA) programs aimed to combat neglected tropical diseases (NTDs), novel selection pressures on these parasites increase. To understand how parasite populations are affected by MDA and how to maximize the success of control programmes, it is imperative for epidemiological, molecular and mathematical modelling approaches to be combined. Modelling of parasite population genetic and genomic structure, particularly of the NTDs, has been limited through the availability of only a few molecular markers to date. The landscape of infectious disease research is being dramatically reshaped by next-generation sequencing technologies and our understanding of how repeated selective pressures are shaping parasite populations is radically altering. Genomics can provide high-resolution data on parasite population structure, and identify how loci may contribute to key phenotypes such as virulence and/or drug resistance. We discuss the incorporation of genetic and genomic data, focussing on the recently sequenced Schistosoma spp., into novel mathematical transmission models to inform our understanding of the impact of MDA and other control methods. We summarize what is known to date, the models that exist and how population genetics has given us an understanding of the effects of MDA on the parasites. We consider how genetic and genomic data have the potential to shape future research, highlighting key areas where data are lacking, and how future molecular epidemiology knowledge can aid understanding of transmission dynamics and the effects of MDA, ultimately informing public health policy makers of the best interventions for NTDs

Replication and shedding kinetics of infectious hematopoietic necrosis virus in juvenile rainbow trout

Viral replication and shedding are key components of transmission and fitness, the kinetics of which are heavily dependent on virus, host, and environmental factors. To date, no studies have quantified the shedding kinetics of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss), or how they are associated with replication, making it difficult to ascertain the transmission dynamics of this pathogen of high agricultural and conservation importance. Here, the replication and shedding kinetics of two M genogroup IHNV genotypes were examined in their naturally co-evolved rainbow trout host. Within host virus replication began rapidly, approaching maximum values by day 3 post-infection, after which viral load was maintained or gradually dropped through day 7. Host innate immune response measured as stimulation of Mx-1 gene expression generally followed within host viral loads. Shedding also began very quickly and peaked within 2 days, defining a generally uniform early peak period of shedding from 1 to 4 days after exposure to virus. This was followed by a post-peak period where shedding declined, such that the majority of fish were no longer shedding by day 12 post-infection. Despite similar kinetics, the average shedding rate over the course of infection was significantly lower in mixed compared to single genotype infections, suggesting a competition effect, however, this did not significantly impact the total amount of virus shed. The data also indicated that the duration of shedding, rather than peak amount of virus shed, was correlated with fish mortality. Generally, the majority of virus produced during infection appeared to be shed into the environment rather than maintained in the host, although there was more retention of within host virus during the post-peak period. Viral virulence was correlated with shedding, such that the more virulent of the two genotypes shed more total virus. This fundamental understanding of IHNV shedding kinetics and variation at the individual fish level could assist with management decisions about how to respond to disease outbreaks when they occur. (C) 2016 Elsevier B.V. All rights reserved

Parsing the Effects of Demography, Climate and Management on Recurrent Brucellosis Outbreaks in Elk

Zoonotic pathogens can harm human health and well‐being directly or by impacting livestock. Pathogens that spillover from wildlife can also impair conservation efforts if humans perceive wildlife as pests. Brucellosis, caused by the bacterium Brucella abortus, circulates in elk and bison herds of the Greater Yellowstone Ecosystem and poses a risk to cattle and humans. Our goal was to understand the relative effects of climatic drivers, host demography and management control programmes on disease dynamics. Using \u3e20 years of serologic, demographic and environmental data on brucellosis in elk, we built stochastic compartmental models to assess the influences of climate forcing, herd immunity, population turnover and management interventions on pathogen transmission. Data were collected at feedgrounds visited in winter by free‐ranging elk in Wyoming, USA. Snowpack, hypothesized as a driver of elk aggregation and thus brucellosis transmission, was strongly correlated across feedgrounds. We expected this variable to drive synchronized disease dynamics across herds. Instead, we demonstrate asynchronous epizootics driven by variation in demographic rates. We evaluated the effectiveness of test‐and‐slaughter of seropositive female elk at two feedgrounds. Test‐and‐slaughter temporarily reduced herd‐level seroprevalence but likely reduced herd immunity while removing few infectious individuals, resulting in subsequent outbreaks once the intervention ceased. We simulated an alternative strategy of removing seronegative female elk and found it would increase herd immunity, yielding fewer infections. We evaluated a second experimental treatment wherein feeding density was reduced at one feedground, but we found no evidence for an effect despite a decade of implementation. Synthesis and applications. Positive serostatus is often weakly correlated with infectiousness but is nevertheless used to make management decisions including lethal removal in wildlife disease systems. We show how this can have adverse consequences whereas efforts that maintain herd immunity can have longer‐term protective effects. Climatic drivers may not result in synchronous disease dynamics across populations unless vital rates are also similar because demographic factors have a large influence on disease patterns

Increasing Malaria Risk in Eastern Africa. A Multi-Causal Analysis

Global climatic change has been analysed as a key driving force of social-ecological change in the coming decades. The increasing spread of Malaria due to warming is named as a major future problem of East Africa. In contrast to much of northern and southern Africa more humid conditions are expected for countries like Kenya, Uganda and Tanzania. Next to changing precipitation patterns and a profound snow melt on the glaciers of Mt. Kilimandjaro and Mt Kenya, warming and potentially higher rates of precipitation may bring about higher rates of Malaria infection. In fact, the empirically recorded cases of Malaria infections in the region seemingly support this argument. Infection rates have been constantly rising over the past two decades and many areas that had not been affected by Malaria for many decades, now have seasonal Malaria epidemics. It is especially the densely settled zone between 1500m and 2000m – the highly fertile Kenyan highlands – which seem to be affected most. Hence many indicators suggest a strong correlation between climatic change and the increase in Malaria. Barbara Solich shows that underlying social-ecological processes are much more complex than that. In a multi-causal analysis she is able to show that a number of other factors may have even a greater effect on Malaria rates than climatic change. In order to present her argument systematically Solich first of all gives a short out-line of the state of research. Unfortunately most research on increasing Malaria rates in East Africa is concentrating on one explanatory variable only. Also reliable long term data is rare. Solich presents her critique of current research foci and discusses a number of drivers that increase Malaria infections. She roughly differentiates between natural and socio- economic/political drivers – indicating a heuristic basis used in this identification. Among the natural drivers, climate change, land-use and cover changes, and drug resistance have been analysed, while demographic changes, poverty, and inadequate political responses have been identified as socio-economic/political drivers of the spread of Malaria in the region. Based on the analysis, she models the inter-connections between the factors and heir influence on various stages of the malaria infectious cycle. Exemplary analysis of the Kenyan Highlands illustrates this interplay of factors and strengthens Solich’s argument for further studies concerning Malaria-risk multiple causation. Michael J. Casimi

2016 Conference Abstracts: Annual Undergraduate Research Conference at the Interface of Biology and Mathematics

Schedule and abstract book for the Eighth Annual Undergraduate Research Conference at the Interface of Biology and Mathematics Date: October 8-9, 2016Location: UT Conference Center, KnoxvillePlenary Speaker: Jorge X. Velasco Hernández, Universidad Nacional Autónoma de MéxicoFeatured Speaker: Judy Day, University of Tennessee, Knoxvill