Epidemiology and molecular characterization of circulating foot-and-mouth disease viruses of cattle and vaccine development in Bangladesh

Abstract

Foot-and Mouth Disease (FMD) is the major impediment of livestock production and trade worldwide. Currently there are seven FMDV serotypes, namely O, A, C, Asia-1 and Southern African Territories (SAT) 1-3, which infect cloven-hoofed animals. Due to huge local demand for meat, milk and sacrificing animals, livestock industries are rapidly growing in Bangladesh. Furthermore, there is a great prospect of healthy meat export in the Middle East. To control FMD, mass vaccination of cattle every six months with a trivalent FMD vaccine (locally produced or imported from type O, A, and Asia-1) is practiced in Bangladesh. But the current vaccination strategy does not provide sufficient protection of the herd. Although FMD vaccines need to be adequately matched to the field virus to ensure sufficient protection against a challenge with a field virus, but limited/ no step is adopted in Bangladesh so far to match vaccines before implementation. Moreover, FAO and OIE have proposed a time-frame strategy for the progressive control of FMD (PCP-FMD) road map and accordingly, Bangladesh will achieve stage 2 in 2016- provided that epidemiological studies, risk identification, and fixed riskbased control plan are completed. Unfortunately, due to poor/no reporting system by the appropriate authorities of FMD to the OIE, inappropriate vaccination, and poor veterinary service care, Bangladesh is placed at stage 0 (non-reporting stage). It is hypothesized that proper epidemiological studies and characterization of circulatory FMDVs to select the appropriate vaccine candidate in Bangladesh is the prime step to fix risk-based strategies to implement FMDcontrol program and achieve the PCP-FMD goal. To address the hypothesis, demographic data were collected using a questionnaire at field level infected farms; 283 FMDV-infected tissues were sampled from the 39 individual FMD outbreaks within May 2012 to April 2016 and characterization was done by PCR based identification of VP1 gene, isolation of viruses in BHK21 cell-culture, genome sequencing and analysis. The results demonstrated that the disease is endemic in Bangladesh. The husbandry systems, practiced in the investigated herds were intensive, semi-intensive with free animal movement or extensive. Demographic data revealed that the average morbidity rate of FMD was 53.8% with a higher incidence in indigenous cattle (55.7%) than that of crossbred cattle (49.2%). The highest number of outbreaks occurred in October (23.1%), followed by December (12.8%) and March or September (10.3%) which was decreased gradually up to mid-August, and in April (0%). Among seven serotypes distributed worldwide, FMDV type O, A and Asia-1 were circulating in Bangladesh and type O FMDV accounted for the most outbreaks (87%), followed by Asia-1 (8%) and A (5%) type virus. Phylogenetic analysis revealed a single lineage and topotype of FMDV serotypes O (Ind2001 lineage and O/ME-SA topotype), A (genotype VII of Asia topotype) and Asia-1 (genetic lineage C) circulatory in Bangladesh; and intrusion of FMDV occurred from India and vice versa. The complete genome of serotype O [KF985189] and A [KJ754939] were retrieved to be 8131 nucleotides (nt) and 8220 nt in length, respectively. Comparative genome analyses with reference sequence or vaccine strain revealed that within serotype O, 82 nt deletion in S-fragment and 43 nt insertion in 5'-UTR resulting introduction of an extra pseudoknot structure, whereas a 84 nt insertion within the 5′-UTR, a lengthened polyC tract was observed in serotype A. Within VP1, variation in B-C loop (40~60), G-H loop (133~160) in both serotypes and a 10 amino acid insertion (position 92~101) in 3A protein within serotype O were found. In summary-(i) three types of FMDVs are prevailing in Bangladesh (ii) intrusion of FMDV occurred from neighboring countries and (iii) inappropriate vaccination with mismatch virus strain caused vaccine failure. Finally, for effective control and prevention of FMD, proper epidemiology data, disease reporting, animals‟ movement quarantine, appropriate vaccination and strong political will of the government are required.