I investigated effects of environmental change on disease, and effects of disease on ecosystems, using a freshwater zooplankton host and its fungal parasite. This research involved lake surveys, manipulative experiments, and mathematical models. My results indicate that ecosystem characteristics such as habitat structure, nutrient availability, and quality of a host’s resources (here, phytoplankton) can affect the spread of disease. For example, a survey of epidemics in lakes revealed direct and indirect links between habitat structure and epidemic size, where indirect connections were mediated by non-host species. Then, in a mesocosm experiment in a lake, manipulations of habitat structure and nutrient availability interactively affected the spread of disease, and nutrient enrichment increased densities of infected hosts. In a separate laboratory experiment, poor quality resources were shown to decrease parasite transmission rate by altering host foraging behavior. My experimental results also suggest that disease can affect ecosystems through effects on host densities and host traits. In the mesocosm experiment, the parasite indirectly increased abundance of algal resources by decreasing densities of the zooplankton host. Disease in the experimental zooplankton populations also impacted nutrient stoichiometry of algae, which could entail a parasite-mediated shift in food quality for grazers such as the host. Additionally, I showed that infection dramatically reduces host feeding rate, and used a dynamic epidemiological model to illustrate how this parasite-mediated trait change could affect densities of resources and hosts, as well as the spread of disease. I discuss the implications of these ecosystem–disease interactions in light of ongoing changes to habitat and nutrient regimes in freshwater ecosystems.

The last two decades have seen several large-scale epidemics of international impact, including human, animal and plant epidemics. Policy makers face health challenges that require epidemic predictions based on limited information. There is therefore a pressing need to construct models that allow us to frame all available information to predict an emerging outbreak and to control it in a timely manner. The aim of this thesis is to develop an early-warning modelling approach that can predict emerging disease outbreaks. Based on Bayesian techniques ideally suited to combine information from different sources into a single modelling and estimation framework, I developed a suite of approaches to epidemiological data that can deal with data from different sources and of varying quality. The SEIR model, particle filter algorithm and a number of influenza-related datasets were utilised to examine various models and methodologies to predict influenza outbreaks. The data included a combination of consultations and diagnosed influenza-like illness (ILI) cases for five influenza seasons. I showed that for the pandemic season, different proxies lead to similar behaviour of the effective reproduction number. For influenza datasets, there exists a strong relationship between consultations and diagnosed datasets, especially when considering time-dependent models. Individual parameters for different influenza seasons provided similar values, thereby offering an opportunity to utilise such information in future outbreaks. Moreover, my findings showed that when the temperature drops below 14°C, this triggers the first substantial rise in the number of ILI cases, highlighting that temperature data is an important signal to trigger the start of the influenza epidemic. Further probing was carried out among Maltese citizens and estimates on the under-reporting rate of the seasonal influenza were established. Based on these findings, a new epidemiological model and framework were developed, providing accurate real-time forecasts with a clear early warning signal to the influenza outbreak. This research utilised a combination of novel data sources to predict influenza outbreaks. Such information is beneficial for health authorities to plan health strategies and control epidemics.

Thesis (MScMedSc)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: Application of molecular fingerprinting highlights transmission as the driving force behind the drug resistant epidemic in South Africa. Different strains dominate within different geographical regions, which is a reflection of micro-epidemics of drug resistance in the different regions. Cluster analysis shows that strains within the same strain family are different. The Beijing drug resistant strain family is the most dominant strain family (31%) in the Western Cape and of particular concern is the highly transmissible Beijing cluster 220 strain in the Western Cape communities. This cluster is widespread in the region and was previously identified in a MDR outbreak in a high school in Cape Town. Results suggest that the spread of Beijing drug resistant cluster 220 in the community was due to a combination of acquisition of drug resistant markers and transmission. This study also indicate that atypical Beijing can acquire drug resistance and become fit amongst HIV infected individuals. This is contrary to believe that atypical Beijing strains are not frequently associated with drug resistance and are attenuated. This implies that HIV levels the playing field for all drug resistant strains. Mechanisms leading to the evolution of MDR-TB and XDR-TB in a mine setting with a wellfunctioning TB control program which exceeds the target for cure rates set by the WHO were investigated. Despite the excellent control program, an alarming increase in the number of drug resistant cases was observed in 2003 and subsequent years. Phylogenetic analysis shows sequential acquisition of resistance to first and second-line anti-TB drugs leading to the development of MDR and XDR-TB. Contact tracing indicate extensive transmission of drug resistant TB in the shafts, hospital and place of residence. This study shows that despite exceeding the WHO cure rate target, it was not possible to control the spread and amplification of drug resistance. In summary, as a top priority, future TB control plans need to address diagnostic delay more vigorously. / AFRIKAANSE OPSOMMING: Molukulêre tegnieke toon transmissie as die hoofrede vir die toename in die anti-tuberkulose middelweerstandigheid epidemie in Suid-Afrika. Die verskillende Mikobakterium tuberkulose rasse wat domineer in verskillende areas is ‘n refleksie van middelweerstandige mikro-epidemies in verskillende gebiede. Analise van identiese rasgroepe demonstreer dat ras families bestaan uit verskillende rasse. Die Beijing middelweerstandige rasfamilie is die mees dominante familie in die Wes-Kaap (31% van monsters van middelweerstandige families) en van spesifieke belang is die hoogs oordraagbare Beijing 220 groep. Hierdie groep is die mees wydverspreide groep in die studie area en was voorheen geïdentifiseer tydens ‘n meervoudige middelweerstandige uitbreking in ‘n hoërskool in Kaapstad. Die resultate dui aan dat die Beijing middelweerstandige groep 220 in die gemeenskap versprei as gevolg van ‘n kombinasie van middelweerstand verwerwing en transmissie. Hierdie studie dui verder aan dat die atipiese Beijing ook middelweerstandigheid kan verwerf en hoogs geskik is vir infeksie veral in MIV geïnfekteerde individue. Hierdie data is in teenstelling met die algemene denke dat atipiese Beijing nie gereeld geassosieer word met middelweerstandigheid nie en dat dit dikwels geattenueer is. Dit beteken dat MIV die hoof faktor is wat alle middelweerstandige rasse kans gee om te versprei. Hierdie studie het die meganisme wat lei tot die evolusie van middelweerstandigheid en “XDRTB” in die myne ondersoek. Die myn besit ‘n goeie funksioneerde tuberkulose kontrole program wat alreeds die Wêreld Gesondheids Organisasie se mikpunt vir tuberkulose genesing oortref. Ten spyte van ‘n uitstekende tuberkulose kontrole program, is daar ‘n bekommerenswaardige toename in die aantal middelweerstandige tuberkulose gevalle waargeneem in 2003 en in die daaropvolgende jare. Filogenetiese analise wys dat opeenvolgende verwerwing van middelweerstandigheid teen eerste en tweede vlak anti-tuberkulose middels gelei het tot die ontwikkeling van meervoudige middelweerstandigheid en “XDR-TB”. Die opsporing van kontakpersone om transmissie te bewys dui aan dat transmissie van middelweerstandige tuberkulose in die werk plek, hospitaal en woon plek plaasvind. Hierdie studie wys dat ongeag die feit dat die Wêreld Gesondheids Organisasie se genesings verwagtinge oortref is, dit steeds onmoontlik was om die verspreiding en amplifisering van middelweerstandigheid te beheer. ‘n Top prioriteit vir tuberkulose kontrole planne in die toekoms behoort die vertraging van diagnose sterk aan te spreek.

Thesis (DTech (Mechanical Engineering))--Cape Peninsula University of Technology, 2012 / In this thesis, we investigate certain key aspects of mathematical modelling to explain the epidemiology of HIV/AIDS at the workplace and to assess the potential benefits of proposed control strategies. Deterministic models to investigate the effects of the transmission dynamics of HIV/AIDS on labour force productivity are formulated. The population is divided into mutually exclusive but exhaustive compartments and a system of differential equations is derived to describe the spread of the epidemic. The qualitative features of their equilibria are analyzed and conditions under which they are stable are provided. Sensitivity analysis of the reproductive number is carried out to determine the relative importance of model parameters to initial disease transmission. Results suggest that optimal control theory in conjunction with standard numerical procedures and cost effective analysis can be used to determine the best intervention strategies to curtail the burden HIV/AIDS is imposing on the human population, in particular to the global economy through infection of the most productive individuals. We utilise Pontryagin’s Maximum Principle to derive and then analyze numerically the conditions for optimal control of the disease with effective use of condoms, enlightenment/educational programs, treatment regime and screening of infectives. We study the potential impact on productivity of combinations of these conventional control measures against HIV. Our numerical results suggest that increased access to antiretroviral therapy (ART) could decrease not only the HIV prevalence but also increase productivity of the infected especially when coupled with prevention, enlightenment and screening efforts.

Indiana University-Purdue University Indianapolis (IUPUI) / Methylmercury (MeHg) exposure from occupational, environmental and food sources is a significant threat to public health. MeHg poisonings in adults may result in severe psychological and neurological deficits, and in utero exposures can confer significant damage to the developing brain and impair neurobehavioral and intellectual development. Recent epidemiological and vertebrate studies suggest that MeHg exposure may contribute to dopamine (DA) neuron vulnerability and the propensity to develop Parkinson’s disease (PD). I have developed a novel Caenorhabditis elegans (C. elegans) model of MeHg toxicity and have shown that low, chronic exposure confers embryonic defects, developmental delays, reduction in brood size, decreased animal viability and DA neuron degeneration. Toxicant exposure results in an increase in reactive oxygen species (ROS) and the robust induction of several glutathione-S-transferases (GSTs) that are largely dependent on the PD-associated phase II antioxidant transcription factor SKN-1/Nrf2. I have also shown that SKN-1 is expressed in the DA neurons, and a reduction in SKN-1 gene expression increases MeHg-induced animal vulnerability and DA neuron degeneration. Furthermore, I incorporated a novel genome wide reverse genetic screen that identified 92 genes involved in inhibiting MeHg-induced animal death. The putative multidrug resistance protein MRP-7 was identified in the screen. I have shown that this transporter is likely expressed in DA neurons, and reduced gene expression increases cellular Hg accumulation and MeHg-associated DA neurodegeneration. My studies indicate that C. elegans is a useful genetic model to explore the molecular basis of MeHg-associated DA neurodegeneration, and may identify novel therapeutic targets to address this highly relevant health issue.

Indiana University-Purdue University Indianapolis (IUPUI) / Phytoestrogens that abound in soy products, legumes, and chickpeas can induce biologic responses in animals and humans due to structural similarity to 17β-estradiol. Although experimental studies suggest that phytoestrogen intake may alter the risk of cancer and cardiovascular disease, few epidemiologic studies have investigated this research question. This dissertation investigated the associations of intake of total and individual phytoestrogens and their urinary biomarkers with these chronic conditions using data previously collected from two US national cohort studies (NHANES and PLCO). Utilizing NHANES data with urinary phytoestrogen concentrations and follow-up mortality, Cox proportional hazards regression (HR; 95% CI) were performed to evaluate the association between total cancer, cardiovascular disease, and all-cause mortality and urinary phytoestrogens. After adjustment for confounders, it was found that higher concentrations of lignans were associated with a reduced risk of death from cardiovascular disease (0.48; 0.24-0.97), whereas higher concentrations of isoflavones (2.14; 1.03-4.47) and daidzein (2.05; 1.02-4.11) were associated with an increased risk. A reduction in all-cause mortality was observed for elevated concentrations of lignans (0.65; 0.43-0.96) and enterolactone (0.65; 0.44-0.97). Utilizing PLCO data and dietary phytoestrogens, Cox proportional hazards regression examined the associations between dietary phytoestrogens and the risk of prostate cancer incidence. After adjustment for confounders, a positive association was found between dietary intake of isoflavones (1.58; 1.11-2.24), genistein (1.42; 1.02-1.98), daidzein (1.62; 1.13-2.32), and glycitein (1.53; 1.09-2.15) and the risk of advanced prostate cancer. Conversely, an inverse association existed between dietary intake of genistein and the risk of non-advanced prostate cancer (0.88; 0.78-0.99) and total prostate cancer (0.90; 0.81-1.00). C-reactive protein (CRP) concentration levels rise in response to inflammation and higher levels are a risk factor for some cancers and cardiovascular disease reported in epidemiologic studies. Logistic regression performed on NHANES data evaluated the association between CRP and urinary phytoestrogen concentrations. Higher concentrations of total and individual phytoestrogens were associated with lower concentrations of CRP. In summary, dietary intake of some phytoestrogens significantly modulates prostate cancer risk and cardiovascular disease mortality. It is possible that these associations may be in part mediated through the influence of phytoestrogen intake on circulating levels of C-reactive protein.