ESTABLISHING AN ANIMAL DIESEASE DIAGNOSTIC NETWORK

Livestock Production/Industries,

A network control theory approach to modeling and optimal control of zoonoses: case study of brucellosis transmission in sub-Saharan Africa

Developing control policies for zoonotic diseases is challenging, both because of the complex spread dynamics exhibited by these diseases, and because of the need for implementing complex multi-species surveillance and control efforts using limited resources. Mathematical models, and in particular network models, of disease spread are promising as tools for control-policy design, because they can provide comprehensive quantitative representations of disease transmission. A layered dynamical network model for the transmission and control of zoonotic diseases is introduced as a tool for analyzing disease spread and designing cost-effective surveillance and control. The model development is achieved using brucellosis transmission among wildlife, cattle herds, and human sub-populations in an agricultural system as a case study. Precisely, a model that tracks infection counts in interacting animal herds of multiple species (e.g., cattle herds and groups of wildlife for brucellosis) and in human subpopulations is introduced. The model is then abstracted to a form that permits comprehensive targeted design of multiple control capabilities as well as model identification from data. Next, techniques are developed for such quantitative design of control policies (that are directed to both the animal and human populations), and for model identification from snapshot and time-course data, by drawing on recent results in the network control community. The modeling approach is shown to provide quantitative insight into comprehensive control policies for zoonotic diseases, and in turn to permit policy design for mitigation of these diseases. For the brucellosis-transmission example in particular, numerous insights are obtained regarding the optimal distribution of resources among available control capabilities (e.g., vaccination, surveillance and culling, pasteurization of milk) and points in the spread network (e.g., transhumance vs. sedentary herds). In addition, a preliminary identification of the network model for brucellosis is achieved using historical data, and the robustness of the obtained model is demonstrated. As a whole, our results indicate that network modeling can aid in designing control policies for zoonotic diseases

Babesia bovis Merozoite Surface Antigen 2 Proteins Are Expressed on the Merozoite and Sporozoite Surface, and Specific Antibodies Inhibit Attachment and Invasion of Erythrocytes

The Babesia bovis merozoite surface antigen 2 (MSA-2) locus encodes four proteins, MSA-2a 1 , -2a 2 , -2b, and -2c. With the use of specific antibodies, each MSA-2 protein was shown to be expressed on the surface of live extracellular merozoites and coexpression on single merozoites was confirmed. Individual antisera against MSA-2a, MSA-2b, and MSA-2c significantly inhibited merozoite invasion of bovine erythrocytes. As tick-derived sporozoites also directly invade erythrocytes, expression of each MSA-2 protein on the sporozoite surface was examined and verified. Finally, statistically significant inhibition of sporozoite binding to the erythrocytes was demonstrated by using antisera specific for MSA-2a, MSA-2b, and MSA-2c. These results indicate an important role for MSA-2 proteins in the initial binding and invasion of host erythrocytes and support the hypothesis that sporozoites and merozoites use common surface molecules in erythrocyte invasion

Strain Composition of the Ehrlichia Anaplasma marginale within Persistently Infected Cattle, a Mammalian Reservoir for Tick Transmission

Tick-borne ehrlichial pathogens of animals and humans require a mammalian reservoir of infection from which ticks acquire the organism for subsequent transmission. In the present study, we examined the strain structure of Anaplasma marginale , a genogroup II ehrlichial pathogen, in both an acute outbreak and in persistently infected cattle that serve as a reservoir for tick transmission. Using the msp1 α genotype as a stable strain marker, only a single genotype was detected in a disease outbreak in a previously uninfected herd. In contrast, a diverse set of genotypes was detected in a persistently infected reservoir herd within a region where A. marginale is endemic. Genotypic diversity did not appear to be rapidly generated within an individual animal, because only a single genotype, identical to that of the inoculating strain, was detected at time points up to 2 years after experimental infection, and only a single identical genotype was found in repeat sampling of individual naturally infected cattle. Similarly, only a single genotype, identical to that of the experimentally inoculated St. Maries or South Idaho strain, was identified in the bloodmeal taken by Dermacentor andersoni ticks, in the midgut and salivary glands of the infected ticks, and in the blood of acutely infected cattle following tick transmission. The results show that mammalian reservoirs harbor genetically heterogeneous A. marginale and suggest that different genotypes are maintained by transmission within the reservoir population

Coinfection with Antigenically and Genetically Distinct Virulent Strains of Babesia bovis Is Maintained through All Phases of the Parasite Life Cycle

Antigenic polymorphism is a defining characteristic of the Babesia bovis variable merozoite surface antigen (VMSA) family. Sequence analysis strongly suggests that recombination between virulent strains contributes to VMSA diversity. While meiosis during the aneuploid stage of the parasite's life cycle in the tick vector Rhipicephalus ( Boophilus ) microplus is the most probable source of interstrain recombination, there is no definitive evidence that coinfection of the mammalian host or R. microplus ticks with more than one virulent strain occurs. Using allele-specific real-time quantitative PCR, we tested the hypotheses that cattle could support coinfection of two antigenically variant virulent tick-transmissible strains of B. bovis and that R. microplus ticks could acquire and transmit these two divergent strains. The results indicate that both calves and ticks can support virulent B. bovis coinfection through all phases of the hemoparasite's life cycle. Neither strain dominated in either the mammalian or invertebrate host, and larval tick progeny, which could be coinfected individually, were also able to transmit both strains, resulting in virulent babesiosis in recipients. While coinfection of the tick vector provides the context in which allelic antigenic diversity can be generated, recombination of VMSA genes could not be confirmed, suggesting that VMSA allelic changes are slow to accumulate

Babesia bovis Merozoite Surface Antigen 1 and Rhoptry-Associated Protein 1 Are Expressed in Sporozoites, and Specific Antibodies Inhibit Sporozoite Attachment to Erythrocytes

We examined Babesia bovis sporozoites for the expression of two molecules, merozoite surface antigen 1 (MSA-1) and rhoptry-associated protein 1 (RAP-1), that are postulated to be involved in the invasion of host erythrocytes. Both MSA-1 and RAP-1 were transcribed and expressed in infectious sporozoites. Importantly, monospecific MSA-1 and RAP-1 antisera each inhibited sporozoite invasion of erythrocytes in vitro. This is the first identification of antigens expressed in Babesia sp. sporozoites and establishes that, at least in part, sporozoites and merozoites share common targets of antibody mediated inhibition of erythrocyte invasion