The Carrier Conundrum; A Review of Recent Advances and Persistent Gaps Regarding the Carrier State of Foot-and-Mouth Disease Virus

Abstract

The existence of a prolonged, subclinical phase of foot-and-mouth disease virus (FMDV) infection in cattle was first recognized in the 1950s. Since then, the FMDV carrier state has been a subject of controversy amongst scientists and policymakers. A fundamental conundrum remains in the discordance between the detection of infectious FMDV in carriers and the apparent lack of contagiousness to in-contact animals. Although substantial progress has been made in elucidating the causal mechanisms of persistent FMDV infection, there are still critical knowledge gaps that need to be addressed in order to elucidate, predict, prevent, and model the risks associated with the carrier state. This is further complicated by the occurrence of a distinct form of neoteric subclinical infection, which is indistinguishable from the carrier state in field scenarios, but may have substantially different epidemiological properties. This review summarizes the current state of knowledge of the FMDV carrier state and identifies specific areas of research in need of further attention. Findings from experimental investigations of FMDV pathogenesis are discussed in relation to experience gained from field studies of foot-and-mouth disease.

Novel Foot-and-Mouth Disease Vaccine Platform: Formulations for Safe and DIVA-Compatible FMD Vaccines With Improved Potency

“…Small amounts of residual non-structural proteins may still be present in traditional FMD vaccines, resulting in some animals with false positive results, especially if multiple revaccinations are required due to the inherent short duration of immunity of conventional vaccines (20)(21)(22)(23)(24)(25)(26). Fourth, traditional FMD vaccines may not fully protect animals from persistent infection (10,(27)(28)(29)(30)(31)(32). In a 2016 study by Stenfeldt et al (30), it was shown that neoteric [new or temporally acute (32)] subclinical infection or persistence resulted following challenge in similar percentage of vaccinated and non-vaccinated animals (62% in vaccinated cattle, 67% in non-vaccinated cattle), indicating that vaccination with traditional vaccines has little impact on the carrier state (30,33,34).…”

“…Fourth, traditional FMD vaccines may not fully protect animals from persistent infection (10,(27)(28)(29)(30)(31)(32). In a 2016 study by Stenfeldt et al (30), it was shown that neoteric [new or temporally acute (32)] subclinical infection or persistence resulted following challenge in similar percentage of vaccinated and non-vaccinated animals (62% in vaccinated cattle, 67% in non-vaccinated cattle), indicating that vaccination with traditional vaccines has little impact on the carrier state (30,33,34).…”

Extinction Dynamics of the Foot-and-Mouth Disease Virus Carrier State Under Natural Conditions

“…Similarly, FMD-free regions must consider the existence of carriers when responding to incursions. Additionally, neoteric subclinical infection is indistinguishable from persistence under field conditions, and may pose a greater threat of transmission (5,42). Although the role of persistently infected animals in FMDV epidemiology remains controversial, persistently infected animals are known to carry virus in a form that is directly infectious to susceptible animals (15).…”

“…Although mortality is usually low, the high morbidity has an important economic impact due to decreased production, regional quarantine practices, and trade restrictions (3,4). The existence of prolonged asymptomatic persistent infection (carrier state) in ruminants has practical implications in FMDV-endemic regions that are distinct from management practices in regions striving to regain FMD-free status after an outbreak (5). Appropriate practices for management of carriers have not been established in either context.…”

Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease

“…Typical FMD clinical signs include fever and the appearance of vesicular lesions on the tongue, mouth, feet, and teats. Among ruminants that recovered from the disease, a relatively large number become asymptomatic virus carriers ( 2 , 3 ), although it is not clear what is the contribution of these carrier animals to disease transmission in nature ( 4 ). The World Organization for Animal Health (OIE) lists FMD as a reportable disease and therefore, by law, participating nations are required to inform the organization about all FMD outbreaks.…”