Analysis of the bovine neutrophil transcriptome during glucocorticoid treatment.

The objective of this study was to characterize a large portion of the bovine neutrophil transcriptome following treatment with the anti-inflammatory glucocorticoid dexamethasone (Dex). Total RNA was isolated from blood neutrophils of healthy cattle (5 castrated male Holsteins) immediately following cell purification (0 h) or after ex vivo aging for 4 h with or without added Dex. Additional neutrophils were cotreated with a glucocorticoid receptor (GR) antagonist (RU486) and Dex for 4 h. RNA was amplified, dye labeled (Cy3 or Cy5), and hybridized to a series of National Bovine Functional Genomics Consortium (NBFGC) microarrays. LOWESS data normalization followed by mixture model analyses showed that 11.15% of the spotted NBFGC cDNAs (2,036/18,263) were expressed in 4-h (untreated) neutrophils. Subsequent two-step mixed-model analysis detected (P < or = 0.05) 1,109 differentially expressed genes, of which contrast analysis indicated those that were independently responsive to aging (1,064), Dex (502), RU486 + Dex (141), or RU486 (357). In silico analysis revealed that 416 of the differentially expressed genes are unknown, 59 did not cluster well based on known function, and 634 clustered into 20 ontological categories. Independent validation of differential expression was done for 14 of the putatively Dex-responsive genes across these categories. Results showed that Dex induced rapid translocation of GR into the neutrophil nucleus and signaled dramatic alterations in expression of genes that delay apoptosis, enhance bactericidal activity, and promote tissue remodeling without inflammation or fibrosis. Thus these findings revealed hitherto unappreciated plasticity of blood neutrophils and potentially novel anti-inflammatory/wound-healing actions of glucocorticoids.

An assessment of the economic impact of heartwater (Cowdria ruminantium infection) and its control in Zimbabwe.

Heartwater, caused by the rickettsial organism Cowdria ruminantium, is a serious constraint to livestock development in much of sub-Saharan Africa. Traditionally, the disease has been controlled by the use of chemical acaricides to control the vector tick. The University of Florida/USAID-supported heartwater research project (based in Zimbabwe) is developing a new inactivated vaccine to control the disease. In order that the vaccine is used effectively, the project has been studying the epidemiology of the disease in different livestock production systems of Zimbabwe, and evaluating the economic impact of the disease and of its future control using a vaccine such as the one under development. Initially, field studies were conducted to characterise the communal and commercial livestock-productions systems at risk from heartwater and to understand the epidemiology of the disease. The data from these studies were then applied to an infection-dynamics model of heartwater, which was used to provide estimates of disease incidence and impact under various scenarios over a period of 10 yr. Two principal outputs of the epidemiological model (cumulative annual heartwater incidence and infection-fatality proportion) were key inputs into an economics model. The estimated total annual national losses amount to Z$ 61.3 million (US$ 5.6 million) in discounted value terms over 10 yr. Annual economic losses per animal in the commercial production system (Z$ 56 discounted values) are 25 times greater than the losses in the communal system (Z$ 2.2). The greatest component of economic loss is acaricide cost (76%), followed by milk loss (18%) and treatment cost (5%). Losses in outputs other than milk (beef, traction and manure) appear to be minimal. A new vaccine has the promise of a benefit: cost ratio of about 2.4:1 in the communal and 7.6:1 in the commercial system. A control strategy based on a new vaccine would yield additional non-financial benefits to farmers and the government resulting from reductions in the use of chemical acaricides.

The control of heartwater on large-scale commercial and smallholder farms in Zimbabwe.

As part of a series of studies associated with the development of improved vaccines for heartwater (a tick-borne disease of ruminant livestock caused by Cowdria ruminantium), field surveys were carried out to assess losses associated with the disease and the costs associated with controlling it in the two main agro-ecological zones of Zimbabwe (lowveld and highveld) where heartwater is believed to be endemic and epidemic, respectively. In each zone, a cross-sectional study was performed in the main farming systems (smallholder (SH) and large-scale commercial (LSC) beef and dairy), followed by longitudinal studies in the same sectors to improve data accuracy for some parameters. Suspected heartwater-specific mortality in cattle was similar in all LSC sectors (p = 0.72) accounting for a median 1% mortality risk. Heartwater-specific mortality in SH areas was not assessed due to poor diagnostic ability of the farmers. Few LSC farms and SH households kept sheep; suspected heartwater-specific mortality in LSC sheep was 0.8% in the lowveld and 2.4% in the highveld. Goats were a major enterprise in SH areas but not on LSC farms. Suspected heartwater mortality in LSC goats was 0.8% at one site in the highveld and 17.5% on a farm in the lowveld. Application of acaricides was the major control method for heartwater and other tick-borne diseases on both SH and LSC farms. On LSC farms, plunge dipping was used most frequently and the number of acaricide applications ranged widely between 3 and 52 per year. The total cost of acaricides per head per annum was higher in highveld dairies than in highveld and lowveld beef enterprises (p = 0.03). In SH areas, cattle plunge dipping was conducted by the government with an average frequency of 8 +/- 2 (sd) immersions per annum in both the lowveld and highveld. The type of tick control on sheep and goats in all production systems was highly variable (ranging from none to hand removal or intensive acaricide treatment). Suspected heartwater cases on LSC farms were treated with tetracyclines; treatment was not reported in SH areas. Reported treatment costs were high (median Z$ 120) and highly variable (range Z$-833). Vaccination against heartwater with the live, blood-based vaccine was reported on only one LSC farm. LSC farms applying acaricide 30 or more times per year reported higher morbidity (p < 0.0001) and mortality (p < 0.0001) than farms applying acaricides less than 30 times a year. This finding supports the use of reduced tick control in the management of heartwater in Zimbabwe.

Reducing a spatial database to its effective dimensionality for logistic-regression analysis of incidence of livestock disease.

Large databases with multiple variables, selected because they are available and might provide an insight into establishing causal relationships, are often difficult to analyse and interpret because of multicollinearity. The objective of this study was to reduce the dimensionality of a multivariable spatial database of Zimbabwe, containing many environmental variables that were collected to predict the distribution of outbreaks of theileriosis (the tick-borne infection of cattle caused by Theileria parva and transmitted by the brown ear tick). Principal-component analysis and varimax rotation of the principal components were first used to select a reduced number of variables. The logistic-regression model was evaluated by appropriate goodness-of-fit tests.

Factors affecting the distributions of the ticks Amblyomma hebraeum and A. variegatum in Zimbabwe: implications of reduced acaricide usage.

The ticks Amblyomma hebraeum and A. variegatum are the main vectors of heartwater, a disease of ruminants caused by Cowdria ruminantium, in the agricultural areas of Zimbabwe. At present, A. hebraeum is widely distributed in the dry southern lowveld, and occurs in at least seven foci in the higher rainfall highveld. Amblyomma variegatum occurs in the Zambezi valley and surrounding dry lowveld areas in the northwest. The distribution of A. hebraeum has changed considerably over the past 70 years, while that of A. variegatum appears to have remained fairly static. The distribution patterns of both species in Zimbabwe display anomalous features; the ticks occur in areas of lowest predicted climatic suitability for survival and development and in areas where the densities of cattle, the most important domestic host, are lowest. The only factor favouring the survival of the species in the lowveld habitats in which they occur is the presence of alternative wildlife hosts for the adult stage. Their absence from more climatically favourable highveld habitats appears to have been the result of intensive acaricide treatment of cattle over a long period and a historic absence of significant numbers of wildlife hosts. Eradication of A. hebraeum and A. variegatum by intensive acaricide treatment of cattle can be achieved in the absence of significant numbers of alternative hosts, because of the long attachment and feeding periods of the adults of these tick species. However, eradication becomes impossible when alternative hosts for the adult stage are present, because a pheromone emitted by attached males attracts the unfed nymphal and adult stages to infested hosts. The unfed ticks are not attracted to uninfested hosts, such as acaricide-treated cattle. Regular acaricide treatment of cattle is expensive and so, for economic reasons, the Government of Zimbabwe is no longer enforcing a policy of strict tick control. It is likely that reduced tick control will result in the spread of Amblyomma ticks to previously uninfested areas. Added to this, recent introductions of various wildlife species to highveld commercial farming areas have created conditions in which the ticks could become established in higher rainfall areas. Amblyomma hebraeum is more likely to spread than A. variegatum, because its adults parasitize a wider range of wildlife hosts (warthogs, medium to large-sized antelope, giraffe, buffalo and rhinoceros), whereas adults of A. variegatum appear to be largely restricted to one wildlife species (buffalo) in Zimbabwe, the distribution of which is now confined to very limited areas of the country, as part of foot and mouth disease control measures.(ABSTRACT TRUNCATED AT 400 WORDS)