Wildlife-Cattle Interactions in Northern Michigan: Implications for the Transmission of Bovine Tuberculosis

Bovine tuberculosis (Mycobacterium bovis) was discovered in northern Michigan white-tailed deer (Odocoileus virginianus) in 1994, and has been known to exist in Michigan cattle herds since 1998. Despite efforts to eradicate the disease in cattle, infection and re-infection of farms continues to occur, suggesting transmission among cattle, deer, or other wildlife reservoirs. The goals of this study were to document wildlife activity on farms and evaluate the possible role wildlife play in the ecology of bovine tuberculosis (TB) in Michigan. Visual observations were conducted on farms in a 5-county area of northern Michigan to document direct wildlife-cattle interactions (i.e., <5 m between individuals) and indirect interactions (e.g., wildlife visitations to food stores and areas accessible to cattle). Observations were conducted primarily during evening and early morning hours between January and August, 2002, and on a 24-hour schedule between January and August, 2003. Total observation time accumulated through the duration of the study was 1,780 hours. Results indicated that direct interaction between deer and cattle was a rare event; no direct interactions were observed during the first year, and only one direct interaction was observed during the second year. However, through the duration of the study 21 direct interactions were documented between cattle and turkey, and 11 direct interactions were documented between cattle and mammals other than deer. In total, 273 indirect interactions by deer, 112 indirect interactions by turkeys, and 248 indirect interactions by mammals other than deer were observed during the 2 field seasons combined. These data supported the hypothesis that indirect interactions among wildlife and cattle are a potential mechanism for the transmission of TB in Michigan. If direct interactions were important mechanisms of TB transmission to cattle in northern Michigan, my data suggested that feral cats were the species of most concern, even though there were more observations between turkey and cattle. Unlike cats, which can become infected with and transmit TB, there is no evidence for such pathogenesis in turkey.

Farmers’ willingness to pay for a tuberculosis cattle vaccine

We use contingent valuation (CV) and choice experiment (CE) methods to assess cattle farmers’ attitudes to and willingness to pay (WTP) for a bovine tuberculosis (bTB) cattle vaccine, to help inform vaccine development and policy. A survey questionnaire was administered by means of telephone interviews to a stratified sample of 300 cattle farmers in annually bTB-tested areas in England and Wales. Farmers felt that bTB was a major risk for the cattle industry and that there was a high risk of their cattle getting the disease. The CE estimate produced a mean WTP of £35 per animal per single dose for a vaccine that is 90% effective at reducing the risk of a bTB breakdown and an estimated £55 for such a vaccine backed by 100% insurance of loss if a breakdown should occur. The CV estimate produced a mean WTP of nearly £17 per dose/per animal/per year for a vaccine (including 100% insurance) which, given the average lifespan of cattle, is comparable to the CE estimate. These WTP estimates are substantially higher than the expected cost of a vaccine which suggests that farmers in high risk bTB ‘hotspot’ areas perceive a substantial net benefit from buying the vaccine.

The Duration of the Effects of Repeated Widespread Badger Culling on Cattle Tuberculosis Following the Cessation of Culling

Background: In the British Isles, control of cattle tuberculosis (TB) is hindered by persistent infection of wild badger (Meles meles) populations. A large-scale field trial—the Randomised Badger Culling Trial (RBCT)—previously showed that widespread badger culling produced modest reductions in cattle TB incidence during culling, which were offset by elevated TB risks for cattle on adjoining lands. Once culling was halted, beneficial effects inside culling areas increased, while detrimental effects on adjoining lands disappeared. However, a full assessment of the utility of badger culling requires information on the duration of culling effects. Methodology/Principal Findings: We monitored cattle TB incidence in and around RBCT areas after culling ended. We found that benefits inside culled areas declined over time, and were no longer detectable by three years post-culling. On adjoining lands, a trend suggesting beneficial effects immediately after the end of culling was insignificant, and disappeared after 18 months post-culling. From completion of the first cull to the loss of detectable effects (an average five-year culling period plus 2.5 years post-culling), cattle TB incidence was 28.7% lower (95% confidence interval [CI] 20.7 to 35.8% lower) inside ten 100 km2 culled areas than inside ten matched no-culling areas, and comparable (11.7% higher, 95% CI: 13.0% lower to 43.4% higher, p = 0.39) on lands #2 km outside culled and no-culling areas. The financial costs of culling an idealized 150 km2 area would exceed the savings achieved through reduced cattle TB, by factors of 2 to 3.5. Conclusions/Significance: Our findings show that the reductions in cattle TB incidence achieved by repeated badger culling were not sustained in the long term after culling ended and did not offset the financial costs of culling. These results, combined with evaluation of alternative culling methods, suggest that badger culling is unlikely to contribute effectively to the control of cattle TB in Britain.

Advances in Bovine Tuberculosis Diagnosis and Pathogenesis: What Policy Makers Need to Know

The mainstay of tuberculosis diagnosis in cattle and deer has been the tuberculin skin test. Recent advances have allowed the incorporation of blood based assays to the diagnostic arsenal for both cattle and deer. Use of defined and specific antigens has allowed for improved specificity of cell mediated assays in both cattle and deer and advances in antibody tests for tuberculosis have potential for use in free-ranging and captive cervid populations. Combined use of blood-based assays with skin testing will require further understanding of the effect of skin testing on the accuracy of blood based assays. Models of experimental infection of cattle have allowed for increased understanding of natural disease pathogenesis. Differences likely exist; however, between cattle and deer in both disease distribution and primary route of inoculation in naturally infected animals.

The Role of a Wildlife Reservoir in the Epidemiology of Bovine Tuberculosis

The objective of this project was to study the epidemiology of bovine tuberculosis in the presence of a wildlife reservoir species. Cross-sectional and longitudinal studies of possum populations with endemic bovine tuberculosis infection were analyzed. The results were used to develop a computer simulation model of the dynamics of bovine tuberculosis infection in possum populations. A case-control study of breakdowns to tuberculosis infection in cattle herds in the Central North Island of New Zealand was conducted to identify risk factors other than exposure to tuberculosis in local possum populations.

Tuberculosis epidemiology in islands: insularity, hosts and trade

Because of their relative simplicity and the barriers to gene flow, islands are ideal systems to study the distribution of biodiversity. However, the knowledge that can be extracted from this peculiar ecosystem regarding epidemiology of economically relevant diseases has not been widely addressed. We used information available in the scientific literature for 10 old world islands or archipelagos and original data on Sicily to gain new insights into the epidemiology of the Mycobacterium tuberculosis complex (MTC). We explored three nonexclusive working hypotheses on the processes modulating bovine tuberculosis (bTB) herd prevalence in cattle and MTC strain diversity: insularity, hosts and trade. Results suggest that bTB herd prevalence was positively correlated with island size, the presence of wild hosts, and the number of imported cattle, but neither with isolation nor with cattle density. MTC strain diversity was positively related with cattle bTB prevalence, presence of wild hosts and the number of imported cattle, but not with island size, isolation, and cattle density. The three most common spoligotype patterns coincided between Sicily and mainland Italy. However in Sicily, these common patterns showed a clearer dominance than on the Italian mainland, and seven of 19 patterns (37%) found in Sicily had not been reported from continental Italy. Strain patterns were not spatially clustered in Sicily. We were able to infer several aspects of MTC epidemiology and control in islands and thus in fragmented host and pathogen populations. Our results point out the relevance of the intensity of the cattle commercial networks in the epidemiology of MTC, and suggest that eradication will prove more difficult with increasing size of the island and its environmental complexity, mainly in terms of the diversity of suitable domestic and wild MTC hosts.

Productivity and health effects of anaplasmosis and babesiosis on Bos indicus cattle and their crosses, and the effects of differing intensity of tick control in Australia

Tick fever is an important disease of cattle where Rhipicephalus (Boophilus) microplus acts as a vector for the three causal organisms Babesia bovis, Babesia bigemina and Anaplasma marginale. Bos indicus cattle and their crosses are more resistant to the clinical effects of infection with B. bovis and B. bigemina than are Bos taurus cattle. Resistance is not complete, however, and herds of B. indicus-cross cattle are still at risk of babesiosis in environments where exposure to B. bovis is light in most years but occasionally high. The susceptibility of B. indicus cattle and their crosses to infection with A. marginale is similar to that of B. taurus cattle. In herds of B. indicus cattle and their crosses the infection rate of Babesia spp. and A. marginale is lowered because fewer ticks are likely to attach per day due to reduced numbers of ticks in the field (long-term effect on population, arising from high host resistance) and because a smaller proportion of ticks that do develop to feed on infected cattle will in turn be infected (due to lower parasitaemia). As a consequence, herds of B. indicus cattle are less likely than herds of B. taurus cattle to have high levels of population immunity to babesiosis or anaplasmosis. The effects of acaricide application on the probability of clinical disease due to anaplasmosis and babesiosis are unpredictable and dependent on the prevalence of infection in ticks and in cattle at the time of application. Attempting to manipulate population immunity through the toleration of specific threshold numbers of ticks with the aim of controlling tick fever is not reliable and the justification for acaricide application should be for the control of ticks rather than for tick fever. Vaccination of B. indicus cattle and their crosses is advisable in all areas where ticks exist, although vaccination against B. bigemina is probably not essential in pure B. indicus animals.

Efficacy of Rhipicephalus (Boophilus) microplus Bm86 against Hyalomma dromedarii and Amblyomma cajennense tick infestations in camels and cattle

The recombinant Bm86-based tick vaccines have shown their efficacy for the control of cattle ticks, Rhipicephalus (Boophilus) microplus and R. annulatus infestations. However, cattle ticks often co-exist with multi-host ticks such as Hyalomma and Amblyomma species, thus requiring the control of multiple tick infestations for cattle and other hosts. Vaccination trials using a R. microplus recombinant Bm86-based vaccine were conducted in cattle and camels against Hyalomma dromedarii and in cattle against Amblyomma cajennense immature and adult ticks. The results showed an 89% reduction in the number of H. dromedarii nymphs engorging on vaccinated cattle, and a further 32% reduction in the weight of the surviving adult ticks. In vaccinated camels, a reduction of 27% and 31% of tick engorgement and egg mass weight, respectively was shown, while egg hatching was reduced by 39%. However, cattle vaccination with Bm86 did not have an effect on A. cajennense tick infestations. These results showed that Bm86 vaccines are effective against R. microplus and other tick species but improved vaccines containing new antigens are required to control multiple tick infestations. (C) 2012 Elsevier Ltd. All rights reserved.

Spirulina (Spirulina platensis) algae supplementation increases microbial protein production and feed intake and decreases retention time of digesta in the rumen of cattle

Cattle consuming pastures low in protein have low liveweight gain due to low rumen degradable protein (RDP) supply and thus low microbial crude protein (MCP) production and efficiency of MCP production [EMCP, g MCP/kg digestible organic matter (DOM)]. Nitrogen supplements can increase MCP production and EMCP of cattle grazing low protein pastures. The objective of this study was to compare the effects of supplementation with a non-protein-N source (NPN), in this case urea and ammonium sulfate (US), with a single-cell algal protein source (Spirulina platensis), on intake, microbial protein supply and digestibility in cattle. Nine cannulated Bos indicus steers [initial liveweight 250.1 ± 10.86 (s.d.) kg] were fed Mitchell grass hay (Astrebla spp; 6.1 g N, 746 g NDF/kg DM) ad libitum and were supplied with increasing amounts of US (0, 6, 13, 19 and 33 g US DM/kg hay DM) or Spirulina 0, 0.5, 1.4, 2.5 and 6.1 g Spirulina DM/kg W.day in an incomplete Latin square design. The response of MCP production and EMCP to increasing amounts of the two supplements was different, with a greater response to Spirulina evident. The MCP production was predicted to peak at 140 and 568 g MCP/day (0.64 and 2.02 g MCP/kg W.day) for the US and Spirulina supplements, respectively. The highest measured EMCP were 92 and 166 g MCP/kg DOM for the US and Spirulina treatments at 170 and 290 g RDP/kg DOM, respectively, or a Spirulina intake of 5.7 g DM/kg W.day. Increasing RDP intake from US and Spirulina resulted in an increase in Mitchell grass hay intake and rumen NH3-N concentration and reduced the retention time of liquid and particulate markers and digesta DM, NDF and lignin in the rumen with greater changes due to Spirulina. Total DM intake peaked at a Spirulina supplement level of 4.6 g Spirulina DM/kg W.day with a 2.3-fold higher DOM intake than Control steers. Rumen NH3-N concentrations reached 128 and 264 mg NH3-N/L for the US and Spirulina treatments with a significant increase in the concentration of branched-chain fatty acids for the Spirulina treatment. The minimum retention time of liquid (Cr-EDTA; 23 and 13 h) and particulate (Yb; 34 and 22 h) markers in the rumen were significantly lower for Spirulina compared with US and lower than unsupplemented animals at 24 and 34 h for Cr-EDTA and Yb, respectively. Spirulina could be provided safely at much higher N intakes than NPN supplements. The results suggest that, at an equivalent RDP supply, Spirulina provided greater increases than US in MCP production, EMCP and feed intake of Bos indicus cattle consuming low protein forage and could also be fed safely at higher levels of N intake.

Factors associated with medication adherence among tuberculosis patients in Timor-Leste

This thesis investigated medication adherence among people living with tuberculosis in Timor Leste. Suboptimal adherence was commonly reported, and was influenced by service inaccessibility, family poverty, patients' absence of disease symptoms and misperception of recovery, untreated depression and a popular cultural belief that luck or chance determines health outcomes. The study has implications for improving health literacy and counselling programs to achieve effective adherence to medication and good health outcomes.

How pantothenol intervenes in Coenzyme-A biosynthesis of Mycobacterium tuberculosis

Coenzyme A is an indispensable cofactor for all organisms and holds a central position in a number of pathways. Prokaryotic enzymes involved in the synthesis of CoA are quite different from their mammalian counterparts; hence, they are good targets for the development of antimicrobials to treat many diseases. There are antimicrobials that act by inhibiting CoA biosynthesis. It has been suggested that pantothenol exhibits antibacterial activity by competitively inhibiting pantothenate kinase, a key regulatory enzyme for CoA synthesis. Contrary to these suggestions, in this paper, we demonstrate that pantothenol acts as a substrate for Mycobacterium tuberculosis and Escherichia coli pantothenate kinases. The product, 4'-phosphopantothenol, thus formed inhibits competitively the utilization of 4'-phosphopantothenate by CoaBC. Thus, it is the failure of CoaBC to utilize 4'-phosphopantothenol as a substrate that accounts for the bactericidal activity of pantothenol. (C) 2007 Elsevier Inc. All rights reserved.

A systems perspective of host-pathogen interactions: predicting disease outcome in tuberculosis

The complex web of interactions between the host immune system and the pathogen determines the outcome of any infection. A computational model of this interaction network, which encodes complex interplay among host and bacterial components, forms a useful basis for improving the understanding of pathogenesis, in filling knowledge gaps and consequently to identify strategies to counter the disease. We have built an extensive model of the Mycobacterium tuberculosis host-pathogen interactome, consisting of 75 nodes corresponding to host and pathogen molecules, cells, cellular states or processes. Vaccination effects, clearance efficiencies due to drugs and growth rates have also been encoded in the model. The system is modelled as a Boolean network. Virtual deletion experiments, multiple parameter scans and analysis of the system's response to perturbations, indicate that disabling processes such as phagocytosis and phagolysosome fusion or cytokines such as TNF-alpha and IFN-gamma, greatly impaired bacterial clearance, while removing cytokines such as IL-10 alongside bacterial defence proteins such as SapM greatly favour clearance. Simulations indicate a high propensity of the pathogen to persist under different conditions.

A systems perspective of host-pathogen interactions: predicting disease outcome in tuberculosis

The complex web of interactions between the host immune system and the pathogen determines the outcome of any infection. A computational model of this interaction network, which encodes complex interplay among host and bacterial components, forms a useful basis for improving the understanding of pathogenesis, in filling knowledge gaps and consequently to identify strategies to counter the disease. We have built an extensive model of the Mycobacterium tuberculosis host-pathogen interactome, consisting of 75 nodes corresponding to host and pathogen molecules, cells, cellular states or processes. Vaccination effects, clearance efficiencies due to drugs and growth rates have also been encoded in the model. The system is modelled as a Boolean network. Virtual deletion experiments, multiple parameter scans and analysis of the system's response to perturbations, indicate that disabling processes such as phagocytosis and phagolysosome fusion or cytokines such as TNF-alpha and IFN-gamma, greatly impaired bacterial clearance, while removing cytokines such as IL-10 alongside bacterial defence proteins such as SapM greatly favour clearance. Simulations indicate a high propensity of the pathogen to persist under different conditions.

A structural basis for the role of nucleotide specifying residues in regulating the Rv1625c adenylyl cyclase oligomerization of the from M-tuberculosis

The Rv1625c Class III adenylyl cyclase from Mycobacterium tuberculosis is a homodimeric enzyme with two catalytic centers at the dimer interface, and shows sequence similarity with the mammalian adenylyl and guanylyl cyclases. Mutation of the substrate-specifying residues in the catalytic domain of Rv1625c, either independently or together, to those present in guanylyl cyclases not only failed to confer guanylyl cyclase activity to the protein, but also severely abrogated the adenylyl cyclase activity of the enzyme. Biochemical analysis revealed alterations in the behavior of the mutants on ion-exchange chromatography, indicating differences in the surface-exposed charge upon mutation of substrate-specifying residues. The mutant proteins showed alterations in oligomeric status as compared to the wild-type enzyme, and differing abilities to heterodimerize with the wild-type protein. The crystal structure of a mutant has been solved to a resolution of 2.7 angstrom. On the basis of the structure, and additional biochemical studies, we provide possible reasons for the altered properties of the mutant proteins, as well as highlight unique structural features of the Rv1625c adenylyl cyclase. (c) 2005 Elsevier Ltd. All rights reserved.