To My Quyen, Nguyen Khanh Thuan, Nguyen Phuc Khanh, Nguyen Thanh Lam*

1. Introduction 

Bovine foot rot (BFR) is an infectious bacterial disease of the interdigital skin and subcutaneous tissue of the feet of cattle. The geographic distribution of this disease is broad, with published reports of cases in North America, South America, Australia, New Zealand, Europe, Asia, and Africa. BFR is a common cause of lameness in dairy and feedlot cattle. BFR has been reported in housed and pastured cattle under a variety of climatic and management conditions. Equally diverse is the nomenclature that has been applied to BFR; it has also been referred to as interdigital necrobacillosis, interdigital pododermatitis, interdigital phlegmon, foul in the foot, and foot abscess. The anaerobic bacterium Fusobacterium necrophorum, formerly Sphaerophorus necrophorum, has long been considered to be centrally involved in the pathogenesis of BFR, but additional bacteria such as Porphyromonas levii and Prevotella intermedia may be involved in the pathogenesis (Van Metre, 2017). 

2. Etiology

2.1 Bacterial characteristics

A variety of bacterial virulence factors have been implicated in the pathogenesis of BFR. For F. necrophorum, these virulence factors include endotoxin (lipopolysaccharide), hemolysin (phospholipase), hemagglutinin, adhesins (pili), proteases, and leukotoxin. Of these, leukotoxin is the most extensively studied. The leukotoxin of F. necrophorum is a large, water-soluble exotoxin that is cytotoxic for ruminant neutrophils, macrophages, hepatocytes, and ruminal epithelial cells. At low concentrations, this exotoxin induces apoptosis of these cells; at higher concentrations, cell lysis occurs. Destruction of these host defense cells (with the release of lysosomal enzymes and reactive oxygen species) is hypothesized to cause tissue necrosis and induce local anaerobiosis. In an Australian study, strains of F. necrophorum that produced negligible levels of leukotoxin failed to induce BFR when inoculated into the interdigital skin of calves, whereas inoculation of leukotoxin-producing strains produced the characteristic disease. Notably, the leukotoxin of F. necrophorum shares no sequence homology with the repeats in toxin (RTX) family of exotoxins produced by other gram-negative bacteria, including the leukotoxin of Mannheimia hemolytica. P. levii is a pleomorphic, gram-negative, anaerobic, rod-shaped bacterium that has been cultured or detected by PCR in cases of bovine metritis, bovine necrotic vulvovaginitis, bovine digital dermatitis, and BFR. In vitro, P. levii does not induce strong chemotactic or oxidative burst responses in bovine macrophages. Further, this organism produces an enzyme that cleaves bovine immunoglobulin (Ig) G2, thereby potentially reducing the host’s capacity to opsonize the organism for neutrophil-mediated phagocytosis. Together, the virulence factors of P. levii have been hypothesized to impair or delay the host’s response to infection, facilitating establishment of BFR by this and other bacteria. P. intermedia is a gram-negative, anaerobic rod that has been isolated from humans and dogs with various oral infections, as well as from cases of BFR. Virulence factors identified for this organism include a potentially robust antimicrobial resistance profile. Specifically, b-lactamase production seems to be common among members of this genus. P. intermedia also can form biofilms during infection, which limit access of antimicrobials to the bacterium. The role of these virulence factors in the pathogenesis of BFR remains undefined (Van Metre, 2017).

3. Epidemiology

3.1. Susceptible hosts

Recent calving (early lactation) seems to be a risk factor for BFR. In a large, 2-year study of dairy cows in Denmark found that nearly 40% of BFR cases occurred in the first 30 days after calving; the incidence during the first month postpartum was 6-fold higher than in any other month postpartum as well as the month preceding calving (Alban et al., 1995). The metabolic, immunologic, nutritional, and environmental changes experienced by freshening dairy cows are speculated to be involved in this spike in incidence of BFR during the postpartum period. In contrast, associations between parity and BFR risk were not consistent between studies in dairy cattle in Denmark, the United Kingdom, and the United States. 

Differences in risk of BFR by breed were also identified but the investigators hypothesized that these differences could have been confounded by breed disparities in milk production. However, when measured in Holstein cows, milk production did not influence the risk for BFR. Estimates of the heritability of BFR susceptibility are variable (0.09–0.38). 

The immune response to natural cases of BFR remains poorly characterized. In Berg and Loan’s experiments, 2 cattle that had recovered after treatment from experimentally induced BFR were reinoculated: both developed recurrent BFR (Berg and Loan, 1975). This finding suggested that protective immunity had not been induced by the previous infection. In a study of large dairy herds found that estimates of repeatability for BFR were high, suggesting that naturally occurring cases can recur (Oberbauer et al., 2013). Dairy cattle with BFR were shown to have higher plasma IgG concentrations than healthy herd mates, but the specificity of the immunoglobulins was not determined. In contrast, immune compromise from bovine viral diarrhea infection may render cattle more susceptible to BFR (Van Metre, 2017).

3.2 Environment factors

Warm, moist environmental conditions are commonly considered to be conducive to BFR. This association may reflect enhanced survival of causative bacteria in the environment or a tendency for cattle to congregate and defecate in shaded or wet areas. In temperate climates, BFR has been documented to occur more frequently in warmer months of the year, although this trend is not consistent across all studies. Similarly, periods of rainfall have been shown to increase the incidence of lameness in pastured cattle; this association has been attributed to muddy conditions, maceration of the digital skin, and carriage of stones from cattle paths (tracks) into concrete floored areas of the dairy. However, monthly rainfall was not associated with the total monthly number of treatments for BFR in Denmark. It is important to consider that seasonal rainfall may coincide with calving season in certain operations, and the increased risk of BFR brought about by parturition may be attributed erroneously to precipitation (Van Metre, 2017).

4. Pathogenesis

The pathogenesis of footrot is very complex and multifactorial. In most cases, co-infection of Dichelobacter nodosus and and Fusobacterium necrophorum

 have the most important roles in footrot and D. nodosus plays the primary role in disease progression, with F. necrophorum playing a secondary role. The viewpoint that footrot is dependent on a mixed bacterial infection is supported by the pharyngotonsillitis in human. Hoof horn separation does not occur without the involvement of D. nodosus. Early histopathological observations of tissue sections from footrot lesions described little inflammatory response in areas with D. nodosus, but severe inflammation in response to invasion by Fusobacterium necrophorum. Even though, some studies have indicated that 

D. nodosus appears to be the primary invader of the epidermal matrix and to initiate the process of hoof separation, providing a necessary environment where F. necrophorum can flourish. The infection appears to be the result of the synergistic action of two kinds of particular bacterial species, of which D. nodosus is the causative transmitting agent and F. necrophorum 

appears to be necessary for the induction and development of the disease. This was confirmed by the results that lesion was infiltration by polymorphonuclear leucocytes and a dense population of filamentous bacteria, visually identified as 

F. necrophorum  in interdigital dermatitis sections. Most studies indicate that both F. necrophorum and D. nodosus  are essential for the invasion of the epidermal matrix of the hoof and neither bacterial species alone will cause a footrot lesion. Firstly, F. necrophorum colonises the stratum corneum, and then facilitates infection with D. nodosus. The established D. nodosus infection allows F. necrophorum to penetrate more deeply into the tissue, causing further inflammation and destruction of epidermal tissue. F. necrophorum establish infection, resulting in the development of interdigital dermatitis. While this condition is itself relatively mild, it provides the necessary pre-disposing conditions for infection with D. nodosus. Additionally, there is evidence that D. nodosusis not a major agent of lameness in New Zealand dairy cattle, while F. necrophorum possibly could be. Anyhow it seems that F. necrophorum either facilitates disease development by increasing the damage to the interdigital skin and promoting Interdigital Dermatitis that subsequently permits replication of D. nodosus or follows D. nodosus or exacerbate the severity and persistence of footrot. In quite large extent, we consider that F. necrophorum plays an opportunistic or secondary role, because it is consistent with understanding of the role of Fusobacterium spp. in other diseases. F. necrophorum is present in lesions and abscesses in many polymicrobial infections, where they are considered to enhance disease severity through synergistic relationships with other pathogens (Xiao et al., 2017). 
5. Clinical signs and pathology

5.1 Clinical signs 

Research suggests that the incubation period of footrot can be a week. The fore- or, more commonly, the hindlimbs can be affected, but more than one foot is rarely involved at the same time in mature cows. However, footrot can occasionally develop in several feet in calves. The first sign is swelling and erythema of the soft tissues of the interdigital space and the adjacent coronary band. The inflammation extends to the pastern and fetlock. Typically, the claws are markedly separated, and the inflammatory edema is uniformly distributed between the two digits. The onset of the disease is rapid, and the extreme pain leads to increasing lameness. In severe cases, the animal is reluctant to bear weight on the affected foot. Fever and anorexia are seen. The skin of the interdigital space first appears discolored; later, it fragments with exudate production. As necrosis of the skin progresses, sloughing of tissue is likely to follow. A characteristic foul odor is produced.

If the disease proceeds unchecked, weight loss is severe and milk yield is significantly reduced. Milk production may not recover during the current lactation. Open lesions can be infected with secondary invaders. If the necrotic lesion is located in the anterior region of the interdigital space, the distal interphalangeal joint can become infected.

Hematogenous infection of the tissues of the interdigital space may account for peracute cases of footrot, which are referred to as either “blind” or “super foul.” This form of footrot is characterized by the initial absence of a skin lesion, extreme pain, and the tendency to progress despite aggressive therapy (Greenough, 2016).

5.2 Pathology

Tissue sections from clinically normal feet had no obvious damage to the interdigital skin. The epidermis had a prominent granular layer and the dermal–epidermal junction had a low number of infiltrating leukocytes. The papillary dermis showed minimal to focally mild perivascular infiltration of lymphocytes and neutrophils (Fig. 5A). Perivascular immune cell infiltration was seen surrounding dilated superficial dermal blood vessels and resulted in a cell dense dermal–epidermal junction, predominantly involving lymphocytes, neutrophils and a few plasma cells (Fig. 5B). Overall, ID presented as a moderate chronic-active pododermatitis with a mixed lymphocytic and neutrophilic infiltration with mild epidermal exocytosis.

In foot rot, in addition to erythema, under running of the hoof horn interface was observed indicating a loss of tissue integrity. The dermis showed large numbers of perivascular lymphocytes, neutrophils and fewer plasma cells leading to a cell dense migration through the papillary dermis and epidermis (Fig. 5C). Lymphocytes and neutrophils accumulated uniformly in all layers of the epidermis. Purulence, composed of large numbers of non-viable neutrophils, necrotic debris and plasma proteins, was seen frequently in areas of epidermal degeneration and necrosis and in areas of epidermal–dermal clefts (Fig. 5D). Epidermal ballooning, characteristic of hydropic cell degeneration, was noted with marked swelling of the cytoplasm and additional condensation (pyknosis) of the nucleus (Fig. 5D). Increased fibrous tissue proliferation (superficial dermal scarring) occurred in some cases indicating a chronic reaction due to the loss of tissue integrity at the skin hoof interface (Fig. 5E). The papillary dermis showed vascular congestion and dilated lymphatic vessels with dermal oedema (Fig. 5C), as a consequence of the intense epidermal and dermal inflammation. In summary, foot rot presented as moderate to focally severe chronic-active pododermatitis with a mixed lymphocytic and neutrophilic infiltration, pus formation, horn clefting in some cases.

6. Diagnosis

6.1 Clinical diagnosis 

Diagnosis is made based on several different lesions and clinical signs that can result from infection with this protozoan. 

• Lameness is sudden in onset and becomes progressively more acute over a relatively short time (6-12 h).
• The whole foot, up to the fetlock, will be swollen; the skin will be pink and tender to the touch.
• The swelling will cause the two digits to separate, and the cleft between the claws will appear to be larger than normal.
• The skin between the claws becomes necrotic and sloughs. The discharge has a typical foul odor.
• The body temperature rises, and the milk yield drops very rapidly.
• Radiography is not useful in most instances but is essential in cases failing to respond to treatment and when either septic pedal arthritis or a retroarticular abscess is suspected.
• A very acute form of foot rot has been described in Europe (Blowey et al., 1994). This form is referred to as either ‘blind foul’ or ‘super foul.’ This form of the disease is characterized by its sudden onset, the absence, initially, of a skin lesion, extreme pain and the tendency to progress despite treatment. It is believed that this condition may be caused by blood-borne organisms.

6.2 Differential diagnosis 

Retroarticular abscess

The condition most commonly confused with foot rot is retroarticular abscess. These cases are usually presented as, ‘a case of foot rot that is resistant to prolonged treatment with one or more antibiotics’. The striking characteristic of the retroarticular abscess is that there is swelling around only one digit. Both digits are swollen if the animal is affected with foot rot. In the case of the retroarticular abscess, careful examination will reveal a sinus opening beneath the abaxial wall. This condition is a complication of white line disease in which pus infiltrates the deeper structure of the foot and an abscess form in the space behind the distal interphalangeal joint. Surgical treatment is necessary.

Septic arthritis of the distal interphalangeal joint

This condition is most frequently a complication of foot rot. The capsule of the joint is very close to the interdigital skin at the dorsal flexure of the digit. When the lesion breaches the skin at this location, infection enters the joint.

Foot and mouth disease

A cow affected by foot and mouth disease can show signs of lameness for a few hours before other more characteristic signs appear. Foot rot is such a commonly occurring disease that lifting a hind foot to confirm the diagnosis does not always take place. This provides an opportunity for foot and mouth disease to be missed. It should be noted that with foot and mouth disease the milk yield of the entire herd can drop before clinical signs become obvious.

7. Treatment 

Most treated animals recover in a few days. Good results are obtained with penicillin G, IM, for 3 days. Treatment should be administered as soon as signs are observed. However, the label dosage may be inadequate to affect a rapid resolution, and increased dosages may be needed, requiring increased withdrawal times. Treatment of “super foul” must be particularly aggressive. Early cases respond well to single doses of long acting oxytetracycline.

Sodium sulfadimidine solution IV or trimethoprim/sulfadoxine, IV or IM, bid for 3 days, can also be used. A single oral administration of a long-acting bolus containing baquiloprim/sulfadimidine may be suitable to treat beef cattle.

High concentration of an agent in the target tissues can be achieved by a regional IV injection. Positive results have been obtained with penicillin or oxytetracycline.

Local treatment is essential for some longstanding cases and in all instances in which the anterior region of the interdigital space has been compromised. The lesion must be thoroughly cleansed, but it is inadvisable to curette or otherwise remove necrotic tissue surgically. The dorsal pouch of the distal phalangeal joint is very superficial at this point. A nonirritant bacteriostatic agent (such as nitrofurazone or a sulfa preparation) should be applied as a topical dressing. The application of gauze, cotton batting, or bandages is contraindicated. However, the lesion can be protected and immobilized by binding the digits together with a bandage. The entire digital region can be protected from contamination if it is enclosed in a plastic bag fixed in place with an adhesive bandage. However, prolonged protection is not advocated, because the enclosed lesion tends to macerate further. Bandages, if used, should be replaced daily (Greenough, 2016).

After the lesion be thoroughly cleansed, using TERRA-BLUE in case loss of skin integrity occurs and administration of CEPTIFI-SUSPEN by subcutaneous injection in the neck with a dosage 1mL/20-40 kg of body weight/day. 

8. Prevention and control 

Hygiene is the most important control measure. Reducing exposure to manure and avoiding chronic wetting of the foot are paramount to reducing the risk of foot rot.

• Frequently remove manure and maximize drainage from all areas of the facility (Gooch, 2003).
• Maintain watering and feeding areas to avoid standing water and/or mud.
• Animals actively shedding infectious organisms should be isolated until signs of lameness have disappeared.
• Waterproof dressing or protective boot should be applied; however, animals wearing protective boots should be monitored carefully to avoid additional damage. Boots should be disinfected between use.
• Animals at pasture might be moved to a clean, dry area, or possibly housed during periods of heavy rainfall. Contaminated concrete must be frequently cleaned and scraped free of manure.
• Use a footbath with a range of disinfectants to clean and disinfect the interdigital skin.
• Provide dry places for cows to lie down.
• Preventive use of a footbath with an antiseptic and astringent solution (eg, copper or zinc sulfate [7%–10% in water]) has given beneficial results. Formaldehyde solution (3%–5% in water) can also be used. Ethylenediamine dihydroiodide has been used as a feed supplement for prevention, but the results are extremely uncertain. Vaccines against F. necrophorum have failed because of the weak immune response to the bacterium. High levels of zinc fed as a supplement have a beneficial effect by improving epidermal resistance to bacterial invaders (Greenough, 2016).

9. References 

Alban, L., Lawson, L., Agger, J., 1995. Foul in the foot (interdigital necrobacillosis) in Danish dairy cows—frequency and possible risk factors. Preventive Veterinary Medicine 24, 73-82.

Berg, J., Loan, R., 1975. Fusobacterium necrophorum and Bacteroides melaninogenicus as etiologic agents of foot rot in cattle. American Journal of Veterinary Research 36, 1115-1122.

Blowey, R., Done, S., Cooley, W., 1994. Observations on the pathogenesis of digital dermatitis in cattle. Veterinary Record 135, 117-115.

Davenport, R., Heawood, C., Sessford, K., Baker, M., Baiker, K., Blacklaws, B., Kaler, J., Green, L., Tötemeyer, S., 2014. Differential expression of Toll-like receptors and inflammatory cytokines in ovine interdigital dermatitis and footrot. Veterinary Immunology and Immunopathology 161, 90-98.

Gooch, C.A., 2003. Foot Health, Animal Health Diagnostic Center, Cornell University. College of Veterinary Medicine 

Greenough, P.R., 2016. Interdigital phlegmon in cattle, MSD Veterinary Manual.

Greenough, P.R., MacCallum, F.J., Weaver, A.D., 1981. Lameness in cattle. John Wright & Sons.

Oberbauer, A., Berry, S., Belanger, J., McGoldrick, R., Pinos-Rodriquez, J., Famula, T., 2013. Determining the heritable component of dairy cattle foot lesions. Journal of Dairy Science 96, 605-613.

Van Metre, D.C., 2017. Pathogenesis and treatment of bovine foot rot. Veterinary Clinics: Food Animal Practice 33, 183-194.

Xiao, J., Sun, D., Wang, H., 2017. Effects of Fusobacterium Necrophorum on pathogenesis and potential disease-associated factors in plasma in cattle with footrot. Br Biomed Bull 5, 299.