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OVERVIEW



Hosts

Species infected by FMD virus include artiodactyl mammals (even-toed ungulates, Figure 1) which include: Bovidae (cattle, zebus, domestic buffaloes, yaks), sheep, goats, swine, all wild ruminants and suidae (pigs). Camelidae (camels, dromedaries, llamas, vicunas) have low susceptibility. Cattle and pigs are of most economic significance.

Species differ in the severity of clinical presentation (Table 1). There have been a few reports of infection in rodents and humans, but are of little clinical significance.

Figure 1:  Artiodactyl limbs. From left, pig, deer and bovine.

feet



Table 1:  Overview of FMD host species and associated disease severity

Species

Cattle and Swine

Other artiodactyl ruminants1

Rodents2

Humans3

Severity

Severe

Moderate

Asymptomatic

Mild

Signs

Painful lesions in the mouth and feet that result in acute inappetance and lameness.

 


Lameness is the predominant sign. 

 

Lesions are few, superficial, and heal rapidly thus small ruminants may be clinically inapparent. 

 

Difficult to diagnose and therefore sometimes ignored or misdiagnosed

N/A

Few reports of clinical disease but symptoms are mild and last for approximately one week.

 


1 All artiodactyl domestic species, including sheep, goats, buffalo and wild species, including deer, giraffe, hippos, camelids, antelope are susceptible.  Exceptions are Old World camels which are resistant and South American camelids such as alpacas and llamas, that are mildly susceptible.  African buffalo, may serve as a reservoir of FMDV and thus are the only wild species of epidemiological significance.

2Rats, mice, and guinea pigs can be infected experimentally.

3 Only a few human cases have been reported in spite of people's regular exposure to infected livestock. The cases that have occurred were due to close contact with infected animals, a virus in the laboratory or consumption of unpasteurized milk.


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Transmission

Transmission can be either direct (contact via compromised skin or aerosol droplets or long-range airborne) or indirect (fomites). Table 2 shows the experimental minimum infectious dose for the most affected species.

Transmission in animals that are in close contact are especially susceptible to infection because all excretions and secretions from the infected animal contain virus although shedding is most concentrated in vesicular fluid (Table 3).


Table 2:  Minimum Infectious doses for bovine and swine experimentally exposed to FMDV via direct routes .

Routes of Infection

Bovine

Swine

Respiratory - aerosol

10 (very low!!!)

>800 (relatively resistant to aerosol exposure)

GI – oral through abrasions

105–106

104–105

Intradermal/Damaged epithelium1

100

Very short incubation period

100

Units are in TCID50 (bovine thyroid tissue culture 50% dose end-point estimates)

1Via common production practices shearing, de-worming and rounding up for lambing or for clinical examination, blood sampling and milking.



Table 3:  Viral loads in bodily secretions and excretions                                                              
Highest



Lowest
Vesicular fluid Pharyngeal fluid Saliva, nasal and larcrimal secretions Blood
Feces and urine


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Site of replication

Like most other RNA viruses replication and virion assembly takes place within the cytoplasm of infected cells (Figure 2). In animals that inhale the virus, the primary site of replication is non-keratinized stratified squamous mucosal epithelium of the pharynx (Table 4). However, the virus migrate to secondary sites of replication (mainly in keratinized epithelial cells) via the lymphatics where amplification occurs. Thus, FMD virions are highest in number within the se cells (Table 5).

Figure 2:  Site of viral replication in FMDV infected susceptible cells (BHK-38).  a)  Normal cell appearance.  Nuclear DNA is blue and microtubule network is green.  b) to d.) Nuclear DNA is blue and FMDV capsids are green.  b) 1.5 hours post infection (hpi).  Low levels of virus in the cytoplasm beside nucleus.  c) 2.0 hpi.  Accumulation of virus in the cytoplasm on one side of the nucleus.  d) 2.5 hpi.  Cytoplasm is full of virions.  The cell is rounded and shows the cytopathic effect of FMDV.

 fmdincell

Table 4:  Sites of primary and secondary replication and sites of amplification

Primary

Respiratory Tract

Non-keratinized stratified squamous mucosal epithelium of the pharynx (specifically the dorsal surface of the soft palate and the roof of the pharynx, just above the soft palate, and tonsil). 

Large particles will be deposited in the upper respiratory tract (nares), medium-sized particles in the middle to upper respiratory tract (pharynx, trachea, bronchi).  Large and medium particles taken to pharynx by the mucociliary escalator. 

Small particles in the lower regions (small bronchioles and alveoli) will travel a different route and enter the pulmonary and then the systemic circulation mainly through the walls of the lower respiratory tract.

Other Sites

Replication will take place in the cells at the site of entry.

Secondary

Systemic

Virus from the primary sites of replication travel via the lymphatic system to sites of AMPLIFICATION in the keratinized stratified squamous epithelium of the mouth, muzzle, feet, and teats, and also to areas of damaged skin (eg, the knees and hocks of pigs kept on concrete).

Other organs such as the salivary glands, kidneys, liver, spleen, lymph nodes, lung and nasal mucosa, produce no more than negligible amounts of virus.

Young animals

Amplification also in the myocardium.


Table 5:  Viral loads in host tissues

internalloads

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Immunity

Immunity to FMD and protection from clinical disease is primarily mediated by circulating antibodies, and protection after recovery from infection or after immunization (active or passive) is closely correlated with the titres of circulating antibodies. Despite this, antibodies are ineffective in clearing virus from the pharynx of carrier ruminants and in preventing primary infection.

 


Carriers

~50% of cattle, sheep and goats will become carriers.  Cattle remain carriers <2 years (<1 year in sheep and goats).  Vaccinated ruminants following natural exposure to infectious virus may become carriers. Carriers may present a potential for virus maintenance. Viral excretion by carrier animals is intermittent and declines progressively.  Pre-disposing factors for the carrier state are the species of the animal and the strain of the virus.




Infection Time Course

FMD is an acute disease with a short incubation period and peak viremia occurs a few days after the onset of symptoms. The immune response is quick and effective as antibody titres peak a few days after peak viremia and viremia is cleared in about one week. However, some individuals can become long term carriers (Table 6).

Table 6: Time course of FMD virus infection in artiodactyls.

timecourse

1Depending on the infecting dose, susceptibility of the host, and strain of virus—in pigs that are highly stressed, it may be as short as 18 hr with some strains of FMD virus.  Mean = 3-5 days in housed direct contact cattle 2 days in intensive sheep

2Onset of clinical symptoms

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Created September 2010
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