Introduction

All bacteria within the order Corynebacteriales having an outer membrane rich in fatty acids tend to be environmentally resistant and, with a few exceptions, they are soil inhabitants. Furthermore, this order has a huge number of bacterial species in it, but only a few are known to cause disease. Nocardia and Dermatophilus both produce bacterial spores further enhancing their environmental survival. Even though Prescottella does not produce spores, it is a soil-associated bacterium.

The most important pathogen in this group is Prescottella equi which was until last year (2022) known as Rhodococcus equi, the agent of rattles a chronic respiratory disease of foals that is endemic in most Australian States. Dermatophilus congolensis is common in the tropical regions of Australia causing exudative and crusting skin lesions in most animals during the wet season. Nocardia, soil-associated branching filamentous bacteria are rare causes of chronic mastitis in cows and, respiratory and cutaneous disease in cats and dogs.

Rattles in foals – Prescottella equi (rhodococcus equi) infections

Prescottella equi (previously known as Rhodococcus equi) is the cause of chronic bronchopneumonia and typhlocolitis in 1 to 6 month old foals (peak 6- to 12-week-old foals).   This non-spore forming bacterium forms a rod in culture and a coccus in the host. Prescotella equi is an opportunistic pathogen in other animals and humans and can infect any tissues, but especially the skin and respiratory tract.

This is an important disease of foals in Australia so you may want to read up more on it. Links to good reviews are provided: Muscatello G. 2012. Rhodococcus equi pneumonia in the foal – Part 1: pathogenesis and epidemiology. The Veterinary Journal, 192:20-26 and Muscatello G. 2012. Rhodococcus equi pneumonia in the foal – Part 2: Diagnostics, treatment and disease management. The Veterinary Journal, 192:27-33.

epidemiology of rattles

This soil saprophyte prefers to grow in warm soils (optimum 30°C) that are high in manure which contains volatile fatty acids. Although P. equi can be found in the manure of all herbivores, equine virulent strains (those that carry in a plasmid, genes that encode for VAPA protein) have a preference for horse manure and will grow well in the large intestine of foals less than 12 weeks of age. Foals can have up to 10⁴P. equi/gram of faeces. Therefore P. equi is more common in the soil of horse breeding farms where it will build-up over the years. Foals are usually infected when they inhale dust particles contaminated by this bacterium. Oral ingestion can lead to colonisation of the large intestine and immunity. Foals are usually infected when antibodies obtained from the colostrum are declining. It is thus important to ensure that foals get their full share of colostral antibody immediately after birth.

pathogenesis of rattles

Once inhaled, the bacterium will enter the alveolar macrophages and stimulate an inflammatory reaction. This leads to a pyogranulomatous inflammation where neutrophils are able to inactivate the bacterium and degranulate, however, macrophages are less effective and the bacterium can survive and multiply in the phagocytic vesicle by preventing its maturation.

Several virulence associated proteins (VAP) especially pVAPA are produced by equine strains of pathogenic P. equi in the phagocytic vesicle when the temperature is greater than 34°C.  VapA reduces lysosome maturation and prevents acidification of the phagolysome. Bacteria coughed up from the lung are swallowed and result in a typhlocolitis.
(Note that virulent pig and ruminant strains of P. equi carry different VAPs: pVAPB and pVAPN respectively – these are less virulent than VAPA).

clinical signs & diagnosis

The early stages of the disease are difficult to detect. Affected foals develop a low-grade cough and wheeze and develop a fever.  A few days later the respiratory rate increases. Often they appear bright and suckle well until they are critically ill. Diarrhoea can develop in 50% of the affected foals.

Diagnosis is based on the age of foal, the presence of lower respiratory disease, a possible colitis, and hyperechoic areas in the lung using thoracic ultrasound. Click here for a video showing lung abscesses on ultrasound. (MSD Manual, Rhodococcus equi pneumonia in foals, Dr. Bonnie Rush). Foals on farms endemic for rattles undergo thoracic ultrasound examination every 2 weeks from 2 weeks of age until 2 months of age.  Other diagnostic tests include the presence of opaque densities in a radiograph of the lungs. Confirmation is by the presence of intracellular bacteria within alveolar macrophages on TTW cytology and the culture of P. equi from a transtracheal wash (TTW).

The early diagnosis of disease can be difficult as TTWs are only 70% sensitive and thus additionally a faecal culture can be requested. More than >100 000 CFU/g is considered to be indicative of a colitis being present. Confirmation of virulent strains can be done by qPCR to detect the choE and vapA genes. Serology using the ELISA can be done on serum to check for immunity.

control of Rattles in foals

Foals with small lung abscesses (<10cm² in total or less than 2cm in diameter) diagnosed on thoracic ultrasound may recover even if they don’t receive antibiotics. Thus antibiotic treatment should target those foals with larger lung abscesses. Treatment with antibiotics is often difficult as very few antibiotics are able to penetrate cells as well as abscesses. The most effective treatment is shown to be prolonged oral treatment with a combination of a macrolide such as erythromycin (also tulathromycin, clarithromycin or azithromycin) and rifampin. The combination should be used for at least one week past cure, determined clinically by the use of radiographs or by blood tests for normal fibrinogen levels.  (Fibrinogen is used to assist in clotting as it is converted by thrombin to fibrin. However, it is also an acute-phase protein with its levels increased in the blood when there is inflammation). Whilst not yet identified in Australia, P. equi strains carrying conjugative plasmid resistant genes to the macrolides/lincosamides/streptogamims, ripampicin and  non-synthetic tetracyclines have been spreading in the USA. Thus it is recommended that isolates from clinical cases are tested for susceptibility to these antibiotics.

The use of immune stimulants to increase the production of cytokines such as IL-6 and interferon gamma by alveolar macrophages may assist in reducing the severity of disease in neonatal foals.

Hyperimmune plasma has been used with success to control the disease on endemic farms. (Hyperimmune plasma is manufactured by repeatedly injecting a horse with killed P. equi in an adjuvant. That horse will develop high titres of P. equi specific antibodies which can be used to provide foals with passive immunity). As yet no successful vaccine has been commercially developed.

Control is based on rotation of foaling and foal camps, sunlight exposure of camps and regular removal of manure and sometimes replacement of the top soil layer in these camps. Ideally, foals should be reared in low-dust environments. Some farms use a practice known as firing where foals are fed live, virulent strain of P. equi at 2, 7 and 14 days of age to stimulate immunity. This method makes use of the natural epidemiological cycle of P. equi.

Nocardiosis in animals

Nocardiosis is a rare disease in animals. These Gram-positive, filamentous, branching bacteria produce spores in their aerial filaments or hyphae. It is a common soil microbe that will infect animals, usually via skin wounds. A number of Nocardia species have been diagnosed to cause infections in animals and people. Thus only learn the Genus name.

Nocardioforms are able to survive within phagocytes as the mycolic acids in their cell walls inhibit phagosome-lysosome fusion. The bacteria induce localized granulomas that rupture draining viscous pus which is often red-tinged. Splendore-Hoepli bodies (sulphur granules) containing microcolonies of Nocardia are often present in the pus. In cattle the most common site of infection is the udder. In cats and dogs lesions are common in the skin, the mouth and thorax (pyothorax). Skin infection and lymph node abscessation are common presentations in horses, with respiratory or disseminated disease in the immunosuppressed. Nocardial abortion may occur in horses and pigs, and respiratory infection in monkeys is common in research colonies. Humans may also be infected with cutaneous, eye, pulmonary and neurological infections being the more common disease manifestations. The diagnosis of nocardiosis is in the Section on dermatophilosis.

Dermatophilosis in animals – dermatophilus congolensis infections

Dermatophilosis, caused by Dermatophilus congolensis,  is an exudative to proliferative pustular dermatitis which is characterised by scab formation. It mainly affects cattle, sheep and horses, but also goats, dogs and cats, many wild mammals, reptiles and, occasionally, humans. Lambs aged between 3 to 9 months of age are especially susceptible.

 It occurs throughout the world but is more prevalent in tropical regions with high rainfall. The related Dermatophilus crocodyli is the commonest skin disease of crocodiles in Australia and has an impact on the farming of this species.

 In livestock, disease results in damage to hides, decreased productivity i.e. a drop in milk production, and occasionally death (up to 20% in lambs).

epidemiology

• Infection is via the skin, either by direct contact with an infected animal or indirectly from plants, insects and ectoparasites harbouring the bacterium. Wet skin and particularly the lesions of affected animals are attractive to flies that can mechanically transfer the causative organism to unaffected animals.
• Trauma to the skin either by injuries (e.g. thorns, ectoparasites, harness damage and shearing) or by constant wetting provides a portal of entry for the zoospores.
• Prolonged wetting of the skin, such as that which occurs during the rainy season (monsoon type weather) in tropical areas, results in emulsification of the protective sebum layer and maceration of the stratum corneum of the skin, which facilitates the spread of the disease.  The spores will also hatch (lose their outer layer) under these conditions and become motile using flagella (zoospores).
• Regular dipping can initiate an outbreak of dermatophilosis or cause the spread of lesions on affected animals. Infected skin crusts of carrier animals will become loose in the dipping tank fluid and susceptible animals with existing skin lesions due to other causes or having macerated skin may on dipping become infected.
• In Africa, especially central Africa, dermatophilosis in cattle is often associated with heavy Ambylomma variegatum burdens. This is thought to be due to skin damage by the ticks, immunosuppressive substances produced in the tick’s saliva and a delayed hypersensitivity reaction caused by the repeated feeding of ticks attached to the skin. Dermatophilosis is less common in tick-resistant cattle.
• Other agents causing immunosuppressive disease or cutaneous lesions e.g. poxviruses (Lumpy skin) in cattle, and Orf virus (Scabby mouth) in sheep (a parapox virus) may predispose to or be associated with dermatophilosis.

pathogenesis

Developmental life cycle of Dermatophilus congolensis

To understand the pathogenesis of rain scald, you have to know the developmental life cycle of D. congolensis. The picture below describes it.

Following infection the zoospores reach susceptible sites of the skin by their own motility and a positive chemotactic response to CO₂ that diffuses through the skin. After germinating, the branching filaments of D. congolensis invade the living cell layers of the epidermis and the sheaths of hair or wool follicles where extensive proliferation of the organism occurs. They stimulate keratinisation of the epidermis and induce an acute inflammation that is characterized by the accumulation of an exudate rich in neutrophils beneath the invaded part of the epidermis. The organisms do not penetrate the layer of exudate, which apparently acts as a barrier to the invasion of the uninfected layers of the epidermis. The new epidermis that forms underneath the exudate is invaded from the side until enough skin is affected to form a thick laminated crust composed of alternating layers of para- and orthokeratotic hyperkeratosis and exudate.

Immunity is thought to be primarily cellular as the presence of circulating antibodies has no effect on the outcome of the disease.

clinical signs

In ruminants

The lesions vary in severity with some mild cases only being detected on palpation of the hair coat or fleece. Acute to chronic cases manifesting localized to widespread lesions occur. Generally, in all susceptible animal species, dermatophilosis is characterized by the appearance, in the affected areas, of an exudative to proliferative epidermitis with subsequent formation of scabs and crusts under which the hairs or wool tend to break or matt together. The matted hairs or wool may at times become detached leaving raw areas. The detached hair or wool and crusts during the early stages of the disease resemble, to some extent, camel hair paint brushes; this stage is often referred to as the ‘paint brush stage’ of the disease. In the chronic stage, the scabs are dry, and when removed, leave only a soft pinkish area because of the healing that already has occurred. Secondary bacterial infections of lesions causing resultant dermatitis are common and can lead to the death of severely affected animals. The disease in wildlife is similar to that in livestock.

For additional information read this review article written by Tellum et al in 2021 on ovine dermatophilosis.

To find out more about lumpy wool in sheep with a possible role of Pseudomonas aeruginosa in this disease and genetic resistance read: Norris BJ, Colditz IG, Dixon TJ. 2008. Fleece rot and dermatophilosis in sheep. Veterinary Microbiology, 128: 217–230

In horses – rain scald

In horses, irregular patches of clumped hair, raised patches or alopecia may be noted in areas of the body that are subject to trauma. Horses maintained under muddy conditions or on very wet pastures may develop chronic lesions on the heels (dew poisoning).  

In reptiles

Dermatophilus crocodyli is the commonest skin disease of crocodiles in Australia and has an impact on farming of this species. It is known as brown spot disease. Skin infections caused by Dermatophilus have also been recorded in other reptiles including lizards.

To find out more about skin diseases in crocodiles read the following article:

Lott MJ, Moore RL, Milic NL, Power M, Shilton CM, and Isberg SR (2018) ‘Dermatological conditions of farmed Crocodilians: A review of pathogenic agents and their proposed impact on skin quality’, Veterinary Microbiology, 225:89-100, doi:10.1016/j.vetmic.2018.09.022

In people

Dermatophilosis in people is rare and usually manifests as pustules on the hands and occasionally feet, which may itch.  It has been suggested that pitted keratolysis or keratoma plantare sulcatum may be associated with D. congolensis.

Diagnosis of dermatophilosis

The disease is suspected when there is an outbreak of proliferative dermatitis (exudative lesions and skin crusts) in more than one species of animal during the wet season. However, other sources of moisture should not be excluded i.e. leaking water troughs, water misters used to cool dairy cows.

However, there are a number of skin diseases that can be confused with dermatophilosis. These are discussed below:

Differential diagnosis of dermatophilosis

Cattle:

• dermatophytosis characterised by circular lesions on the face and neck
• mange (usually pruritic)
• subacute to chronic photodermatitis of non-pigmented skin
• pseudo-lumpy skin disease
• (not Australia) lumpy skin disease.

Sheep:

• contagious pustular dermatitis (orf/scabby mouth)
• sarcoptic and chorioptic mange, sheep-itch mite (Psorergates ovis) (sheep cab – not in Australia)
• dermatophytosis
• photodermatitis
• fleece rot caused primarily by Pseudomonas aeruginosa.

Equines:

• dermatophytosis.

The diagnosis is confirmed by the examination of biopsy material from lesions or smears prepared from the affected skin, the concave base of freshly removed scabs, or of suspensions of some of the most recently formed scabs in distilled water. Smears should be stained with Gram stain or aniline dyes (e.g. Giemsa, CAM’s Quick) and examined for the presence of branched filaments that are transversely and longitudinally septate, and characteristic parallel rows of coccoid elements. The bacterial morphology is typical for Dermatophilus and is used together with the case history and clinical signs to diagnose dermatophilosis.

The table below shows how Dermatophilus and Nocardia, both branching filamentous bacteria that produce endospores can be differentiated cytologically

Fresh scabs or biopsy material can be placed in a clean envelope or sterile specimen container and sent to the laboratory for bacterial culture. Please notify the laboratory that you suspect Dermatophilosis as the laboratory will use special methods to concentrate and germinate the spores. Serological methods of diagnosis are of little practical value but may be useful as flock/herd-screening tests.

Below is a table that compares the isolation and identification of Nocardia and Dermatophilus species

Control of dermatophilosis

Cattle

Cattle are rarely treated as most cases heal spontaneously when the conditions become drier and the causes of the skin damage are rectified.

Sheep

• Isolate infected from non-infected sheep.
• Cull chronically or severely affected sheep.
• Valuable sheep can be treated with long-acting oxytetracycline.
• Shearing of sheep with severe but inactive lesions can promote healing. It should not be done if the scabs are tightly adherent to the skin.
• Husbandry measures to control predisposing factors i.e. tick and fly control and the avoidance of excessive wetting if possible. Modern ectoparaside control avoids the need for dip tanks. Good dip tank management such as regular draining of dip tanks and adding quaternary ammonium compounds to dipping fluid.
• Sheep can be sprayed with 0.5 % zinc sulphate solution to prevent infection of shearing wounds.
• Shearing and dipping should preferably be done during dry climatic conditions.
• Currently, no vaccine is available.

 Horses

Since the condition can be unsightly in horses and possibly transmissible to humans, local as well as systemic therapy is carried out.

• Emollients or gentle bathing of the crusts with warm water and soap will aid in the removal of thick crusts. They can be adherent and painful to remove – so wait until they are soft enough to remove. Where possible, wash the entire animal with a non-irritant shampoo containing an antiseptic such as chlorhexidine or benzoyl peroxide. This should be done daily until the crusts are gone. The addition of fly repellents to emollients may reduce fly-induced spread of the causative bacterium.
• Severe lesions should be treated with antibiotics. A single intramuscular treatment of penicillin (70 000 IU/kg) or combined with streptomycin. Otherwise, 20 mg/kg of a long-acting oxytetracycline can be administered.
• Equipment used on animals should be kept clean and dry. Chloride-based products can be used to disinfect them.

In the quiz chapter, there are quizzes based on case studies of rattles, dermatophilosis and nocardiosis.

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