Foot-and-Mouth Disease (Aftosa, Aphthous Fever)

Pamela J. HuIlinger • Danelle A. Bickett-Weddle

Definition and Etiology

FMD is an acute, highly contagious viral disease of cloven- hoofed livestock that is characterized by vesicular lesions, erosions, and ulcers in the mouth and interdigital areas and on the muzzle, teats, and coronary bands.

FMD is caused by a picornavirus of the genus Aphthovirus. At least seven immunologically distinct types of FMD virus have been identified: A; O; C; SAT 1, 2, and 3; and Asia 1. Within the seven types, at least 60 subtypes have been recognized.¹ African buffalo can be a maintenance host of SAT serotypes in sub-Saharan Africa and may harbor the virus for at least 5 years. They have not been shown to play an epidemiological role outside of Africa or to transmit the virus naturally to domestic cattle.² Vaccination against one subtype generally does not protect adequately against another. This fact, together with the fact that immunity is generally short term, means that developing effective vaccination programs is challenging.

The virus is rapidly inactivated by pH above 9.0 or below 6.0 and by very high temperatures. For example, the OIE Terrestrial Animal Health Code recommends that deboned, defatted meat products be subjected to 70°C for a minimum of 30 minutes.

Clinical Signs and Differential Diagnosis

FMD is clinically indistinguishable from vesicular stomatitis except that the latter also affects horses. Clinical signs of FMD in cattle include fever, depression, anorexia, listlessness, occasional shivering, excess salivation, lip smacking, nasal discharge, and lameness. Milk production may be reduced. In addition to vesicular stomatitis, the differential diagnosis includes BPS, BVD, bluetongue, rinderpest, MCF, and severe cases of infectious bovine rhinotracheitis. Teat lesions can be confused with those caused by bovine herpes mammillitis or parapoxviruses.

Vesicular lesions (blisters) 0.5 to 5 cm in diameter rupture within 48 hours, followed by a mucosal slough and large erosions. These lesions appear to be very painful, and affected animals are reluctant to eat or move. In general, the morbidity rate is high, but the mortality rate is low. Death may occur in young animals, mainly from myocardial necrosis and secondary bacterial pneumonia. Because of the response to the disease and its effect on trade, it is economically devastating, and its rapid spread and clinical signs (e.g., weight loss, mastitis, lameness) have significant effects on animal health and pro­ductivity. An outbreak of FMD in a country previously free of the disease can cost billions of dollars in trade loss over ensuing years.

Laboratory Diagnosis

FMD is clinically indistinguishable from vesicular stomatitis and other viral mucosal diseases. Therefore laboratory confirma­tion is obtained through demonstration of FMD viral antigen or nucleic acid in samples of tissue or vesicular fluid, either by RT-PCR or by virus isolation. Detection of virus-specific antibody can also be used for diagnosis, and the presence of antibodies to viral nonstructural proteins is an indicator of infection, irrespective of vaccination status.

Pathophysiology

In cattle, the usual incubation period is 2 to 14 days. The primary sites of infection and replication by FMD virus are the pharyngeal and digestive mucosa and alveolar epithelium of the udder. The virus replicates in the cells of the stratum spinosum. It spreads locally and also enters the circulation and is carried to other susceptible tissues. The mucosal cell disruption results in separation of superficial epithelium from basal epithelium, which fills with tissue fluids. Within 2 to 21 days, a fever begins and some vesicles appear. Vesicles develop in the mouth, on ruminal pillars, and in coronary bands. When the epithelial layers slough, erosions are left behind that take days to weeks to heal, depending on their size.

Necropsy Findings

In addition to oral erosions and ulcerations, ulcers may be seen on the ruminal pillars. In young cattle, myocardial and skeletal muscle degeneration and necrosis may be noted. The vesicles are characterized histologically by ballooning, cellular degeneration, intracellular and extracellular edema, and separa­tion of the basal epithelium. There are no inclusion bodies. Myocardial and skeletal muscle degeneration characterized by Zenker necrosis may occur in young cattle.

Epidemiology

Transmission occurs primarily through animal contact, inasmuch as the virus is shed in bodily fluids (saliva, feces, urine, milk, semen). Contaminated fomites such as clothing, footwear, tires, equipment, and bedding spread the virus, and aerosol transmis­sion can occur in favorable environmental conditions. Recovered cattle usually stop shedding the virus within 2 weeks. Detection of virus for longer periods from the oropharynx of cattle has been documented, but such “carriers” have, to date, not been shown to transmit disease to other cattle in natural environ­ments. African Cape buffaloes can be lifelong carriers, but outside of Africa, they have not been shown to play a role in the transmission of the disease.²

The virus exists in milk, and at low levels, it may survive high-temperature short-time pasteurization (72° C [161° F] for 15 seconds or more).

FmD is endemic in Asia, Africa, the Middle East, and small regions in South America and southern Europe (Turkey), where losses involve not only those caused by the disease itself but also the monetary losses resulting from loss of export markets. Noteworthy are some outbreaks in previously FMD-free regions, including Great Britain in 2001 and 2007, Uruguay in 2001,Japan in 2010, South Korea in 2011, and Bulgaria and Turkey in 2011. A 2012 outbreak involving an SAT 2 strain in the endemic regions of Egypt produced an unusually high rate of mortality in adult cattle.

Treatment and Prognosis

Where FMD is endemic, understanding the epidemiology of the disease can provide insights on how to reduce and possibly eliminate the disease through management, movement control, and targeted vaccination. Good nursing care and judicious use of systemic antimicrobial drugs to limit secondary bacterial pneumonia and mastitis can be beneficial. Soft feeds such as chopped green grass (or soaked hay) are much more palatable than dry hay to sore-mouthed animals. The prognosis for survival is good, although affected animals may lose weight, have reduced milk production, and experience mastitis secondary to viral teat lesions.

Prevention and Control

The OIE and USDA websites contain information about current global disease status, which changes frequently. In FMD- endemic areas, managed movement and vaccination can reduce disease incidence. In FMD-free areas (Great Britain, the United States, Canada, Mexico, Japan, New Zealand, and Australia), control programs are based on rapid detection and response, including quarantine, biosecurity, managed movement, depopu­lation, vaccination, or a combination of these.⁴

The current vaccination strategy used globally is to use a serotype-specific, killed FMD vaccine. Immunity, both vaccine induced and naturally occurring, is short-lived, and vaccination usually must be repeated two or three times a year.¹ Vaccine provides partial protection, and subsequent infections usually result in subclinical or mild disease. Calves nursing immune dams are likewise partially protected by passive antibody for up to 5 months. Molecular vaccines are currently under development globally and in 2012, an adenovirus-vectored FMD vaccine was approved for conditional license in the United States. This vaccine does not require live virus production and could be used in the event of an outbreak in the United States. The decision to use FMD vaccine to control an outbreak is complex, and strategies related to production, distribution, and animal identification require adequate resources for effective implementation.