Lack of Transmission of Foot-and-Mouth Disease Virus From Persistently Infected Cattle to Naïve Cattle Under Field Conditions in Vietnam

Abstract

Foot-and-mouth disease (FMD), caused by FMD virus (FMDV; Aphthovirus, Picornaviridae), is a highly contagious and economically important disease of cloven-hoofed domestic livestock and wildlife species worldwide. Subsequent to the clinical phase of FMD, a large proportion of FMDV-infected ruminants become persistently infected carriers, defined by detection of FMDV in oropharyngeal fluid (OPF) samples 28 days or more post-infection. The goal of this prospective study was to characterize the FMD carrier state in cattle subsequent to natural infection under typical husbandry practices in Vietnam. Ten persistently infected cattle on eight farms in the Long An province in southern Vietnam were monitored by monthly screening of serum and oropharyngeal fluid samples for 12 months. To assess transmission from FMDV carriers, 16 naïve cattle were intentionally brought into direct contact with the persistently infected animals for 6 months, and were monitored by clinical and laboratory methods. The restricted mean duration of the FMD carrier state was 27.7 months, and the rate of decrease of the proportion of carrier animals was 0.03 per month. There was no evidence of transmission to naïve animals throughout the study period. Additionally, there was no detection of FMDV infection or seroconversion in three calves born to carrier animals during the study. The force of infection for carrier-to-contact transmission was 0 per month, with upper 95% confidence limit of 0.064 per month. Phylogenetic analysis of viral protein 1 (VP1) coding sequences obtained from carriers indicated that all viruses recovered in this study belonged to the O/ME-SA/PanAsia lineage, and grouped phylogenetically with temporally and geographically related viruses. Analysis of within-host evolution of FMDV, based upon full-length open reading frame sequences recovered from consecutive samples from one animal, indicated that most of the non-synonymous changes occurred in Lpro, VP2, and VP3 protein coding regions. This study suggests that the duration of FMDV persistent infection in cattle may be longer than previously recognized, but the risk of transmission is low. Additional novel insights are provided into within-host viral evolution under natural conditions in an endemic setting.

Foot‐and‐mouth disease virus transmission dynamics and persistence in a herd of vaccinated dairy cattle in India

“…The length of the carrier state has rarely been studied longitudinally in natural settings (Bertram et al ; Hayer et al., ). Our estimate that the carrier state would be terminated within 12 months in 86% of animals is shorter than what has been observed elsewhere in India (Hayer et al., ).…”

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

“…That study concluded that the average time to termination of the FMDV carrier state was 13 months, which defined a decrease in the proportion of carriers of 0.07 per month. A different field investigation following an outbreak of FMDV O/ME-SA/PanAsia in Vietnam concluded that the mean duration of the FMDV carrier state in 10 longitudinally sampled cattle was 27.7 months, with a monthly decrease in the proportion of carriers of 0.03% [109]. However, in the latter investigation, four of the 10 persistently infected cattle were still FMDV-positive in OPF at the study conclusion 32 months after the outbreak [109].…”

“…A limited number of studies have investigated changes in the FMDV genome in association with the establishment or maintenance of persistent infection. The most common conclusion of these studies have been that no specific mutations in the viral genome were consistently associated with persistent infection [41,67,[107][108][109]. Two separate investigations identified two different amino acid substitutions, VP1 Q172R and VP2 Y80H, which were consistently found in viruses recovered from persistent phase OPF samples within each of the investigations [110,111]; however, these findings were not corroborated by further studies.…”

“…However, while genomic variations observed during early infection reflected inherent variability present in the experimental inoculum, the accrual of novel mutations (not present in the infecting virus population) increased through later stages of infection [113]. Field studies have confirmed that changes to the FMDV genome, potentially affecting viral antigenicity, continue to occur during persistent infection [109,114]. There is, however, no evidence of such processes leading to the emergence of novel viral lineages [112].…”

Genetic and antigenic variation of foot-and-mouth disease virus during persistent infection in naturally infected cattle and Asian buffalo in India

“…Several studies have reported the antigenic and genetic variants of FMDV in the virus population recovered from persistently infected cattle and buffalo under experimental conditions (12, 25, 28-32) or under natural field conditions (14, 17, 21, 33-37). Although within-host genetic variation is common during persistent infection, no consistent genetic changes associated with persistent infection have been identified across studies.…”