Table 1 Research needs for bovine and human babesioses by scientific and technological topic.

Epidemiology & surveillance

Integrate refinement of tick population dynamics models, data gathering, as well as the knowledge of land use, numbers and species of Babesia tick vectors and domestic and wildlife hosts with economic analyses of their relevance in order to facilitate and enhance decision-making processes for optimal allocation of resources for regulatory and research programs

Assess current status and forecast future epidemiologic trends of babesioses in humans and keystone hosts through the expansion of field data capture methods and through collaborations between federal and state regulatory agencies and academic institutions

Refine existing methods and develop new tools for active surveillance, such as serological tests and alternatives or refinement to "scratching" (use of inspector's fingers to feel the skin of the animal in its entirety, from head to tail, searching for ticks) of wildlife to evaluate tick exposure, the detection of Babesia in ticks and hosts, and the control of cattle movement

Investigate the tick vectors and pathogenesis of babesiosis caused by B. microti, which is the primary etiologic agent of human disease

Explore genetic structure of CFT populations across the range of outbreaks in South Texas to determine tick geographic origin(s) and population dynamics

Continue studies of Babesia-host interactions for infection in humans

Determine whether CFT from outbreaks in South Texas are infected with B. bigemina and/or B. bovis to assess risk potential for outbreaks of clinical infection in the U.S.

Continue studies of Babesia-host interactions for infection in cattle and wildlife

Ecology & biology of tick vectors & wildlife

Evaluate the host suitability of non-native wild ungulates common to South Texas for CFT

Define the ecological role of native and non-native wild ungulates in maintaining CFT populations in the absence of cattle

Conduct ecological studies to determine whether native and non-native wild ungulates play a role in the long term maintenance and dissemination of CFT populations, particularly between infested and tick-free areas

Characterize molecular and cellular interactions at the host-blood feeding tick interface for bovine and non-bovine hosts

Conduct immunological studies to simultaneously characterize and correlate R. microplus and R. annulatus salivary gland gene expression with host gene expression for infestations with uninfected ticks and for infestations with ticks infected with B.bovis or B.bigemina

Characterize tick-host interactions and tick feeding and developmental time for R. microplus and R. annulatus infestation of white-tailed deer under controlled experimental infestations

Determine the developmental periods and survivorship of cattle ticks throughout the year, number of tick generations per year under field conditions, and seasonal dynamics in southern Texas and/or Northern Mexico

Determine if pathogen-free R. microplus and R. annulatus can become infected by taking a blood meal from Babesia-infected white-tailed deer

Diagnosis, treatment, & prevention

Improve and make commercially available diagnostic assays to rapidly detect Texas cattle fever and CFT

Assess level of preparedness by federal and state regulatory agencies and the national animal health laboratory network to handle an outbreak of Texas cattle fever

Establish a surveillance program to assess prevalence of B. bovis and B. bigemina in wildlife and cattle in the permanent quarantine zone

Conduct field research with cattle as tracer species in similar way as suggested for the use of other species as sentinels of ecological health [52], to generate science-based information for developing decision-support tools for the CFT eradication program

Develop new technologies for CFT surveillance and detection in cattle and wildlife

Develop risk assessment systems to evaluate tick dispersal in wildlife species adjacent to infested premises vacated of cattle

Continue research to develop and test live attenuated and recombinant vaccines for the control of babesiosis

Integrated approaches for sustainable CFT eradication

Revisit sterile tick techniques. In the late 1980s, sterile tick experiments were performed on St. Croix with R. annulatus × R. microplus tick hybrids (R. Davey, unpublished results). One hundred and eighty million hybrid larvae were put in tea bags in the field. When sterile larvae were dropped in the field, the tick population decreased over 7 to 8 months, but then began to increase again. The disadvantages of this method are the difficulties for a laboratory to produce enough sterile larvae, the immobility of ticks and acceptance by owners to put more ticks on their animals. Alternative methods to produce sterile ticks using RNA interference have been proposed [53]. However, this strategy has serious limitations relative to large-scale field trials and practical application on broad geographical areas. However, these new technologies coupled with further observations on crosses between R. annulatus and R. microplus and between some R. microplus geographical strains that produce sterile ticks warrant further studies on the potential use of the sterile tick technique for CFT eradication [[54, 55] and references thereof].

Not applicable

Continue and improve research on the mechanisms and dynamics of tick genetic resistance to acaricides. Apply this knowledge on the enhanced use of acaricides and acaride combinations

Develop acaricide combinations. The combination of acaricides and tick growth regulators offers the potential to achieve the high levels of efficacy required for eradication. These efforts need to be pursued despite current challenges to seek and secure approval for registration by the regulatory agencies. The use of novel application technologies like electro-charged spray systems that could improve the spray/dip process should be investigated

Investigate passive administration of systemic acaricides for cattle. Mineral/protein blocks are commonly used in cattle production systems. The use of a mineral/protein block medicated with a systemic acaricide such as ivermectin could be a useful tool for the eradication of CFT

Develop sustained acaricide delivery systems. When applicable per eradication regulations, the practice of dipping cattle in a vat with Coumaphos every 14 days is both a costly and laborious effort. Thus, systems delivering acaricides in a sustained fashion to achieve eradication efficacy levels for at least 2 months are needed. This approach requires fine-tuning of available formulations and sustained-release technologies to address safety and withdrawal period issues to deliver a registerable and marketable product accessible to the producer. Microspheres and other sustained release technologies have the potential to provide those solutions. However, these formulations face the same commercial barriers mentioned above for traditional acaricides. Business models like the public-private partnership for product development to treat neglected diseases requires consideration as a strategy to achieve solutions for the Cattle Fever Eradication Program involving proven technologies that remain undeveloped and collecting dust on the shelf [56]

Research for natural products. Natural products like fungi and botanicals although shown to be potential alternatives [57, 58], are not yet available and more research is needed before these products can be considered and integrated into tick control programs

Enhance exchange of information between regulatory agencies, research institutions, and the public to facilitate the development and implementation of evidence-based regulations for the CFT eradication program addressing the ecology of wildlife/cattle-tick-Babesia interactions

Increase efforts and collaborations with agricultural extension systems to disseminate current knowledge and research findings among producers and the public in the U.S. to raise awareness of current national biosecurity threat involving CFT and bovine babesiosis. Additionally, similar efforts need to be established in Mexican states bordering the permanent quarantine zone in Texas through collaboration with colleagues in Mexico

Tick vaccines

Compare the nucleotide sequences of Bm86 orthologs in U.S. strains of R. microplus and R. annulatus with those of the commercial Bm86 vaccines to determine whether antigen sources need to be derived from geographic strains

Tick-vaccines and delivery methods for white-tailed deer to prevent human babesiosis

Identify new tick protective antigens and delivery systems for cattle and wildlife

Conduct studies to determine whether the treatment of cattle with Gavac® or other Bm86-based vaccines in Mexico and the U.S. permanent quarantine zone prevents CFT outbreaks in Texas