Coral disease dynamics and environmental drivers in the northern Florida Keys and Lee Stocking Island, Bahamas

Coral reefs are experiencing declines worldwide and recently coral diseases have been identified as significant contributors to coral mortality. However, little is known regarding the factors that drive coral disease distributions and dynamics. Current knowledge of the organisms that cause coral diseases is also limited, with pathogens having been identified for only 5 of the 21 described coral diseases. The study presented here describes coral disease dynamics in terms of occurrence, prevalence, spatial distribution, and host species susceptibility from 2002--2004 on reefs of the Northern Florida Keys (NFK) and Lee Stocking Island (LSI) in the Bahamas' Exuma chain. In addition, this research investigated the influence of temperature, sediment, and nutrient availability on coral disease prevalence and severity. Finally, microbial communities associated with a polymicrobial disease, black band, were examined to address spatial and temporal variability. ^ Four scleractinian diseases were observed in repeated surveys conducted during June-August of each year: black band disease (BBD), white plague type 2 (WP), dark spots syndrome (DSS), and yellow band disease-(YBD). Coral disease prevalence was generally low in both the NFK and LSI as compared to epizootic levels reported previously in the NFK and other regions of the Caribbean. Disease prevalence and species susceptibility varied spatially and temporally. Massive framework species, including Siderastrea siderea, Colpophyllia natans, and Montastraea annularis, along with relatively smaller colonies of Meandrina meandrites and Dichocoenia stokesi, were most susceptible to disease. Temperature, sedimentation, and dissolved inorganic nitrogen were positively correlated with BBD infections. Furthermore, experimental nutrient enrichment exacerbated coral tissue loss to BBD both in situ and in vivo. Profiling of BBD microbial communities using length heterogeneity PCR revealed variation over space and time, with significantly distinct bacterial assemblages in the NFK, LSI, and US Virgin Islands. ^ This study contributes to knowledge of the relationship between coral diseases and the environment, and facilitates predictions regarding potential changes in coral reef communities under differing environmental conditions. Additionally, this research provides further understanding of coral disease dynamics at both the host and microbial pathogen levels.^

Mycobacteriosis in Chesapeake Bay Striped Bass (Morone saxatilis): The Interaction of Nutrition and Disease

Field and laboratory studies were conducted from 1998 - 2005 to examine the relationship between nutritional status and mycobacteriosis in Chesapeake Bay striped bass (Morone saxatilis). A review of DNA from archived tissue blocks indicated that the disease has been present since at least 1984. Field surveys and feeding trials were conducted from 1998-1999 to determine the nutritional condition of striped bass and the association with disease state. Proximate composition revealed elevated moisture (~ 80%) and low storage lipids (< 0.5% ww), characteristic of a poorly nourished population. These findings were not consistent with data collected in 1990-1991, or with experimentally fed fish. Mycobacteriosis explained little of the variance in chemical composition (p > 0.2); however elevated moisture and low lipid concentration were associated with fish with ulcerative lesions (p < 0.05). This suggests that age 3 and 4 striped bass were in poor nutritional health in 1998-1999, which may be independent from the disease process. Challenge studies were performed to address the hypothesis that disease progression and severity may be altered by nutritional status of the host. Intraperitoneal inoculation of 104 CFU M. marinum resulted in high mortality, elevated bacterial density, and poor granuloma formation in low ration (0.15% bw/d) groups while adequately fed fish (1% bw/d) followed a normal course of granulomatous inflammation with low mortality to a steady, equilibrium state. Further, we demonstrated that an active inflammatory state could be reactivated in fish through reductions in total diet. The energetic demand of mycobacteriosis, was insignificant in comparison to sham inoculated controls in adequately fed fish (p > 0.05). Declines in total body energy were only apparent during active, inflammatory stages of disease. Overall, these findings suggest that: 1) mycobacteriosis is not a new disease of Chesapeake Bay striped bass, 2) the disease has little energetic demand in the normal, chronic progression, and 3) poor nutritional health can greatly enhance the progression and severity, and reactivation of disease. The implications of this research are that management strategies focused on enhancing the nutritional state of striped bass could potentially alter the disease dynamics in Chesapeake Bay.

Linking genetic and environmental factors in amphibian disease risk

A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L.yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source-sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines.

Seeking a Second Opinion: Uncertainty in Disease Ecology

Analytical methods accounting for imperfect detection are often used to facilitate reliable inference in population and community ecology. We contend that similar approaches are needed in disease ecology because these complicated systems are inherently difficult to observe without error. For example, wildlife disease studies often designate individuals, populations, or spatial units to states (e.g., susceptible, infected, post-infected), but the uncertainty associated with these state assignments remains largely ignored or unaccounted for. We demonstrate how recent developments incorporating observation error through repeated sampling extend quite naturally to hierarchical spatial models of disease effects, prevalence, and dynamics in natural systems. A highly pathogenic strain of avian influenza virus in migratory waterfowl and a pathogenic fungus recently implicated in the global loss of amphibian biodiversity are used as motivating examples. Both show that relatively simple modifications to study designs can greatly improve our understanding of complex spatio-temporal disease dynamics by rigorously accounting for uncertainty at each level of the hierarchy.

Digital Epidemiology Reveals Global Childhood Disease Seasonality and the Effects of Immunization

ACKNOWLEDGMENTS. We would like to thank Fernando Gonzalez-Dominguez and Gilberto Vaughan for providing the chicken pox case reports from Mexico, and the Estonia Health Board, Department of Communicable Disease Surveillance and Control, for Estonian chicken pox case reports. KB would like to thank Mercedes Pascual, her lab, and Marisa Eisenberg for helpful comments. Jesus Cantu (research assistant, Princeton University) translated and categorized chicken pox searches from Mexico, Thailand, Australia, and the US.

Investigating disease persistence in host vector systems: dengue as a case study

The investigation of pathogen persistence in vector-borne diseases is important in different ecological and epidemiological contexts. In this thesis, I have developed deterministic and stochastic models to help investigating the pathogen persistence in host-vector systems by using efficient modelling paradigms. A general introduction with aims and objectives of the studies conducted in the thesis are provided in Chapter 1. The mathematical treatment of models used in the thesis is provided in Chapter 2 where the models are found locally asymptotically stable. The models used in the rest of the thesis are based on either the same or similar mathematical structure studied in this chapter. After that, there are three different experiments that are conducted in this thesis to study the pathogen persistence. In Chapter 3, I characterize pathogen persistence in terms of the Critical Community Size (CCS) and find its relationship with the model parameters. In this study, the stochastic versions of two epidemiologically different host-vector models are used for estimating CCS. I note that the model parameters and their algebraic combination, in addition to the seroprevalence level of the host population, can be used to quantify CCS. The study undertaken in Chapter 4 is used to estimate pathogen persistence using both deterministic and stochastic versions of a model with seasonal birth rate of the vectors. Through stochastic simulations we investigate the pattern of epidemics after the introduction of an infectious individual at different times of the year. The results show that the disease dynamics are altered by the seasonal variation. The higher levels of pre-existing seroprevalence reduces the probability of invasion of dengue. In Chapter 5, I considered two alternate ways to represent the dynamics of a host-vector model. Both of the approximate models are investigated for the parameter regions where the approximation fails to hold. Moreover, three metrics are used to compare them with the Full model. In addition to the computational benefits, these approximations are used to investigate to what degree the inclusion of the vector population in the dynamics of the system is important. Finally, in Chapter 6, I present the summary of studies undertaken and possible extensions for the future work.

Phylodynamic modelling of foot-and-mouth disease virus sequence data

The under-reporting of cases of infectious diseases is a substantial impediment to the control and management of infectious diseases in both epidemic and endemic contexts. Information about infectious disease dynamics can be recovered from sequence data using time-varying coalescent approaches, and phylodynamic models have been developed in order to reconstruct demographic changes of the numbers of infected hosts through time. In this study I have demonstrated the general concordance between empirically observed epidemiological incidence data and viral demography inferred through analysis of foot-and-mouth disease virus VP1 coding sequences belonging to the CATHAY topotype over large temporal and spatial scales. However a more precise and robust relationship between the effective population size (

Predictive Models for Tomato Spotted Wilt Virus Spread Dynamics, Considering Frankliniella occidentalis Specific Life Processes as Influenced by the Virus

Several models have been studied on predictive epidemics of arthropod vectored plant viruses in an attempt to bring understanding to the complex but specific relationship between the three cornered pathosystem (virus, vector and host plant), as well as their interactions with the environment. A large body of studies mainly focuses on weather based models as management tool for monitoring pests and diseases, with very few incorporating the contribution of vector's life processes in the disease dynamics, which is an essential aspect when mitigating virus incidences in a crop stand. In this study, we hypothesized that the multiplication and spread of tomato spotted wilt virus (TSWV) in a crop stand is strongly related to its influences on Frankliniella occidentalis preferential behavior and life expectancy. Model dynamics of important aspects in disease development within TSWV-F. occidentalis-host plant interactions were developed, focusing on F. occidentalis' life processes as influenced by TSWV. The results show that the influence of TSWV on F. occidentalis preferential behaviour leads to an estimated increase in relative acquisition rate of the virus, and up to 33% increase in transmission rate to healthy plants. Also, increased life expectancy; which relates to improved fitness, is dependent on the virus induced preferential behaviour, consequently promoting multiplication and spread of the virus in a crop stand. The development of vector-based models could further help in elucidating the role of tri-trophic interactions in agricultural disease systems. Use of the model to examine the components of the disease process could also boost our understanding on how specific epidemiological characteristics interact to cause diseases in crops. With this level of understanding we can efficiently develop more precise control strategies for the virus and the vector.

Novel insights into the dynamics of green turtle fibropapillomatosis

Outbreaks of fibropapillomatosis (FP), a neoplastic infectious disease of marine turtles, have occurred worldwide since the 1980s. Its most likely aetiological agent is a virus, but disease expression depends on external factors, typically associated with altered environments. The scarcity of robust long-term data on disease prevalence has limited interpretations on the impacts of FP on turtle populations. Here we model the dynamics of FP at 2 green turtle foraging aggregations in Puerto Rico, through 18 yr of capture-mark-recapture data (1997−2014). We observed spatiotemporal variation in FP prevalence, potentially modulated via individual site-fidelity. FP ex pression was residency dependent, and FP-free individuals developed tumours after 1.8 ± 0.8 yr (mean ± SD) in the infected area. Recovery from the disease was likely, with complete tumour regression occurring in 2.7 ± 0.7 yr (mean ± SD). FP does not currently seem to be a major threat to marine turtle populations; however, disease prevalence is yet unknown in many areas. Systematic monitoring is highly advisable as human-induced stressors can lead to deviations in host− pathogen relationships and disease virulence. Finally, data collection should be standardized for a global assessment of FP dynamics and impacts.

A systematic review of mathematical models of mosquito-borne pathogen transmission: 1970-2010

Mathematical models of mosquito-borne pathogen transmission originated in the early twentieth century to provide insights into how to most effectively combat malaria. The foundations of the Ross–Macdonald theory were established by 1970. Since then, there has been a growing interest in reducing the public health burden of mosquito-borne pathogens and an expanding use of models to guide their control. To assess how theory has changed to confront evolving public health challenges, we compiled a bibliography of 325 publications from 1970 through 2010 that included at least one mathematical model of mosquito-borne pathogen transmission and then used a 79-part questionnaire to classify each of 388 associated models according to its biological assumptions. As a composite measure to interpret the multidimensional results of our survey, we assigned a numerical value to each model that measured its similarity to 15 core assumptions of the Ross–Macdonald model. Although the analysis illustrated a growing acknowledgement of geographical, ecological and epidemiological complexities in modelling transmission, most models during the past 40 years closely resemble the Ross–Macdonald model. Modern theory would benefit from an expansion around the concepts of heterogeneous mosquito biting, poorly mixed mosquito-host encounters, spatial heterogeneity and temporal variation in the transmission process.

Hot spot detection and spatio-temporal dispersion of dengue fever in Hanoi, Vietnam

INTRODUCTION Dengue fever (DF) in Vietnam remains a serious emerging arboviral disease, which generates significant concerns among international health authorities. Incidence rates of DF have increased significantly during the last few years in many provinces and cities, especially Hanoi. The purpose of this study was to detect DF hot spots and identify the disease dynamics dispersion of DF over the period between 2004 and 2009 in Hanoi, Vietnam. METHODS Daily data on DF cases and population data for each postcode area of Hanoi between January 1998 and December 2009 were obtained from the Hanoi Center for Preventive Health and the General Statistic Office of Vietnam. Moran's I statistic was used to assess the spatial autocorrelation of reported DF. Spatial scan statistics and logistic regression were used to identify space-time clusters and dispersion of DF. RESULTS The study revealed a clear trend of geographic expansion of DF transmission in Hanoi through the study periods (OR 1.17, 95% CI 1.02-1.34). The spatial scan statistics showed that 6/14 (42.9%) districts in Hanoi had significant cluster patterns, which lasted 29 days and were limited to a radius of 1,000 m. The study also demonstrated that most DF cases occurred between June and November, during which the rainfall and temperatures are highest. CONCLUSIONS There is evidence for the existence of statistically significant clusters of DF in Hanoi, and that the geographical distribution of DF has expanded over recent years. This finding provides a foundation for further investigation into the social and environmental factors responsible for changing disease patterns, and provides data to inform program planning for DF control.

Spatial-temporal epidemiological analyses of two sympatric, co-endemic alphaviral diseases in Queensland, Australia

Background: The two most reported mosquito-borne diseases in Queensland, a northern state of Australia, are Ross River virus (RRV) disease and Barmah Forest virus (BFV) disease. Both diseases are endemic in Queensland and have similar clinical symptoms and comparable transmission cycles involving a complex inter-relationship between human hosts, various mosquito vectors, and a range of nonhuman vertebrate hosts, including marsupial mammals that are unique to the Australasian region. Although these viruses are thought to share similar vectors and vertebrate hosts, RRV is four times more prevalent than BFV in Queensland. Methods: We performed a retrospective analysis of BFV and RRV human disease notification data collected from 1995 to 2007 in Queensland to ascertain whether there were differences in the incidence patterns of RRV and BFV disease. In particular, we compared the temporal incidence and spatial distribution of both diseases and considered the relationship between their disease dynamics. We also investigated whether a peak in BFV incidence during spring was indicative of the following RRV and BFV transmission season incidence levels. Results: Although there were large differences in the notification rates of the two diseases, they had similar annual temporal patterns, but there were regional variations between the length and magnitude of the transmission seasons. During periods of increased disease activity, however, there was no association between the dynamics of the two diseases. Conclusions: The results from this study suggest that while RRV and BFV share similar mosquito vectors, there are significant differences in the ecology of these viruses that result in different epidemic patterns of disease incidence. Further investigation is required into the ecology of each virus to determine which factors are important in promoting RRV and BFV disease outbreaks.

Pupal cocoons affect sanitary brood care and limit fungal infections in ant colonies.

BACKGROUND: The brood of ants and other social insects is highly susceptible to pathogens, particularly those that penetrate the soft larval and pupal cuticle. We here test whether the presence of a pupal cocoon, which occurs in some ant species but not in others, affects the sanitary brood care and fungal infection patterns after exposure to the entomopathogenic fungus Metarhizium brunneum. We use a) a comparative approach analysing four species with either naked or cocooned pupae and b) a within-species analysis of a single ant species, in which both pupal types co-exist in the same colony. RESULTS: We found that the presence of a cocoon did not compromise fungal pathogen detection by the ants and that species with cocooned pupae increased brood grooming after pathogen exposure. All tested ant species further removed brood from their nests, which was predominantly expressed towards larvae and naked pupae treated with the live fungal pathogen. In contrast, cocooned pupae exposed to live fungus were not removed at higher rates than cocooned pupae exposed to dead fungus or a sham control. Consistent with this, exposure to the live fungus caused high numbers of infections and fungal outgrowth in larvae and naked pupae, but not in cocooned pupae. Moreover, the ants consistently removed the brood prior to fungal outgrowth, ensuring a clean brood chamber. CONCLUSION: Our study suggests that the pupal cocoon has a protective effect against fungal infection, causing an adaptive change in sanitary behaviours by the ants. It further demonstrates that brood removal-originally described for honeybees as "hygienic behaviour"-is a widespread sanitary behaviour in ants, which likely has important implications on disease dynamics in social insect colonies.

Genotype and temperature influence pea aphid resistance to a fungal entomopathogen

The influence of temperature on life history traits of four Acyrthosiphon pisum clones was investigated, together with their resistance to one genotype of the fungal entomopathogen Erynia neoaphidis . There was no difference among aphid clones in development rate, but they did differ in fecundity. Both development rate and fecundity were influenced by temperature, but all clones showed similar responses to the changes in temperature (i.e. the interaction term was nonsignificant). However, there were significant differences among clones in susceptibility to the pathogen, and this was influenced by temperature. Furthermore, the clones differed in how temperature influenced susceptibility, with susceptibility rankings changing with temperature. Two clones showed changes in susceptibility which mirrored changes in the in vitro vegetative growth rate of E. neoaphidis at different temperatures, whereas two other clones differed considerably from this expected response. Such interactions between genotype and temperature may help maintain heritable variation in aphid susceptibility to fungal pathogen attack and have implications for our understanding of disease dynamics in natural populations. This study also highlights the difficulties of drawing conclusions about the efficacy of a biological control agent when only a restricted range of pest genotypes or environmental conditions are considered.

A comparative evaluation of open loop and closed loop drug administration strategies in the treatment of AIDS.

In recent years, many researchers in the field of biomedical sciences have made successful use of mathematical models to study, in a quantitative way, a multitude of phenomena such as those found in disease dynamics, control of physiological systems, optimization of drug therapy, economics of the preventive medicine and many other applications. The availability of good dynamic models have been providing means for simulation and design of novel control strategies in the context of biological events. This work concerns a particular model related to HIV infection dynamics which is used to allow a comparative evaluation of schemes for treatment of AIDS patients. The mathematical model adopted in this work was proposed by Nowak & Bangham, 1996 and describes the dynamics of viral concentration in terms of interaction with CD4 cells and the cytotoxic T lymphocytes, which are responsible for the defense of the organism. Two conceptually distinct techniques for drug therapy are analyzed: Open Loop Treatment, where a priori fixed dosage is prescribed and Closed Loop Treatment, where the doses are adjusted according to results obtained by laboratory analysis. Simulation results show that the Closed Loop Scheme can achieve improved quality of the treatment in terms of reduction in the viral load and quantity of administered drugs, but with the inconvenience related to the necessity of frequent and periodic laboratory analysis.