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Introduction
Dermatophilosis is an exudative dermatitis caused by the branching filamentous actinomycete, Dermatophilus congolensis. This organism has been isolated from skin lesions on a wide range of domestic and wild animal species worldwide. However, a particularly severe form of the disease is endemic in cattle in West and Central Africa and some of the Caribbean islands where it is one of the most important constraints to increased livestock production. Although more sporadic in occurrence, the severe form of the disease is also seen in other African countries including Ethiopia, Malawi and Zambia and Southern Sudan. High- producing exotic breeds are more susceptible to the disease which has had a devastating effect on efforts to develop the dairy industry in many of these areas. In Malawi chronic dermatophilosis was responsible for the majority of deaths or culls in pure-bred Boer goats released in upgrading programmes for small holder herds. However, attempts at immunoprophylaxis against natural infection using D. congolensis whole cell antigen have been disappointing (1,2). It is not possible to produce chronic lesions, similar to those seen in natural cases of the disease by simply infecting skin with the causal organism-which could in part account for the failure of the vaccines in the field. In vivo and in vitro techniques have shown the presence of cell mediated immune responses to D. congolensis in experimentally infected animals (3).
Amblyomma variegatum and dermatophilosis
The severe clinical form of dermatophilosis seen in cattle in the tropics is usually associated with infestation by A. variegatum (4,5,6). This association is based on their similar seasonal occurrence (4,7) and geographic distribution (8,9) and the observed effect of tick control in reducing the prevalence of the disease (10). The incidence of the skin disease increases two months after seasonal increases in the number of these ticks on cattle. It would appear that with increasing numbers of ticks above 20 there is a steady increase in the incidence of dermatophilosis on the indigenous Ghana Sanga cattle of southern Ghana (6). Breeds of animals traditionally regarded as more susceptible to the disease were shown to carry higher tick burdens (11). However, the threshold number of ticks required for the development of severe dermatophilosis probably also varies from animal to animal and between breeds (6). It has been reported that N’Dama cattle are less susceptible to infestation with A. variegatum compared to Zebu type cattle (11,12,13,14). N’Dama have traditionally also been regarded as comparatively resistant to dermatophilosis (15,16). The comparative resistance of the N’Dama cattle would appear to be related to their resistance to ticks and evidence from field studies suggests that when they are infested with similar numbers of A. variegatum ticks to the Zebu-type Ghana Sanga they are equally, if not more, susceptible to the skin infection (6).
Immunopathogenesis
Chronic progressive lesions similar to those seen in natural cases of the disease have been produced experimentally in sheep infested with adult but not other stages of this tick (17). Possible mechanisms suggested to account for the involvement of A. variegatum ticks in the pathogenesis of dermatophilosis include transmission of the organism and the creation of skin lesions which become infected (16,18). Their involvement in transmission is highly unlikely as this would involve transtadial transmission and dermatophilosis lesions are also often not confined to the predilection feeding sites of this tick, especially in more susceptible breeds where lesions rapidly become generalised (5,11). Studies carried out in Ghana suggest that infestation with A. variegatum modifies the immune response of the host (11). The in vitro proliferative responsiveness of lymphocytes from a group of tick-infested Friesian cattle to the T-lymphocyte mitogen, concanavalin A, fell to almost 50% of that of the tick-free group soon after they became tick infested. This marked immunosuppression was associated clinically with the occurrence of severe dermatophilosis (11). Over time, the tick-infested Zebu-type Ghana Sanga cattle also showed a decreased responsiveness to Con A compared to tick-free controls. Immunohistochemical studies were carried out to assess the cellular responses at D. congolensis infection sites on sheep which were experimentally infested with A. variegatum and in uninfested control sheep. Lesions on the tick infested sheep persisted longer than those on the control sheep. It was noted that in the lesions on the tick-infested sheep, 14 days post infection, CD4+(helper T-cells) and CD8+(suppressor/cytotoxic T-cells) cells were present in similar numbers whereas in lesions on the uninfested control sheep there were greater numbers of CD4+ than CD8+ cells (19).
Parameters associated with cell mediated immune responses, including lymphocyte proliferation and Interferon-g (IFN-g) production, are suppressed in tick infested animals while antibody levels to D. congolensis parallel the severity of the infection, with very high levels present in animals with extensive lesions (Morrow, unpublished observations). Infestation with A. variegatum would therefore appear to shift the balance from a predominantly Th1 or IFN-g/IL-12 to a predominantly Th2 or IL-4/antibody type immune response. Studies in which D. congolensis-specific IgG1 and IgG2 responses in naturally occurring dermatophilosis were investigated revealed that IgG1 accounts for a significantly higher proportion of the IgG antibody response of tick-infested animals compared to tick-free animals. Given that IgG1 is associated with Th2 type responses and IgG2 with Th1 responses, these results support the hypothesis that infestation with A. variegatum shifts the balance of immune responses from a predominantly Th1 to a predominantly Th2 type. Shifting the balance from a predominantly Th1 to a predominantly Th2 type response would result in less IFN-g being produced at infection sites and thus decrease intercellular adhesion molecule-1 (ICAM-1) expression on epidermal keratinocytes. This would result in less interaction between mononuclear cells and epidermal keratinocytes.
Amblyomma variegatum and immunosuppression
Different species of ticks have been shown to produce pharmacologically active agents in their saliva which maintain blood flow and prevent clotting while the tick is feeding. These include apyrase and vasoactive prostaglandins. Because of their prolonged feeding time, (individual Amblyomma variegatum ticks can remain attached to and feeding from their hosts for periods of up to several months) ticks must also be able to cause immunosuppression. A number of factors have been implicated in this respect. Prostaglandins of the 2 series are known to have immunosuppressive as well as anti-haemostatic and vasodilatory activities. Prostaglandin E2 (PGE2), which is present in the saliva of several tick species including A. variegatum (20), can inhibit the production of Th1 lymphokines (including IL-2 and IFN-g) but not Th2 lymphokines (21). PGE2 inhibits many T-lymphocyte functions including in vitro proliferation in response to antigen and mitogens. Peripheral blood mononuclear cells prepared from A. variegatum infested cattle show a marked decrease in Concanavalin A-induced proliferation (11). The addition of autologous serum to the lymphocyte cultures derived from tick-infested animals caused further suppression of their response to Con A. Further experiments have indicated that there are factors present in tick salivary gland extracts which suppress the proliferative response of bovine lymphocytes to Con-A (Morrow, unpublished observations).
Bovine dermatophilosis also occurred in association with the use of some of the early rinderpest vaccines (G.R. Scott, personal communication). It is interesting to note that PGE2 appears to be an important mediator in the post-viraemic phase of immunosuppression observed in canine distemper, a related morbillivirus infection of dogs (22). Perhaps PGE2 is a common factor in the pathogenesis of the disease under a number of different epidemiological situations.
Prostaglandins act as “local hormones” regulating a range of physiological processes. PGE2 has comparatively long-lasting effects on cutaneous blood vessels (but not in other vascular beds) resulting in erythema and increased blood flow which may persist for up to 10 hours-an effect with obvious advantages for the tick. PGE2 in vivo often complexes with albumin (23) in which form it is highly active as a suppressor of lymphocyte transformation. The physiological effects of Prostaglandin E2 are mediated through four receptor subtypes, EP1, EP2, EP3 (of which there are three forms) and EP4. However, their role in various physiological and pathophysiological situations has not been fully determined due, in part, to the lack of receptor specific competitive antagonists for PGE2.
Prostaglandins of the 2 series, including PGE2, and thromboxanes are derived from the polyunsaturated fatty acid arachidonic acid metabolism via the cyclooxygenase pathway. Leukotriene B4, a powerful chemotactic substance for leukocytes, is a product of the 5-lipoxygenase pathway of arachidonic acid metabolism. Arachidonic acid is either derived from dietary linoleic acid or ingested as a dietary constituent by mammals. However, some ticks, including Amblyomma americanum, appear to be unable to manufacture arachidonic acid (24) and thus it must be obtained from the blood meal. The uptake of arachidonic acid by the tick can be affected by dietary modification of host lipids, reducing the ticks ability to produce PGE2 and feed successfully (25).
Tick control and the control of dermatophilosis
Rigorous tick control was shown to prevent the occurrence of dermatophilosis in highly susceptible breeds of cattle (11). The limited use of acaricides, applied either at the preferred feeding sites of the tick or at selected times when the level of challenge increases, is sufficient to control the occurrence of the disease in less susceptible indigenous cattle. Fortnightly applications of amitraz (Triatix ) at the predilection feeding sites using a high concentration minimum volume (HCMV) spraying technique greatly reduced the tick load and was shown to be sufficient to control the occurrence of dermatophilosis in local cattle (10). Applying around 50-100 per animal using a small hand sprayer provides good coverage of predilection sites with little wasteful runoff. At less than three pence per treatment this offers a very cost effective approach to controlling the disease.
Acknowledgements
Professor Ramachandran will have seen cases of chronic dermatophilosis during the time he spent in Southern Sudan. His interest in and discussion of our work, during his many visits to Edinburgh, was much appreciated.
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