Frameworks for Preventing, Detecting, and Controlling Zoonotic Diseases.

Preventing zoonotic diseases requires coordinated actions by government authorities responsible for human and animal health. Constructing the frameworks needed to foster intersectoral collaboration can be approached in many ways. We highlight 3 examples of approaches to implement zoonotic disease prevention and control programs. The first, rabies control in Ethiopia, was implemented using an umbrella approach: a comprehensive program designed for accelerated impact. The second, a monkeypox program in Democratic Republic of the Congo, was implemented in a stepwise manner, whereby incremental improvements and activities were incorporated into the program. The third approach, a pathogen discovery program, applied in the country of Georgia, was designed to characterize and understand the ecology, epidemiology, and pathogenesis of a new zoonotic pathogen. No one approach is superior, but various factors should be taken into account during design, planning, and implementation.

Barriers and opportunities for canine rabies vaccination campaigns in Addis Ababa, Ethiopia.

BACKGROUND: Canine rabies is endemic in Ethiopia and presents a significant burden for both animal and human health. We investigate barriers to dog vaccination in Addis Ababa, Ethiopia. These results can be utilized to improve and target future rabies control efforts. METHODOLOGY/PRINCIPLE FINDINGS: During May of 2017, dog owners were surveyed during a free canine rabies vaccination programs that utilized both door-to-door (DtD) and central point (CP) vaccination methods. Surveys collected information on preferences for rabies vaccine delivery and were administered in Amharic. A total of 1057 surveys were completed. Of those surveyed, 62.4 % indicated that their dogs had been vaccinated against rabies within the last year. Commonly reported barriers to vaccination were a lack of awareness that dogs required rabies vaccines (18.1 %) and lack of knowledge about where to find vaccine (15.0 %). The median price owners were willing to pay for vaccination was 25 birr ($0.91 USD) and the median distance willing to travel was 1.0 km; however, 48.9 % of those surveyed during DtD were unwilling to travel at all. We identified 3 classes of respondents who were grouped due to their responses by latent class analysis: 'the Unaware', 'the Vaccinators', and 'the Multiple Barriers'. CONCLUSIONS/SIGNIFICANCE: Although many respondents were willing to pay for rabies vaccine (94.0 %); the preferred cost (median) was less than the actual cost of providing the vaccine. This supports the need for reduced-cost or free vaccine to achieve and sustain the 70 % vaccine coverage target threshold for canine rabies elimination. Additionally, a significant portion (41.5 %) of those surveyed indicated that they were unwilling to travel in order to have their dog vaccinated. The latent class analysis provides useful guidance on how to reach target vaccination. Owners from 'the Unaware' group made up 18.1 % of respondents and their high rate of allowing their dogs to roam identifies them as a prime target for canine health and behavior education. 'The Multiple Barriers' owners reported lower degrees of dog roaming and were substantially more likely to be found by DtD campaigns, possibly because they have limited ability/interest in handling their dogs. These results demonstrate the importance of incorporating DtD vaccination as well as subsidies to maximize vaccine coverage in Addis Ababa.

Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors.

Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1 alpha Delta 184-236 (R1 alpha Delta 6)]. We compared in vitro R1 alpha Delta 6 with wild-type (wt) R1 alpha. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1 alpha and mutant (mt) R1 alpha; we observed by confocal microscopy R1 alpha tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (C alpha). Introduction of the R1 alpha Delta 6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1 alpha protein in wt-R1 alpha- and R1 alpha Delta 6-transfected cells but the former also exhibited discrete aggregates of R1 alpha that bound C alpha; these were absent in R1 alpha Delta 6-transfected cells and did not bind C alpha at baseline or in response to cyclic AMP. Other changes induced by R1 alpha Delta 6 included decreased nuclear C alpha. We conclude that R1 alpha Delta 6 leads to increased PKA activity through the mt-R1 alpha decreased binding to C alpha and does not involve changes in other PKA subunits, suggesting that a switch to type II PKA activity is not necessary for increased kinase activity or tumorigenesis.