Sample records for hand-foot-and-mouth disease hfmd

  1. Hand, Foot, and Mouth Disease (HFMD)

    MedlinePlus

    ... gov . Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Hand, foot, and mouth disease is a common viral illness that usually affects infants and children younger than 5 years old. ...

  2. Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy.

    PubMed

    Aswathyraj, S; Arunkumar, G; Alidjinou, E K; Hober, D

    2016-10-01

    Hand, foot, and mouth disease (HFMD) is a contagious viral disease and mainly affects infants and young children. The main manifestations are fever, vesicular rashes on hand, feet and buttocks and ulcers in the oral mucosa. Usually, HFMD is self-limiting, but a small proportion of children may experience severe complications such as meningitis, encephalitis, acute flaccid paralysis and neurorespiratory syndrome. Historically, outbreaks of HFMD were mainly caused by two enteroviruses: the coxsackievirus A16 (CV-A16) and the enterovirus 71 (EV-A71). In the recent years, coxsackievirus A6 and coxsackievirus A10 have been widely associated with both sporadic cases and outbreaks of HFMD worldwide, particularly in India, South East Asia and Europe with an increased frequency of neurological complications as well as mortality. Currently, there is no pharmacological intervention or vaccine available for HFMD. A formalin-inactivated EV-A71 vaccine has completed clinical trial in several Asian countries. However, this vaccine cannot protect against other major emerging etiologies of HFMD such as CV-A16, CV-A6 and CV-A10. Therefore, the development of a globally representative multivalent HFMD vaccine could be the best strategy.

  3. [The early diagnosis value of EV 71 IgM class antibodies in the hand, foot and mouth disease].

    PubMed

    Zhao, Jing; Xu, Jun; Chen, Wei-wei; Li, Yong-li; Tang, Yan; Li, Jia; Wang, Hai-bin; Guo, Tong-sheng; Zhao, Min; Li, Bo-an; Mao, Yuan-li

    2011-04-01

    Assessment of detection of IgM antibodies for human enterovirus 71 (EV 71) in early diagnosis for the hand, foot and mouth disease (HFMD). The sera and throat swabs from 38 patients which were clinical diagnosis as HFMD, were continuous daily collected in our hospital in 2010. These specimens were detected by EV 71 IgM antibodies assay, real time RT-PCR methods for EV 71 and Enterovirus. Among 38 HFMD patients, the cumulative positive rates of EV 71 IgM antibodies were: 60.5% on day 1, 71.1% on day 2, 81.5% in the first 3-4 days, 92.1% on day 5, 92.1% on day 6, and the positive rate of nucleic acid detected by the real time RT-PCR for EV 71 and Enterovirus were 60.5%, 73.6%. The positive rate of EV 71 IgM antibodies in the hand, foot and mouth disease just can occur on day 1, and reach to peak on day 5, which can be used as one of indicators of early diagnosis of hand, foot and mouth disease.

  4. Economic costs and health-related quality of life for hand, foot and mouth disease (HFMD) patients in China

    PubMed Central

    Zheng, Yaming; Jit, Mark; Wu, Joseph T.; Yang, Juan; Leung, Kathy; Liao, Qiaohong; Yu, Hongjie

    2017-01-01

    Background Hand, foot and mouth disease (HFMD) is a common illness in China that mainly affects infants and children. The objective of this study is to assess the economic cost and health-related quality of life associated with HFMD in China. Method A telephone survey of caregivers were conducted in 31 provinces across China. Caregivers of laboratory-confirmed HFMD patients who were registered in the national HFMD enhanced surveillance database during 2012–2013 were invited to participate in the survey. Total costs included direct medical costs (outpatient care, inpatient care and self-medication), direct non-medical costs (transportation, nutrition, accommodation and nursery), and indirect costs for lost income associated with caregiving. Health utility weights elicited using EuroQol EQ-5D-3L and EQ-Visual Analogue Scale (VAS) were used to calculate associated loss in quality adjusted life years (QALYs). Results The subjects comprised 1136 mild outpatients, 1124 mild inpatients, 1170 severe cases and 61 fatal cases. The mean total costs for mild outpatients, mild inpatients, severe cases and fatal cases were $201 (95%CI $187, $215), $1072 (95%CI $999, $1144), $3051 (95%CI $2905, $3197) and $2819 (95%CI $2068, $3571) respectively. The mean QALY losses per HFMD episode for mild outpatients, mild inpatients and severe cases were 3.6 (95%CI 3.4, 3,9), 6.9 (95%CI 6.4, 7.4) and 13.7 (95%CI 12.9, 14.5) per 1000 persons. Cases who were diagnosed with EV-A71 infection and had longer duration of illness were associated with higher total cost and QALY loss. Conclusion HFMD poses a high economic and health burden in China. Our results provide economic and health utility data for cost-effectiveness analysis for HFMD vaccination in China. PMID:28934232

  5. Economic costs and health-related quality of life for hand, foot and mouth disease (HFMD) patients in China.

    PubMed

    Zheng, Yaming; Jit, Mark; Wu, Joseph T; Yang, Juan; Leung, Kathy; Liao, Qiaohong; Yu, Hongjie

    2017-01-01

    Hand, foot and mouth disease (HFMD) is a common illness in China that mainly affects infants and children. The objective of this study is to assess the economic cost and health-related quality of life associated with HFMD in China. A telephone survey of caregivers were conducted in 31 provinces across China. Caregivers of laboratory-confirmed HFMD patients who were registered in the national HFMD enhanced surveillance database during 2012-2013 were invited to participate in the survey. Total costs included direct medical costs (outpatient care, inpatient care and self-medication), direct non-medical costs (transportation, nutrition, accommodation and nursery), and indirect costs for lost income associated with caregiving. Health utility weights elicited using EuroQol EQ-5D-3L and EQ-Visual Analogue Scale (VAS) were used to calculate associated loss in quality adjusted life years (QALYs). The subjects comprised 1136 mild outpatients, 1124 mild inpatients, 1170 severe cases and 61 fatal cases. The mean total costs for mild outpatients, mild inpatients, severe cases and fatal cases were $201 (95%CI $187, $215), $1072 (95%CI $999, $1144), $3051 (95%CI $2905, $3197) and $2819 (95%CI $2068, $3571) respectively. The mean QALY losses per HFMD episode for mild outpatients, mild inpatients and severe cases were 3.6 (95%CI 3.4, 3,9), 6.9 (95%CI 6.4, 7.4) and 13.7 (95%CI 12.9, 14.5) per 1000 persons. Cases who were diagnosed with EV-A71 infection and had longer duration of illness were associated with higher total cost and QALY loss. HFMD poses a high economic and health burden in China. Our results provide economic and health utility data for cost-effectiveness analysis for HFMD vaccination in China.

  6. Virological investigation of hand, foot, and mouth disease in a tertiary care center in South India.

    PubMed

    Vijayaraghavan, Pavithra M; Chandy, Sara; Selvaraj, Kavitha; Pulimood, Susanne; Abraham, Asha M

    2012-07-01

    Hand, foot, and mouth disease (HFMD) remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. The aim of this study was to characterize HFMD-related isolates by molecular techniques. Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC), Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot) were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD) cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE) in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR) and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST) algorithm. The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP). Of the 30 suspected HFMD cases, only 17 (57%) were laboratory confirmed and Coxsackievirus A16 (CVA16) was identified as the etiological agent in all these cases. Coxsackievirus A16 (CVA16) was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the epidemiology of HFMD in India.

  7. Coxsackievirus A6 and enterovirus 71 causing hand, foot and mouth disease in Cuba, 2011-2013.

    PubMed

    Fonseca, Magilé C; Sarmiento, Luis; Resik, Sonia; Martínez, Yenisleidys; Hung, Lai Heng; Morier, Luis; Piñón, Alexander; Valdéz, Odalys; Kourí, Vivian; González, Guelsys

    2014-09-01

    Hand, foot and mouth disease (HFMD) is usually caused by coxsackievirus A16 or enterovirus 71 (EV71). Between 2011 and 2013, HFMD cases were reported from different Cuban provinces. A total of 42 clinical specimens were obtained from 23 patients. Detection, identification and phylogenetic analysis of enterovirus-associated HFMD were carried out by virus isolation, specific enterovirus PCR and partial VP1 sequences. HEV was detected in 11 HFMD cases. Emerging genetic variants of coxsackievirus A6 and EV71 were identified as the causative agents of the Cuban HFMD cases.

  8. Hand, foot and mouth disease: spatiotemporal transmission and climate.

    PubMed

    Wang, Jin-feng; Guo, Yan-Sha; Christakos, George; Yang, Wei-Zhong; Liao, Yi-Lan; Li, Zhong-Jie; Li, Xiao-Zhou; Lai, Sheng-Jie; Chen, Hong-Yan

    2011-04-05

    The Hand-Foot-Mouth Disease (HFMD) is the most common infectious disease in China, its total incidence being around 500,000~1,000,000 cases per year. The composite space-time disease variation is the result of underlining attribute mechanisms that could provide clues about the physiologic and demographic determinants of disease transmission and also guide the appropriate allocation of medical resources to control the disease. HFMD cases were aggregated into 1456 counties and during a period of 11 months. Suspected climate attributes to HFMD were recorded monthly at 674 stations throughout the country and subsequently interpolated within 1456 × 11 cells across space-time (same as the number of HFMD cases) using the Bayesian Maximum Entropy (BME) method while taking into consideration the relevant uncertainty sources. The dimensionalities of the two datasets together with the integrated dataset combining the two previous ones are very high when the topologies of the space-time relationships between cells are taken into account. Using a self-organizing map (SOM) algorithm the dataset dimensionality was effectively reduced into 2 dimensions, while the spatiotemporal attribute structure was maintained. 16 types of spatiotemporal HFMD transmission were identified, and 3-4 high spatial incidence clusters of the HFMD types were found throughout China, which are basically within the scope of the monthly climate (precipitation) types. HFMD propagates in a composite space-time domain rather than showing a purely spatial and purely temporal variation. There is a clear relationship between HFMD occurrence and climate. HFMD cases are geographically clustered and closely linked to the monthly precipitation types of the region. The occurrence of the former depends on the later.

  9. Is a multivalent hand, foot, and mouth disease vaccine feasible?

    PubMed Central

    Klein, Michel; Chong, Pele

    2015-01-01

    Enterovirus A infections are the primary cause of hand, foot and mouth disease (HFMD) in infants and young children. Although enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the predominant causes of HFMD epidemics worldwide, EV-A71 has emerged as a major neurovirulent virus responsible for severe neurological complications and fatal outcomes. HFMD is a serious health threat and economic burden across the Asia-Pacific region. Inactivated EV-A71 vaccines have elicited protection against EV-A71 but not against CV-A16 infections in large efficacy trials. The current development of a bivalent inactivated EV-A71/CV-A16 vaccine is the next step toward that of multivalent HFMD vaccines. These vaccines should ultimately include other prevalent pathogenic coxsackieviruses A (CV-A6 and CV-A10), coxsackieviruses B (B3 and B5) and echovirus 30 that often co-circulate during HFMD epidemics and can cause severe HFMD, aseptic meningitis and acute viral myocarditis. The prospect and challenges for the development of such multivalent vaccines are discussed. PMID:26009802

  10. Dermatological spectrum of hand, foot and mouth disease from classical to generalized exanthema.

    PubMed

    Hubiche, Thomas; Schuffenecker, Isabelle; Boralevi, Franck; Léauté-Labrèze, Christine; Bornebusch, Laure; Chiaverini, Christine; Phan, Alice; Maruani, Annabel; Miquel, Juliette; Lafon, Marie-Edith; Lina, Bruno; Del Giudice, Pascal

    2014-04-01

    Hand, foot and mouth disease (HFMD) is classically defined as a childhood fever accompanied by a rash with vesicles or erosions of the oral mucosa, hands, feet and sometimes the buttocks. Severe neurological complications are associated with enterovirus 71 outbreaks in Asia. Recently, it has been suggested that HFMD is related to coxsackie virus A6 (CV-A6) when there is an atypical rash. The objective of the study is to determine the dermatological pattern of HFMD and to identify the virus serotypes associated with a specific dermatological pattern. A prospective, cross-sectional study was conducted in 7 pediatric dermatology units in France from March 2010 to February 2012. All children with clinically suspected diagnosis of HFMD were included. Clinical data were collected and swabs from the nasopharynx and vesicles were taken for reverse transcription polymerase chain reaction and genotyping. Only children with confirmed HFMD--defined by clinical diagnosis of HFMD and positive enterovirus polymerase chain reaction results--were included for analysis. One hundred and four children consulted for suspected HFMD, including 89 (mean age: 25.7 months; sex ratio M/F 1.54) with confirmed HFMD. Seventy-eight (87.6%) had skin lesions on sites other than hand, feet and mouth. Thirty-seven (41.5%) had 5 or more anatomical sites involved (hand, feet and mouth, buttocks, legs, arms and trunk) considered as widespread exanthema. Widespread vesicular exanthema was observed with both CV-A6 and CV-A16. Peri-oral rash was associated with CV-A6 (P < 0.001). HFMD has a clinical spectrum ranging from classical to generalized vesicular exanthema. Generalized and atypical exanthema were observed with both CV-A6 and CV-A16 infections. CV-A6 is associated with peri-oral rash.

  11. Temporal and spatial mapping of hand, foot and mouth disease in Sarawak, Malaysia.

    PubMed

    Sham, Noraishah M; Krishnarajah, Isthrinayagy; Ibrahim, Noor Akma; Lye, Munn-Sann

    2014-05-01

    Hand, foot and mouth disease (HFMD) is endemic in Sarawak, Malaysia. In this study, a geographical information system (GIS) was used to investigate the relationship between the reported HFMD cases and the spatial patterns in 11 districts of Sarawak from 2006 to 2012. Within this 7-years period, the highest number of reported HFMD cases occurred in 2006, followed by 2012, 2008, 2009, 2007, 2010 and 2011, in descending order. However, while there was no significant distribution pattern or clustering in the first part of the study period (2006 to 2011) based on Moran's I statistic, spatial autocorrelation (P = 0.068) was observed in 2012.

  12. Characterization of severe hand, foot, and mouth disease in Shenzhen, China, 2009-2013.

    PubMed

    Huang, Yun; Zhou, Yuanping; Lu, Hong; Yang, Hong; Feng, Qianjin; Dai, Yingchun; Chen, Long; Yu, Shouyi; Yao, Xiangjie; Zhang, Hailong; Jiang, Ming; Wang, Yujie; Han, Ning; Hu, Guifang; He, Yaqing

    2015-09-01

    Hand, foot, and mouth disease (HFMD) is caused by human enteroviruses, especially by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Patients infected with different enteroviruses show varied clinical symptoms. The aim of this study was to determine whether the etiological spectrum of mild and severe HFMD changed, and the association between pathogens and clinical features. From 2009 to 2013, a total of 2,299 stool or rectal specimens were collected with corresponding patient data. A dynamic view of the etiological spectrum of mild and severe HFMD in Shenzhen city of China was provided. EV71 accounted for the majority proportion of severe HFMD cases and fatalities during 2009-2013. CA16 and EV71 were gradually replaced by coxsackievirus A6 (CA6) as the most common serotype for mild HFMD since 2010. Myoclonic jerk and vomiting were the most frequent severe symptoms. Nervous system complications, including aseptic encephalitis and aseptic meningitis were observed mainly in patients infected by EV71. Among EV71, CA16, CA6, and CA10 infection, fever and pharyngalgia were more likely to develop, vesicles on the hand, foot, elbow, knee and buttock were less likely to develop in patients infected with CA10. Vesicles on the mouth more frequently occurred in the patients with CA6, but less in the patient with EV71. Associations between diverse enterovirus serotypes and various clinical features were discovered in the present study, which may offer further insight into early detection, diagnosis and treatment of HFMD. © 2015 Wiley Periodicals, Inc.

  13. Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam

    PubMed Central

    Anh, Nguyen To; Nhu, Le Nguyen Truc; Van, Hoang Minh Tu; Hong, Nguyen Thi Thu; Thanh, Tran Tan; Hang, Vu Thi Ty; Ny, Nguyen Thi Han; Nguyet, Lam Anh; Phuong, Tran Thi Lan; Nhan, Le Nguyen Thanh; Hung, Nguyen Thanh; Khanh, Truong Huu; Tuan, Ha Manh; Viet, Ho Lu; Nam, Nguyen Tran; Viet, Do Chau; Qui, Phan Tu; Wills, Bridget; Sabanathan, Sarawathy; Chau, Nguyen Van Vinh; Thwaites, Louise; Rogier van Doorn, H.; Thwaites, Guy; Rabaa, Maia A.

    2018-01-01

    Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011–2015. Of these patients, 93 (18%) had severe HFMD. Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare. Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6–associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies. PMID:29553326

  14. Monitoring hand, foot and mouth disease by combining search engine query data and meteorological factors.

    PubMed

    Huang, Da-Cang; Wang, Jin-Feng

    2018-01-15

    Hand, foot and mouth disease (HFMD) has been recognized as a significant public health threat and poses a tremendous challenge to disease control departments. To date, the relationship between meteorological factors and HFMD has been documented, and public interest of disease has been proven to be trackable from the Internet. However, no study has explored the combination of these two factors in the monitoring of HFMD. Therefore, the main aim of this study was to develop an effective monitoring model of HFMD in Guangzhou, China by utilizing historical HFMD cases, Internet-based search engine query data and meteorological factors. To this end, a case study was conducted in Guangzhou, using a network-based generalized additive model (GAM) including all factors related to HFMD. Three other models were also constructed using some of the variables for comparison. The results suggested that the model showed the best estimating ability when considering all of the related factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A literature review and case report of hand, foot and mouth disease in an immunocompetent adult.

    PubMed

    Omaña-Cepeda, Carlos; Martínez-Valverde, Andrea; del Mar Sabater-Recolons, María; Jané-Salas, Enric; Marí-Roig, Antonio; López-López, José

    2016-03-15

    To report an uncommon case of hand, foot and mouth disease, (HFMD) in an immunocompetent adult; a highly infectious disease, characterized by the appearance of vesicles on the mouth, hands and feet, associated with coxsackieviruses and enteroviruses; including a literature review. A 23 year Caucasian male with no medical or surgical history, no allergies, was not taking any medication and smoked ten cigarettes a day, suffering from discomfort in the oral cavity; itching, burning and pain when swallowing associated with small erythematous lesions located on the hard palate, and small ulcers in tonsillar pillars and right buccal mucosa. Mild fever of 37.8 °C and general malaise. The patient reported he had had contact with a child diagnosed with HFMD. From his background and symptoms, the patient was diagnosed with HFMD. Following symptomatic treatment, the symptoms remitted in 7 days. A literature review in MEDLINE (PubMed). The inclusion criteria were for studies on humans over the last 5 years, using the keywords HFMD. We found 925 articles, which were subsequently reduced to 52 documents after applying the inclusion criteria. Maculopapular lesions were found on hands and feet. Dentists may have a key role diagnosing the disease. A surveillance system to predict future outbreaks, encourage early diagnosis, put appropriate public health measures in place and research vaccine development is vitally important in order to control the disease.

  16. A novel Enterovirus 96 circulating in China causes hand, foot, and mouth disease.

    PubMed

    Xu, Yi; Sun, Yisuo; Ma, Jinmin; Zhou, Shuru; Fang, Wei; Ye, Jiawei; Tan, Limei; Ji, Jingkai; Luo, Dan; Li, Liqiang; Li, Jiandong; Fang, Chunxiao; Pei, Na; Shi, Shuo; Liu, Xin; Jiang, Hui; Gong, Sitang; Xu, Xun

    2017-06-01

    Enterovirus 96 (EV-96) is a recently described member of the species Enterovirus C and is associated with paralysis and myelitis. In this study, using metagenomic sequencing, we identified a new enterovirus 96 strain (EV-96-SZ/GD/CHN/2014) as the sole pathogen causing hand, foot, and mouth disease (HFMD). A genomic comparison showed that EV-96-SZ/GD/CHN/2014 is most similar to the EV-96-05517 strain (85% identity), which has also been detected in Guangdong Province. This is the first time that metagenomic sequencing has been used to identify an EV-96 strain shown to be associated with HFMD.

  17. Coxsackievirus A6: a new emerging pathogen causing hand, foot and mouth disease outbreaks worldwide.

    PubMed

    Bian, Lianlian; Wang, Yiping; Yao, Xin; Mao, Qunying; Xu, Miao; Liang, Zhenglun

    2015-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the predominant pathogens causing outbreaks of hand, foot and mouth disease (HFMD) worldwide. Other human enterovirus A (HEV-A) serotypes tend to cause only sporadic HFMD cases. However, since a HFMD caused by coxsackievirus A6 broke out in Finland in 2008, CA6 has been identified as the responsible pathogen for a series of HFMD outbreaks in Europe, North America and Asia. Because of the severity of the clinical manifestations and the underestimated public health burden, the epidemic of CA6-associated HFMD presents a new challenge to the control of HFMD. This article reviewed the epidemic characteristics, molecular epidemiology, clinical features and laboratory diagnosis of CA6 infection. The genetic evolution of CA6 strains associated with HFMD was also analyzed. It indicated that the development of a multivalent vaccine combining EV71, CA16 and CA6 is an urgent necessity to control HFMD.

  18. [The etiological and clinical characteristics of hospitalized children with hand, foot and mouth disease in Beijing in 2013].

    PubMed

    Gu, Hongyan; Liu, Zhida; Zhang, Ling; Chen, Yong; Yang, Siyuan; Zhang, Weiyan; Li, Xingwang

    2015-06-01

    To investigate the etiology of hand, foot and mouth disease (HFMD) in Beijing during 2013, and study the clinical characteristics of HFMD caused by the main serotypes of enterovirus in the study. Clinical data and 128 stool samples were collected from 128 hospitalized children with HFMD in Beijing Ditan Hospital during 2013. One step RT-PCR method was used for enterovirus genotyping to investigate the etiology of HFMD. Clinical characteristics of HFMD caused by the main serotypes of enterovirus were analyzed. And VP1 segments of the main virus were amplified to construct phylogenetic tree for the phylogenetic analysis. A total of 128 hospitalized children with HFMD were included. HFMD was more likely developed in children under 2 years of age (81.6%, 102/125); 11 different enteroviruses were genotyped, with a total enterovirus positive rate of 76.6% (98/128); the positive rate of coxsackievirus A6 (CA6), 43.0% ( 55/128), was the highest, followed by enterovirus 71 (EV71), accounting for 14.8% (19/128). HFMD caused by CA6 was atypical, the rashes of which involved the perioral, trunk, limbs, face and neck (47%, 26/55), besides the common parts. Of the 55 cases caused by CA6, 6 children had clinical manifestations of nervous system involvement, one of whom even displayed type 2 respiratory failure. Mental status change more likely to occur in EV71-infected children than in CA6-infected ones (42% (8/19) vs. 11% (6/55) (χ(2)=7.041, P=0.008)); 13 children displayed onychomadesis, including 12 CA6 cases (23%, 12/53) and 1 CA10 cases (17%, 1/6), in the convalescence of hand, foot and mouth disease, and the correlation between onychomadesis and CA6 infection was significant (χ(2)=9.297, P=0.002). Phylogenetic analysis of 33 CA6 VP1 showed that the CA6 isolates of this study were highly similar to that of Taiwan and the nucleotide similarity was 95.91%-98.89%. CA6 was the major pathogen of hospitalized children with hand, foot and mouth disease in Beijing during 2013

  19. The Epidemiology of Hand, Foot and Mouth Disease in Asia

    PubMed Central

    Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y.; Tan, Chong Yew; Chen, Mark IC; Horby, Peter

    2016-01-01

    Context: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). Objective: This study reports a systematic review of the epidemiology of HFMD in Asia. Data Sources: PubMed, Web of Science and Google Scholar were searched up to December 2014. Study Selection: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. Data Extraction: Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. Results: HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies. The uncertainty in these estimates inhibits their use for further analysis. Limitations: Diversity of study designs complicates attempts to identify features of HFMD epidemiology. Conclusions: Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps. PMID:27273688

  20. Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China.

    PubMed

    Zhao, Jijun; Li, Xinmin

    2016-01-01

    Severe outbreaks of hand, foot and mouth disease (HFMD) have occurred in China for decades. Our understanding of the HFMD transmission process and its determinants is still limited. In this paper, factors that affect the local variation of HFMD transmission process were studied. Three classes of factors, including meteorological, demographic and public health intervention factors, were carefully selected and their effects on HFMD transmission were investigated with Pearson's correlation coefficient and multiple linear regression models. The determining factors for the variation of HFMD transmission were different for the southeastern and the northwestern regions of China. In the northwest, fadeouts occurred yearly, and the average age at infection and the fadeout were negatively correlated with the population density. In the southeast, HFMD transmission was governed by the combined effects of the birth rate, the relative humidity and the interaction of the Health System Performance and the log of the population density. When the Health System Performance was low, HFMD transmission increased with the population density, but when the Health System Performance was high, the better health performance counteracted the transmission increase due to the higher population density.

  1. Determinants of the Transmission Variation of Hand, Foot and Mouth Disease in China

    PubMed Central

    Li, Xinmin

    2016-01-01

    Severe outbreaks of hand, foot and mouth disease (HFMD) have occurred in China for decades. Our understanding of the HFMD transmission process and its determinants is still limited. In this paper, factors that affect the local variation of HFMD transmission process were studied. Three classes of factors, including meteorological, demographic and public health intervention factors, were carefully selected and their effects on HFMD transmission were investigated with Pearson’s correlation coefficient and multiple linear regression models. The determining factors for the variation of HFMD transmission were different for the southeastern and the northwestern regions of China. In the northwest, fadeouts occurred yearly, and the average age at infection and the fadeout were negatively correlated with the population density. In the southeast, HFMD transmission was governed by the combined effects of the birth rate, the relative humidity and the interaction of the Health System Performance and the log of the population density. When the Health System Performance was low, HFMD transmission increased with the population density, but when the Health System Performance was high, the better health performance counteracted the transmission increase due to the higher population density. PMID:27701445

  2. The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing.

    PubMed

    Dong, Weihua; Li, Xian'en; Yang, Peng; Liao, Hua; Wang, Xiaoli; Wang, Quanyi

    2016-01-12

    The morbidity and mortality of hand, foot and mouth disease (HFMD) are increasing in Beijing, China. Previous studies have indicated an association between incidents of HFMD and weather factors. However, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (EV71) and Coxsackie virus A16 (CV-A16) viruses are not well documented. We analysed 84,502 HFMD cases from 2008 to 2011 in Beijing to explore the seasonal influence of weather factors (average temperature [AT], average relative humidity [ARH], total precipitation [TP] and average wind speed [AWS]) on incidents of HFMD by using a geographically weighted regression (GWR) model. The results indicated that weather factors differ significantly in their influence on HFMD depending on the season. AT had the greatest effect among the four weather factors, and while the influence of AT and AWS was greater in the summer than in the winter, the influence of TP was positive in the summer and negative in the winter. ARH was negatively correlated with HFMD. Also, we observed more EV71-associated cases than CV-A16 but there is no convincing evidence to show significant differences between the influences of the weather factors on EV71 and CV-A16.

  3. The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing

    NASA Astrophysics Data System (ADS)

    Dong, Weihua; Li, Xian'En; Yang, Peng; Liao, Hua; Wang, Xiaoli; Wang, Quanyi

    2016-01-01

    The morbidity and mortality of hand, foot and mouth disease (HFMD) are increasing in Beijing, China. Previous studies have indicated an association between incidents of HFMD and weather factors. However, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (EV71) and Coxsackie virus A16 (CV-A16) viruses are not well documented. We analysed 84,502 HFMD cases from 2008 to 2011 in Beijing to explore the seasonal influence of weather factors (average temperature [AT], average relative humidity [ARH], total precipitation [TP] and average wind speed [AWS]) on incidents of HFMD by using a geographically weighted regression (GWR) model. The results indicated that weather factors differ significantly in their influence on HFMD depending on the season. AT had the greatest effect among the four weather factors, and while the influence of AT and AWS was greater in the summer than in the winter, the influence of TP was positive in the summer and negative in the winter. ARH was negatively correlated with HFMD. Also, we observed more EV71-associated cases than CV-A16 but there is no convincing evidence to show significant differences between the influences of the weather factors on EV71 and CV-A16.

  4. The Effects of Weather Factors on Hand, Foot and Mouth Disease in Beijing

    PubMed Central

    Dong, Weihua; Li, Xian’en; Yang, Peng; Liao, Hua; Wang, Xiaoli; Wang, Quanyi

    2016-01-01

    The morbidity and mortality of hand, foot and mouth disease (HFMD) are increasing in Beijing, China. Previous studies have indicated an association between incidents of HFMD and weather factors. However, the seasonal influence of these factors on the disease is not yet understood, and their relationship with the enterovirus 71 (EV71) and Coxsackie virus A16 (CV-A16) viruses are not well documented. We analysed 84,502 HFMD cases from 2008 to 2011 in Beijing to explore the seasonal influence of weather factors (average temperature [AT], average relative humidity [ARH], total precipitation [TP] and average wind speed [AWS]) on incidents of HFMD by using a geographically weighted regression (GWR) model. The results indicated that weather factors differ significantly in their influence on HFMD depending on the season. AT had the greatest effect among the four weather factors, and while the influence of AT and AWS was greater in the summer than in the winter, the influence of TP was positive in the summer and negative in the winter. ARH was negatively correlated with HFMD. Also, we observed more EV71-associated cases than CV-A16 but there is no convincing evidence to show significant differences between the influences of the weather factors on EV71 and CV-A16. PMID:26755102

  5. Statistical monitoring of the hand, foot and mouth disease in China.

    PubMed

    Zhang, Jingnan; Kang, Yicheng; Yang, Yang; Qiu, Peihua

    2015-09-01

    In a period starting around 2007, the Hand, Foot, and Mouth Disease (HFMD) became wide-spreading in China, and the Chinese public health was seriously threatened. To prevent the outbreak of infectious diseases like HFMD, effective disease surveillance systems would be especially helpful to give signals of disease outbreaks as early as possible. Statistical process control (SPC) charts provide a major statistical tool in industrial quality control for detecting product defectives in a timely manner. In recent years, SPC charts have been used for disease surveillance. However, disease surveillance data often have much more complicated structures, compared to the data collected from industrial production lines. Major challenges, including lack of in-control data, complex seasonal effects, and spatio-temporal correlations, make the surveillance data difficult to handle. In this article, we propose a three-step procedure for analyzing disease surveillance data, and our procedure is demonstrated using the HFMD data collected during 2008-2009 in China. Our method uses nonparametric longitudinal data and time series analysis methods to eliminate the possible impact of seasonality and temporal correlation before the disease incidence data are sequentially monitored by a SPC chart. At both national and provincial levels, our proposed method can effectively detect the increasing trend of disease incidence rate before the disease becomes wide-spreading. © 2015, The International Biometric Society.

  6. Hand-foot-mouth disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000965.htm Hand-foot-mouth disease To use the sharing features ... Duplication for commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map ...

  7. Using an autologistic regression model to identify spatial risk factors and spatial risk patterns of hand, foot and mouth disease (HFMD) in Mainland China

    PubMed Central

    2014-01-01

    Background There have been large-scale outbreaks of hand, foot and mouth disease (HFMD) in Mainland China over the last decade. These events varied greatly across the country. It is necessary to identify the spatial risk factors and spatial distribution patterns of HFMD for public health control and prevention. Climate risk factors associated with HFMD occurrence have been recognized. However, few studies discussed the socio-economic determinants of HFMD risk at a space scale. Methods HFMD records in Mainland China in May 2008 were collected. Both climate and socio-economic factors were selected as potential risk exposures of HFMD. Odds ratio (OR) was used to identify the spatial risk factors. A spatial autologistic regression model was employed to get OR values of each exposures and model the spatial distribution patterns of HFMD risk. Results Results showed that both climate and socio-economic variables were spatial risk factors for HFMD transmission in Mainland China. The statistically significant risk factors are monthly average precipitation (OR = 1.4354), monthly average temperature (OR = 1.379), monthly average wind speed (OR = 1.186), the number of industrial enterprises above designated size (OR = 17.699), the population density (OR = 1.953), and the proportion of student population (OR = 1.286). The spatial autologistic regression model has a good goodness of fit (ROC = 0.817) and prediction accuracy (Correct ratio = 78.45%) of HFMD occurrence. The autologistic regression model also reduces the contribution of the residual term in the ordinary logistic regression model significantly, from 17.25 to 1.25 for the odds ratio. Based on the prediction results of the spatial model, we obtained a map of the probability of HFMD occurrence that shows the spatial distribution pattern and local epidemic risk over Mainland China. Conclusions The autologistic regression model was used to identify spatial risk factors and model spatial risk patterns of HFMD. HFMD

  8. Estimating the incubation period of hand, foot and mouth disease for children in different age groups.

    PubMed

    Yang, Zhongzhou; Zhang, Qiqi; Cowling, Benjamin J; Lau, Eric H Y

    2017-11-28

    Hand, foot and mouth disease (HFMD) is a childhood disease causing large outbreaks frequently in Asia and occasionally in Europe and the US. The incubation period of HFMD was typically described as about 3-7 days but empirical evidence is lacking. In this study, we estimated the incubation period of HFMD from school outbreaks in Hong Kong, utilizing information on symptom onset and sick absence dates of students diagnosed with HFMD. A total of 99 HFMD cases from 12 schools were selected for analysis. We fitted parametric models accounting for interval censoring. Based on the best-fitted distributions, the estimated median incubation periods were 4.4 (95% CI 3.8-5.1) days, 4.7 (95% CI 4.5-5.1) days and 5.7 (95% CI 4.6-7.0) days for children in kindergartens, primary schools and secondary schools respectively. From the fitted distribution, the estimated incubation periods can be longer than 10 days for 8.8% and 23.2% of the HFMD cases in kindergarten and secondary schools respectively. Our results show that the incubation period of HFMD for secondary schools students can be longer than the ranges commonly described. An extended period of enhanced personal hygiene practice and disinfection of the environment may be needed to control outbreaks.

  9. Is high relative humidity associated with childhood hand, foot, and mouth disease in rural and urban areas?

    PubMed

    Yang, H; Wu, J; Cheng, J; Wang, X; Wen, L; Li, K; Su, H

    2017-01-01

    To examine the relationship between relative humidity and childhood hand, foot and mouth disease (HFMD) in Hefei, China, and to explore whether the effect is different between urban and rural areas. Retrospective ecological study. A Poisson generalized linear model combined with a distributed lag non-linear model was used to examine the relationship between relative humidity and childhood HFMD in a temperate Chinese city during 2010-2012. The effect of relative humidity on childhood HFMD increased above a humidity of 84%, with a 0.34% (95% CI: 0.23%-0.45%) increase of childhood HFMD per 1% increment of relative humidity. Notably, urban children, male children, and children aged 0-4 years appeared to be more vulnerable to the effect of relative humidity on HFMD. This article study indicates that high relative humidity may trigger childhood HFMD in a temperate area, Hefei, particularly for those who are young and from urban areas. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Detection and characterization of viruses causing hand, foot and mouth disease from children in Seri Kembangan, Malaysia.

    PubMed

    Ling, Beh Poay; Jalilian, Farid Azizi; Harmal, Nabil Saad; Yubbu, Putri; Sekawi, Zamberi

    2014-12-01

    Hand, foot and mouth disease (HFMD) is a common viral infection among infants and children. The major causative agents of HFMD are enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). Recently, coxsackievirus A6 (CVA6) infections were reported in neighboring countries. Infected infants and children may present with fever, mouth/throat ulcers, rashes and vesicles on hands and feet. Moreover, EV71 infections might cause fatal neurological complications. Since 1997, EV71 caused fatalities in Sarawak and Peninsula Malaysia. The purpose of this study was to identify and classify the viruses which detected from the patients who presenting clinical signs and symptoms of HFMD in Seri Kembangan, Malaysia. From December 2012 until July 2013, a total of 28 specimens were collected from patients with clinical case definitions of HFMD. The HFMD viruses were detected by using semi-nested reverse transcription polymerase chain reaction (snRT-PCR). The positive snRT-PCR products were sequenced and phylogenetic analyses of the viruses were performed. 12 of 28 specimens (42.9%) were positive in snRT-PCR, seven are CVA6 (58.3%), two CVA16 (16.7%) and three EV71 (25%). Based on phylogenetic analysis studies, EV71 strains were identified as sub-genotype B5; CVA16 strains classified into sub-genotype B2b and B2c; CVA6 strains closely related to strains in Taiwan and Japan. In this study, HFMD in Seri Kembangan were caused by different types of Enterovirus, which were EV71, CVA6 and CVA16.

  11. The influence of temperature and humidity on the incidence of hand, foot, and mouth disease in Japan.

    PubMed

    Onozuka, Daisuke; Hashizume, Masahiro

    2011-12-01

    The increasing evidence for rapid global climate change has highlighted the need for investigations examining the relationship between weather variability and infectious diseases. However, the impact of weather fluctuations on hand, foot, and mouth disease (HFMD), which primarily affects children, is not well understood. We acquired data related to cases of HFMD and weather parameters of temperature and humidity in Fukuoka, Japan between 2000 and 2010, and used time-series analyses to assess the possible relationship of weather variability with pediatric HFMD cases, adjusting for seasonal and interannual variations. Our analysis revealed that the weekly number of HFMD cases increased by 11.2% (95% CI: 3.2-19.8) for every 1°C increase in average temperature and by 4.7% (95% CI: 2.4-7.2) for every 1% increase in relative humidity. Notably, the effects of temperature and humidity on HFMD infection were most significant in children under the age of 10 years. Our study provides quantitative evidence that the number of HFMD cases increased significantly with increasing average temperature and relative humidity, and suggests that preventive measures for limiting the spread of HFMD, particularly in younger children, should be considered during extended periods of high temperature and humidity. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Nonlinear and Interactive Effects of Temperature and Humidity on Childhood Hand, Foot and Mouth Disease in Hefei, China.

    PubMed

    Wu, Jinju; Cheng, Jian; Xu, Zhiwei; Zhao, Kefu; Zhao, Desheng; Xie, Mingyu; Yang, Huihui; Wen, Liying; Li, Kesheng; Su, Hong

    2016-10-01

    Hand, foot and mouth disease (HFMD) is one of the major infectious diseases among children and remains a health threat, especially among Asian countries. Many epidemiologic studies suggested significant association of air temperature and humidity with childhood HFMD; however, evidence on the temperature effects on childhood HFMD in temperate cities is limited, and the interactive effects of temperature and humidity have not been studied yet. Daily counts of HFMD in children younger than 15 years of age and daily meteorologic variables during 2010 to 2012 were obtained in Hefei, China. A distributed lag nonlinear model was applied to estimate the potential nonlinear association between temperature and childhood HFMD. The interactive effects between temperature and humidity on childhood HFMD were also investigated. Temperature rise was associated with higher risk of childhood HFMD. Within the incubation period of HFMD, temperature rise appeared to have the acute effects on childhood HFMD, and a 5°C increase of temperature at lag 0-6 days was associated with 24.8% (95% confidence interval: 11.94%-39.10%) increase of childhood HFMD. Females and children of 0-4 years of agewere more vulnerable to temperature rise. Notably, there were obvious combined effects between temperature and humidity on childhood HFMD-the risk of childhood HFMD elevated at higher temperature and humidity level. This study provides evidence that temperature and humidity may jointly affect childhood HFMD, and such interactive impact needs to be considered when evaluating the temperature-childhood HFMD relationship.

  13. Quantifying the influence of temperature on hand, foot and mouth disease incidence in Wuhan, Central China.

    PubMed

    Huang, Jiao; Chen, Shi; Wu, Yang; Tong, Yeqing; Wang, Lei; Zhu, Min; Hu, Shuhua; Guan, Xuhua; Wei, Sheng

    2018-01-31

    Hand, foot and mouth disease (HFMD) is a substantial burden throughout Asia, but the effects of temperature pattern on HFMD risk are inconsistent. To quantify the effect of temperature on HFMD incidence, Wuhan was chosen as the study site because of its high temperature variability and high HFMD incidence. Daily series of HFMD counts and meteorological variables during 2010-2015 were obtained. Distributed lag non-linear models were applied to characterize the temperature-HFMD relationship and to assess its variability across different ages, genders, and types of child care. Totally, 80,219 patients of 0-5 years experienced HFMD in 2010-2015 in Wuhan. The cumulative relative risk of HFMD increased linearly with temperature over 7 days (lag0-7), while it presented as an approximately inverted V-shape over 14 days (lag0-14). The cumulative relative risk at lag0-14 peaked at 26.4 °C with value of 2.78 (95%CI: 2.08-3.72) compared with the 5 th percentile temperature (1.7 °C). Subgroup analyses revealed that children attended daycare were more vulnerable to temperature variation than those cared for at home. This study suggests that public health actions should take into consideration local weather conditions and demographic characteristics.

  14. Risk factors for death in children with severe hand, foot, and mouth disease in Hunan, China.

    PubMed

    Long, Lu; Gao, Li-Dong; Hu, Shi-Xiong; Luo, Kai-Wei; Chen, Zhen-Hua; Ronsmans, Carine; Zhou, Ding-Lun; Lan, Ya-Jia

    2016-10-01

    In recent years, outbreaks of hand, foot, and mouth disease (HFMD) have increased throughout East and Southeast Asia, especially in mainland China. The disease now presents as an increasingly serious public health threat in China. A case-control study was designed to examine risk factors associated with death from severe HFMD. A total of 553 severe HFMD cases were collected from the National Surveillance System. Multifactorial logistic regression was used to analyse independent associations between potential influence factors and death from severe HFMD. We found that the migrants were more likely to die from severe HFMD than the resident population (OR = 3.07, 95%CI: 1.39-8.32). Additionally, the children whose first visit was to a village-level clinic had a high risk of death from severe HFMD. Patients with EV71 infection or symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting had an increased risk of death from severe HFMD. While breastfeeding children, having a confirmed diagnosis at the first visit to the hospital and with symptom of hyperarousal were identified as protective factors for death from severe HFMD. To reduce the mortality from severe HFMD, doctors and health care providers need to pay attention to the patients with EV71 infection or with symptoms of convulsion, dyspnoea, cyanosis, coolness of extremities, and vomiting. Health administration departments should pay more attention to the rational allocation of health resources. Furthermore, they should increase financial support and manpower in village-level health institutions.

  15. Seasonal modeling of hand, foot, and mouth disease as a function of meteorological variations in Chongqing, China

    NASA Astrophysics Data System (ADS)

    Wang, Pin; Zhao, Han; You, Fangxin; Zhou, Hailong; Goggins, William B.

    2017-08-01

    Hand, foot, and mouth disease (HFMD) is an enterovirus-induced infectious disease, mainly affecting children under 5 years old. Outbreaks of HFMD in recent years indicate the disease interacts with both the weather and season. This study aimed to investigate the seasonal association between HFMD and weather variation in Chongqing, China. Generalized additive models and distributed lag non-linear models based on a maximum lag of 14 days, with negative binomial distribution assumed to account for overdispersion, were constructed to model the association between reporting HFMD cases from 2009 to 2014 and daily mean temperature, relative humidity, total rainfall and sun duration, adjusting for trend, season, and day of the week. The year-round temperature and relative humidity, rainfall in summer, and sun duration in winter were all significantly associated with HFMD. An inverted-U relationship was found between mean temperature and HFMD above 19 °C in summer, with a maximum morbidity at 27 °C, while the risk increased linearly with the temperature in winter. A hockey-stick association was found for relative humidity in summer with increasing risks over 60%. Heavy rainfall, relative to no rain, was found to be associated with reduced HFMD risk in summer and 2 h of sunshine could decrease the risk by 21% in winter. The present study showed meteorological variables were differentially associated with HFMD incidence in two seasons. Short-term weather variation surveillance and forecasting could be employed as an early indicator for potential HFMD outbreaks.

  16. The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis.

    PubMed

    Koh, Wee Ming; Bogich, Tiffany; Siegel, Karen; Jin, Jing; Chong, Elizabeth Y; Tan, Chong Yew; Chen, Mark Ic; Horby, Peter; Cook, Alex R

    2016-10-01

    Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16). This study reports a systematic review of the epidemiology of HFMD in Asia. PubMed, Web of Science and Google Scholar were searched up to December 2014. Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies. The uncertainty in these estimates inhibits their use for further analysis. Diversity of study designs complicates attempts to identify features of HFMD epidemiology. Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps.

  17. Impact of temperature variability on childhood hand, foot and mouth disease in Huainan, China.

    PubMed

    Xu, J; Zhao, D; Su, H; Xie, M; Cheng, J; Wang, X; Li, K; Yang, H; Wen, L; Wang, B

    2016-05-01

    The short-term temperature variation has been shown to be significantly associated with human health. However, little is known about whether temperature change between neighbouring days (TCN) and diurnal temperature range (DTR) have any effect on childhood hand, foot and mouth disease (HFMD). This study aims to explore whether temperature variability has any effect on childhood HFMD. Ecological study. The association between meteorological variables and HFMD cases in Huainan, China, from January 1st 2012 to December 31st 2014 was analysed using Poisson generalized linear regression combined with distributed lag non-linear model (DLNM) after controlling for long-term trend and seasonality, mean temperature and relative humidity. An adverse effect of TCN on childhood HFMD was observed, and the impact of TCN was the greatest at five days lag, with a 10% (95% CI: 4%-15%) increase of daily number of HFMD cases per 3 °C (10th percentile) decrease of TCN. Male children, children aged 0-5 years, scattered children and children in high-risk areas appeared to be more vulnerable to the TCN effect than others. However, there was no significant association between DTR and childhood HFMD. Our findings indicate that TCN drops may increase the incidence of childhood HFMD in Huainan, highlighting the importance of protecting children from forthcoming TCN drops, particularly for those who are male, young, scattered and from high-risk areas. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  18. Clinical and Etiological Characteristics of Atypical Hand-Foot-and-Mouth Disease in Children from Chongqing, China: A Retrospective Study.

    PubMed

    Yan, Xiang; Zhang, Zhen-Zhen; Yang, Zhen-Hua; Zhu, Chao-Min; Hu, Yun-Ge; Liu, Quan-Bo

    2015-01-01

    Hand-foot-and-mouth disease (HFMD) is a disease that had similar manifestations to chickenpox, impetigo, and measles, which is easy to misdiagnose and subsequently causes delayed therapy and subsequent epidemic. To date, no study has been conducted to report the clinical and epidemiological characteristics of atypical HFMD. 64 children with atypical HFMD out of 887 HFMD children were recruited, stool was collected, and viral VP1 was detected. The atypical HFMD accounted for 7.2% of total HFMD in the same period (64/887) and there were two peaks in its prevalence in nonepidemic seasons. Ten children (15.6%) had manifestations of neurologic involvement, of whom 4 (6.3%) were diagnosed with severe HFMD and 1 with critically severe HFMD, but all recovered smoothly. Onychomadesis and desquamation were found in 14 patients (21.9%) and 15 patients (23.4%), respectively. The most common pathogen was coxsackievirus A6 (CV-A6) which accounted for 67.2%, followed by nontypable enterovirus (26.6%), enterovirus 71 (EV-A71) (4.7%), and coxsackievirus A16 (A16) (1.5%). Atypical HFMD has seasonal prevalence. The manifestations of neurologic involvement in atypical HFMD are mild and usually have a good prognosis. CV-A6 is a major pathogen causing atypical HFMD, but not a major pathogen in Chongqing, China.

  19. Effect of Climatic Factors on Hand, Foot, and Mouth Disease in South Korea, 2010-2013.

    PubMed

    Kim, Bryan Inho; Ki, Hyunok; Park, Sunhee; Cho, Eunhi; Chun, Byung Chul

    2016-01-01

    Hand, foot, and mouth disease (HFMD) causes characteristic blisters and sores mainly in infants and children, and has been monitored in South Korea through sentinel surveillance since 2009. We described the patterns of HFMD occurrence and analyzed the effect of climatic factors on national HFMD incidence. Weekly clinically diagnosed HFMD case rates (per 1,000 outpatients) in sentinel sites and weekly climatic factors, such as average temperature, relative humidity, duration of sunshine, precipitation, and wind speed from 2010 to 2013, were used in this study. A generalized additive model with smoothing splines and climatic variables with time lags of up to 2 weeks were considered in the modeling process. To account for long-term trends and seasonality, we controlled for each year and their corresponding weeks. The autocorrelation issue was also adjusted by using autocorrelation variables. At an average temperature below 18°C, the HFMD rate increased by 10.3% for every 1°C rise in average temperature (95% confidence interval (CI): 8.4, 12.3%). We also saw a 6.6% increase in HFMD rate (95% CI: 3.6, 9.7%) with every 1% increase in relative humidity under 65%, with a 1.5% decrease in HFMD rate observed (95% CI: 0.4, 2.7%) with each 1% humidity increase above 65%. Modeling results have shown that average temperature and relative humidity are related to HFMD rate. Additional research on the environmental risk factors of HFMD transmission is required to understand the underlying mechanism between climatic factors and HFMD incidence.

  20. Ambient temperature, humidity and hand, foot, and mouth disease: A systematic review and meta-analysis.

    PubMed

    Cheng, Qiang; Bai, Lijun; Zhang, Yanwu; Zhang, Heng; Wang, Shusi; Xie, Mingyu; Zhao, Desheng; Su, Hong

    2018-06-01

    The relationship between ambient temperature, humidity and hand, foot, and mouth disease (HFMD) has been highlighted in East and Southeast Asia, which showed multiple different results. Therefore, our goal is to conduct a meta-analysis to further clarify this relationship and to quantify the size of these effects as well as the susceptible populations. PubMed, Web of science, and Cochrane library were searched up to November 22, 2017 for articles analyzing the relationships between ambient temperature, humidity and incidence of HFMD. We assessed sources of heterogeneity by study design (temperature measure and exposed time resolution), population vulnerability (national income level and regional climate) and evaluated pooled effect estimates for the subgroups identified in the heterogeneity analysis. We identified 11 studies with 19 estimates of the relationship between ambient temperature, humidity and incidence of HFMD. It was found that per 1°C increase in the temperature and per 1% increase in the relative humidity were both significantly associated with increased incidence of HFMD (temperature: IRR, 1.05; 95% CI, 1.02-1.08; relative humidity: IRR, 1.01; 95% CI, 1.00-1.02). Subgroup analysis showed that people living in subtropical and middle income areas had a higher risk of incidence of HFMD. Ambient temperature and humidity may increase the incidence of HFMD in Asia-Pacific regions. Further studies are needed to clarify the relationship between ambient temperature, humidity and incidence of HFMD in various settings with distinct climate, socioeconomic, and demographic features. Copyright © 2018. Published by Elsevier B.V.

  1. PREVALENCE OF HUMAN ENTEROVIRUS AMONG PATIENTS WITH HAND, FOOT, AND MOUTH DISEASE AND HERPANGINA IN THAILAND, 2013.

    PubMed

    Mauleekoonphairoj, John; Puenpa, Jiratchaya; Korkong, Sumeth; Vongpunsawad, Sompong; Poovorawan, Yong

    2015-11-01

    Human enterovirus (EV) infection causes hand, foot, and mouth disease (HFMD) and herpangina (HA). We studied the prevalence of enterovirus (EV) among patients with HFMD and HA in Thailand during 2013. We conducted a study in archived specimens of patients sent for screening for enterovirus. A total of 203 clinical specimens from 184 individuals with painful blister in the oropharynx and on the palms, soles, knees, elbows or buttock were examined by semi-nested polymerase chain reaction (PCR) for the 5'UTR and VP1 genes of EV. Eighty-six samples were positive: EV71 was detected in 14 (30%), CV-A8 in 12 (26%) and CV-A16 in 10 (21%). Classification of EV species detected revealed that 46 specimens were EV-A, 14 specimens were EV-B, 1 specimen was EV-D, and 16 specimens were positive for unclassified enterovirus. The majority of individuals with EV infection were aged 2-6 years. Multiple EV-A serotypes were detected among HFMD and HA patients in our study.

  2. Geographical Detector-Based Risk Factors Assessment of the Hand-Foot-Mouth Disease in China

    NASA Astrophysics Data System (ADS)

    Huang, J.

    2017-12-01

    Background: Hand, foot and mouth disease(HFMD) is a common infectious disease, causing thousands of deaths among children in China. This study focused on analyzing the impacts of different populations and different industry structures on HFMD incidence in China. Methods: We collected HFMD cases from 2307 counties during May 2008 in China. The potential risk factors included: monthly mean temperature, monthly mean relative humidity, monthly precipitation, different population density, different industry structures. Geographical detector technique was used to analyze the main and interactive effect of potential risk factors on HFMD incidence. Result: Using risk detector, we found the most serious HFMD incidence mainly located in the Yangtze River delta and the Pearl River delta. When the temperature was high, the incidence of HFMD was also high. This finding indicates that there is a correlation between monthly mean temperature and the incidence of HFMD. Similar analysis was undertaken to analyze the correlation between other variables and the incidence of HFMD using the risk detector. Using factor detector, we found the effect of risk factors on the incidence of HFMD, and this was ranked by PD value as follows: density of children aged 0-9 years (0.25) > tertiary industry (0.23) > GDP (0.20) >middle school student density (0.13) > relative humidity (0.12) >average temperature (0.11) >first industry (0.05). Using ecological detector, we found that child density, tertiary industry, and GDP had a strong effect on the incidence of HFMD. Using interactive detector, we found that the interactive PD value of tertiary industry and child population density was 0.42, which of GDP and tertiary industry was 0.34, that of child population density and GDP was 0.35, and that of average temperature and relative humidity was 0.28. All of these interactive PD values appeared to be higher than any PD value of sole risk factors. The combinations of the above-mentioned risk factors

  3. Outcomes following severe hand foot and mouth disease: A systematic review and meta-analysis.

    PubMed

    Jones, Eben; Pillay, Timesh D; Liu, Fengfeng; Luo, Li; Bazo-Alvarez, Juan Carlos; Yuan, Chen; Zhao, Shanlu; Chen, Qi; Li, Yu; Liao, Qiaohong; Yu, Hongjie; Rogier van Doorn, H; Sabanathan, Saraswathy

    2018-04-20

    Hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is associated with acute neurological disease in children. This study aimed to estimate the burden of long-term sequelae and death following severe HFMD. This systematic review and meta-analysis pooled all reports from English and Chinese databases including MEDLINE and Wangfang on outbreaks of clinically diagnosed HFMD and/or laboratory-confirmed EV-A71 with at least 7 days' follow-up published between 1st January 1966 and 19th October 2015. Two independent reviewers assessed the literature. We used a random effects meta-analysis to estimate cumulative incidence of neurological sequelae or death. Studies were assessed for methodological and reporting quality. PROSPERO registration number: 10.15124/CRD42015021981. 43 studies were included in the review, and 599 children from 9 studies were included in the primary analysis. Estimated cumulative incidence of death or neurological sequelae at maximum follow up was 19.8% (95% CI:10.2%, 31.3%). Heterogeneity (Iˆ2) was 88.57%, partly accounted for by year of data collection and reporting quality of studies. Incidence by acute disease severity was 0.00% (0.00, 0.00) for grade IIa; 17.0% (7.9, 28.2) for grade IIb/III; 81.6% (65.1, 94.5) for grade IV (p = 0.00) disease. HFMD with neurological involvement is associated with a substantial burden of long-term neurological sequelae. Grade of acute disease severity was a strong predictor of outcome. Strengths of this study include its bilingual approach and clinical applicability. Future prospective and interventional studies must use rigorous methodology to assess long-term outcomes in survivors. There was no specific funding for this study. See below for researcher funding. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Ambulatory Pediatric Surveillance of Hand, Foot and Mouth Disease as Signal of an Outbreak of Coxsackievirus A6 Infections, France, 2014–2015

    PubMed Central

    le Sage, François Vié; Pereira, Bruno; Cohen, Robert; Levy, Corinne; Archimbaud, Christine; Peigue-Lafeuille, Hélène; Bailly, Jean-Luc; Henquell, Cécile

    2016-01-01

    The clinical impact of enteroviruses associated with hand, foot and mouth disease (HFMD) is unknown outside Asia, and the prevalence of enterovirus A71 (EV-A71) in particular might be underestimated. To investigate the prevalence of enterovirus serotypes and the clinical presentations associated with HFMD in France, we conducted prospective ambulatory clinic–based surveillance of children during April 2014–March 2015. Throat or buccal swabs were collected from children with HFMD and tested for the enterovirus genome. Physical examinations were recorded on a standardized form. An enterovirus infection was detected in 523 (79.3%) of 659 children tested. Two epidemic waves occurred, dominated by coxsackievirus (CV) A6, which was detected in 53.9% of enterovirus-infected children. CV-A6 was more frequently related to atypical HFMD manifestations (eruptions extended to limbs and face). Early awareness and documentation of HFMD outbreaks can be achieved by syndromic surveillance of HFMD by ambulatory pediatricians and rapid enterovirus testing and genotyping. PMID:27767012

  5. Socio-ecological factors and hand, foot and mouth disease in dry climate regions: a Bayesian spatial approach in Gansu, China

    NASA Astrophysics Data System (ADS)

    Gou, Faxiang; Liu, Xinfeng; Ren, Xiaowei; Liu, Dongpeng; Liu, Haixia; Wei, Kongfu; Yang, Xiaoting; Cheng, Yao; Zheng, Yunhe; Jiang, Xiaojuan; Li, Juansheng; Meng, Lei; Hu, Wenbiao

    2017-01-01

    The influence of socio-ecological factors on hand, foot and mouth disease (HFMD) were explored in this study using Bayesian spatial modeling and spatial patterns identified in dry regions of Gansu, China. Notified HFMD cases and socio-ecological data were obtained from the China Information System for Disease Control and Prevention, Gansu Yearbook and Gansu Meteorological Bureau. A Bayesian spatial conditional autoregressive model was used to quantify the effects of socio-ecological factors on the HFMD and explore spatial patterns, with the consideration of its socio-ecological effects. Our non-spatial model suggests temperature (relative risk (RR) 1.15, 95 % CI 1.01-1.31), GDP per capita (RR 1.19, 95 % CI 1.01-1.39) and population density (RR 1.98, 95 % CI 1.19-3.17) to have a significant effect on HFMD transmission. However, after controlling for spatial random effects, only temperature (RR 1.25, 95 % CI 1.04-1.53) showed significant association with HFMD. The spatial model demonstrates temperature to play a major role in the transmission of HFMD in dry regions. Estimated residual variation after taking into account the socio-ecological variables indicated that high incidences of HFMD were mainly clustered in the northwest of Gansu. And, spatial structure showed a unique distribution after taking account of socio-ecological effects.

  6. Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease.

    PubMed

    Zhang, Chao; Chen, Shuaiyin; Zhou, Guangyuan; Jin, Yuefei; Zhang, Rongguang; Yang, Haiyan; Xi, Yuanlin; Ren, Jingchao; Duan, Guangcai

    2018-01-01

    Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD. In the present study, 162 children including HFMD patients and healthy controls were recruited. The data was analyzed by time-series fashion. Concentrations of angiotensin II (Ang II) and noradrenaline (NA) in serum of patients were measured with ELISA. We established a mouse model for enterovirus 71 (EV71) infection and determined concentrations of Ang II, NA in tissue lysates at 3, 5 and 7 days post infection (dpi). The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. Additionally, the concentrations of Ang II and NA in serum of severe cases were significantly higher than those mild cases and the increased concentrations of Ang II and NA showed the same time trend during the progression of HFMD in the severe cases. Furthermore, the concentrations of Ang II and NA in target organs of EV71-infected mice including brains, skeletal muscle, and lungs were increased with the progression of EV71 infection in mice. Histopathological alterations were observed in the brains, skeletal muscle and lungs of EV71-infected mice. Our study suggested that activation of the RAS is implicated in the pathogenesis of severe HFMD.

  7. [Relationship between G6PD deficiency and hand-foot-mouth disease induced by enterovirus 71].

    PubMed

    Ou, Jun-Bin; Zhang, Cui-Mei; Fu, Si-Mao; Huang, Xiang; Huang, Lian-Hong

    2013-09-01

    To study the influence of glucose-6-phosphate dehydrogenase (G6PD) deficiency on hand-foot-mouth disease (HFMD) induced by enterovirus 71 (EV71) , and possible mechanisms. A total of 220 boys with HFMD induced by EV71 were classified into two groups based on disease severity: mild/moderate (n=145) and severe HFMD groups (n=75), and 132 healthy boys were selected as the control group. The activity of G6PD and levels of reduced glutathione (GSH) and malonaldehyde (MDA) in blood were measured using the automatic biochemical analyzer. The percentage of G6PD deficiency cases in the severe HFMD group was significantly higher than in the control group (P<0.0125). In the severe HFMD group, the durations of fever, mental abnormality, limb trembling and hospital stay were significantly longer in children with G6PD deficiency than in those with normal G6PD activity (P<0.05). In the acute and recovery stages, patients in the mild/moderate and severe HFMD groups had significantly lower GSH levels and G6PD activity and significantly higher MDA levels compared with those in the control group (P<0.05). In the acute stage, children in the mild/moderate and severe HFMD groups with G6PD deficiency had significantly lower GSH levels and significantly higher MDA levels compared with those with normal G6PD activity (P<0.01). In the acute and recovery stages, GSH level in children with HFMD was positively correlated with G6PD activity (r=0.61, P<0.01; r=0.58, P<0.01), and in the acute stage, MDA level was negatively correlated with G6PD activity (r=-0.29, P<0.01). G6PD deficiency is probably a predisposing factor for HFMD induced by EV71 and may aggravate the patient's condition. Its mechanism might be related to oxidative stress.

  8. HAND-FOOT-AND-MOUTH DISEASE EPIDEMIOLOGICAL STATUS AND RELATIONSHIP WITH METEOROLOGICAL VARIABLES IN GUANGZHOU, SOUTHERN CHINA, 2008-2012

    PubMed Central

    Li, Tiegang; Yang, Zhicong; Liu, Xiangyi; Kang, Yan; Wang, Ming

    2014-01-01

    Hand-foot-and-mouth disease (HFMD) is becoming one of the extremely common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, it was used an ecological study plus the negative binomial regression to identify the epidemic status of HFMD and its relationship with meteorological variables. During 2008-2012, a total of 173,524 HFMD confirmed cases were reported, 12 cases of death, yielding a fatality rate of 0.69 per 10,000. The annual incidence rates from 2008 to 2012 were 60.56, 132.44, 311.40, 402.76, and 468.59 (per 100,000), respectively, showing a rapid increasing trend. Each 1 °C rise in temperature corresponded to an increase of 9.47% (95% CI 9.36% to 9.58%) in the weekly number of HFMD cases, while a one hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 7.53% (95% CI -7.60% to -7.45%). Similarly, each one percent rise in relative humidity corresponded to an increase of 1.48% or 3.3%, and a one meter per hour rise in wind speed corresponded to an increase of 2.18% or 4.57%, in the weekly number of HFMD cases, depending on the variables considered in the model. These findings revealed that epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on the incidence of HFMD. PMID:25351550

  9. An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010

    PubMed Central

    2011-01-01

    Background In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak. Methods Patients who had HFMD with positive enterovirus isolation results were enrolled. We performed a telephone interview with enrolled patients or their caregivers to collect information concerning symptoms, treatments, the presence of desquamation, and the presence of nail abnormalities. The serotypes of the enterovirus isolates were determined using indirect immunofluorescence assays. The VP1 gene was sequenced and the phylogenetic tree for the current CA6 strains in 2010, 52 previous CA6 strains isolated in Taiwan from 1998 through 2009, along with 8 reference sequences from other countries was constructed using the neighbor-joining command in MEGA software. Results Of the 130 patients with laboratory-confirmed CA6 infection, some patients with CA6 infection also had eruptions around the perioral area (28, 22%), the trunk and/or the neck (39, 30%) and generalized skin eruptions (6, 5%) in addition to the typical presentation of skin eruptions on the hands, feet, and mouths. Sixty-six (51%) CA6 patients experienced desquamation of palms and soles after the infection episode and 48 (37%) CA6 patients developed onychomadesis, which only occurred in 7 (5%) of 145 cases with non-CA6 enterovirus infection (p < 0.001). The sequences of viral protein 1 of CA6 in 2010 differ from those found in Taiwan before 2010, but are similar to those found in patients in Finland in 2008. Conclusions HFMD patients with CA6 infection experienced symptoms targeting a broader spectrum of skin sites and more profound tissue destruction, i.e., desquamation and nail abnormalities. PMID:22168544

  10. Epidemiological analysis, detection, and comparison of space-time patterns of Beijing hand-foot-mouth disease (2008-2012).

    PubMed

    Wang, Jiaojiao; Cao, Zhidong; Zeng, Daniel Dajun; Wang, Quanyi; Wang, Xiaoli; Qian, Haikun

    2014-01-01

    Hand, foot, and mouth disease (HFMD) mostly affects the health of infants and preschool children. Many studies of HFMD in different regions have been published. However, the epidemiological characteristics and space-time patterns of individual-level HFMD cases in a major city such as Beijing are unknown. The objective of this study was to investigate epidemiological features and identify high relative risk space-time HFMD clusters at a fine spatial scale. Detailed information on age, occupation, pathogen and gender was used to analyze the epidemiological features of HFMD epidemics. Data on individual-level HFMD cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify the spatial autocorrelation of HFMD incidence. Spatial filtering combined with scan statistics methods were used to detect HFMD clusters. A total of 157,707 HFMD cases (60.25% were male, 39.75% were female) reported in Beijing from 2008 to 2012 included 1465 severe cases and 33 fatal cases. The annual average incidence rate was 164.3 per 100,000 (ranged from 104.2 in 2008 to 231.5 in 2010). Male incidence was higher than female incidence for the 0 to 14-year age group, and 93.88% were nursery children or lived at home. Areas at a higher relative risk were mainly located in the urban-rural transition zones (the percentage of the population at risk ranged from 33.89% in 2011 to 39.58% in 2012) showing High-High positive spatial association for HFMD incidence. The most likely space-time cluster was located in the mid-east part of the Fangshan district, southwest of Beijing. The spatial-time patterns of Beijing HFMD (2008-2012) showed relatively steady. The population at risk were mainly distributed in the urban-rural transition zones. Epidemiological features of Beijing HFMD were generally consistent with the previous research. The findings generated computational insights useful for disease surveillance, risk assessment and early warning.

  11. Children’s Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease

    NASA Astrophysics Data System (ADS)

    Li, Pengyuan; Li, Tao; Gu, Qiuyun; Chen, Xiaomin; Li, Jiahui; Chen, Xiashi; Chen, Yan; Zhang, Danwei; Gao, Rong; He, Zhenjian; Zhu, Xun; Zhang, Wangjian; Hao, Yuantao; Zhang, Dingmei

    2016-11-01

    Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children’s caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children’s 257 samples (98 children’s caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children’s caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children’s caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities.

  12. Prevalence and characterization of enterovirus infections among pediatric patients with hand foot mouth disease, herpangina and influenza like illness in Thailand, 2012.

    PubMed

    Puenpa, Jiratchaya; Mauleekoonphairoj, John; Linsuwanon, Piyada; Suwannakarn, Kamol; Chieochansin, Thaweesak; Korkong, Sumeth; Theamboonlers, Apiradee; Poovorawan, Yong

    2014-01-01

    Hand, foot, and mouth disease (HFMD) and herpangina are common infectious diseases caused by several genotypes of human enterovirus species A and frequently occurring in young children. This study was aimed at analyzing enteroviruses from patients with these diseases in Thailand in 2012. Detection and genotype determination of enteroviruses were accomplished by reverse transcription-polymerase chain reaction and sequencing of the VP1 region. Enterovirus-positive samples were differentiated into 17 genotypes (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5, echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8 (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus infections were most prevalent during July with 34.4% in HFMD, 39.8% in herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD and herpangina occurred in infants over one year-old. This represents the first report describing the circulation of multiple enteroviruses in Thailand.

  13. Short-term effects of meteorological factors on children hand, foot and mouth disease in Guangzhou, China

    NASA Astrophysics Data System (ADS)

    Chen, Chun; Lin, Hualiang; Li, Xiaoquan; Lang, Lingling; Xiao, Xincai; Ding, Peng; He, Peng; Zhang, Ying; Wang, Ming; Liu, Qiyong

    2014-09-01

    Hand, foot and mouth disease (HFMD) is a contagious viral illness that commonly affects infants and children. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effects of meteorological factors on children HFMD in Guangzhou, China. Daily count of HFMD among children younger than 15 years and meteorological variables from 2009 to 2011 were collected to construct the time series. A generalized additive model was applied to estimate the effects of meteorological factors on HFMD occurrence, after adjusting for long-term trend, seasonal trend, day of week, and public holidays. A negative association between temperature and children HFMD occurrence was observed at lag days 1-3, with the relative risk (RR) for a 1 °C increase on lag day 2 being 0.983 (95 % confidence intervals (CI) 0.977 to 0.989); positive effect was found for temperature at lag days 5-9, with the highest effect at lag day 6 (RR = 1.014, 95 % CI 1.006 to 1.023). Higher humidity was associated with increased HFMD at lag days 3-10, with the highest effect at lag day 8 (RR = 1.009 for 1 % increase in relative humidity, 95 % CI 1.007 to 1.010). And we also observed significant positive effect for rainfall at lag days 4 and 8 (RR = 1.001, 95 % CI 1.000 to 1.002) for 1-mm increase. Subgroup analyses showed that the positive effects of temperature were more pronounced among younger children. This study suggests that meteorological factors might be important predictors of children HFMD occurrence in Guangzhou.

  14. Short-term effects of meteorological factors on children hand, foot and mouth disease in Guangzhou, China.

    PubMed

    Chen, Chun; Lin, Hualiang; Li, Xiaoquan; Lang, Lingling; Xiao, Xincai; Ding, Peng; He, Peng; Zhang, Ying; Wang, Ming; Liu, Qiyong

    2014-09-01

    Hand, foot and mouth disease (HFMD) is a contagious viral illness that commonly affects infants and children. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effects of meteorological factors on children HFMD in Guangzhou, China. Daily count of HFMD among children younger than 15 years and meteorological variables from 2009 to 2011 were collected to construct the time series. A generalized additive model was applied to estimate the effects of meteorological factors on HFMD occurrence, after adjusting for long-term trend, seasonal trend, day of week, and public holidays. A negative association between temperature and children HFMD occurrence was observed at lag days 1-3, with the relative risk (RR) for a 1 °C increase on lag day 2 being 0.983 (95% confidence intervals (CI) 0.977 to 0.989); positive effect was found for temperature at lag days 5-9, with the highest effect at lag day 6 (RR = 1.014, 95% CI 1.006 to 1.023). Higher humidity was associated with increased HFMD at lag days 3-10, with the highest effect at lag day 8 (RR = 1.009 for 1% increase in relative humidity, 95% CI 1.007 to 1.010). And we also observed significant positive effect for rainfall at lag days 4 and 8 (RR = 1.001, 95% CI 1.000 to 1.002) for 1-mm increase. Subgroup analyses showed that the positive effects of temperature were more pronounced among younger children. This study suggests that meteorological factors might be important predictors of children HFMD occurrence in Guangzhou.

  15. [Downscaling research of spatial distribution of incidence of hand foot and mouth disease based on area-to-area Poisson Kriging method].

    PubMed

    Wang, J X; Hu, M G; Yu, S C; Xiao, G X

    2017-09-10

    Objective: To understand the spatial distribution of incidence of hand foot and mouth disease (HFMD) at scale of township and provide evidence for the better prevention and control of HFMD and allocation of medical resources. Methods: The incidence data of HFMD in 108 counties (district) in Shandong province in 2010 were collected. Downscaling interpolation was conducted by using area-to-area Poisson Kriging method. The interpolation results were visualized by using geographic information system (GIS). The county (district) incidence was interpolated into township incidence to get the distribution of spatial distribution of incidence of township. Results: In the downscaling interpolation, the range of the fitting semi-variance equation was 20.38 km. Within the range, the incidence had correlation with each other. The fitting function of scatter diagram of estimated and actual incidence of HFMD at country level was y =1.053 1 x , R (2)=0.99. The incidences at different scale were consistent. Conclusions: The incidence of HFMD had spatial autocorrelation within 20.38 km. When HFMD occurs in one place, it is necessary to strengthen the surveillance and allocation of medical resource in the surrounding area within 20.38 km. Area to area Poisson Kriging method based downscaling research can be used in spatial visualization of HFMD incidence.

  16. Predicting the incidence of hand, foot and mouth disease in Sichuan province, China using the ARIMA model.

    PubMed

    Liu, L; Luan, R S; Yin, F; Zhu, X P; Lü, Q

    2016-01-01

    Hand, foot and mouth disease (HFMD) is an infectious disease caused by enteroviruses, which usually occurs in children aged <5 years. In China, the HFMD situation is worsening, with increasing number of cases nationwide. Therefore, monitoring and predicting HFMD incidence are urgently needed to make control measures more effective. In this study, we applied an autoregressive integrated moving average (ARIMA) model to forecast HFMD incidence in Sichuan province, China. HFMD infection data from January 2010 to June 2014 were used to fit the ARIMA model. The coefficient of determination (R 2), normalized Bayesian Information Criterion (BIC) and mean absolute percentage of error (MAPE) were used to evaluate the goodness-of-fit of the constructed models. The fitted ARIMA model was applied to forecast the incidence of HMFD from April to June 2014. The goodness-of-fit test generated the optimum general multiplicative seasonal ARIMA (1,0,1) × (0,1,0)12 model (R 2 = 0·692, MAPE = 15·982, BIC = 5·265), which also showed non-significant autocorrelations in the residuals of the model (P = 0·893). The forecast incidence values of the ARIMA (1,0,1) × (0,1,0)12 model from July to December 2014 were 4103-9987, which were proximate forecasts. The ARIMA model could be applied to forecast HMFD incidence trend and provide support for HMFD prevention and control. Further observations should be carried out continually into the time sequence, and the parameters of the models could be adjusted because HMFD incidence will not be absolutely stationary in the future.

  17. Hand, Foot, and Mouth Disease Preliminarily Diagnosed as Hypochondriasis.

    ERIC Educational Resources Information Center

    Davidson, Michael Jay; And Others

    1990-01-01

    A case in which a dental student with hand, foot, and mouth disease was told he had "medical student disease" (MSD), or hypochondriasis, is related; literature pertaining to the occurrence and treatment of MSD is reviewed, and the importance of care in approaches to both students and patients are discussed. (MSE)

  18. A Laboratory Evaluation of Medicinal Herbs Used in China for the Treatment of Hand, Foot, and Mouth Disease

    PubMed Central

    Chen, Xiaoqing; Wang, Chunyang; Xu, Lanfang; Chen, Xiaoshuang; Wang, Wei; Yang, Guang; Tan, Ren Xiang; Li, Erguang; Jin, Yu

    2013-01-01

    Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the causative agents of hand, foot, and mouth disease (HFMD). During recent epidemics of HFMD in China, medicinal herbals and preparations containing herbal extracts have demonstrated therapeutic efficacy with relative safety profiles. There have been no microbiological studies to validate their usefulness for HFMD. We selected 12 commonly used herbs for HFMD from government recommended guidelines as well as published reports and tested for their antiviral activity and anti-inflammatory activity. A water extract of Houttuynia cordata Thunb. (HCT) inhibited EV71 infection significantly and was marginally active against CVA16 infection. The IC50 (concentration to have 50% inhibitory effect) values of HCT against a Fuyang strain and a BrCr strain of EV71 were determined at 8.9 μg/mL and 20.6 μg/mL, respectively. Mentha haplocalyx Briq. (MHB) water extract was active against CVA16, with an IC50 value of 70.3 μg/mL. The extract did not exhibit activity against EV71 infection. Although the majority of the extracts showed no activity against viral infection, several extracts demonstrated activity in blocking proinflammatory response by viral infection. This study therefore validates the effectiveness of Chinese herbs for HFMD since some formulations containing the correct combination of the herbs can block viral replication as well as proinflammatory response of HFMD. PMID:23554831

  19. Prevalence and Characterization of Enterovirus Infections among Pediatric Patients with Hand Foot Mouth Disease, Herpangina and Influenza Like Illness in Thailand, 2012

    PubMed Central

    Puenpa, Jiratchaya; Mauleekoonphairoj, John; Linsuwanon, Piyada; Suwannakarn, Kamol; Chieochansin, Thaweesak; Korkong, Sumeth; Theamboonlers, Apiradee; Poovorawan, Yong

    2014-01-01

    Hand, foot, and mouth disease (HFMD) and herpangina are common infectious diseases caused by several genotypes of human enterovirus species A and frequently occurring in young children. This study was aimed at analyzing enteroviruses from patients with these diseases in Thailand in 2012. Detection and genotype determination of enteroviruses were accomplished by reverse transcription-polymerase chain reaction and sequencing of the VP1 region. Enterovirus-positive samples were differentiated into 17 genotypes (coxsackievirus A4 (CAV4), A5, A6, A8, A9, A10, A12, A16, A21, B1, B2, B4, B5, echovirus 7, 16, 25 and Enterovirus 71). The result showed CAV6 (33.5%), followed by CAV16 (9.4%) and EV71 (8.8%) as the most frequent genotypes in HFMD, CAV8 (19.3%) in herpangina and CAV6 (1.5%) in influenza like illness. Enterovirus infections were most prevalent during July with 34.4% in HFMD, 39.8% in herpangina and 1.6% in ILI. The higher enterovirus infection associated with HFMD and herpangina occurred in infants over one year-old. This represents the first report describing the circulation of multiple enteroviruses in Thailand. PMID:24887237

  20. Impact of temperature variation between adjacent days on childhood hand, foot and mouth disease during April and July in urban and rural Hefei, China

    NASA Astrophysics Data System (ADS)

    Cheng, Jian; Zhu, Rui; Xu, Zhiwei; Wu, Jinju; Wang, Xu; Li, Kesheng; Wen, Liying; Yang, Huihui; Su, Hong

    2016-06-01

    Previous studies have found that both high temperature and low temperature increase the risk of childhood hand, foot and mouth disease (HFMD). However, little is known about whether temperature variation between neighboring days has any effects on childhood HFMD. A Poisson generalized linear regression model, combined with a distributed lag non-linear model, was applied to examine the relationship between temperature change and childhood HFMD in Hefei, China, from 1st January 2010 to 31st December 2012. Temperature change was defined as the difference of current day's mean temperature and previous day's mean temperature. Late spring and early summer (April-July) were chosen as the main study period due to it having the highest childhood HFMD incidence. There was a statistical association between temperature change between neighboring days and childhood HFMD. The effects of temperature change on childhood HFMD increased below a temperature change of 0 °C (temperature drop). The temperature change has the greatest adverse effect on childhood HFMD at 7 days lag, with 4 % (95 % confidence interval 2-7 %) increase per 3 °C drop of temperature. Male children and urban children appeared to be more vulnerable to the effects of temperature change. Temperature change between adjacent days might be an alternative temperature indictor for exploring the temperature-HFMD relationship.

  1. Enterovirus genotypes causing hand foot and mouth disease in Shanghai, China: a molecular epidemiological analysis.

    PubMed

    Xu, Menghua; Su, Liyun; Cao, Lingfeng; Zhong, Huaqing; Dong, Niuniu; Xu, Jin

    2013-10-22

    A rapid expansion of hand, foot, and mouth disease (HFMD) outbreaks has occurred and caused deaths in China in recent years, but little is known about the other etiologic agents except enterovirus 71 (EV71) and coxsackievirus A 16 (CA16). The objective of this study is to determine the genotype compositions of enterovirus causing HFMD in Shanghai and identify any associations between enterovirus types and clinical manifestations. Stool specimens were collected from patients hospitalized for treatment of HFMD, from May 2010 to April 2011. Enterovirus was detected by reverse transcription PCR and directly genotyped by sequencing the PCR products. Phylogenetic analysis was based on the VP1 partial gene. Of 290 specimens, 277 (95.5%) tested positive for enterovirus. The major genotypes were EV71 (63.8%), CA10 (9.0%), CA6 (8.3%), CA16 (6.9%), CA12 (2.4%), and CA4 (1.4%). The EV71 strains belonged to the C4a subtype and CA16 belonged to the B subtype. CA6 was closely related to strains detected in Japan, Taiwan and China, and CA10, CA12 and CA4 were phylogenetically similar to other strains circulating in China. Mean hospital stays and the prevalence of complications in patients with EV71 infection were higher than those in patients in CA6, CA10 or CA16 infection (P < 0.05 for all comparisons). Children with CA12 infection were the youngest, and most likely have the highest risk of complications when compared to the other non-EV71 infection groups. This study demonstrated a diversified pathogen compositions attributing to HFMD and clinical symptoms differing in enterovirus genotypes. It deserves our attention as early identification of enterovirus genotypes is important for diagnosis and treatment of HFMD patients.

  2. Enterovirus genotypes causing hand foot and mouth disease in Shanghai, China: a molecular epidemiological analysis

    PubMed Central

    2013-01-01

    Background A rapid expansion of hand, foot, and mouth disease (HFMD) outbreaks has occurred and caused deaths in China in recent years, but little is known about the other etiologic agents except enterovirus 71 (EV71) and coxsackievirus A 16 (CA16). The objective of this study is to determine the genotype compositions of enterovirus causing HFMD in Shanghai and identify any associations between enterovirus types and clinical manifestations. Methods Stool specimens were collected from patients hospitalized for treatment of HFMD, from May 2010 to April 2011. Enterovirus was detected by reverse transcription PCR and directly genotyped by sequencing the PCR products. Phylogenetic analysis was based on the VP1 partial gene. Results Of 290 specimens, 277 (95.5%) tested positive for enterovirus. The major genotypes were EV71 (63.8%), CA10 (9.0%), CA6 (8.3%), CA16 (6.9%), CA12 (2.4%), and CA4 (1.4%). The EV71 strains belonged to the C4a subtype and CA16 belonged to the B subtype. CA6 was closely related to strains detected in Japan, Taiwan and China, and CA10, CA12 and CA4 were phylogenetically similar to other strains circulating in China. Mean hospital stays and the prevalence of complications in patients with EV71 infection were higher than those in patients in CA6, CA10 or CA16 infection (P < 0.05 for all comparisons). Children with CA12 infection were the youngest, and most likely have the highest risk of complications when compared to the other non-EV71 infection groups. Conclusions This study demonstrated a diversified pathogen compositions attributing to HFMD and clinical symptoms differing in enterovirus genotypes. It deserves our attention as early identification of enterovirus genotypes is important for diagnosis and treatment of HFMD patients. PMID:24148902

  3. Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

    PubMed

    Zhu, Yu; Jiang, Zhou; Xiao, Guoguang; Cheng, Suting; Wen, Yang; Wan, Chaomin

    2015-03-01

    Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications. Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method. Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature and respiratory rate were significantly different among 3 groups. But no statistical difference of amplitude in temperature and respiratory rate was observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was significantly different in 3 groups. However, amplitude and acrophase revealed no statistical difference in circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for

  4. Genetic characterization of enterovirus strains identified in Hand, Foot and Mouth Disease (HFMD): Emergence of B1c, C1 subgenotypes, E2 sublineage of CVA16, EV71 and CVA6 strains in India.

    PubMed

    Ganorkar, Nital N; Patil, Pooja R; Tikute, Sanjay S; Gopalkrishna, Varanasi

    2017-10-01

    Hand, Foot and Mouth disease (HFMD) is a common childhood disease and caused due to Enterovirus-A (EV-A), EV-B and EV-C species worldwide. Cases of HFMD were reported from, Ahmedabad (Gujarat, 2012) and Pune (Maharashtra, 2013-2014) in India. The present study highlights the identification of EV strains (CVA16, CVA6, CVA4 and Echo12), characterization of subgenotypes of CVA16, CVA6 strains during 2012-14 and CVA16, CVA6, EV71 strains reported from the earlier study (2009-10) in HFMD cases from India. A total 158 clinical specimens collected from 64 HFMD cases (2012-2014) were included in the study. EV detection was carried out by 5'NCR based RT-PCR, molecular typing and subgenotyping was by VP1/2A junction or VP1, full VP1 gene amplification respectively followed by phylogenetic analysis. The present study reports 63.92% (101/158) EV positivity by RT-PCR. Ninety four of the 101 (93.06%) EV positive strains were amplified by VP1/2A junction or VP1 regions. Sequence analysis revealed the presence of CVA16 (61.7%), CVA6 (34.04%), CVA4 and Echo12 (4.3%). A total of 114 EV positive strains were genotyped using full and partial VP1 region. All CVA16 Indian strains (n=70) clustered with rarely reported B1c subgenotype, CVA6 (n=43) and EV71 (n=1) strains clustered with sub-lineage E2 and C1 subgenotypes respectively. In summary, the study reports genetic characterization of CVA16, CVA6, CVA4 and Echo12 strains in HFMD cases from India. Circulation of B1c subgenotype of CVA16, E2 sub-lineage of CVA6 and C1 subgenotype of EV 71 strains in HFMD cases were reported for the first time from India. This study helps to understand the genotype distribution, genetic diversity of EV strains associated with HFMD from Eastern, Western and Southern regions in India. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Different responses of weather factors on hand, foot and mouth disease in three different climate areas of Gansu, China.

    PubMed

    Gou, Faxiang; Liu, Xinfeng; He, Jian; Liu, Dongpeng; Cheng, Yao; Liu, Haixia; Yang, Xiaoting; Wei, Kongfu; Zheng, Yunhe; Jiang, Xiaojuan; Meng, Lei; Hu, Wenbiao

    2018-01-08

    To determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission. Weekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways. GLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui. Average temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity's effect on HFMD showed a non-linear interacting relationship with average temperature.

  6. Impact of weather factors on hand, foot and mouth disease, and its role in short-term incidence trend forecast in Huainan City, Anhui Province

    NASA Astrophysics Data System (ADS)

    Zhao, Desheng; Wang, Lulu; Cheng, Jian; Xu, Jun; Xu, Zhiwei; Xie, Mingyu; Yang, Huihui; Li, Kesheng; Wen, Lingying; Wang, Xu; Zhang, Heng; Wang, Shusi; Su, Hong

    2017-03-01

    Hand, foot, and mouth disease (HFMD) is one of the most common communicable diseases in China, and current climate change had been recognized as a significant contributor. Nevertheless, no reliable models have been put forward to predict the dynamics of HFMD cases based on short-term weather variations. The present study aimed to examine the association between weather factors and HFMD, and to explore the accuracy of seasonal auto-regressive integrated moving average (SARIMA) model with local weather conditions in forecasting HFMD. Weather and HFMD data from 2009 to 2014 in Huainan, China, were used. Poisson regression model combined with a distributed lag non-linear model (DLNM) was applied to examine the relationship between weather factors and HFMD. The forecasting model for HFMD was performed by using the SARIMA model. The results showed that temperature rise was significantly associated with an elevated risk of HFMD. Yet, no correlations between relative humidity, barometric pressure and rainfall, and HFMD were observed. SARIMA models with temperature variable fitted HFMD data better than the model without it (s R 2 increased, while the BIC decreased), and the SARIMA (0, 1, 1)(0, 1, 0)52 offered the best fit for HFMD data. In addition, compared with females and nursery children, males and scattered children may be more suitable for using SARIMA model to predict the number of HFMD cases and it has high precision. In conclusion, high temperature could increase the risk of contracting HFMD. SARIMA model with temperature variable can effectively improve its forecast accuracy, which can provide valuable information for the policy makers and public health to construct a best-fitting model and optimize HFMD prevention.

  7. Impact of weather factors on hand, foot and mouth disease, and its role in short-term incidence trend forecast in Huainan City, Anhui Province.

    PubMed

    Zhao, Desheng; Wang, Lulu; Cheng, Jian; Xu, Jun; Xu, Zhiwei; Xie, Mingyu; Yang, Huihui; Li, Kesheng; Wen, Lingying; Wang, Xu; Zhang, Heng; Wang, Shusi; Su, Hong

    2017-03-01

    Hand, foot, and mouth disease (HFMD) is one of the most common communicable diseases in China, and current climate change had been recognized as a significant contributor. Nevertheless, no reliable models have been put forward to predict the dynamics of HFMD cases based on short-term weather variations. The present study aimed to examine the association between weather factors and HFMD, and to explore the accuracy of seasonal auto-regressive integrated moving average (SARIMA) model with local weather conditions in forecasting HFMD. Weather and HFMD data from 2009 to 2014 in Huainan, China, were used. Poisson regression model combined with a distributed lag non-linear model (DLNM) was applied to examine the relationship between weather factors and HFMD. The forecasting model for HFMD was performed by using the SARIMA model. The results showed that temperature rise was significantly associated with an elevated risk of HFMD. Yet, no correlations between relative humidity, barometric pressure and rainfall, and HFMD were observed. SARIMA models with temperature variable fitted HFMD data better than the model without it (sR 2 increased, while the BIC decreased), and the SARIMA (0, 1, 1)(0, 1, 0) 52 offered the best fit for HFMD data. In addition, compared with females and nursery children, males and scattered children may be more suitable for using SARIMA model to predict the number of HFMD cases and it has high precision. In conclusion, high temperature could increase the risk of contracting HFMD. SARIMA model with temperature variable can effectively improve its forecast accuracy, which can provide valuable information for the policy makers and public health to construct a best-fitting model and optimize HFMD prevention.

  8. Predicting the outbreak of hand, foot, and mouth disease in Nanjing, China: a time-series model based on weather variability

    NASA Astrophysics Data System (ADS)

    Liu, Sijun; Chen, Jiaping; Wang, Jianming; Wu, Zhuchao; Wu, Weihua; Xu, Zhiwei; Hu, Wenbiao; Xu, Fei; Tong, Shilu; Shen, Hongbing

    2017-10-01

    Hand, foot, and mouth disease (HFMD) is a significant public health issue in China and an accurate prediction of epidemic can improve the effectiveness of HFMD control. This study aims to develop a weather-based forecasting model for HFMD using the information on climatic variables and HFMD surveillance in Nanjing, China. Daily data on HFMD cases and meteorological variables between 2010 and 2015 were acquired from the Nanjing Center for Disease Control and Prevention, and China Meteorological Data Sharing Service System, respectively. A multivariate seasonal autoregressive integrated moving average (SARIMA) model was developed and validated by dividing HFMD infection data into two datasets: the data from 2010 to 2013 were used to construct a model and those from 2014 to 2015 were used to validate it. Moreover, we used weekly prediction for the data between 1 January 2014 and 31 December 2015 and leave-1-week-out prediction was used to validate the performance of model prediction. SARIMA (2,0,0)52 associated with the average temperature at lag of 1 week appeared to be the best model (R 2 = 0.936, BIC = 8.465), which also showed non-significant autocorrelations in the residuals of the model. In the validation of the constructed model, the predicted values matched the observed values reasonably well between 2014 and 2015. There was a high agreement rate between the predicted values and the observed values (sensitivity 80%, specificity 96.63%). This study suggests that the SARIMA model with average temperature could be used as an important tool for early detection and prediction of HFMD outbreaks in Nanjing, China.

  9. Impact of temperature variation between adjacent days on childhood hand, foot and mouth disease during April and July in urban and rural Hefei, China.

    PubMed

    Cheng, Jian; Zhu, Rui; Xu, Zhiwei; Wu, Jinju; Wang, Xu; Li, Kesheng; Wen, Liying; Yang, Huihui; Su, Hong

    2016-06-01

    Previous studies have found that both high temperature and low temperature increase the risk of childhood hand, foot and mouth disease (HFMD). However, little is known about whether temperature variation between neighboring days has any effects on childhood HFMD. A Poisson generalized linear regression model, combined with a distributed lag non-linear model, was applied to examine the relationship between temperature change and childhood HFMD in Hefei, China, from 1st January 2010 to 31st December 2012. Temperature change was defined as the difference of current day's mean temperature and previous day's mean temperature. Late spring and early summer (April-July) were chosen as the main study period due to it having the highest childhood HFMD incidence. There was a statistical association between temperature change between neighboring days and childhood HFMD. The effects of temperature change on childhood HFMD increased below a temperature change of 0 °C (temperature drop). The temperature change has the greatest adverse effect on childhood HFMD at 7 days lag, with 4 % (95 % confidence interval 2-7 %) increase per 3 °C drop of temperature. Male children and urban children appeared to be more vulnerable to the effects of temperature change. Temperature change between adjacent days might be an alternative temperature indictor for exploring the temperature-HFMD relationship.

  10. Enterovirus-related diarrhoea in Guangdong, China: clinical features and implications in hand, foot and mouth disease and herpangina.

    PubMed

    Zhou, Hong-Tao; Yi, Hai-Su; Guo, Yong-Hui; Pan, Yu-Xian; Tao, Shao-Hua; Wang, Bin; Chen, Man-Jun; Yang, Mei; Yu, Nan

    2016-03-16

    A series of complications caused by enteroviruses, including meningitis, encephalitis, acute flaccid paralysis, acute cardiopulmonary failure, respiratory infection, and myocardial injury have been reported in hand, foot and mouth disease/herpangina (HFMD/HA). However, the complication of diarrhoea caused by enteroviruses has been neglected, and a summary of its clinical features and impact on HFMD/HA is unavailable. We included inpatients with HFMD/HA admitted to the Paediatric Department of Zhujiang Hospital during 2009-2012. We summarised and compared clinical data for cases with and without diarrhoea, and determined enterovirus serotypes by reverse transcriptase polymerase chain reaction and genotyping based on a partial-length fragment of viral protein 1 or the 5'-untranslated region. There were 804 inpatients with HFMD/HA and 28 (3.5%) presented with diarrhoea. Gastrointestinal symptoms were mild in most cases of diarrhoea (82.1%), with high prevalence of no dehydration (82.1%), short duration of diarrhoea (78.6%) and watery stools (75.0%). The prevalence of multi-organ dysfunction syndrome (10.7 vs 0.40%) (p = 0.001), hepatic injury (14.3 vs 3.4%) (p = 0.019), myocardial injury (21.4 vs 6.1%) (p = 0.002) and convulsion (21.4 vs 7.2%) (p = 0.016) was significantly higher in the diarrhoea than no diarrhoea group. There was no significant difference between the two groups regarding prevalence of death, altered consciousness, paralysis, central nervous system involvement, or acute respiratory infection. Most patients with diarrhoea caused by enteroviruses circulating in Guangdong Province in 2009-2012 had mild or moderate gastrointestinal symptoms. Although enterovirus-related diarrhoea caused additional multi-organ dysfunction syndrome, hepatic injury and myocardial injury in children with HFMD/HA, timely intervention efficiently reduced disease severity and improved outcome.

  11. Time series analysis of reported cases of hand, foot, and mouth disease from 2010 to 2013 in Wuhan, China.

    PubMed

    Chen, Banghua; Sumi, Ayako; Toyoda, Shin'ichi; Hu, Quan; Zhou, Dunjin; Mise, Keiji; Zhao, Junchan; Kobayashi, Nobumichi

    2015-11-03

    Hand, foot, and mouth disease (HFMD) is an infectious disease caused by a group of enteroviruses, including Coxsackievirus A16 (CVA16) and Enterovirus A71 (EV-A71). In recent decades, Asian countries have experienced frequent and widespread HFMD outbreaks, with deaths predominantly among children. In several Asian countries, epidemics usually peak in the late spring/early summer, with a second small peak in late autumn/early winter. We investigated the possible underlying association between the seasonality of HFMD epidemics and meteorological variables, which could improve our ability to predict HFMD epidemics. We used a time series analysis composed of a spectral analysis based on the maximum entropy method (MEM) in the frequency domain and the nonlinear least squares method in the time domain. The time series analysis was applied to three kinds of monthly time series data collected in Wuhan, China, where high-quality surveillance data for HFMD have been collected: (i) reported cases of HFMD, (ii) reported cases of EV-A71 and CVA16 detected in HFMD patients, and (iii) meteorological variables. In the power spectral densities for HFMD and EV-A71, the dominant spectral lines were observed at frequency positions corresponding to 1-year and 6-month cycles. The optimum least squares fitting (LSF) curves calculated for the 1-year and 6-month cycles reproduced the bimodal cycles that were clearly observed in the HFMD and EV-A71 data. The peak months on the LSF curves for the HFMD data were consistent with those for the EV-A71 data. The risk of infection was relatively high at 10 °C ≤ t < 15 °C (t, temperature [°C]) and 15 °C ≤ t < 20 °C, and peaked at 20 °C ≤ t < 25 °C. In this study, the HFMD infections occurring in Wuhan showed two seasonal peaks, in summer (June) and winter (November or December). The results obtained with a time series analysis suggest that the bimodal seasonal peaks in HFMD epidemics are attributable to EV-A71 epidemics

  12. Modeling the Present and Future Incidence of Pediatric Hand, Foot, and Mouth Disease Associated with Ambient Temperature in Mainland China.

    PubMed

    Zhao, Qi; Li, Shanshan; Cao, Wei; Liu, De-Li; Qian, Quan; Ren, Hongyan; Ding, Fan; Williams, Gail; Huxley, Rachel; Zhang, Wenyi; Guo, Yuming

    2018-04-20

    There is limited evidence about the association between ambient temperature and the incidence of pediatric hand, foot, and mouth disease (HFMD) nationwide in China. We examined the childhood temperature-HFMD associations across mainland China, and we projected the change in HFMD cases due to projected temperature change by the 2090s. Data on daily HFMD (children 0-14 y old) counts and weather were collected from 362 sites during 2009-2014. Daily temperature by the 2090s was downscaled under the Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios. Temperature-HFMD associations were quantified using a two-stage Poisson regression with a distributed lag nonlinear model. The impact of changes in temperature on the incidence of HFMD was estimated by combining the fitted temperature-HFMD associations with projected temperatures under each scenario, assuming a constant population structure. Sensitivity analyses were performed to assess the influence of primary model assumptions. During 2009-2014, >11 million HFMD cases were reported. In most regions, the temperature-HFMD association had an inverted U shape with a peak at approximately 20°C, but the association leveled off or continued to increase in the Inner Mongolia and Northeast regions. When estimates were pooled across all regions and the population size was held constant, the projected incidence of HFMD increased by 3.2% [95% empirical confidence interval (eCI): −13.5%, 20.0%] and 5.3% (95% eCI: −33.3%, 44.0%) by the 2090s under the RCP 4.5 and 8.5 scenarios, respectively. However, regional projections suggest that HFMD may decrease with climate change in temperate areas of central and eastern China. Our estimates suggest that the association between temperature and HFMD varies across China and that the future impact of climate change on HFMD incidence will vary as well. Other factors, including changes in the size of the population at risk (children 0-14 y old) will also influence future HFMD

  13. Enterovirus 71 infection in children with hand, foot, and mouth disease in Shanghai, China: epidemiology, clinical feature and diagnosis.

    PubMed

    Wang, Ying; Zou, Gang; Xia, Aimei; Wang, Xiangshi; Cai, Jiehao; Gao, Qianqian; Yuan, Shilin; He, Guimei; Zhang, Shuyi; Zeng, Mei; Altmeyer, Ralf

    2015-06-03

    In 2012 a large outbreak of hand, foot, and mouth disease (HFMD) widely spread over China, causing more than 2 million cases and 567 deaths. Our purpose was to characterize the major pathogens responsible for the 2012 HFMD outbreak and analyze the genetic characterization of the enterovirus 71 (EV71) strains in Shanghai; also, to analyze the dynamic patterns of neutralizing antibody (NAb) against EV71 and evaluate the diagnostic value of several methods for clinical detection of EV71. Clinical samples including stool, serum and CSF were collected from 396 enrolled HFMD inpatients during the peak seasons in 2012. We analyzed the molecular epidemiology, clinical feature, and diagnostic tests of EV71 infection. EV71 was responsible for 60.35 % of HFMD inpatients and 88.46 % of severe cases. The circulating EV71 strains belonged to subgenogroup C4a. The nucleotide sequences of VP1 between severe cases and uncomplicated cases shared 99.2 ~ 100 % of homology. Among 218 cases with EV71 infection, 211 (96.79 %) serum samples showed NAb positive against EV71 and NAb titer reached higher level 3 days after disease onset. Of 92 cases with EV71-associated meningitis or encephalitis, 5 (5.43 %) of 92 had EV71 RNA detected in CSF samples. The blood anti-EV71 IgM assay showed a sensitivity of 93.30 % and a specificity of 50 %. EV71 C4a remained the predominant subgenotype circulating in Shanghai. The severity of the EV71 infection is not associated with the virulence determinants in VP1. RT-PCR together with IgM detection can enhance the early diagnosis of severe EV71-associated HFMD.

  14. [Outbreak of hand, foot and mouth disease with onychomadesis caused by Coxsackie virus A16 in Granada].

    PubMed

    Navarro Moreno, E; Almagro López, D; Jaldo Jiménez, R; Del Moral Campaña, M C; Árbol Fernández, G; Pérez Ruiz, M; Almagro Nievas, D

    2015-04-01

    Due to the significant increase in the number of cases of hand, foot and mouth disease (HFMD) among pre-school children population during late 2011 and early 2012. A study has been proposed with the aim of describing the HFMD outbreak and analyzing the risk factors associated with suffering onychomadesis. A descriptive and analytical case-control study was designed. The study population was 376 children between 6 and 36 months old, living in the Basic Health Catchment area of Peligros (Granada). The study inclued an epidemiological survey of 28 cases and paired controls in order to collect data on the time, person and place, and implementing preventive actions and family health education. Finally a microbiological viral study of stool samples was made. There were 64% of girls with average age 20.8 months. The clinical signs fornd were, fever (75%), vesicular palmar eruption (71%), plantar eruption (68%), erosive stomatitis (64%), and nail loss (46%). The risk of getting sick was 14 times greater for those children attending a childcare centre and had contact with sick cases (OR 13.8; 95% CI; 3.79-50.18). The average time since onset of symptoms and onychomadesis was 52 days, and its appearance was linked to the presence of ulcers in mouth (P=.006). Five samples were positive to enteroviruses Coxsackie A16. There was an outbreak of HFMD detected by pediatricians and families. The cases presented with marked clinical symptoms, and the nail loss (onychomadesis) generated a social alarm. The cause of the outbreak was an enterovirus Coxsackie A16 transmitted among sick cases and through childcare centres. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  15. Transcutaneous immunization via rapidly dissolvable microneedles protects against hand-foot-and-mouth disease caused by enterovirus 71.

    PubMed

    Zhu, Zhuangzhi; Ye, Xiaohua; Ku, Zhiqiang; Liu, Qingwei; Shen, Chaoyun; Luo, Huafei; Luan, Hansen; Zhang, Chenghao; Tian, Shaoqiong; Lim, CheeYen; Huang, Zhong; Wang, Hao

    2016-12-10

    Recent large outbreaks of hand-foot-and-mouth disease (HFMD) have seriously affected the health of young children. Enterovirus 71 (EV71) is the main causative agent of HFMD. Herein, for the first time, rapidly dissolvable microneedles (MNs) loaded with EV71 virus-like particles (VLPs) were evaluated whether they could induce robust immune responses that confer protection against EV71 infection. The characteristics of prepared MNs including hygroscopy, mechanical strength, insertion capacity, dissolution profile, skin irritation and storage stability were comprehensively assessed. EV71 VLPs remained morphologically stable during fabrication. The MNs made of sodium hyaluronate maintained their insertion ability for at least 3h even at a high relative humidity of 75%. With the aid of spring-operated applicator, EV71 MNs (approximately 500μm length) could be readily penetrated into the mouse skin in vivo, and then rapidly dissolved to release encapsulated antigen within 2min. Additionally, MNs induced slight erythema that disappeared within a few hours. More importantly, mouse immunization and virus challenge studies demonstrated that MNs immunization induced high level of antibody responses conferring full protection against lethal EV71 virus challenge that were comparable to conventional intramuscular injection, but with only 1/10th of the delivered antigen (dose sparing). Consequently, our rapidly dissolving MNs may present as an effective and promising transcutaneous immunization device for HFMD prophylaxis among children. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam.

    PubMed

    Geoghegan, Jemma L; Tan, Le Van; Kühnert, Denise; Halpin, Rebecca A; Lin, Xudong; Simenauer, Ari; Akopov, Asmik; Das, Suman R; Stockwell, Timothy B; Shrivastava, Susmita; Ngoc, Nghiem My; Uyen, Le Thi Tam; Tuyen, Nguyen Thi Kim; Thanh, Tran Tan; Hang, Vu Thi Ty; Qui, Phan Tu; Hung, Nguyen Thanh; Khanh, Truong Huu; Thinh, Le Quoc; Nhan, Le Nguyen Thanh; Van, Hoang Minh Tu; Viet, Do Chau; Tuan, Ha Manh; Viet, Ho Lu; Hien, Tran Tinh; Chau, Nguyen Van Vinh; Thwaites, Guy; Grenfell, Bryan T; Stadler, Tanja; Wentworth, David E; Holmes, Edward C; Van Doorn, H Rogier

    2015-09-01

    Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71

  17. Phylodynamics of Enterovirus A71-Associated Hand, Foot, and Mouth Disease in Viet Nam

    PubMed Central

    Kühnert, Denise; Halpin, Rebecca A.; Lin, Xudong; Simenauer, Ari; Akopov, Asmik; Das, Suman R.; Stockwell, Timothy B.; Shrivastava, Susmita; Ngoc, Nghiem My; Uyen, Le Thi Tam; Tuyen, Nguyen Thi Kim; Thanh, Tran Tan; Hang, Vu Thi Ty; Qui, Phan Tu; Hung, Nguyen Thanh; Khanh, Truong Huu; Thinh, Le Quoc; Nhan, Le Nguyen Thanh; Van, Hoang Minh Tu; Viet, Do Chau; Tuan, Ha Manh; Viet, Ho Lu; Hien, Tran Tinh; Chau, Nguyen Van Vinh; Thwaites, Guy; Grenfell, Bryan T.; Stadler, Tanja; Wentworth, David E.; Holmes, Edward C.; Van Doorn, H. Rogier

    2015-01-01

    ABSTRACT Enterovirus A71 (EV-A71) is a major cause of hand, foot, and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011 and 2013 and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time frame of sampling, whereas that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated area of endemicity. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a

  18. Quantifying the adverse effect of excessive heat on children: An elevated risk of hand, foot and mouth disease in hot days.

    PubMed

    Zhang, Wangjian; Du, Zhicheng; Zhang, Dingmei; Yu, Shicheng; Hao, Yuantao

    2016-01-15

    Hand, foot and mouth disease (HFMD) is a common childhood infection and has become a major public health issue in China. Considerable research has focused on the role of meteorological factors such as temperature and relative humidity in HFMD development. However, no studies have specifically quantified the impact of another major environmental agent, excessive heat, on HFMD. The current study was designed to help address this research gap. Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from China CDC and the National Meteorological Information Center, respectively. Distributed lag nonlinear models were applied to assess the impact of excessive heat on HFMD and its variability across social-economic status and age groups. After controlling the effects of several potential confounders, the commonly hot days were found to positively affect the HFMD burdens with the relative risk (RR) peaking at around 6 days of lag. The RR of HFMD in the Pearl-River Delta Region was generally higher and persisted longer than that in the remaining developing areas. Regarding the inter-age group discrepancy, children aged 3-6 years old had the highest risk of HFMD under conditions of excessive heat whereas those greater than 6 years old had the lowest. The lag structure of the impact of the extremely hot days was quite similar to that of the commonly hot days, although the relative effect of these two kinds of conditions of excessive heat might vary across regions. This study indicated significantly facilitating effects of excessive heat on HFMD especially among those aged 3-6 and from developed areas. Results from the current study were particularly practical and important for developing area-and-age-targeted control programs in the context of climate change and urbanization. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Application and Comparison of Laboratory Parameters for Forecasting Severe Hand-Foot-Mouth Disease Using Logistic Regression, Discriminant Analysis and Decision Tree.

    PubMed

    Sui, Meili; Huang, Xueyong; Li, Yi; Ma, Xiaomei; Zhang, Chao; Li, Xingle; Chen, Zhijuan; Feng, Huifen; Ren, Jingchao; Wang, Fang; Xu, Bianli; Duan, Guangcai

    2016-01-01

    In recent years, the prevalence of hand-foot-mouth disease (HFMD) in China and some other countries has caused worldwide concern. Mild cases tend to recover within a week, while severe cases may progress rapidly and tend to have bad outcome. Since there is no vaccine for HFMD and anti-inflammatory treatment is not ideal. In this study, we aimed to establish a valid forecasting model for severe HFMD using common laboratory parameters. Retrospectively, 77 severe HFMD cases from Zhengzhou Children's hospital in the peaking period between years 2013 to 2015 were collected, with 77 mild HFMD cases in the same area. The study recorded common laboratory parameters to assist in establishment of the severe HFMD model. After screening the important variables using Mann-Whitney U test, the study also matched the logistic regression (LR), discriminant analysis (DA), and decision tree (DT) to make a comparison. Compared with that of the mild group, serum levels of WBC, PLT, PCT, MCV, MCH, LCR, SCR, LCC, GLO, CK-MB, K, S100, and B in the severe group were higher (p < 0.05), while MCR, EOR, BASOR, SCC, MCC, EO, BASO, NA, CL, T, Th, and Th/Ts were lower (p < 0.05). Five indicators including MCR, LCC, Th, CK-MB, and CL were screened out by LR and the same for DA, and five variables including EO, LCC, CL, GLO, and MCC screened out by DT. The area under the curve (AUC) of LR, DA, and DT was 0.805, 0.779 and 0.864, respectively. The findings were that common laboratory indexes were effectively used to distinguish the mild HFMD cases and severe HFMD cases by LR, DA, and DT, and DT had the best classification effect with an AUC of 0.864.

  20. Effect of meteorological variables on the incidence of hand, foot, and mouth disease in children: a time-series analysis in Guangzhou, China.

    PubMed

    Huang, Yong; Deng, Te; Yu, Shicheng; Gu, Jing; Huang, Cunrui; Xiao, Gexin; Hao, Yuantao

    2013-03-13

    Over the last decade, major outbreaks of hand, foot, and mouth disease (HFMD) have been reported in Asian countries, resulting in thousands of deaths among children. However, less is known regarding the effect of meteorological variables on the incidence of HFMD in children. This study aims at quantifying the relationship between meteorological variables and the incidence of HFMD among children in Guangzhou, China. The association between weekly HFMD cases in children aged <15 years and meteorological variables in Guangzhou from 2008 to 2011 were analyzed using the generalized additive model (GAM) and time-series method, after controlling for long-term trend and seasonality, holiday effects, influenza period and delayed effects. Temperature and relative humidity with one week lag were significantly associated with HFMD infection among children. We found that a 1°C increase in temperature led to an increase of 1.86% (95% CI: 0.92, 2.81%) in the weekly number of cases in the 0-14 years age group. A one percent increase in relative humidity may lead to an increase of 1.42% (95% CI: 0.97, 1.87%) in the weekly number of cases in the 0-14 years age group. This study provides quantitative evidence that the incidence of HFMD in children was associated with high average temperature and high relative humidity. The one-week delay in the effects of temperature and relative humidity on HFMD is consistent with the enterovirus incubation period and the potential time lag between onset of children's sickness and parental awareness and response.

  1. Epidemiology of hand, foot and mouth disease in China, 2008 to 2015 prior to the introduction of EV-A71 vaccine.

    PubMed

    Yang, Bingyi; Liu, Fengfeng; Liao, Qiaohong; Wu, Peng; Chang, Zhaorui; Huang, Jiao; Long, Lu; Luo, Li; Li, Yu; Leung, Gabriel M; Cowling, Benjamin J; Yu, Hongjie

    2017-12-01

    Hand, foot and mouth disease (HFMD) is usually caused by several serotypes from human enterovirus A species, including enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16). Two inactivated monovalent EV-A71 vaccines have been recently licensed in China and monovalent CV-A16 vaccine and bivalent EV-A71 and CV-A16 vaccine are under development. Using notifications from the national surveillance system, we describe the epidemiology and dynamics of HFMD in the country, before the introduction of EV-A71 vaccination, from 2008 through 2015. Laboratory-identified serotype categories, i.e. CV-A16, EV-A71 and other enteroviruses, circulated annually. EV-A71 remained the most virulent serotype and was the major serotype for fatal cases (range: 88.5-95.4%) and severe cases (range: 50.7-82.3%) across years. Except for 2013 and 2015, when other enteroviruses were more frequently found in mild HFMD (48.8% and 52.5%), EV-A71 was more frequently detected from mild cases in the rest of the years covered by the study (range: 39.4-52.6%). The incidence rates and severity risks of HFMD associated with all serotype categories were the highest for children aged 1 year and younger, and decreased with increasing age. This study provides baseline epidemiology for evaluation of vaccine impact and potential serotype replacement.

  2. Fourteen types of co-circulating recombinant enterovirus were associated with hand, foot, and mouth disease in children from Wenzhou, China.

    PubMed

    Guo, Wen-Ping; Lin, Xian-Dan; Chen, Yi-Ping; Liu, Qi; Wang, Wen; Wang, Cai-Qiao; Li, Ming-Hui; Sun, Xiao-Yu; Shi, Mang; Holmes, Edward C; Zhang, Yong-Zhen

    2015-09-01

    Although hand, foot, and mouth disease (HFMD) is a major public concern in China, the prevalence and clinical symptoms associated with the different agents of HFMD in this country remain poorly understood. We investigated the clinical and molecular characteristics of enteroviruses in patients with HFMD from Wenzhou, China. Patients with laboratory-confirmed HFMD admitted to the Yuying Children's Hospital in Wenzhou, China during 2013 were included in this study. Viral RNA sequences were amplified using RT-PCR, determined by sequencing, and compared by phylogenetic analysis. A total of 955 clinically diagnosed HFMD cases were determined using PCR, with whole viral genomes obtained for each enterovirus type. 14 types of enterovirus belonging to two viral species were identified. Notably, Coxsackievirus A6 (CV-A6) was the most common species detected (77.8%), followed by EV-A71 (8.2%) and CV-A10 (8.1%). Phylogenetic analysis revealed multiple independent introductions of these viruses into Wenzhou. In addition, the enterovirus observed in Wenzhou had a recombinant history, with two or three recombination breakpoints. Although the illness associated with CV-A6 was milder than that of EV-A71, CV-A6 infection caused more widespread rash, larger blisters, and subsequent skin peeling and/or nail shedding. Our study revealed the co-circulation of 14 types of enteroviruses in a single location - Wenzhou, China - with CV-A6 virus the predominant agent of HFMD. This work highlights the need to perform larger-scale surveillance to fully understand the epidemiology of enteroviruses in China and the wider Asia-Pacific region. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Spectrum of Enterovirus Serotypes Causing Uncomplicated Hand, Foot, and Mouth Disease and Enteroviral diagnostic yield of different clinical samples.

    PubMed

    Gao, Lidong; Zou, Gang; Liao, Qiaohong; Zhou, Yonghong; Liu, Fengfeng; Dai, Bingbing; Liu, Jia; Chen, Zhiyong; Xing, Weijia; Yang, Le; Liang, Hong; Zhang, Yi; Chen, Zhenhua; Luo, Li; Li, Qing; Luo, Kaiwei; Wu, Peng; Mo, Xiaowei; Wang, Lili; Lan, Ke; Horby, Peter W; Cowling, Benjamin J; Simmonds, Peter; Altmeyer, Ralf; van Doorn, H Rogier; Yu, Hongjie

    2018-04-24

    Hand, foot, and mouth disease (HFMD) represents a substantial disease burden in the Western Pacific region. We investigated the spectrum of causative enteroviruses of HFMD, and evaluated different clinical samples' diagnostic yield for enteroviruses. We enrolled pediatric patients hospitalized for HFMD among six hospitals in Anhua County, Hunan Province, China between October 2013 and September 2016. Throat swabs and stool samples (or rectal swabs) were collected to detect the enterovirus serotypes by real time RT-PCR or nested PCR. Among the 2,836 patients only one developed severe illness. Seventeen serotypes were identified in 2,401 patients (85%), with the most frequently detected being CV-A16 (29%, 814), CV-A6 (28%, 784), EV-A71 (17%, 491), CV-A10 (4%, 114), and CV-A4 (2%, 53). Children were younger in CV-A6, CV-A10, and CV-A4 infections (median 12 months, IQR 12-24 months) than EV-A71 and CV-A16 infections (median 24 months, IQR 12-36 months, p<0.05). Annual peaks of HFMD hospitalization occurred during April-June. The predominant enterovirus serotype shifted between CV-A16 and CV-A6 during the three years. Stool had a higher diagnostic yield (89%) than rectal (79%) and throat swabs (74%). Detection rates reached 93% when testing stools followed by throat swabs if stools were negative, and 89% when testing rectal swabs followed by throat swabs if rectal swabs were negative. Our results provide a virological benchmark for future surveillance and diagnostics. Continuous comprehensive virological surveillance is essential, especially after implementation of the EV-A71 vaccine in China, to monitor serotype replacement and the impact of EV-A71 vaccine.

  4. Efficacy of a Trivalent Hand, Foot, and Mouth Disease Vaccine against Enterovirus 71 and Coxsackieviruses A16 and A6 in Mice.

    PubMed

    Caine, Elizabeth A; Fuchs, Jeremy; Das, Subash C; Partidos, Charalambos D; Osorio, Jorge E

    2015-11-17

    Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates.

  5. Predicting the hand, foot, and mouth disease incidence using search engine query data and climate variables: an ecological study in Guangdong, China

    PubMed Central

    Du, Zhicheng; Xu, Lin; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng; Hao, Yuantao

    2017-01-01

    Objectives Hand, foot, and mouth disease (HFMD) has caused a substantial burden in China, especially in Guangdong Province. Based on the enhanced surveillance system, we aimed to explore whether the addition of temperate and search engine query data improves the risk prediction of HFMD. Design Ecological study. Setting and participants Information on the confirmed cases of HFMD, climate parameters and search engine query logs was collected. A total of 1.36 million HFMD cases were identified from the surveillance system during 2011–2014. Analyses were conducted at aggregate level and no confidential information was involved. Outcome measures A seasonal autoregressive integrated moving average (ARIMA) model with external variables (ARIMAX) was used to predict the HFMD incidence from 2011 to 2014, taking into account temperature and search engine query data (Baidu Index, BDI). Statistics of goodness-of-fit and precision of prediction were used to compare models (1) based on surveillance data only, and with the addition of (2) temperature, (3) BDI, and (4) both temperature and BDI. Results A high correlation between HFMD incidence and BDI (r=0.794, p<0.001) or temperature (r=0.657, p<0.001) was observed using both time series plot and correlation matrix. A linear effect of BDI (without lag) and non-linear effect of temperature (1 week lag) on HFMD incidence were found in a distributed lag non-linear model. Compared with the model based on surveillance data only, the ARIMAX model including BDI reached the best goodness-of-fit with an Akaike information criterion (AIC) value of −345.332, whereas the model including both BDI and temperature had the most accurate prediction in terms of the mean absolute percentage error (MAPE) of 101.745%. Conclusions An ARIMAX model incorporating search engine query data significantly improved the prediction of HFMD. Further studies are warranted to examine whether including search engine query data also improves the prediction of

  6. Epidemiological characteristics of hand-foot-and-mouth disease in China, 2008-2012

    PubMed Central

    Sun, Junling; Wu, Joseph T; Chang, Zhaorui; Liu, Fengfeng; Fang, Vicky J; Zheng, Yingdong; Cowling, Benjamin J; Varma, Jay K; Farrar, Jeremy J; Leung, Gabriel M; Yu, Hongjie

    2014-01-01

    Summary Background Hand–foot–and–mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Increasingly it imposes a substantial disease burden throughout East and Southeast Asia. To better inform vaccine and other interventions, we characterized the epidemiology of HFMD in China based on enhanced surveillance. Methods We extracted epidemiological, clinical and laboratory data from reported HFMD cases during 2008–2012 and compiled climatic, geographic and demographic information. All analyses were stratified by age, disease severity, laboratory confirmation status and enterovirus subtype. Findings The surveillance registry captured 7,200,092 probable HFMD cases (annualized incidence, 1·2 per 1,000), of whom 3·7% were laboratory–confirmed and 0·03% died. Incidence and mortality were highest in children aged 12–23 months (in 2012: 38·2 cases per 1,000 and 1·5 death per 100,000). Median durations from onset to diagnosis and death were 1·5 days and 3·5 days respectively. The risk of cardiopulmonary or neurological complications was 1·1% and the severe-case fatality risk was 3·0%, with >90% of deaths associated with enterovirus 71. HFMD peaked annually in June in the North, whereas Southern China experienced semi-annual outbreaks in May and September/October. Geographic differences in seasonal patterns were weakly associated with climate and demographic factors (variance explained 8-23% and 3–19%, respectively). Interpretation This is the largest population-based study to date of the epidemiology of HFMD. Future mitigation policies should take full account of the heterogeneities of disease burden identified. Additional epidemiologic and serologic studies are warranted to elucidate local HFMD dynamics and immunity patterns and optimize interventions. Funding China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases; World Health Organization; The Li Ka Shing Oxford Global Health Programme and Wellcome Trust

  7. Short-Term Effects of Climatic Variables on Hand, Foot, and Mouth Disease in Mainland China, 2008-2013: A Multilevel Spatial Poisson Regression Model Accounting for Overdispersion.

    PubMed

    Liao, Jiaqiang; Yu, Shicheng; Yang, Fang; Yang, Min; Hu, Yuehua; Zhang, Juying

    2016-01-01

    Hand, Foot, and Mouth Disease (HFMD) is a worldwide infectious disease. In China, many provinces have reported HFMD cases, especially the south and southwest provinces. Many studies have found a strong association between the incidence of HFMD and climatic factors such as temperature, rainfall, and relative humidity. However, few studies have analyzed cluster effects between various geographical units. The nonlinear relationships and lag effects between weekly HFMD cases and climatic variables were estimated for the period of 2008-2013 using a polynomial distributed lag model. The extra-Poisson multilevel spatial polynomial model was used to model the exact relationship between weekly HFMD incidence and climatic variables after considering cluster effects, provincial correlated structure of HFMD incidence and overdispersion. The smoothing spline methods were used to detect threshold effects between climatic factors and HFMD incidence. The HFMD incidence spatial heterogeneity distributed among provinces, and the scale measurement of overdispersion was 548.077. After controlling for long-term trends, spatial heterogeneity and overdispersion, temperature was highly associated with HFMD incidence. Weekly average temperature and weekly temperature difference approximate inverse "V" shape and "V" shape relationships associated with HFMD incidence. The lag effects for weekly average temperature and weekly temperature difference were 3 weeks and 2 weeks. High spatial correlated HFMD incidence were detected in northern, central and southern province. Temperature can be used to explain most of variation of HFMD incidence in southern and northeastern provinces. After adjustment for temperature, eastern and Northern provinces still had high variation HFMD incidence. We found a relatively strong association between weekly HFMD incidence and weekly average temperature. The association between the HFMD incidence and climatic variables spatial heterogeneity distributed across

  8. Using interrupted time series design to analyze changes in hand, foot, and mouth disease incidence during the declining incidence periods of 2008-2010 in China.

    PubMed

    Yu, Shi Cheng; Hao, Yuan Tao; Zhang, Jing; Xiao, Ge Xin; Liu, Zhuang; Zhu, Qi; Ma, Jia Qi; Wang, Yu

    2012-12-01

    To identify patterns of hand, foot and mouth disease (HFMD) incidence in China during declining incidence periods of 2008, 2009, and 2010. Reported HFMD cases over a period of 25 months were extracted from the National Disease Reporting System (NDRS) and analyzed. An interrupted time series (ITS) technique was used to detect changes in HFMD incidence rates in terms of level and slope between declining incidence periods of the three years. Over 3.58 million HFMD cases younger than 5 years were reported to the NDRS between May 1, 2008, and May 31, 2011. Males comprised 63.4% of the cases. ITS analyses demonstrated a significant increase in incidence rate level (P<0.0001) when comparing the current period with the previous period. There were significant changes in declining slopes when comparing 2010 to 2009, and 2010 to 2008 (all P<0.005), but not 2009 to 2008. Incremental changes in incidence rate level during the declining incidence periods of 2009 and 2010 can potentially be attributed to a few factors. The more steeply declining slope in 2010 compared with previous years could be ascribed to the implementation of more effective interventions and preventive strategies in 2010. Further investigation is required to examine this possibility. Copyright © 2012 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

  9. [Model of multiple seasonal autoregressive integrated moving average model and its application in prediction of the hand-foot-mouth disease incidence in Changsha].

    PubMed

    Tan, Ting; Chen, Lizhang; Liu, Fuqiang

    2014-11-01

    To establish multiple seasonal autoregressive integrated moving average model (ARIMA) according to the hand-foot-mouth disease incidence in Changsha, and to explore the feasibility of the multiple seasonal ARIMA in predicting the hand-foot-mouth disease incidence. EVIEWS 6.0 was used to establish multiple seasonal ARIMA according to the hand-foot- mouth disease incidence from May 2008 to August 2013 in Changsha, and the data of the hand- foot-mouth disease incidence from September 2013 to February 2014 were served as the examined samples of the multiple seasonal ARIMA, then the errors were compared between the forecasted incidence and the real value. Finally, the incidence of hand-foot-mouth disease from March 2014 to August 2014 was predicted by the model. After the data sequence was handled by smooth sequence, model identification and model diagnosis, the multiple seasonal ARIMA (1, 0, 1)×(0, 1, 1)12 was established. The R2 value of the model fitting degree was 0.81, the root mean square prediction error was 8.29 and the mean absolute error was 5.83. The multiple seasonal ARIMA is a good prediction model, and the fitting degree is good. It can provide reference for the prevention and control work in hand-foot-mouth disease.

  10. Application of seasonal auto-regressive integrated moving average model in forecasting the incidence of hand-foot-mouth disease in Wuhan, China.

    PubMed

    Peng, Ying; Yu, Bin; Wang, Peng; Kong, De-Guang; Chen, Bang-Hua; Yang, Xiao-Bing

    2017-12-01

    Outbreaks of hand-foot-mouth disease (HFMD) have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average (ARIMA) model for time series analysis was designed in this study. Eighty-four-month (from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination (R 2 ), normalized Bayesian Information Criterion (BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as (1,0,1)(0,1,1) 12 , with the largest coefficient of determination (R 2 =0.743) and lowest normalized BIC (BIC=3.645) value. The residuals of the model also showed non-significant autocorrelations (P Box-Ljung (Q) =0.299). The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.

  11. [Application of R-based multiple seasonal ARIMA model, in predicting the incidence of hand, foot and mouth disease in Shaanxi province].

    PubMed

    Liu, F; Zhu, N; Qiu, L; Wang, J J; Wang, W H

    2016-08-10

    To apply the ' auto-regressive integrated moving average product seasonal model' in predicting the number of hand, foot and mouth disease in Shaanxi province. In Shaanxi province, the trend of hand, foot and mouth disease was analyzed and tested, under the use of R software, between January 2009 and June 2015. Multiple seasonal ARIMA model was then fitted under time series to predict the number of hand, foot and mouth disease in 2016 and 2017. Seasonal effect was seen in hand, foot and mouth disease in Shaanxi province. A multiple seasonal ARIMA (2,1,0)×(1,1,0)12 was established, with the equation as (1 -B)(1 -B12)Ln (Xt) =((1-1.000B)/(1-0.532B-0.363B(2))*(1-0.644B12-0.454B12(2)))*Epsilont. The mean of absolute error and the relative error were 531.535 and 0.114, respectively when compared to the simulated number of patients from Jun to Dec in 2015. RESULTS under the prediction of multiple seasonal ARIMA model showed that the numbers of patients in both 2016 and 2017 were similar to that of 2015 in Shaanxi province. Multiple seasonal ARIMA (2,1,0)×(1,1,0)12 model could be used to successfully predict the incidence of hand, foot and mouth disease in Shaanxi province.

  12. [Step Fisher discriminant analysis on severe clinical features of hand foot and mouth disease between enterovirus (EV) 71 and other EV].

    PubMed

    Ruan, Feng; Tan, Ai-jun; Zhang, Xue-bao; Chen, Xue-qin; Xiao, Song-jian; Ye, Zhong-wen; Wang, Song

    2011-07-01

    To compare the clinical features of severe hand foot and mouth disease between enterovirus (EV) 71 and other EV to find specific diagnosis index of EV71 severe hand foot and mouth disease. Case definition were adopted from national guideline of hand foot and mouth disease diagnose (Version 2010). Clinical data of severe hand foot and mouth disease came from case history and contents of questionnaire would include the ones between the time of onset and diagnoses being made. EV and EV71, Cox A16 nucleic acid tested were by RT-PCR in stool samples. Clinical features of severe hand foot and mouth disease between EV71 and other EV were compare. There appeared statistical differences between neurologic symptoms such as tremor, myoclonic jerk, listlessness, convulsion and white blood cell counts in CSF (P < 0.05). Results from the step Fisher discriminant analysis showed only tremor and white blood cell had an increase in CSF, with statistically significant differences. The discriminant equation of EV71 was Y = 3.059X(1) + 3.83X(5) - 2.742 and the equation of other EV was Y = 1.634X(1) + 1.623X(5) - 1.693. The specificity of EV71 was 91% and the specificity of other EV was 40%. The increase of clinical features of tremor and white blood cell in CSF could be used as diagnosis index of severe EV71.

  13. Predicting the hand, foot, and mouth disease incidence using search engine query data and climate variables: an ecological study in Guangdong, China.

    PubMed

    Du, Zhicheng; Xu, Lin; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng; Hao, Yuantao

    2017-10-06

    Hand, foot, and mouth disease (HFMD) has caused a substantial burden in China, especially in Guangdong Province. Based on the enhanced surveillance system, we aimed to explore whether the addition of temperate and search engine query data improves the risk prediction of HFMD. Ecological study. Information on the confirmed cases of HFMD, climate parameters and search engine query logs was collected. A total of 1.36 million HFMD cases were identified from the surveillance system during 2011-2014. Analyses were conducted at aggregate level and no confidential information was involved. A seasonal autoregressive integrated moving average (ARIMA) model with external variables (ARIMAX) was used to predict the HFMD incidence from 2011 to 2014, taking into account temperature and search engine query data (Baidu Index, BDI). Statistics of goodness-of-fit and precision of prediction were used to compare models (1) based on surveillance data only, and with the addition of (2) temperature, (3) BDI, and (4) both temperature and BDI. A high correlation between HFMD incidence and BDI ( r =0.794, p<0.001) or temperature ( r =0.657, p<0.001) was observed using both time series plot and correlation matrix. A linear effect of BDI (without lag) and non-linear effect of temperature (1 week lag) on HFMD incidence were found in a distributed lag non-linear model. Compared with the model based on surveillance data only, the ARIMAX model including BDI reached the best goodness-of-fit with an Akaike information criterion (AIC) value of -345.332, whereas the model including both BDI and temperature had the most accurate prediction in terms of the mean absolute percentage error (MAPE) of 101.745%. An ARIMAX model incorporating search engine query data significantly improved the prediction of HFMD. Further studies are warranted to examine whether including search engine query data also improves the prediction of other infectious diseases in other settings. © Article author(s) (or their

  14. Integrating GIS with AHP and Fuzzy Logic to generate hand, foot and mouth disease hazard zonation (HFMD-HZ) model in Thailand

    NASA Astrophysics Data System (ADS)

    Samphutthanon, R.; Tripathi, N. K.; Ninsawat, S.; Duboz, R.

    2014-12-01

    The main objective of this research was the development of an HFMD hazard zonation (HFMD-HZ) model by applying AHP and Fuzzy Logic AHP methodologies for weighting each spatial factor such as disease incidence, socio-economic and physical factors. The outputs of AHP and FAHP were input into a Geographic Information Systems (GIS) process for spatial analysis. 14 criteria were selected for analysis as important factors: disease incidence over 10 years from 2003 to 2012, population density, road density, land use and physical features. The results showed a consistency ratio (CR) value for these main criteria of 0.075427 for AHP, the CR for FAHP results was 0.092436. As both remained below the threshold of 0.1, the CR value were acceptable. After linking to actual geospatial data (disease incidence 2013) through spatial analysis by GIS for validation, the results of the FAHP approach were found to match more accurately than those of the AHP approach. The zones with the highest hazard of HFMD outbreaks were located in two main areas in central Muang Chiang Mai district including suburbs and Muang Chiang Rai district including the vicinity. The produced hazardous maps may be useful for organizing HFMD protection plans.

  15. Short-Term Effects of Climatic Variables on Hand, Foot, and Mouth Disease in Mainland China, 2008–2013: A Multilevel Spatial Poisson Regression Model Accounting for Overdispersion

    PubMed Central

    Yang, Fang; Yang, Min; Hu, Yuehua; Zhang, Juying

    2016-01-01

    Background Hand, Foot, and Mouth Disease (HFMD) is a worldwide infectious disease. In China, many provinces have reported HFMD cases, especially the south and southwest provinces. Many studies have found a strong association between the incidence of HFMD and climatic factors such as temperature, rainfall, and relative humidity. However, few studies have analyzed cluster effects between various geographical units. Methods The nonlinear relationships and lag effects between weekly HFMD cases and climatic variables were estimated for the period of 2008–2013 using a polynomial distributed lag model. The extra-Poisson multilevel spatial polynomial model was used to model the exact relationship between weekly HFMD incidence and climatic variables after considering cluster effects, provincial correlated structure of HFMD incidence and overdispersion. The smoothing spline methods were used to detect threshold effects between climatic factors and HFMD incidence. Results The HFMD incidence spatial heterogeneity distributed among provinces, and the scale measurement of overdispersion was 548.077. After controlling for long-term trends, spatial heterogeneity and overdispersion, temperature was highly associated with HFMD incidence. Weekly average temperature and weekly temperature difference approximate inverse “V” shape and “V” shape relationships associated with HFMD incidence. The lag effects for weekly average temperature and weekly temperature difference were 3 weeks and 2 weeks. High spatial correlated HFMD incidence were detected in northern, central and southern province. Temperature can be used to explain most of variation of HFMD incidence in southern and northeastern provinces. After adjustment for temperature, eastern and Northern provinces still had high variation HFMD incidence. Conclusion We found a relatively strong association between weekly HFMD incidence and weekly average temperature. The association between the HFMD incidence and climatic

  16. [Polymorphisms of TLR7 rs3853839 and rs179010 are associated with susceptibility to and severity of hand, foot and mouth disease caused by enterovirus 71 in male children].

    PubMed

    Li, Yaping; Zhai, Song; Li, Mei; Wang, Yuan; Lu, Tong; Deng, Huiling; Zhang, Xin; Dang, Shuangsuo

    2017-07-01

    Objective To investigate whether the polymorphisms of TLR7/MyD88 signaling pathway is associated with the susceptibility to and severity of hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) in children. Methods We collected 180 EV71 HFMD cases and 201 healthy controls from both the Second Affiliated Hospital of Xi'an Jiaotong University and Xi'an Children's Hospital. The genotypes including rs3853839, rs179010 of TLR7, and rs7744 of MyD88 were detected in the 381 samples by SNPscan kit. Results The susceptibility risk (OR=2.343, 95%CI:1.516-3.621) and severity risk (OR=1.939, 95%CI: 1.064-3.521) of TLR7 rs3853839 allele C significantly increased in the male children with EV71 HFMD. Also, the susceptibility risk (OR=1.701, 95%CI: 1.142-2.535) and severity risk (OR=1.852, 95%CI: 1.038-3.305) of TLR7 rs179010 allele T significantly increased in the male children with EV71 HFMD. But there was no significant difference in the distribution of TLR7 rs179010 and rs3853839 genes between female children with EV71 HFMD and female controls. There was no correlation between the genetic polymorphisms of MyD88 rs7744 and the susceptibility to and severity of EV71 HFMD in the children. Conclusion Polymorphisms of TLR7 rs3853839 and rs179010 are correlated to the susceptibility to and severity of EV71 HFMD in male children.

  17. Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia

    PubMed Central

    NikNadia, NMN; Sam, I-Ching; Rampal, Sanjay; WanNorAmalina, WMZ; NurAtifah, Ghazali; Verasahib, Khebir; Ong, Chia Ching; MohdAdib, MohdAidinniza; Chan, Yoke Fun

    2016-01-01

    Enterovirus A71 (EV-A71) is an important emerging pathogen causing large epidemics of hand, foot and mouth disease (HFMD) in children. In Malaysia, since the first EV-A71 epidemic in 1997, recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear. We hypothesize that this cyclical pattern is due to changes in population immunity in children (measured as seroprevalence). Neutralizing antibody titers against EV-A71 were measured in 2,141 residual serum samples collected from children ≤12 years old between 1995 and 2012 to determine the seroprevalence of EV-A71. Reported national HFMD incidence was highest in children <2 years, and decreased with age; in support of this, EV-A71 seroprevalence was significantly associated with age, indicating greater susceptibility in younger children. EV-A71 epidemics are also characterized by peaks of increased genetic diversity, often with genotype changes. Cross-sectional time series analysis was used to model the association between EV-A71 epidemic periods and EV-A71 seroprevalence adjusting for age and climatic variables (temperature, rainfall, rain days and ultraviolet radiance). A 10% increase in absolute monthly EV-A71 seroprevalence was associated with a 45% higher odds of an epidemic (adjusted odds ratio, aOR1.45; 95% CI 1.24–1.69; P<0.001). Every 10% decrease in seroprevalence between preceding and current months was associated with a 16% higher odds of an epidemic (aOR = 1.16; CI 1.01–1.34 P<0.034). In summary, the 2–3 year cyclical pattern of EV-A71 epidemics in Malaysia is mainly due to the fall of population immunity accompanying the accumulation of susceptible children between epidemics. This study will impact the future planning, timing and target populations for vaccine programs. PMID:27010319

  18. Basic reproduction number of coxsackievirus type A6 and A16 and enterovirus 71: estimates from outbreaks of hand, foot and mouth disease in Singapore, a tropical city-state.

    PubMed

    Lim, C T K; Jiang, L; Ma, S; James, L; Ang, L W

    2016-04-01

    Coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and enterovirus 71 (EV-A71) were the major enteroviruses causing nationwide hand, foot and mouth disease (HFMD) epidemics in Singapore in the last decade. We estimated the basic reproduction number (R 0) of these enteroviruses to obtain a better understanding of their transmission dynamics. We merged records of cases from HFMD outbreaks reported between 2007 and 2012 with laboratory results from virological surveillance. R 0 was estimated based on the cumulative number of reported cases in the initial growth phase of each outbreak associated with the particular enterovirus type. A total of 33 HFMD outbreaks were selected based on the inclusion criteria specified for our study, of which five were associated with CV-A6, 13 with CV-A16, and 15 with EV-A71. The median R 0 was estimated to be 5·04 [interquartile range (IQR) 3·57-5·16] for CV-A6, 2·42 (IQR 1·85-3·36) for CV-A16, and 3·50 (IQR 2·36-4·53) for EV-A71. R 0 was not significantly associated with number of infected children (P = 0·86), number of exposed children (P = 0·94), and duration of the outbreak (P = 0·05). These enterovirus-specific R 0 estimates will be helpful in providing insights into the potential growth of future HFMD epidemics and outbreaks for timely implementation of disease control measures, together with disease dynamics such as severity of the cases.

  19. Enterovirus spectrum from the active surveillance of hand foot and mouth disease patients under the clinical trial of inactivated Enterovirus A71 vaccine in Jiangsu, China, 2012-2013.

    PubMed

    Yao, Xin; Bian, Lian-Lian; Lu, Wei-Wei; Li, Jing-Xin; Mao, Qun-Ying; Wang, Yi-Ping; Gao, Fan; Wu, Xing; Ye, Qiang; Xu, Miao; Li, Xiu-Ling; Zhu, Feng-Cai; Liang, Zheng-Lun

    2015-12-01

    Epidemiological data from active surveillance on human enterovirus, which could cause hand, foot, and mouth disease, were limited. An active surveillance system was used to investigate the enterovirus spectrum and the incidence of different enteroviruses in infants aged 6-35 months in Jiangsu Province from 2012 to 2013. Fifty-nine infants were randomly selected from 522 non-EV-A71/CV-A16 HFMD patients. We collected 173 throat swabs and 174 rectal swabs from these infants. RT-PCR was used to amplify 5'-UTR and VP1 regions of enteroviruses and the serotypes were determined by the sequence comparison using BLAST. Twenty-one non-EV-A71/CA16 enterovirus serotypes were detected in those infants. E16, E18 were firstly reported in HFMD patients. The four top common non-EV-A71/CV-A enteroviruses among infants were CV-B3, CV-A10, CV-A6, and E9 with the HFMD incidence rates at 1.4%, 0.84%, 0.56%, and 0.47%, respectively. Over 20.8% patients were co-infected with multiple enteroviruses. Neither the course of sickness nor clinical symptoms of the co-infected patients was more severe than those infected with single enterovirus. Two patients were infected different enterovirus successively within 2 months. Several new enterovirus serotypes and multiple models of infection associated with HFMD were discovered through the active surveillance system. These data provide a better understanding of the viral etiology of HFMD. © 2015 Wiley Periodicals, Inc.

  20. Detection of human enterovirus 71 and coxsackievirus A16 in children with hand, foot and mouth disease in China.

    PubMed

    Chen, Ling; Mou, Xiaozhou; Zhang, Qiong; Li, Yifei; Lin, Jian; Liu, Fanlong; Yuan, Li; Tang, Yiming; Xiang, Charlie

    2012-04-01

    The aims of the present study were to investigate the genetic characteristics of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) strains in China and to evaluate the relationship between the genotypes of CVA16 and EV71 and their geographical distribution. A total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (HFMD) in Zhejiang Province. The presence of enteroviruses was determined using reverse transcription-semi-nested PCR targeted to the VP1 gene of all human enteroviruses and DNA sequencing. EV71 and CVA16, the major etiological agents of HFMD, were detected in 38.4% (38/99) and 35.4% (35/99) of HEV-A species-positive cases, respectively. Based on the phylogenetic analysis of the VP1 gene, EV71 strains identified in this study belong to subgenotype C4, and CVA16 strains herein were classified into clusters B2a and B2b within the genotype B2. Taking into consideration other published data, we conclude that the genetic characteristics of enteroviruses in China reflect the pattern of the endemic circulation of the subgenotype C4 to EV71 and clusters B2a and B2b within genotype B2 to CVA16, which have been continuously circulating in China since 1997. This observation indicates that the genetic characteristics of enteroviruses in China seem to depend on their special geographical and climatical features allowing them to be sustained with little external effect.

  1. Detection of human enterovirus 71 and coxsackievirus A16 in children with hand, foot and mouth disease in China

    PubMed Central

    CHEN, LING; MOU, XIAOZHOU; ZHANG, QIONG; LI, YIFEI; LIN, JIAN; LIU, FANLONG; YUAN, LI; TANG, YIMING; XIANG, CHARLIE

    2012-01-01

    The aims of the present study were to investigate the genetic characteristics of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) strains in China and to evaluate the relationship between the genotypes of CVA16 and EV71 and their geographical distribution. A total of 399 stool specimens were collected from children with symptoms of hand, foot and mouth disease (HFMD) in Zhejiang Province. The presence of enteroviruses was determined using reverse transcription-semi-nested PCR targeted to the VP1 gene of all human enteroviruses and DNA sequencing. EV71 and CVA16, the major etiological agents of HFMD, were detected in 38.4% (38/99) and 35.4% (35/99) of HEV-A species-positive cases, respectively. Based on the phylogenetic analysis of the VP1 gene, EV71 strains identified in this study belong to subgenotype C4, and CVA16 strains herein were classified into clusters B2a and B2b within the genotype B2. Taking into consideration other published data, we conclude that the genetic characteristics of enteroviruses in China reflect the pattern of the endemic circulation of the subgenotype C4 to EV71 and clusters B2a and B2b within genotype B2 to CVA16, which have been continuously circulating in China since 1997. This observation indicates that the genetic characteristics of enteroviruses in China seem to depend on their special geographical and climatical features allowing them to be sustained with little external effect. PMID:22218731

  2. Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination

    PubMed Central

    Takahashi, Saki; Liao, Qiaohong; Van Boeckel, Thomas P.; Xing, Weijia; Sun, Junling; Hsiao, Victor Y.; Metcalf, C. Jessica E.; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Wu, Joseph T.; Cowling, Benjamin J.; Leung, Gabriel M.; Farrar, Jeremy J.; van Doorn, H. Rogier; Grenfell, Bryan T.; Yu, Hongjie

    2016-01-01

    Background Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Methods and Findings Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible–infected–recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R 0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces

  3. Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination.

    PubMed

    Takahashi, Saki; Liao, Qiaohong; Van Boeckel, Thomas P; Xing, Weijia; Sun, Junling; Hsiao, Victor Y; Metcalf, C Jessica E; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Wu, Joseph T; Cowling, Benjamin J; Leung, Gabriel M; Farrar, Jeremy J; van Doorn, H Rogier; Grenfell, Bryan T; Yu, Hongjie

    2016-02-01

    Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71

  4. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases

    PubMed Central

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-01-01

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases. PMID:27436364

  5. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases.

    PubMed

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-07-20

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases.

  6. Short-term effects of meteorological factors on hand, foot and mouth disease among children in Shenzhen, China: Non-linearity, threshold and interaction.

    PubMed

    Zhang, Zhen; Xie, Xu; Chen, Xiliang; Li, Yuan; Lu, Yan; Mei, Shujiang; Liao, Yuxue; Lin, Hualiang

    2016-01-01

    Various meteorological factors have been associated with hand, foot and mouth disease (HFMD) among children; however, fewer studies have examined the non-linearity and interaction among the meteorological factors. A generalized additive model with a log link allowing Poisson auto-regression and over-dispersion was applied to investigate the short-term effects daily meteorological factors on children HFMD with adjustment of potential confounding factors. We found positive effects of mean temperature and wind speed, the excess relative risk (ERR) was 2.75% (95% CI: 1.98%, 3.53%) for one degree increase in daily mean temperature on lag day 6, and 3.93% (95% CI: 2.16% to 5.73%) for 1m/s increase in wind speed on lag day 3. We found a non-linear effect of relative humidity with thresholds with the low threshold at 45% and high threshold at 85%, within which there was positive effect, the ERR was 1.06% (95% CI: 0.85% to 1.27%) for 1 percent increase in relative humidity on lag day 5. No significant effect was observed for rainfall and sunshine duration. For the interactive effects, we found a weak additive interaction between mean temperature and relative humidity, and slightly antagonistic interaction between mean temperature and wind speed, and between relative humidity and wind speed in the additive models, but the interactions were not statistically significant. This study suggests that mean temperature, relative humidity and wind speed might be risk factors of children HFMD in Shenzhen, and the interaction analysis indicates that these meteorological factors might have played their roles individually. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Phylogenetic analysis of the major causative agents of hand, foot and mouth disease in Suzhou city, Jiangsu province, China, in 2012–2013

    PubMed Central

    Zhang, Chao; Zhu, Rui; Yang, Yong; Chi, Yudan; Yin, Jieyun; Tang, Xinying; Yu, Luogang; Zhang, Chiyu; Huang, Zhong; Zhou, Dongming

    2015-01-01

    Hand, foot and mouth disease (HFMD) is a serious public health problem that has emerged over the past several decades. Pathogen detection by the Chinese national HFMD surveillance system has focused mainly on enterovirus 71 (EV71) and coxsackievirus A16 (CA16). Therefore, epidemiological information regarding the other causative enteroviruses is limited. To identify the pandemic enterovirus in Suzhou, Jiangsu province, China, clinical samples from patients with HFMD were collected from 2012 to 2013 and analyzed. The results revealed that CA16 was the most dominant HFMD pathogen in 2012, whereas CA6 and CA10 were the dominant pathogens in 2013. Phylogenetic analysis revealed that the C4a sub-genogroup of EV71 and the B1a and B1b sub-genogroups of CA16 continued to evolve and circulate in Suzhou. The CA6 strains were assigned to six genotypes (A–F) and the CA10 strains were assigned to seven genotypes (A–G), with clear geographical and temporal distributions. All of the CA6 strains in Suzhou belonged to genogroup F, and there were several lineages circulating in Suzhou. All of the CA10 strains in Suzhou belonged to genogroup G, and they had the same genetic origin. Co-infections of EV71/CA16 and CA6/CA10 were found in the samples, and bootscan analysis of 5′-untranslated regions (UTRs) revealed that some CA16 strains in Suzhou had genetic recombination with EV71. This property might allow CA16 to alter its evolvability and circulating ability. This study underscores the need for surveillance of CA6 and CA10 in the Yangtze River Delta and East China. PMID:26038764

  8. Serum cytokine profiles of children with human enterovirus 71-associated hand, foot, and mouth disease.

    PubMed

    Han, Jun; Wang, Ying; Gan, Xing; Song, Juan; Sun, Peng; Dong, Xiao-Ping

    2014-08-01

    Cytokine profiles may impact the pathogenicity and severity of hand, foot, and mouth disease caused by human enterovirus (HEV) 71. In 91 severe or mild HEV 71-associated hand, foot, and mouth disease children, serum was collected between days 2 and 10 or day >10. Serum cytokines including Type 1 T helper (Th1) cytokines: interleukin (IL)-2, interferon-gamma (IFN-γ), IL-12, and IL-18, Type 1 T helper (Th2) cytokines: IL-4, IL-10, IL-13, proinflammatory cytokines: IL-1α, IL-1β, IL-6, IL-8, IL-17, and tumor necrosis factor alpha (TNF-α), were assessed during the early stage and recovery. In the patients with mild illness, the peaks of IL-8 and IL-10 were observed on day 6 and that of IL-18 was on day 4. In the patients with severe illness, all cytokines spiked on day 3 and peaked on day 11. All cytokines except IL-6, IL-8, IL-18, and TNF-α were significantly correlated with immunoglobulin M levels by the end of the disease course. Cytokine profile variations between the patients with mild and severe illness may indicate prognosis and strain virulence, useful in clinical treatment of patients. © 2014 Wiley Periodicals, Inc.

  9. Identification and validation of clinical predictors for the risk of neurological involvement in children with hand, foot, and mouth disease in Sarawak

    PubMed Central

    2009-01-01

    Background Human enterovirus 71 (HEV71) can cause Hand, foot, and mouth disease (HFMD) with neurological complications, which may rapidly progress to fulminant cardiorespiratory failure, and death. Early recognition of children at risk is the key to reduce acute mortality and morbidity. Methods We examined data collected through a prospective clinical study of HFMD conducted between 2000 and 2006 that included 3 distinct outbreaks of HEV71 to identify risk factors associated with neurological involvement in children with HFMD. Results Total duration of fever ≥ 3 days, peak temperature ≥ 38.5°C and history of lethargy were identified as independent risk factors for neurological involvement (evident by CSF pleocytosis) in the analysis of 725 children admitted during the first phase of the study. When they were validated in the second phase of the study, two or more (≥ 2) risk factors were present in 162 (65%) of 250 children with CSF pleocytosis compared with 56 (30%) of 186 children with no CSF pleocytosis (OR 4.27, 95% CI2.79–6.56, p < 0.0001). The usefulness of the three risk factors in identifying children with CSF pleocytosis on hospital admission during the second phase of the study was also tested. Peak temperature ≥ 38.5°C and history of lethargy had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 28%(48/174), 89%(125/140), 76%(48/63) and 50%(125/251), respectively in predicting CSF pleocytosis in children that were seen within the first 2 days of febrile illness. For those presented on the 3rd or later day of febrile illness, the sensitivity, specificity, PPV and NPV of ≥ 2 risk factors predictive of CSF pleocytosis were 75%(57/76), 59%(27/46), 75%(57/76) and 59%(27/46), respectively. Conclusion Three readily elicited clinical risk factors were identified to help detect children at risk of neurological involvement. These risk factors may serve as a guide to clinicians to decide the need for

  10. Best practices to prevent transmission and control outbreaks of hand, foot, and mouth disease in childcare facilities: a systematic review.

    PubMed

    Chan, J Hy; Law, C K; Hamblion, E; Fung, H; Rudge, J

    2017-04-01

    Hand, foot, and mouth disease continues to cause seasonal epidemics in the Asia-Pacific Region. Since the current Enterovirus 71 vaccines do not provide cross-protection for all Enterovirus species that cause hand, foot, and mouth disease, there is an urgent need to identify appropriate detection tools and best practice to prevent its transmission and to effectively control its outbreaks. This systematic review aimed to identify characteristics of outbreak and assess the impact and effectiveness of detection tools and public health preventive measures to interrupt transmission. The findings will be used to recommend policy on the most effective responses and interventions in Hong Kong to effectively minimise and contain the spread of the disease within childcare facilities. We searched the following databases for primary studies written in Chinese or English: MEDLINE, EMBASE, Global Health, WHO Western Pacific Region Index Medicus database, China National Knowledge Infrastructure Databases, and Chinese Scientific Journals Database. Studies conducted during or retrospective to outbreaks of hand, foot, and mouth disease caused by Enterovirus 71 from 1980 to 2012 within childcare facilities and with a study population of 0 to 6 years old were included. Sixteen studies conducted on outbreaks in China showed that hand, foot, and mouth disease spread rapidly within the facility, with an outbreak length of 4 to 46 days, especially in those with delayed notification (after 24 hours) of clustered outbreak (with five or more cases discovered within the facility) to the local Center for Disease Control and Prevention and delayed implementation of a control response. The number of classes affected ranged from 1 to 13, and the attack rate for children ranged from 0.97% to 28.18%. Communication between key stakeholders about outbreak confirmation, risk assessment, and surveillance should be improved. Effective communication facilitates timely notification (within 24 hours) of

  11. Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2017-07-12

    Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 10 4 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.

  12. Modelling person-to-person transmission in an Enterovirus A71 orally infected hamster model of hand-foot-and-mouth disease and encephalomyelitis

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2017-01-01

    Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal–oral or oral–oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3–4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission. PMID:28698666

  13. Epidemiological and genetic analysis concerning the non-enterovirus 71 and non-coxsackievirus A16 causative agents related to hand, foot and mouth disease in Anyang city, Henan Province, China, from 2011 to 2015.

    PubMed

    Li, Yang; Bao, Honghong; Zhang, Xiangping; Zhai, Mingqiang; Bao, Xiaobing; Wang, Demin; Zhang, Shuanhu

    2017-10-01

    Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are major pathogens of hand, foot, and mouth disease (HFMD) and have been associated with consecutive outbreaks of HFMD in China over the past years. Although several other human enteroviruses (HEVs) have also acted as causative agents of HFMD, published information on their roles in the prevalence of HFMD is limited. This study was conducted to reveal the characteristics of the pathogenic spectrum and molecular epidemiology of the non-EV-71 and -CV-A16 HEVs in Anyang City, which is located in north-central China and has a population of five million. From 2011 to 2015, 2270 samples were collected from HFMD patients (3.89 ± 1.06 years of age), and 1863 HEV-positive samples, including 524 samples with 23 non-EV-71 and non-CV-A16 serotypes, were identified. Based on the nucleotide sequence of the VP1 gene, 6 common non-EV-71 and non-CV-A16 HEVs, including coxsackievirus A2, A6, A10, A14, B2, and B5, were studied to determine their phylogenies and selective pressures. Phylogenetic analyses revealed a high level of genetic divergence and a pattern of lineage replacement over time in Mainland China. Selective pressure analyses showed that purifying selection was predominant in the evolution of the VP1 gene, whereas positive selection acted on individual codons. Overall, non-EV-71 and non-CV-A16 HEVs were important constituents of the pathogenic spectrum of HFMD in Anyang City during 2011-2015. Some of these HEVs with complex and active phylogenies represent a potential threat to public health, suggesting that long-term monitoring of these pathogens should be implemented to prevent HFMD outbreaks. © 2017 Wiley Periodicals, Inc.

  14. [Rash and fever illness caused by herpes simplex virus type 1 needs to be distinguished from hand, foot and mouth disease].

    PubMed

    Zhu, Shuang-Li; Liu, Jian-Feng; Sun, Qiang; Li, Jing; Li, Xiao-Lei; Zhang, Yong; Chen, Ying; Wen, Xiao-Yun; Yan, Dong-Mei; Huang, Guo-Hong; Zhang, Bao-Min; Zhang, Bo; An, Hong-Qiu; Li, Hui; Xu, Wen-Bo

    2013-06-01

    An epidemic of rash and fever illnesses suspected of hand, foot and mouth disease (HFMD) occurred in Gansu Province of China in 2008, laboratory tests were performed in order to identify the pathogen that caused this epidemic. Eight clinical specimens collected from the 4 patients (each patient has throat swab and herpes fluid specimens) with rash and febrile illness, were inoculated onto RD and HEp-2 cells for virus isolation, and the viral nucleic acid was then extracted with the positive virus isolates, the dual-channel real-time reverse transcript-polymerase chain reaction (RT-PCR) was performed to detect the nucleic acid of human enterovirus (HEV) in the viral isolates at the same time. For the viral isolates with the negative results of HEV, a sequence independent single primer amplification technique (SISPA) was used for "unknown pathogen" identification. Totally, 6 viral isolates were identified as herpes simplex virus type 1 (HSV-1). Comprehensive analyses results of the clinical manifestations of the patients, epidemiological findings and laboratory test indicated that this epidemic of rash and febrile illness was caused by HSV-1. The differences among the gG region of 6 HSV-1 isolates at nucleotide level and amino acid level were all small, and the identities were up to 98. 8% and 97.9%, respectively, showing that this outbreak was caused by only one viral transmission chain of HSV-1. HSV-1 and other viruses that cause rash and febrile illnesses need differential diagnosis with HFMD. The etiology of rash and febrile illness is sometimes difficult to distinguish from the clinical symptoms and epidemiological data, the laboratory diagnosis is therefore critical.

  15. Modelling the effects of contaminated environments on HFMD infections in mainland China.

    PubMed

    Wang, Jinyan; Xiao, Yanni; Cheke, Robert A

    2016-02-01

    Hand-foot-mouth disease (HFMD) has spread widely in mainland China increasing in prevalence in most years with serious consequences for child health. The HFMD virus can survive for a long period outside the host in suitable conditions, and hence contaminated environments may play important roles in HFMD infection. A new mathematical model was proposed and used to investigate the roles that asymptomatic individuals and contaminated environments played in HFMD dynamics. The model includes both direct transmission between susceptible and infected individuals and indirect transmission via free-living infectious unites in the environment. Theoretical analysis shows that the disease goes to extinction if the basic reproduction number is less than unity, whilst otherwise the disease persists. By fitting the proposed model to surveillance data we estimated the basic reproduction number as 1.509. Numerical simulations show that increasing the rate of virus clearance and decreasing transmission rates can delay epidemic outbreaks and weaken the severity of HFMD. Sensitivity analysis indicated that the basic reproduction number is sensitive to the transmission rate induced by asymptomatic infectious individuals and parameters associated with contaminated environments such as the indirect transmission rate, the rate of clearance and the virus shedding rates. This implies that asymptomatic infectious individuals and contaminated environments contribute substantially to new HFMD infections, and so would be targets for effective control measures. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Foot-and-mouth disease

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. An outbreak of FMD can have a significant economic impact because of the restrictions on international trade of susceptible animals and their products with FMD-free countries. In this chapter we discuss vario...

  17. Development of single-step multiplex real-time RT-PCR assays for rapid diagnosis of enterovirus 71, coxsackievirus A6, and A16 in patients with hand, foot, and mouth disease.

    PubMed

    Puenpa, Jiratchaya; Suwannakarn, Kamol; Chansaenroj, Jira; Vongpunsawad, Sompong; Poovorawan, Yong

    2017-10-01

    Real-time reverse-transcription polymerase chain reaction (rRT-PCR) to detect enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) has facilitated the rapid and accurate identification of the two most common etiological agents underlying hand, foot, and mouth disease (HFMD). However, the worldwide emergence of CV-A6 infection in HFMD necessitates development of an improved multiplex rRT-PCR method. To rapidly determine the etiology of HFMD, two rRT-PCR assays using TaqMan probes were developed to differentiate among three selected common enteroviruses (EV-A71, CV-A16 and CV-A6) and to enable broad detection of enteroviruses (pan-enterovirus assay). No cross-reactions were observed with other RNA viruses examined. The detection limits of both assays were 10 copies per microliter for EV-A71, CV-A6 and CV-A16, and pan-enterovirus. The methods showed high accuracy (EV-A71, 90.6%; CV-A6, 92.0%; CV-A16, 100%), sensitivity (EV-A71, 96.5%; CV-A6, 95.8%; CV-A16, 99.0%), and specificity (EV-A71, 100%; CV-A6, 99.9%; CV-A16, 99.9%) in testing clinical specimens (n=1049) during 2014-2016, superior to those of conventional RT-PCR. Overall, the multiplex rRT-PCR assays enabled highly sensitive detection and rapid simultaneous typing of EV-A71, CV-A6 and CV-A16, and enteroviruses, rendering them feasible and attractive methods for large-scale surveillance of enteroviruses associated with HFMD outbreaks. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. [Analysis on the change of genotype of enteroviruses associated hand, foot and mouth disease in Beijing during 2013 to 2014].

    PubMed

    Song, Qinwei; Huang, Hui; Deng, Jie; Zhao, Linqing; Deng, Li; Sun, Yu; Wang, Fang; Oian, Yuan; Zhu, Runan

    2015-08-01

    To analyze the genotype, epidemic pattern and the characteristics of the disease of enteroviruses during the epidemic season of hand, foot and mouth disease (HMFD) in children from 2013 to 2014 in Beijing to provide the scientific evidence for prevention and treatment of HFMD. During April to September in 2013 and March to October in 2014, a total of 977 throat swabs were collected from children who visited the Children's Hospital Affiliated to Capital Institute of Pediatrics, including 147 from patients with HFMD in 2013, 343 with HFMD, 201 with atypical HFMD, 83 with herpangina, 25 with fever with convulsions, 64 fever with rash and 114 with rash in 2014. Enteroviruses universal type (EV), Enteroviruses type 71 (EV71) and Coxsackievirus group A 16 (CA16) were detected by real-time RT-PCR respectively. The nucleic acid of specimens which were identified with non-EV71, non-CA16 was tested by nested PCR and analyzed by VP1 sequencing. The detection rate and epidemic pattern of different genotypes of enterovirus were analyzed among different age groups and between 2013 and 2014. Of 977 throat swabs, 80. 1% samples were detected positive for enteroviruses. The positive rates of CA16, EV71, CA6, CA10, CA4 and other EVs were 25. 6% (250/977), 18. 9% (185/977), 20. 0% (195/977), 5. 0% (49/977), 1.5% (15/977) and 9.1% (89/977), respectively. Twenty six of the 89 other EVs included CA2, CA5, CA8, CA9, CA12, CA14, CB2, CB5, E6, E9 and E25, each genotype of which was no more than 3. The nucleotide homologies shared among CA6, CA10 and CA4 strains between 2013 and 2014 were 94. 3% - 100%, 93. 8% - 99. 1% and 92.7% - 99. 8%, respectively. The positive rates of ≤1 year group were 71. 1% (106/149), which was lower than that of other age groups (all P <0. 05), but similar to that of >5 year group (χ2 =1. 181,P = 0. 277). In 2013, the positive rate of EV was 85. 7% (126/147) and the predominant genotype was CA6 54. 8% (69/126), followed by CA16 20. 6% (26/126) and EV71 11. 9

  19. Foot-and-mouth disease vaccines

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild cloven-hoofed animals. This disease has affected most areas of the world, often causing extensive epizootics in livestock, mostly farmed cattle and swine, although sheep, goats and many wild species are also susceptible...

  20. Development of a highly sensitive real-time nested RT-PCR assay in a single closed tube for detection of enterovirus 71 in hand, foot, and mouth disease.

    PubMed

    Niu, Peihua; Qi, Shunxiang; Yu, Benzhang; Zhang, Chen; Wang, Ji; Li, Qi; Ma, Xuejun

    2016-11-01

    Enterovirus 71 (EV71) is one of the major causative agents of outbreaks of hand, foot, and mouth disease (HFMD). A commercial TaqMan probe-based real-time PCR assay has been widely used for the differential detection of EV71 despite its relatively high cost and failure to detect samples with a low viral load (Ct value > 35). In this study, a highly sensitive real-time nested RT-PCR (RTN RT-PCR) assay in a single closed tube for detection of EV71 in HFMD was developed. The sensitivity and specificity of this assay were evaluated using a reference EV71 stock and a panel of controls consisting of coxsackievirus A16 (CVA16) and common respiratory viruses, respectively. The clinical performance of this assay was evaluated and compared with those of a commercial TaqMan probe-based real-time PCR (qRT-PCR) assay and a traditional two-step nested RT-PCR assay. The limit of detection for the RTN RT-PCR assay was 0.01 TCID50/ml, with a Ct value of 38.3, which was the same as that of the traditional two-step nested RT-PCR assay and approximately tenfold lower than that of the qRT-PCR assay. When testing the reference strain EV71, this assay showed favorable detection reproducibility and no obvious cross-reactivity. The testing results of 100 clinical throat swabs from HFMD-suspected patients revealed that 41 samples were positive for EV71 by both RTN RT-PCR and traditional two-step nested RT-PCR assays, whereas only 29 were EV71 positive by qRT-PCR assay.

  1. Co-Circulation and Genomic Recombination of Coxsackievirus A16 and Enterovirus 71 during a Large Outbreak of Hand, Foot, and Mouth Disease in Central China

    PubMed Central

    Liu, Weiyong; Wu, Shimin; Xiong, Ying; Li, Tongya; Wen, Zhou; Yan, Mingzhe; Qin, Kai; Liu, Yingle; Wu, Jianguo

    2014-01-01

    A total of 1844 patients with hand, foot, and mouth disease (HFMD), most of them were children of age 1–3-year-old, in Central China were hospitalized from 2011 to 2012. Among them, 422 were infected with coxsackievirus A16 (CVA16), 334 were infected with enterovirus 71 (EV71), 38 were co-infected with EV71 and CVA16, and 35 were infected with other enteroviruses. Molecular epidemiology analysis revealed that EV71 and CVA16 were detected year-round, but EV71 circulated mainly in July and CVA16 circulated predominantly in November, and incidence of HFMD was reduced in January and February and increased in March. Clinical data showed that hyperglycemia and neurologic complications were significantly higher in EV71-infected patients, while upper respiratory tract infection and C-reactive protein were significantly higher in CVA16-associated patients. 124 EV71 and 80 CVA16 strains were isolated, among them 56 and 68 EV71 strains were C4a and C4b, while 25 and 55 CVA16 strains were B1a and B1b, respectively. Similarity plots and bootscan analyses based on entire genomic sequences revealed that the three C4a sub-genotype EV71 strains were recombinant with C4b sub-genotype EV71 in 2B–2C region, and the three CVA16 strains were recombinant with EV71 in 2A–2B region. Thus, CVA16 and EV71 were the major causative agents in a large HFMD outbreak in Central China. HFMD incidence was high for children among household contact and was detected year-round, but outbreak was seasonal dependent. CVA16 B1b and EV71 C4b reemerged and caused a large epidemic in China after a quiet period of many years. Moreover, EV71 and CVA16 were co-circulated during the outbreak, which may have contributed to the genomic recombination between the pathogens. It should gain more attention as there may be an upward trend in co-circulation of the two pathogens globally and the new role recombination plays in the emergence of new enterovirus variants. PMID:24776922

  2. [Myocardial protective effect of L-carnitine in children with hand, foot and mouth disease caused by Coxsackie A16 virus].

    PubMed

    Cui, Ya-Jie; Song, Chun-Lan; Chen, Fang; Li, Peng; Cheng, Yi-Bing

    2017-08-01

    To investigate the myocardial protective effect of L-carnitine in children with hand, foot and mouth disease (HFMD) caused by Coxsackie A16 virus and possible mechanisms. A total of 60 HFMD children with abnormal myocardial enzyme after Coxsackie A16 virus infection were enrolled and randomly divided into L-carnitine group and fructose-1,6-diphosphate group (fructose group), with 30 children in each group. The two groups were given L-carnitine or fructose diphosphate in addition to antiviral and heat clearance treatment. Another 30 healthy children who underwent physical examination were enrolled as control group. The changes in myocardial zymogram, malondialdehyde (MDA), superoxide dismutase (SOD), and apoptosis factors sFas and sFasL after treatment were compared between groups. There was no significant difference in treatment response between the L-carnitine group and the fructose group (P>0.05). One child in the fructose group progressed to critical HFMD, which was not observed in the L-carnitine group. Before treatment, the L-carnitine group and the fructose group had significantly higher indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significantly lower level of SOD than the control group (P<0.05), while there were no significant differences in these indices between the L-carnitine group and the fructose group (P>0.05). After treatment, the L-carnitine group and the fructose group had significant reductions in the indices of myocardial zymogram and levels of MDA, sFas, and sFasL and a significant increase in the level of SOD (P<0.05); the fructose group had a significantly higher level of creatine kinase (CK) than the control group and the L-carnitine group, and there were no significant differences in other myocardial enzyme indices, MDA, sFas, and sFasL between the L-carnitine group and the fructose group, as well as between the L-carnitine and fructose groups and the control group (P>0.05). SOD level was negatively correlated with

  3. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease.

    PubMed

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4-8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer's patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines.

  4. A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

    PubMed Central

    Phyu, Win Kyaw; Ong, Kien Chai; Wong, Kum Thong

    2016-01-01

    Enterovirus A71 (EV-A71) causes self-limiting, hand-foot-and-mouth disease (HFMD) that may rarely be complicated by encephalomyelitis. Person-to-person transmission is usually by fecal-oral or oral-oral routes. To study viral replication sites in the oral cavity and other tissues, and to gain further insights into virus shedding and neuropathogenesis, we developed a consistent, orally-infected, 2-week-old hamster model of HFMD and EV-A71 encephalomyelitis. Tissues from orally-infected, 2-week-old hamsters were studied by light microscopy, immunohistochemistry and in situ hybridization to detect viral antigens and RNA, respectively, and by virus titration. Hamsters developed the disease and died after 4–8 days post infection; LD50 was 25 CCID50. Macroscopic cutaneous lesions around the oral cavity and paws were observed. Squamous epithelium in the lip, oral cavity, paw, skin, and esophagus, showed multiple small inflammatory foci around squamous cells that demonstrated viral antigens/RNA. Neurons (brainstem, spinal cord, sensory ganglia), acinar cells (salivary gland, lacrimal gland), lymphoid cells (lymph node, spleen), and muscle fibres (skeletal, cardiac and smooth muscles), liver and gastric epithelium also showed varying amounts of viral antigens/RNA. Intestinal epithelium, Peyer’s patches, thymus, pancreas, lung and kidney were negative. Virus was isolated from oral washes, feces, brain, spinal cord, skeletal muscle, serum, and other tissues. Our animal model should be useful to study squamous epitheliotropism, neuropathogenesis, oral/fecal shedding in EV-A71 infection, person-to-person transmission, and to test anti-viral drugs and vaccines. PMID:26815859

  5. Survival of foot-and-mouth disease virus in cheese.

    PubMed

    Blackwell, J H

    1976-09-01

    Persistence of foot-and-mouth disease virus during the manufacture of Cheddar, Mozzarella, Camembert cheese prepared from milk of cows experimentally infected with the virus was studied. Cheese samples were made on a laboratory scale with commercial lactic acid starter cultures and the microbial protease MARZYME as a coagulant. Milk was heated at different temperatures for different intervals before it was made into cheese. Food-and-mouth disease virus survived the acidic conditions of Cheddar and Camembert cheese processing but not that of Mozzarella. Foot-and-mouth disease virus survived processing but not curing for 30 days in Cheddar cheese preparaed from heated milk. However, the virus survived curing for 60 days but not for 120 days in cheese (pH 5) prepared from unheated milk. Foot-and-mouth disease virus survived in Camembert cheese (pH 5) for 21 days at 2 C but not for 35 days.

  6. 75 FR 65431 - Change in Disease Status of Japan Because of Foot-and-Mouth Disease

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-25

    .... APHIS-2010-0077] Change in Disease Status of Japan Because of Foot-and-Mouth Disease AGENCY: Animal and... removing Japan from the list of regions considered to be free of foot-and-mouth disease (FMD) and also from.... SUPPLEMENTARY INFORMATION: Background Foot-and-mouth disease (FMD) is a severe and highly contagious viral...

  7. [Neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease : clinical features, MRI findings and follow-up study].

    PubMed

    Liu, Kun; Ma, Yan-xu; Zhang, Cheng-bing; Chen, Yi-ping; Ye, Xin-jian; Bai, Guang-hui; Yu, Zhi-kang; Yan, Zhi-han

    2012-07-03

    To explore the clinical and magnetic resonance imaging (MRI) characteristics and the follow-up outcomes of neurologic complications in children with enterovirus 71-infected hand-foot-mouth disease. The clinical and MRI manifestations and follow-up outcomes in 35 children, at Second Affiliated Hospital, Wenzhou Medical College from August 2008 to November 2010, hospitalized with neurologic complications of enterovirus 71-infected hand-foot-mouth disease were retrospectively analyzed. Six children with aseptic meningitis presented the clinical symptoms and signs of meningitis. Five of them showed subdural effusion and ventriculomegaly, or both on MRI. At follow-ups, neurologic sequel could not be found. Among 24 cases with brainstem encephalitis, there were myoclonic jerks and tremor, ataxia, or both (grade I disease, n = 12), myoclonus and cranial-nerve involvement (grade II disease, n = 4), and cardiopulmonary failure after brain-stem infection (grade III disease, n = 8). In patients with brainstem encephalitis, lesions were predominantly located at the posterior portions of medulla and pons with hypointensity on T1WI and hyperintensity on T2WI. Cerebellar dentate nucleus, caudate nucleus and lenticular nucleus could also be involved. At follow-ups, the patients with mild symptoms had no neurologic sequel and the lesions within brain stem became small or vanished in most cases. While in the majority of serious patients, neurologic sequel could be found and the lesions located at brain stem became encephalomalacia. Fourteen cases with acute flaccid paralysis presented acute limb myasthenia with tendon reflex and muscular tension decreased. On spinal MRI, the lesions predominantly involved anterior horn regions of spinal cord with hypointensity on T1WI and hyperintensity on T2WI. Most patients improved their muscle strength and most lesions of spinal cord became smaller or vanished during follow-ups. MRI is the most effective modality of diagnosis and follow-up for

  8. Immunodominant IgM and IgG Epitopes Recognized by Antibodies Induced in Enterovirus A71-Associated Hand, Foot and Mouth Disease Patients

    PubMed Central

    Aw-Yong, Kam Leng; Sam, I-Ching; Koh, Mia Tuang

    2016-01-01

    Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD). Unlike other enteroviruses that cause HFMD, EV-A71 is more frequently associated with severe neurological complications and fatality. To date, no effective licensed antivirals are available to combat EV-A71 infection. Little is known about the immunogenicity of viral non-structural proteins in humans. Previous studies have mainly focused on characterization of epitopes of EV-A71 structural proteins by using immunized animal antisera. In this study, we have characterized human antibody responses against the structural and non-structural proteins of EV-A71. Each viral protein was cloned and expressed in either bacterial or mammalian systems, and tested with antisera by western blot. Results revealed that all structural proteins (VP1-4), and non-structural proteins 2A, 3C and 3D were targets of EV-A71 IgM, whereas EV-A71 IgG recognized all the structural and non-structural proteins. Sixty three synthetic peptides predicted to be immunogenic in silico were synthesized and used for the characterization of EV-A71 linear B-cell epitopes. In total, we identified 22 IgM and four IgG dominant epitopes. Synthetic peptide PEP27, corresponding to residues 142–156 of VP1, was identified as the EV-A71 IgM-specific immunodominant epitope. PEP23, mapped to VP1 41–55, was recognized as the EV-A71 IgG cross-reactive immunodominant epitope. The structural protein VP1 is the major immunodominant site targeted by anti-EV-A71 IgM and IgG antibodies, but epitopes against non-structural proteins were also detected. These data provide new understanding of the immune response to EV-A71 infection, which benefits the development of diagnostic tools, potential therapeutics and subunit vaccine candidates. PMID:27806091

  9. Foot-and-mouth disease virus receptors: multiple gateways to initiate infection

    USDA-ARS?s Scientific Manuscript database

    Since its discovery over 100 years ago as the causative agent of foot-and-mouth disease (FMD), research has been directed at understanding the biology of the foot-and-mouth disease virus (FMDV) so as to be able to control this devastating and highly contagious disease of cloven-hoofed livestock. Giv...

  10. Neuro-Magnetic Resonance Imaging in Hand, Foot, and Mouth Disease: Finding in 412 Patients and Prognostic Features.

    PubMed

    Lian, Zhou-Yang; Li, He-Hong; Zhang, Bin; Dong, Yu-Hao; Deng, Wu-Xu; Liu, Jing; Luo, Xiao-Ning; Huang, Biao; Liang, Chang-Hong; Zhang, Shui-Xing

    The aims of this study were to describe the neuroimaging findings in hand, foot, and mouth disease and determine those who may provide prognosis. Magnetic resonance imaging scans in 412 severe hand, foot, and mouth disease between 2009 and 2014 were retrospectively evaluated. The patients who had the neurological signs were followed for 6 months to 1 year. According to the good or poor prognosis, 2 groups were categorized. The incidence of lesions in different sites between the 2 groups was compared, and multivariate analysis was used to look for risk factors. The major sites of involvement for all patients with percentages were the medulla oblongata (16.1%), spinal anterior nerve roots (12.4%), thoracic segments (11.1%), brain or spinal meninges (8.3%), and so on. There were 347 patients (84.2%) with good prognosis and 65 (15.8%) with poor prognosis in the follow-up. There was a significantly higher rate of lesions involving the cerebral white substance, thalamus, medulla oblongata, pons, midbrain, and spinal cord in the group with poor prognosis. Multivariate analysis showed 2 independent risk factors associated with poor prognosis: lesions located in the medulla oblongata (P < 0.015) and spinal cord (P < 0.001) on magnetic resonance imaging; the latter was the most significant prognostic factor (odds ratio, 29.11; P < 0.001). We found that the distribution patterns for all patients mainly involved the medulla oblongata, spinal anterior nerve roots, thoracic segments, and brain or spinal meninges. Our findings suggested that patients with lesions located in the medulla oblongata and spinal cord may be closely monitored for early intervention and meticulous management. For children with the symptom of nervous system, they are strongly recommended for magnetic resonance examination.

  11. Estimating the basic reproduction rate of HFMD using the time series SIR model in Guangdong, China

    PubMed Central

    Du, Zhicheng; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng

    2017-01-01

    Hand, foot, and mouth disease (HFMD) has caused a substantial burden of disease in China, especially in Guangdong Province. Based on notifiable cases, we use the time series Susceptible-Infected-Recovered model to estimate the basic reproduction rate (R0) and the herd immunity threshold, understanding the transmission and persistence of HFMD more completely for efficient intervention in this province. The standardized difference between the reported and fitted time series of HFMD was 0.009 (<0.2). The median basic reproduction rate of total, enterovirus 71, and coxsackievirus 16 cases in Guangdong were 4.621 (IQR: 3.907–5.823), 3.023 (IQR: 2.289–4.292) and 7.767 (IQR: 6.903–10.353), respectively. The heatmap of R0 showed semiannual peaks of activity, including a major peak in spring and early summer (about the 12th week) followed by a smaller peak in autumn (about the 36th week). The county-level model showed that Longchuan (R0 = 33), Gaozhou (R0 = 24), Huazhou (R0 = 23) and Qingxin (R0 = 19) counties have higher basic reproduction rate than other counties in the province. The epidemic of HFMD in Guangdong Province is still grim, and strategies like the World Health Organization’s expanded program on immunization need to be implemented. An elimination of HFMD in Guangdong might need a Herd Immunity Threshold of 78%. PMID:28692654

  12. Comparative Analysis of Serum Proteins from Patients with Severe and Mild EV-A71-induced HFMD using iTRAQ-Coupled LC-MS/MS Screening.

    PubMed

    Fan, Peihu; Chen, Wei; Yu, Pin; Bao, Linlin; Xu, Lili; Qin, Chuan

    2017-12-01

    This study was designed to provide a rationale for monitoring the development of severe hand, foot, and mouth disease (HFMD) and predicting the onset of this disease via global comparative analysis between patients with severe and mild HFMD. The authors collected serum from five groups: mild (E-M) and severe (E-S) EV-A71-induced HFMD; mild (NE-M) and severe (NE-S) non-EV-A71-induced HFMD; and healthy control subjects (CON). The authors then performed comparative analysis and identified specific differentially expressed proteins (DEPs) of E-S using isobaric mass tag (isobaric tags for relative and absolute quantitation, iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Moreover, The authors validated specific DEPs by multiple reaction monitoring (MRM). The authors identified 10 specific proteins that were significantly altered in E-S patients. Bioinformatics analysis revealed that most of these DEPs are primarily involved in the acute response to infection, which was common to all groups. More importantly, up-regulated proteins associated with neural injury were specifically identified in the E-S group. These findings conclude that severe HFMD symptoms may be caused by EV-A71 infection-mediated injury of the neural system and provide a reference for future research on the course and prognosis of severe HFMD. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Outbreak of variant hand-foot-and-mouth disease caused by coxsackievirus A6 in Auckland, New Zealand.

    PubMed

    Hayman, Rebecca; Shepherd, Michael; Tarring, Claire; Best, Emma

    2014-10-01

    Hand-foot-and-mouth disease is a common, usually mild childhood illness caused by enteroviruses. Over the last five years, coxsackievirus A6 has been identified as a causative agent in outbreaks in Europe, South-East Asia and America. It has an atypical presentation compared with other enteroviruses, with more widespread rash, larger blisters and subsequent skin peeling and/or nail shedding. We give the first description of an outbreak of coxsackievirus A6 in New Zealand and how health-care communication networks enabled detection of and dissemination of information about this emergent strain. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  14. Assessing the impact of humidex on HFMD in Guangdong Province and its variability across social-economic status and age groups

    NASA Astrophysics Data System (ADS)

    Zhang, Wangjian; Du, Zhicheng; Zhang, Dingmei; Yu, Shicheng; Huang, Yong; Hao, Yuantao

    2016-01-01

    Humidex is a meteorological index that combines the impacts of temperature and humidity, and is directly comparable with dry temperature in degrees Celsius. However, to date, no research has focused on the effect of humidex on hand, foot and mouth disease (HFMD). The current study was designed to address this research need. Case-based HFMD surveillance data and daily meteorological data collected between 2010 and 2012 was obtained from the China CDC and the National Meteorological Information Center, respectively. Distributed lag nonlinear models were applied to assess the impact of humidex on HFMD among children under 15 years oldin Guangdong, and its variability across social-economic status and age groups. We found that relative risk (RR) largely increased with humidex. Lag-specific and cumulative humidex-RR curves for children from the Pearl-River Delta Region as well as older children were more likely to show two-peak distribution patterns. One RR peak occurred at a humidex of between 15 and 20, and the other occurred between 30 and 35. This study provides a comprehensive picture of the impact of humidex on HFMD incidence in Guangdong Province. Results from the present study should be important in the development of area-and-age-targeted control programs.

  15. Immunopathogenesis and Virus–Host Interactions of Enterovirus 71 in Patients with Hand, Foot and Mouth Disease

    PubMed Central

    Cox, Jonathan A.; Hiscox, Julian A.; Solomon, Tom; Ooi, Mong-How; Ng, Lisa F. P.

    2017-01-01

    Enterovirus 71 (EV71) is a global infectious disease that affects millions of people. The virus is the main etiological agent for hand, foot, and mouth disease with outbreaks and epidemics being reported globally. Infection can cause severe neurological, cardiac, and respiratory problems in children under the age of 5. Despite on-going efforts, little is known about the pathogenesis of EV71, how the host immune system responds to the virus and the molecular mechanisms behind these responses. Moreover, current animal models remain limited, because they do not recapitulate similar disease patterns and symptoms observed in humans. In this review the role of the host–viral interactions of EV71 are discussed together with the various models available to examine: how EV71 utilizes its proteins to cleave host factors and proteins, aiding virus replication; how EV71 uses its own viral proteins to disrupt host immune responses and aid in its immune evasion. These discoveries along with others, such as the EV71 crystal structure, have provided possible targets for treatment and drug interventions. PMID:29238324

  16. Airborne spread of foot-and-mouth disease - model intercomparison

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gloster, J; Jones, A; Redington, A

    2008-09-04

    Foot-and-mouth disease is a highly infectious vesicular disease of cloven-hoofed animals caused by foot-and-mouth disease virus. It spreads by direct contact between animals, by animal products (milk, meat and semen), by mechanical transfer on people or fomites and by the airborne route - with the relative importance of each mechanism depending on the particular outbreak characteristics. Over the years a number of workers have developed or adapted atmospheric dispersion models to assess the risk of foot-and-mouth disease virus spread through the air. Six of these models were compared at a workshop hosted by the Institute for Animal Health/Met Office duringmore » 2008. A number of key issues emerged from the workshop and subsequent modelling work: (1) in general all of the models predicted similar directions for 'at risk' livestock with much of the remaining differences strongly related to differences in the meteorological data used; (2) determination of an accurate sequence of events is highly important, especially if the meteorological conditions vary substantially during the virus emission period; and (3) differences in assumptions made about virus release, environmental fate, and subsequent infection can substantially modify the size and location of the downwind risk area. Close relationships have now been established between participants, which in the event of an outbreak of disease could be readily activated to supply advice or modelling support.« less

  17. Foot-and-mouth disease: global status and Indian perspective

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious and transboundary viral disease of domesticated and wild cloven-hoofed animals. Wide prevalence of the disease in Asia and Africa associated with huge economic loss to the livestock farming and industry has increased the concern worldwide. The di...

  18. Unilateral acute maculopathy associated with adult onset hand, foot and mouth disease: case report and review of literature.

    PubMed

    Agrawal, Rupesh; Bhan, Kanchan; Balaggan, Kam; Lee, Richard Wj; Pavesio, Carlos E; Addison, Peter Kf

    2015-01-01

    Acute maculopathy is a rare condition of unknown aetiology and Coxsackie virus is known to be associated with this macular chorioretinitis. We report a case of acute unilateral maculopathy in a 35-year-old woman with concurrent hand foot and mouth disease. Furthermore, we display multimodal imaging (colour fundus photographs, autofluorescence, spectral domain ocular coherence tomography, fluorescein angiography and indocyanine green angiography) charting the course of the disease. The source of the virus was thought to be the patient's child. Empirical treatment with oral corticosteroids was commenced and the inflammation resolved, leaving a residual macular scar. We present this case combined with the review of literature of adult onset Coxsackie-virus-associated retinitis. This case reiterates the fact that Coxsackie virus is an uncommon but important consideration in the differential diagnosis of chorioretinitis and posterior uveitis with atypical retinopathy.

  19. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs

    USDA-ARS?s Scientific Manuscript database

    Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South Africa...

  20. Global foot-and-mouth disease research update and gap analysis: 7 - pathogenesis and molecular biology

    USDA-ARS?s Scientific Manuscript database

    In 2014, the GFRA (Global Foot-and-mouth disease Research Alliance) conducted a gap analysis of FMD (Foot-and-Mouth Disease) research. This work has been updated and reported in a series of papers, in this article we report findings in the fields of 1) pathogenesis and 2) molecular biology. The arti...

  1. Cloned Viral Protein Vaccine for Foot-and-Mouth Disease: Responses in Cattle and Swine

    NASA Astrophysics Data System (ADS)

    Kleid, Dennis G.; Yansura, Daniel; Small, Barbara; Dowbenko, Donald; Moore, Douglas M.; Grubman, Marvin J.; McKercher, Peter D.; Morgan, Donald O.; Robertson, Betty H.; Bachrach, Howard L.

    1981-12-01

    A DNA sequence coding for the immunogenic capsid protein VP3 of foot-and-mouth disease virus A12, prepared from the virion RNA, was ligated to a plasmid designed to express a chimeric protein from the Escherichia coli tryptophan promoter-operator system. When Escherichia coli transformed with this plasmid was grown in tryptophan-depleted media, approximately 17 percent of the total cellular protein was found to be an insoluble and stable chimeric protein. The purified chimeric protein competed equally on a molar basis with VP3 for specific antibodies to foot-and-mouth disease virus. When inoculated into six cattle and two swine, this protein elicited high levels of neutralizing antibody and protection against challenge with foot-and-mouth disease virus.

  2. Foot-and-mouth disease: past, present and future

    PubMed Central

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions. PMID:24308718

  3. The pathogenesis of Foot-and-Mouth Disease in pigs

    USDA-ARS?s Scientific Manuscript database

    The greatest segment of foot-and-mouth disease (FMD) clinical research has been dedicated to elucidating pathogenesis and enhancing vaccine protection in cattle with less efforts invested in studies that are specific to pigs. However, accumulated evidence from FMD outbreaks and experimental invest...

  4. 75 FR 1697 - Change in Disease Status of the Republic of Korea With Regard to Foot-and-Mouth Disease and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ...-0147] Change in Disease Status of the Republic of Korea With Regard to Foot-and-Mouth Disease and... Republic of Korea to the list of regions that are considered free of rinderpest and foot-and-mouth disease... free of these diseases, but that are subject to certain restrictions because of their proximity to or...

  5. Foot-and-mouth disease in British deer: transmission of virus to cattle, sheep and deer.

    PubMed

    Gibbs, E P; Herniman, K A; Lawman, M J; Sellers, R F

    1975-06-28

    After exposure for two hours to cattle with foot-and-mouth disease, each of the five species of deer found in the British countryside became infected. Clinical disease was typical and severe in the roe and muntjac deer, with some animals dying, less severe in the sika deer and usually subclinical in the fallow and red deer. Each species transmitted disease to its own species and to cattle and sheep. The amounts of virus present in the blood, and in oesophageal/pharyngeal samples and excreted as an aerosol during the course of the infection in the deer were similar to those recorded for the sheep and cattle in the same experiment. The fallow and sika deer commonly carried virus in the pharynx beyond 28 days after exposure; some red deer also became carriers. In epidemics of foot-and-mouth disease in the UK, it is likely that deer would have such intimate contact with farm animals as occurred in this study. The natural behavior of free-living deer in the UK suggests that, although the five species are susceptible to foot-and-mouth disease, they are unlikely to be an important factor in the maintenance and transmission of the virus during an epidemic of foot-and-mouth disease in domestic livestock.

  6. Elimination of foot-and-mouth disease in South America: lessons and challenges.

    PubMed

    Naranjo, José; Cosivi, Ottorino

    2013-08-05

    Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988-2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988-2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011-2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable.

  7. Elimination of foot-and-mouth disease in South America: lessons and challenges

    PubMed Central

    Naranjo, José; Cosivi, Ottorino

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly transmissible and economically devastating disease of cloven-hoofed livestock. Although vaccines are available and have been instrumental in eliminating the disease from most of the South American animal population, viral circulation still persists in some countries and areas, posing a threat to the advances of the last 60 years by the official veterinary services with considerable support of the livestock sectors. The importance of the disease for the social and economic development of the American continent led to the establishment in 1951 of the Pan American Centre for Foot-and-Mouth Disease (PANAFTOSA), which has been providing technical cooperation to countries for the elimination of the disease. The first FMD national elimination programmes were established in South America around the 1960s and 1970s. To advance the regional elimination efforts in the 1980s, countries agreed on a Plan of Action 1988–2009 of the Hemispheric Program for the Eradication of Foot-and-Mouth Disease. The Plan of Action 1988–2009 did not reach the goal of elimination from the continent; and a new Plan of Action 2011–2020 was developed in 2010 based on the experience acquired by the countries and PANAFTOSA during the past 60 years. This plan is now being implemented; several challenges are still to be overcome to ensure the elimination of FMD from the Americas by 2020, however, the goal is achievable. PMID:23798699

  8. Predicting infection risk of airborne foot-and-mouth disease.

    PubMed

    Schley, David; Burgin, Laura; Gloster, John

    2009-05-06

    Foot-and-mouth disease is a highly contagious disease of cloven-hoofed animals, the control and eradication of which is of significant worldwide socio-economic importance. The virus may spread by direct contact between animals or via fomites as well as through airborne transmission, with the latter being the most difficult to control. Here, we consider the risk of infection to flocks or herds from airborne virus emitted from a known infected premises. We show that airborne infection can be predicted quickly and with a good degree of accuracy, provided that the source of virus emission has been determined and reliable geo-referenced herd data are available. A simple model provides a reliable tool for estimating risk from known sources and for prioritizing surveillance and detection efforts. The issue of data information management systems was highlighted as a lesson to be learned from the official inquiry into the UK 2007 foot-and-mouth outbreak: results here suggest that the efficacy of disease control measures could be markedly improved through an accurate livestock database incorporating flock/herd size and location, which would enable tactical as well as strategic modelling.

  9. The foot-and-mouth disease carrier state divergence in cattle

    USDA-ARS?s Scientific Manuscript database

    The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated following simulated-natural virus exposure of 43 cattle that were either naïve or vaccinated using a recombinant, adenovirus-vectored vaccine. Although vaccinated cattle were protected against clinical dise...

  10. 9 CFR 94.1 - Regions where rinderpest or foot-and-mouth disease exists; importations prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY...

  11. 9 CFR 94.1 - Regions where rinderpest or foot-and-mouth disease exists; importations prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...-mouth disease exists; importations prohibited. 94.1 Section 94.1 Animals and Animal Products ANIMAL AND... (INCLUDING POULTRY) AND ANIMAL PRODUCTS RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER, SWINE VESICULAR DISEASE, AND BOVINE SPONGIFORM ENCEPHALOPATHY...

  12. Foot-and-mouth disease virus during the incubation period in pigs

    USDA-ARS?s Scientific Manuscript database

    Understanding the quantitative characteristics of a pathogen’s capability to transmit during distinct phases of infection is important to enable accurate predictions of the spread and impact of a disease outbreak. In the current investigation, the potential for transmission of foot-and-mouth disease...

  13. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER...

  14. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER...

  15. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER...

  16. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, EXOTIC NEWCASTLE DISEASE, AFRICAN SWINE FEVER, CLASSICAL SWINE FEVER...

  17. 9 CFR 94.17 - Dry-cured pork products from regions where foot-and-mouth disease, rinderpest, African swine...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... where foot-and-mouth disease, rinderpest, African swine fever, classical swine fever, or swine vesicular disease exists. 94.17 Section 94.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... RINDERPEST, FOOT-AND-MOUTH DISEASE, NEWCASTLE DISEASE, HIGHLY PATHOGENIC AVIAN INFLUENZA, AFRICAN SWINE FEVER...

  18. Application of a new hybrid model with seasonal auto-regressive integrated moving average (ARIMA) and nonlinear auto-regressive neural network (NARNN) in forecasting incidence cases of HFMD in Shenzhen, China.

    PubMed

    Yu, Lijing; Zhou, Lingling; Tan, Li; Jiang, Hongbo; Wang, Ying; Wei, Sheng; Nie, Shaofa

    2014-01-01

    Outbreaks of hand-foot-mouth disease (HFMD) have been reported for many times in Asia during the last decades. This emerging disease has drawn worldwide attention and vigilance. Nowadays, the prevention and control of HFMD has become an imperative issue in China. Early detection and response will be helpful before it happening, using modern information technology during the epidemic. In this paper, a hybrid model combining seasonal auto-regressive integrated moving average (ARIMA) model and nonlinear auto-regressive neural network (NARNN) is proposed to predict the expected incidence cases from December 2012 to May 2013, using the retrospective observations obtained from China Information System for Disease Control and Prevention from January 2008 to November 2012. The best-fitted hybrid model was combined with seasonal ARIMA [Formula: see text] and NARNN with 15 hidden units and 5 delays. The hybrid model makes the good forecasting performance and estimates the expected incidence cases from December 2012 to May 2013, which are respectively -965.03, -1879.58, 4138.26, 1858.17, 4061.86 and 6163.16 with an obviously increasing trend. The model proposed in this paper can predict the incidence trend of HFMD effectively, which could be helpful to policy makers. The usefulness of expected cases of HFMD perform not only in detecting outbreaks or providing probability statements, but also in providing decision makers with a probable trend of the variability of future observations that contains both historical and recent information.

  19. Structure-based discovery of foot-and-mouth disease inhibitors that target the 3Dpol RNA-dependent RNA polymerase

    USDA-ARS?s Scientific Manuscript database

    Foot-and-Mouth Disease Virus (FMDV) primarily targets cloven-hoofed animals. The FMDV outbreak results in significant economic losses. There are currently no available antiviral drugs for Foot-and-Mouth Disease (FMD) treatment, and vaccination needs at least 7 days to effectively trigger the immune...

  20. Epidemiological characterizations, pathogen spectrum and molecular characteristics of Coxsackievirus A16 from patients with HFMD in Yantai, Shandong, China between 2011 and 2015

    PubMed Central

    Sun, Zhenlu; Zhang, Guifang; Guo, Peijun; Liu, Juan; Gao, Qiao; Xu, Xiaowen; Gong, Lianfeng

    2017-01-01

    ABSTRACT This study aimed to investigate the epidemiological characterizations and pathogen spectrum of hand, foot, and mouth disease (HFMD) in Yantai City, Shandong Province, China, during 2011–2015, and to study the nucleotide evolution and amino acid variation of coxsackievirus A16 (CV-A16) epidemic strains that caused HFMD. The HFMD epidemic began to rise in March, and became prevalent from May to August, reached its peak in June, and then declined in September every year, children aged one to 5 years-old had the highest incidence rate whereas the incidence in children under 6 months was very low, and there were more males than females. Enterovirus nucleic acid detection using real-time reverse transcription polymerase chain reaction was performed on 2130 clinical specimens collected from patients with HFMD between 2011 and 2015, and 2012 enterovirus positive samples were detected, including 678 CV-A16, 639 EV-A71, and 695 other enteroviruses. In total, 60 CV-A16 isolates were randomly selected each year for virus isolation, of which 33 CV-A16 strains were randomly selected for further characterization because CV-A16 is the predominant serotype that caused HFMD in Yantai City, and a phylogenetic tree based on the VP1 region was constructed. All 33 CV-A16 strains belonged to the Bla and B1b genotypes, with a nucleotide similarity of 87.9–100% and deduced amino acid similarity of 98.6–100%. Compared with the reference strain Tainan/5079/98 (AF177911), amino acid mutations were identified at positions 11, 23, 25, 31, 99, 145, and 289, where differences were observed among 33 strains, indicating a unique mutation map of CV-A16 in Yantai City. Our findings demonstrate the etiologic characteristics of HFMD, provide supporting evidence for the prevention and control of HFMD, and open a promising avenue for vaccine development against HFMD, by targeting CV-A16. PMID:28537484

  1. Foot-and-mouth disease virus serotype SAT1 in cattle, Nigeria.

    PubMed

    Ehizibolo, D O; Haegeman, A; De Vleeschauwer, A R; Umoh, J U; Kazeem, H M; Okolocha, E C; Van Borm, S; De Clercq, K

    2017-06-01

    The knowledge of foot-and-mouth disease virus (FMDV) dynamics and epidemiology in Nigeria and the West Africa subregion is important to support local and regional control plans and international risk assessment. Foot-and-mouth disease virus serotype South African territories (SAT)1 was isolated, identified and characterized from an FMD outbreak in cattle in Nigeria in 2015, 35 years after the last report of FMDV SAT1 in West Africa. The VP1 coding sequence of the Nigerian 2015 SAT1 isolates diverges from reported SAT1 topotypes resulting in a separate topotype. The reporting of a novel FMDV SAT1 strain in the virus pool 5 (West and Central Africa) highlights the dynamic and complex nature of FMDV in this region of Africa. Sustained surveillance is needed to understand the origin, the extent and distribution of this novel SAT1 topotype in the region as well as to detect and monitor the occurrence of (re-)emerging FMDV strains. © 2017 Blackwell Verlag GmbH.

  2. The pathogenesis of foot-and-mouth disease I; viral pathways in cattle

    USDA-ARS?s Scientific Manuscript database

    In 1898 foot-and-mouth disease (FMD) earned a place in history as the first disease of animals shown to be caused by a virus. Yet, despite over a century of active investigation and elucidation of many aspects of FMD pathogenesis, critical knowledge about the virus-host interactions is still lacking...

  3. Global foot-and-mouth disease research update and gap analysis: 2 - epidemiology, wildlife and economics

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-and-mouth disease Research ings in the fields of (i) epidemiology, (ii) wildlife and (iii) Alliance (GFRA) conducted a gap analysis of foot-and- economics. Although the three sections, epidemiology, wildlife and economics are presented as separate entities, the fields are ...

  4. Heterogeneity in the antibody response to foot-and-mouth disease primo-vaccinated calves

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is the most economically important viral disease of wild and domesticated biungulate species and presents a major constraint to international trade of livestock and their associated products. FMD vaccines are routinely used as effective control tools in large regions wor...

  5. Pathogenesis of virulent and attenuated foot and mouth disease virus in cattle

    USDA-ARS?s Scientific Manuscript database

    The factors defining virulence of foot-and-mouth disease virus (FMDV) in cattle were investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). After simulated-natural, aerosol inoculation, both vi...

  6. Evaluation of Gaussia luciferase and foot-and-mouth disease virus 2A translational interrupter chimeras as polycistronic reporters for transgene expression.

    PubMed

    Puckette, Michael; Burrage, Thomas; Neilan, John G; Rasmussen, Max

    2017-06-12

    The Gaussia princeps luciferase is used as a stand-alone reporter of transgene expression for in vitro and in vivo expression systems due to the rapid and easy monitoring of luciferase activity. We sought to simultaneously quantitate production of other recombinant proteins by transcriptionally linking the Gaussia princeps luciferase gene to other genes of interest through the foot-and-mouth disease virus 2A translational interrupter sequence. We produced six plasmids, each encoding a single open reading frame, with the foot-and-mouth disease virus 2A sequence placed either N-terminal or C-terminal to the Gaussia princeps luciferase gene. Two plasmids included novel Gaussia princeps luciferase variants with the position 1 methionine deleted. Placing a foot-and-mouth disease virus 2A translational interrupter sequence on either the N- or C-terminus of the Gaussia princeps luciferase gene did not prevent the secretion or luminescence of resulting chimeric luciferase proteins. We also measured the ability of another polycistronic plasmid vector with a 2A-luciferase sequence placed downstream of the foot-and-mouth disease virus P1 and 3C protease genes to produce of foot-and-mouth disease virus-like particles and luciferase activity from transfected cells. Incorporation of the 2A-luciferase sequence into a transgene encoding foot-and-mouth disease virus structural proteins retained luciferase activity and the ability to form virus-like particles. We demonstrated a mechanism for the near real-time, sequential, non-destructive quantitative monitoring of transcriptionally-linked recombinant proteins and a valuable method for monitoring transgene expression in recombinant vaccine constructs.

  7. Differential replication of foot-and-mouth disease viruses in mice determine lethality

    USDA-ARS?s Scientific Manuscript database

    Adult C57BL/6J mice have been used to study foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a let...

  8. Global foot-and-mouth disease research update and gap analysis: 4 - diagnostics

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-And-Mouth Disease Research Alliance (GFRA) conducted a gap analysis of FMD research. Published as a series of seven papers, in this paper, we report updated findings in the field of diagnostics. The paper consists of the following four sections: 1. Research priorities identi...

  9. Global foot-and-mouth disease research update and gap analysis: 6 - immunology

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. This has been updated with findings reported in a series of papers. Here we present findings for FMD immunology research. The paper consists of the following four sections: 1. Research prior...

  10. [Establishment of chemiluminescent enzyme immunoassay for detecting antibodies against foot-and-mouth disease virus serotype O in swine].

    PubMed

    Cui, Chen; Huang, Ligang; Li, Jing; Zou, Xingqi; Zhu, Yuanyuan; Xie, Lei; Zhao, Qizu; Yang, Limin; Liu, Wenjun

    2016-11-25

    Recombinant structural protein VP1 of foot-and-mouth disease virus serotype O was expressed in Escherichia coli and then purified using Nickel affinity chromatography. A chemiluminescent enzyme immunoassay (CLEIA) method was established using the purified recombinant protein as coating antigen to detect antibody of foot-and-mouth disease virus serotype O in swine. The specificity of VP1-CLEIA method is 100%. The coefficients of variation in the plate and between plates are 1.10%-6.70% and 0.66%-4.80%, respectively. Comparing with the commercial indirect ELISA kit or liquid phase block ELISA kit, the calculated coincidence rate is 93.50% or 94.00%. The high specificity and stability suggested this detection method can be used to monitor the antibody level of foot-and-mouth disease virus serotype O in swine.

  11. Global foot-and-mouth disease research update and gap analysis: 3 - vaccines

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. In this paper, we report updated findings in the field of FMD vaccine research. This paper consists of the following four sections: 1) Research priorities identified in the 2010 GFRA gap ana...

  12. Attenuation of foot-and-mouth disease virus by engineered viral polymerase fidelity

    USDA-ARS?s Scientific Manuscript database

    The foot-and-mouth disease virus (FMDV) RNA dependent RNA polymerase (RdRp or 3Dpol) catalyzes viral RNA synthesis. The 3Dpol is a low fidelity enzyme incapable of proofreading which results in a high mutation frequencies that allow the virus to rapidly adapt to different environments. In this study...

  13. Phylodynamics of epidemic and asymptomatic foot-and-mouth disease in Vietnam 2010-2014

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in animal trade within Southeast Asia. The large populations of buffalo, cattle and pigs (all FMDV susceptible species) in Vietnam are important components of food production and of the national livelih...

  14. The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation

    USDA-ARS?s Scientific Manuscript database

    The goal of the efforts described in this dissertation was to characterize the early pathogenesis of foot-and-mouth disease (FMD) in cattle after simulated natural infection. More specifically, emphasis was placed upon two critical knowledge gaps: identification of the primary site(s) of infectio...

  15. Foot & Mouth Disease & Ulcerative/Vesicular Rule-outs: Challenges Encountered in Recent Outbreaks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hullinger, P

    2008-01-28

    Foot and mouth disease (FMD) is a highly infectious and contagious viral disease affecting bovidae (cattle, zebus, domestic buffaloes, yaks), sheep, goats, swine, all wild ruminants and suidae. Camelidae (camels, dromedaries, llamas, vicunas) have low susceptibility. Foot and mouth disease is caused by a RNS virus of the family Picornaviridae, genus Aphthovirus. There are seven immunologically distinct serotypes: A, O, C, SAT1, SAT2, SAT3, Asia 1. Foot and mouth disease causes significant economic loss both to countries who manage it as an endemic disease (with or without vaccination), as well as those FMD free countries which may become infected. Themore » mortality rate is low in adult animals, but often higher in young due to myocarditis. Foot and mouth disease is endemic in parts of Asia, Africa, the Middle East and South America (sporadic outbreaks in free areas). The Office of International Epizootics (OIE), also referred to the World Organization for Animal Health maintains an official list of free countries and zones.1 The OIE Terrestrial Code (Chapter 2.2.10) provides detailed information on the categories of freedom that can be allocated to a country as well as guidelines for the surveillance for foot and mouth disease (Appendix 3.8.7). In short, countries may be completely free of FMD, free with vaccination or infected with foot and mouth disease virus (FMDV). Source of FMDV include incubating and clinically affected animals with virus present in breath, saliva, faeces, urine, milk and semen. In experimental settings virus has been detected in milk several days before the onset of clinical signs2. Additional sources of virus are meat and by-products in which pH has remained above 6.0 as well as persistently infected carrier animals. Carrier animals may include cattle and water buffalo; convalescent animals and exposed vaccinates (virus persists in the oropharynx for up to 30 months in cattle or longer in buffalo, 9 months in sheep). Pigs do not become

  16. Global foot-and-mouth disease research update and gap analysis: 5 - biotherapeutics and disinfectants

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-and-mouth disease Research Alliance(GFRA)conducted a gap analysis of FMD research. This work has been updated and reported in a series of papers with the focus of this article being (i) biotherapeutics and (ii) disinfectants, including environmental contamination. The paper ...

  17. Cloning of cDNA of major antigen of foot and mouth disease virus and expression in E. coli

    NASA Astrophysics Data System (ADS)

    Küpper, Hans; Keller, Walter; Kurz, Christina; Forss, Sonja; Schaller, Heinz

    1981-02-01

    Double-stranded DNA copies of the single-stranded genomic RNA of foot and mouth disease virus have been cloned into the Escherichia coli plasmid pBR322. A restriction map of the viral genome was established and aligned with the biochemical map of foot and mouth disease virus. The coding sequence for structural protein VP1, the major antigen of the virus, was identified and inserted into a plasmid vector where the expression of this sequence is under control of the phage λ PL promoter. In an appropriate host the synthesis of antigenic polypeptide can be demonstrated by radioimmunoassay.

  18. Thermal inactivation of foot and mouth disease virus in extruded pet food.

    PubMed

    Gubbins, S; Forster, J; Clive, S; Schley, D; Zuber, S; Schaaff, J; Corley, D

    2016-12-01

    The risk of importing foot and mouth disease, a highly contagious viral disease of livestock, severely restricts trade and investment opportunities in many developing countries where the virus is present. This study was designed to investigate the inactivation of foot and mouth disease virus (FMDV) by heat treatments used in extruded commercial pet food manufacture. If extrusion could be shown to reliably inactivate the virus, this could potentially facilitate trade for FMDV-endemic countries. The authors found that there was no detectable virus following: i) treatment of FMDVspiked meat slurry at 68°C for 300 s; ii) treatment of FMDV-spiked slurry and meal mix at 79°C for 10 or 30 s, or iii) treatment of homogenised bovine tongue epithelium, taken from an FMDV-infected animal, at 79°C for 10 s. This corresponds to an estimated 8 log10 reduction in titre (95% credible interval: 6 log10 -13 log10). Furthermore, the authors found that the pH of the slurry and meal mix was sufficient to inactivate FMDV in the absence of heat treatment. This demonstrates that heat treatments used in commercial pet food manufacture are able to substantially reduce the titre of FMDV in infected raw materials. © OIE (World Organisation for Animal Health), 2016.

  19. Foot-and-Mouth Disease in a small sample of experimentally infected pronghorn (Antilocapra americana)

    USDA-ARS?s Scientific Manuscript database

    There is limited information on the pathogenesis and epidemiology of foot-and-mouth disease (FMD) in North American wildlife, and none concerning pronghorn (Antilocapra americana). In this experimental study, we compared the susceptibility of pronghorn to FMD virus (FMDV) strain O, with that of ...

  20. Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle

    USDA-ARS?s Scientific Manuscript database

    Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O,A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutral...

  1. Effect of vaccination on cattle herds previously exposed to foot and mouth disease in Cameroon

    USDA-ARS?s Scientific Manuscript database

    Foot and mouth disease (FMD), caused by FMD virus (FMDV), is one of the most contagious and economically important livestock diseases worldwide. Four serotypes of FMDV are endemic in Cameroon (O, A, SAT1, SAT2), and a trivalent inactivated vaccine against the three most common serotypes (O, A, SAT2)...

  2. Disease burden of enterovirus 71 in rural central China: A community-based survey.

    PubMed

    Gan, Zheng-kai; Jin, Hui; Li, Jing-xin; Yao, Xue-jun; Zhou, Yang; Zhang, Xue-feng; Zhu, Feng-cai

    2015-01-01

    In recent years, the epidemics of hand, foot, and mouth disease (HFMD) centered in the Asian-Pacific region have been characterized by high morbidity and mortality. Enterovirus 71 (EV71) infections were responsible for the majority of the infections leading to severe cases of HFMD and death. This is a community-based survey aimed to estimate the disease burden of EV71 in rural central China, especially for HFMD. From 2011 to 2013, demographic and socio-economic data were gathered from 343 ill children and their parents using a structured questionnaire. We quantified the health burden of disease resulting from EV71 infection in disability-adjusted life years (DALYs). Among 343 cases, 303 had confirmed HFMD, 6 presented with herpangina, 25 presented with respiratory symptoms, and 9 presented with non-specific symptoms. The number of severe cases was 47 (including 1 death) and all of these presented with HFMD. The total cost per patient for severe HFMD, mild HFMD, herpangina, respiratory disease, and non-specific disease was $2149.47, $513.22, $53.28, $31.95, and $39.25, respectively. The overall cost of EV71-related diseases as a proportion of local farmers' per capita net income ranged from 0.18% for those with non-specific disease to 187.12% for those with severe HFMD. The loss of DALYs for the 5 forms of disease were 3.47, 1.76, 1.07, 1.44, 1.22 person-years per 1000 persons, respectively. This study provides data on cost of treatment and health burden for diseases caused by EV71, which can be used in the evaluation of EV71 vaccine cost-effectiveness.

  3. Epidemiological analysis, serological prevalence, and genotypic analysis of foot-and-mouth disease in Nigeria 2008-2009

    USDA-ARS?s Scientific Manuscript database

    The epidemiological situation of foot and mouth disease virus (FMDV) is uncertain in Nigeria, where the disease is endemic, and the majority of outbreaks are unreported. Control measures for FMD in Nigeria are not being implemented due to the absence of locally produced vaccines and an official ban ...

  4. Probability of introducing foot and mouth disease into the United States via live animal importation.

    PubMed

    Miller, G Y; Ming, J; Williams, I; Gorvett, R

    2012-12-01

    Foot and mouth disease (FMD) continues to be a disease of major concern for the United States Department of Agriculture (USDA) and livestock industries. Foot and mouth disease virus is a high-consequence pathogen for the United States (USA). Live animal trade is a major risk factor for introduction of FMD into a country. This research estimates the probability of FMD being introduced into the USA via the legal importation of livestock. This probability is calculated by considering the potential introduction of FMD from each country from which the USA imports live animals. The total probability of introduction into the USA of FMD from imported livestock is estimated to be 0.415% per year, which is equivalent to one introduction every 241 years. In addition, to provide a basis for evaluating the significance of risk management techniques and expenditures, the sensitivity of the above result to changes in various risk parameter assumptions is determined.

  5. Dynamic impacts of a catastrophic production event: the foot-and-mouth disease case.

    PubMed

    Cordier, Alexandre; Gohin, Jean; Krebs, Stephane; Rault, Arnaud

    2013-03-01

    In foot-and-mouth disease (FMD) free countries, the occurrence of an FMD outbreak is a rare event with potentially large economic losses. We explore the dynamic effects of an FMD outbreak on market variables and economic surplus taking into account the largely neglected issue of farm bankruptcy. Simulations are performed on a stylized agricultural economy, which is a net exporter before the outbreak. We find complex dynamic market effects when the farm credit market suffers from information imperfections leading to farm closure. Welfare effects are also dramatically altered. Domestic consumers may lose in the long run from an FMD outbreak because domestic supply contracts. On the other hand, farmers able to resist this event may ultimately gain. Our analysis also shows that these effects are not monotone, making any efficient policy response to this catastrophic event quite challenging. © 2012 Society for Risk Analysis.

  6. Growth of Foot-and-Mouth Disease Virus in Dispersed Tissue Cells

    PubMed Central

    Patty, R. E.; Tozzini, F.; Seibold, H. R.; Callis, J. J.

    1962-01-01

    Methods are described for rapid and economical production of large quantities of foot-and-mouth disease virus in stationary cultures of trypsin-dispersed bovine kidney cells in a simple medium. Yields of between 107 and 108 plaque-forming units per milliliter were obtained from serum-free cultures containing approximately a million and a half viable trypsin-dispersed cells per milliliter. Some of the advantages and disadvantages of these methods of virus production are discussed. ImagesFig. 1Fig. 2Fig. 3 PMID:17649388

  7. Constitutively active IRF7/IRF3 fusion protein completely protects swine against Foot-and-Mouth Disease

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) remains one of the most devastating livestock diseases around the world. Several serotype specific vaccine formulations exist but require about 5-7 days to induce protective immunity. Our previous studies have shown that a constitutively active fusion protein of porcine ...

  8. Collaborative Response and Recovery from a Foot-and-Mouth Disease Animal Health Emergency: Supporting Decision Making in a Complex Environment with Multiple Stakeholders

    DTIC Science & Technology

    2013-12-01

    RESPONSE AND RECOVERY FROM A FOOT-AND- MOUTH DISEASE ANIMAL HEALTH EMERGENCY: SUPPORTING DECISION MAKING IN A COMPLEX ENVIRONMENT WITH MULTIPLE...Thesis 4. TITLE AND SUBTITLE COLLABORATIVE RESPONSE AND RECOVERY FROM A FOOT-AND- MOUTH DISEASE ANIMAL HEALTH EMERGENCY: SUPPORTING DECISION MAKING...200 words ) This thesis recommends ways to support decision makers who must operate within the multi-stakeholder complex situation of response and

  9. Identification of a serotype-independent linear epitope of foot-and-mouth disease virus.

    PubMed

    Yang, Baolin; Wang, Mingxia; Liu, Wenming; Xu, Zhiqiang; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

    2017-12-01

    Foot-and-mouth disease (FMD), caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. VP2 is a structural protein of FMDV. In this study, an FMDV serotype-independent monoclonal antibody (MAb), 10B10, against the viral capsid protein VP2 was generated, and a series of GST fusion proteins expressing a truncated peptide of VP2 was subjected to Western blot analysis using MAb 10B10. Their results indicated that the peptide 8 TLLEDRILT 16 of VP2 is the minimal requirement of the epitope recognized by MAb 10B10. Importantly, this linear epitope was highly conserved among all seven serotypes of FMDV in a sequence alignment analysis. Subsequent alanine-scanning mutagenesis analysis revealed that the residues Thr 8 and Asp 12 of the epitope were crucial for MAb-10B10 binding. Furthermore, Western blot analysis also revealed that the MAb 10B10-directed epitope could be recognized by positive sera from FMDV-infected cattle. The discovery that MAb 10B10 recognizes a serotype-independent linear epitope of FMDV suggests potential applications for this MAb in the development of serotype-independent tests for FMDV.

  10. First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam

    USDA-ARS?s Scientific Manuscript database

    In recent years, foot-and-mouth disease virus (FMDV) serotype O, lineage Ind2001d has spread to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Dak Nong province which borders Cambodia. Three subsequ...

  11. Quantitative characteristics of the foot-and-mouth disease carrier state under natural conditions in India

    USDA-ARS?s Scientific Manuscript database

    The goal of the current study was to characterize serological and virological parameters of the foot-and-mouth disease (FMD) carrier state at two farms in Nainital District, Uttarakhand State in northern India. Despite previous vaccination of cattle in these herds, clinical signs of FMD occurred in ...

  12. First detection of foot-and-mouth disease virus O/ME-SA/Ind2001 in China.

    PubMed

    Zhu, Z; Yang, F; He, J; Li, J; Cao, W; Li, J; Xia, Y; Guo, J; Jin, Y; Zhang, K; Zheng, H; Liu, X

    2018-05-09

    Foot-and-mouth disease (FMD) is endemic in China and is predominantly due to foot-and-mouth disease virus (FMDV) serotype O Mya-98 lineage. In recent years, FMDV O/ME-SA/Ind2001 lineage has spread from the Indian subcontinent to South-East Asia, Middle East and Africa, which may pose potential threats for future trans-regional livestock movements. In this study, we identified the appearance of FMDV O/ME-SA/Ind2001 in China; the first time that this virus lineage has been found there. Sequencing and phylogenetic analysis of VP1 sequences revealed that this newly determined strain belongs to O/ME-SA/Ind2001 sublineage d and is closely related to strains that have caused recent outbreaks of FMD in Nepal, Myanmar, Russia and South Korea. The results suggest extensive movements of the current O/ME-SA/Ind2001 sublineage d viruses and provide essential information for an effective national FMDV control programme in China. © 2018 Blackwell Verlag GmbH.

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

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is an important transboundary disease with substantial economic impacts. Although between-herd transmission of the disease has been well studied, studies focusing on within-herd transmission using farm-level outbreak data are rare. The aim of this study was to estimate p...

  14. Evaluation of Multiplexed Foot-and-Mouth Disease Nonstructural Protein Antibody Assay Against Standardized Bovine Serum Panel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Perkins, J; Parida, S; Clavijo, A

    2007-05-14

    Liquid array technology has previously been used to show proof-of-principle of a multiplexed non structural protein serological assay to differentiate foot-and-mouth infected and vaccinated animals. The current multiplexed assay consists of synthetically produced peptide signatures 3A, 3B and 3D and recombinant protein signature 3ABC in combination with four controls. To determine diagnostic specificity of each signature in the multiplex, the assay was evaluated against a naive population (n = 104) and a vaccinated population (n = 94). Subsequently, the multiplexed assay was assessed using a panel of bovine sera generated by the World Reference Laboratory for foot-and-mouth disease in Pirbright,more » UK. This sera panel has been used to assess the performance of other singleplex ELISA-based non-structural protein antibody assays. The 3ABC signature in the multiplexed assay showed comparative performance to a commercially available non-structural protein 3ABC ELISA (Cedi test{reg_sign}) and additional information pertaining to the relative diagnostic sensitivity of each signature in the multiplex is acquired in one experiment. The encouraging results of the evaluation of the multiplexed assay against a panel of diagnostically relevant samples promotes further assay development and optimization to generate an assay for routine use in foot-and-mouth disease surveillance.« less

  15. Control of foot-and-mouth disease by using replication-defective human adenoviruses to deliver vaccines and biotherapeutics

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  16. An uncommon clinical form of foot-and-mouth disease in beef cattle presented with cornual skin lesions.

    PubMed

    Mohebbi, M R; Barani, S M; Mahravani, H

    2017-01-01

    Foot-and-mouth disease (FMD) is a major infectious disease in livestock. The common clinical signs in cattle include epidermal vesicles that are majorly distributed around oronasal cavity, feet and teats. The aim of this report is to document an uncommon clinical form of the disease which comprises the occurrence of classic vesicular lesion in a rarely observed location of the horn vegetative tissue. During Iran's outbreak of FMD in 2013, field investigation, clinical examination and sampling from the affected herds in Qom province were performed. Specimens of mouth epithelium and horn vegetative tissue were collected for virology and histopathologic study. All the samples collected from horns were positive for foot-and-mouth disease virus (FMDV) in both enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) tests, and the strain of the virus was identified as A05. Surprisingly, all the animals with horn lesion came from beef herds, were less than 12 months old and had more severe signs of the systemic disease. Since the same strain of virus did not cause similar lesions in surrounding dairy cows, it was concluded that occurrence of horn lesions may be more associated with host factors rather than virus strain.

  17. Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

    PubMed

    Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

    2017-07-01

    Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

  18. Foot-and-mouth disease virus-associated abortion and vertical transmission following acute infection in cattle under natural conditions

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic as well as more than 70 wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. T...

  19. 75 FR 54589 - Availability of an Environmental Assessment for Field Testing Foot-and-Mouth Disease Vaccine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    ... DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service [Docket No. APHIS-2010-0011] Availability of an Environmental Assessment for Field Testing Foot-and-Mouth Disease Vaccine, Live Adenovirus Vector AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice. SUMMARY: We are advising...

  20. Challenges of Generating and Maintaining Protective Vaccine-Induced Immune Responses for Foot-and-Mouth Disease Virus in Pigs

    PubMed Central

    Lyons, Nicholas A.; Lyoo, Young S.; King, Donald P.; Paton, David J.

    2016-01-01

    Vaccination can play a central role in the control of outbreaks of foot-and-mouth disease (FMD) by reducing both the impact of clinical disease and the extent of virus transmission between susceptible animals. Recent incursions of exotic FMD virus lineages into several East Asian countries have highlighted the difficulties of generating and maintaining an adequate immune response in vaccinated pigs. Factors that impact vaccine performance include (i) the potency, antigenic payload, and formulation of a vaccine; (ii) the antigenic match between the vaccine and the heterologous circulating field strain; and (iii) the regime (timing, frequency, and herd-level coverage) used to administer the vaccine. This review collates data from studies that have evaluated the performance of foot-and-mouth disease virus vaccines at the individual and population level in pigs and identifies research priorities that could provide new insights to improve vaccination in the future. PMID:27965966

  1. Enterovirus 71: a whole virion inactivated enterovirus 71 vaccine.

    PubMed

    Zhou, Yang; Li, Jing-Xin; Jin, Peng-Fei; Wang, Yu-Xiao; Zhu, Feng-Cai

    2016-07-01

    Enterovirus A71 (EV71) is the predominant causative agent of hand, foot, and mouth disease (HFMD), which is often associated with severe cases and even deaths. EV71-associated epidemics have emerged as a serious threat to public health, particularly in the Asia-Pacific region. We searched PubMed using the terms 'enterovirus 71', 'hand, foot, and mouth disease', and 'vaccine', with no date or language restrictions for all publications before April 27, 2016. Among various vaccine candidates, the alum-adjuvant inactivated EV71 vaccines are most promising. Three alum-adjuvant inactivated EV71 vaccines developed by mainland China showed high efficacy, good immunogenicity persistence and acceptable safety profiles in clinical trials. Recently, two of these EV71 vaccines have been approved for marketing in China and the other one is undergoing the review process of licensure. In this manuscript, we summarized previous study results as well as discussed the regulatory affairs and post-market surveillances issues. Expert commentary: The marketing of EV71 vaccines is a milestone in the controlling of HFMD. International clinical trials are needed to further assess the efficacy and cross-immunogenicity. Establishing a sensitive pathogen monitoring system would be essential to monitor the variation of genotypes and control HFMD epidemics.

  2. Early dissemination of foot-and-mouth disease virus through sheep marketing in February 2001.

    PubMed

    Mansley, L M; Dunlop, P J; Whiteside, S M; Smith, R G H

    2003-07-12

    The results of epidemiological investigations suggest that livestock on up to 79 premises, spread widely throughout the British Isles, may have been exposed to infection by foot-and-mouth disease (FMD) virus by the movement of infected sheep before the first case of the disease was confirmed at an abattoir in Essex on February 20, 2001. A further 36 premises may have been infected by this route before the national livestock movement ban was imposed on February 23.

  3. 76 FR 44503 - Availability of a Risk Analysis Evaluating the Foot-and-Mouth Disease Status of Japan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-26

    ... Foot-and-Mouth Disease Status of Japan AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION... disease (FMD) status of Japan and the risk of susceptible animals and animal products from Japan harboring... Health Inspection again recognizes Japan as free of FMD and allows the importation of whole cuts of...

  4. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FM...

  5. Infection dynamics of foot-and-mouth disease virus in cattle following intra-nasopharyngeal inoculation or contact exposure

    USDA-ARS?s Scientific Manuscript database

    For the purpose of developing an improved experimental model for studies of foot-and-mouth disease virus (FMDV) infection in cattle, three different experimental systems based on natural or simulated-natural virus exposure were compared under standardized experimental conditions. Antemortem infecti...

  6. Characterization of a chimeric foot-and-mouth disease virus bearing bovine rhinitis B virus leader proteinase

    USDA-ARS?s Scientific Manuscript database

    Our recent study has shown that bovine rhinovirus type 2 (BRV2), a new member of the Aphthovirus genus, shares many motifs and sequence similarities with foot-and-mouth disease virus (FMDV). Despite low sequence conservation (36percent amino acid identity) and N- and C-terminus folding differences,...

  7. Impact of the 2001 Foot-and-Mouth Disease Outbreak in Britain: Implications for Rural Studies

    ERIC Educational Resources Information Center

    Scott, Alister; Christie, Michael; Midmore, Peter

    2004-01-01

    This paper assesses the impact of the 2001 foot-and-mouth disease outbreak in terms of its implications for the discipline of rural studies. In particular, it focuses on the position of agriculture in rural economy and society, the standing of the government after its management of the outbreak, and the performance of the new devolved regional…

  8. Optimization of immunohistochemical and fluorescent antibody techniques for localization of foot-and-mouth disease virus in animal tissues

    USDA-ARS?s Scientific Manuscript database

    Immunohistochemical (IHC) and immunofluorescent (IF) techniques were optimized for the detection of foot-and-mouth disease virus (FMDV) structural and non-structural proteins in frozen and paraformaldehyde-fixed paraffin embedded (PFPE) tissues of bovine and porcine origin. Immunohistochemical local...

  9. Foot-and-mouth disease virus serotype O phylodynamics: genetic variability associated with epidemiological factors in Pakistan

    USDA-ARS?s Scientific Manuscript database

    One of the most challenging aspects of foot-and-mouth disease (FMD) control is the high genetic variability of the FMD virus (FMDV). In endemic settings such as the Indian subcontinent, this variability has resulted in the emergence of pandemic strains that have spread widely and caused devastating ...

  10. [Epidemiological characteristics of enterovirus type 71 diseases].

    PubMed

    Gan, Zhengkai; Li, Jingxin; Meng, Fanyue; Hu, Yuemei; Yao, Xuejun; Zhang, Xuefeng; Zhu, Fengcai

    2015-01-01

    The objective of this study was to investigate the epidemiological characteristics of disease caused by enterovirus type 71. A total of 10 158 children aged between 6 and 35 months, were recruited from 7 sites where EV71 inactivated vaccine phase 3 clinical trial was carried out. All the subjects were followed up to one year to investigate the epidemiological characteristics of the disease caused by EV71. The accumulate incidence density of disease caused by EV71 was 15.17/1 000 person-year. Of all the cases, hand, foot and mouth disease (HFMD), herpangina, respiratory system diseases, digestive system diseases and other diseases accounted for 82.00%, 2.67%, 13.33%, 1.33% and 0.67%, respectively. The difference of the incidence density between boys and girls showed no statistical significance. Majority of the patients were between 12 and 23 months of age, which accounted for 58.67% of the total patients. The differences of incidence density between different months of age were statistically significant (χ(2) = 7.789, P = 0.020). The peak incidence density of disease caused by EV71 occurred from April to June. Nine cases showed severe symptoms or signs that accounted for 6.00% of all the cases. All severe cases were identified as HFMD, of which 7 were boys and 2 were girls. The number of severe cases in different months of age appeared to be 1, 7, and 1, all occurred between April and June. The median courses of HFMD cases and non-HFMD cases were 9 and 6 days, with difference statistically significant (Z = -4.000, P < 0.001). Median of excretion cycle for HFMD and non-HFMD cases were 9 and 11 days respectively. But with no statistically significant difference between the two. Majority of the disease that caused by EV71 appeared as HFMD. Most of them were younger children and with seasonal variation.

  11. Venezuelan Equine Encephalitis Virus replicon particles can induce rapid protection against Foot-and-Mouth Disease Virus

    USDA-ARS?s Scientific Manuscript database

    We have previously shown that swine pretreated with a replication-defective human adenovirus vector (Ad5) containing the porcine type I interferon gene (poIFN-alpha/Beta) are sterilely protected when challenged one day later with Foot-and-Mouth Disease Virus (FMDV), but the dose required is relativ...

  12. Protection of Cattle against Foot-and-Mouth Disease by a Synthetic Peptide

    NASA Astrophysics Data System (ADS)

    Dimarchi, Richard; Brooke, Gerald; Gale, Charles; Cracknell, Victor; Doel, Timothy; Mowat, Noel

    1986-05-01

    A chemically synthesized peptide consisting essentially of two separate regions (residues 141 to 158 and 200 to 213) of a virus coat protein (VP1) from the 01 Kaufbeuren strain of foot-and-mouth disease virus was prepared free of any carrier protein. It elicited high levels of neutralizing antibody and protected cattle against intradermolingual challenge by inoculation with infectious virus. Comparative evaluation of this peptide with a single-site peptide (residues 141 to 158) in guinea pigs suggests the importance of the VP1 carboxyl terminal residues in enhancing the protective response.

  13. Early detection of foot-and-mouth disease virus from infected cattle using a dry filter air sampling system

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of high economic impact. Early detection of FMD virus (FMDV) is fundamental for rapid outbreak control. Air sampling collection has been demonstrated as a useful technique for detection of FMDV RNA in infected animals, related to ...

  14. Foot-and-mouth disease in pigs: current epidemiological situation and control methods.

    PubMed

    León, Emilio A

    2012-03-01

    Foot-and-mouth disease (FMD) is the paradigm of a transboundary animal disease. Beyond any doubt, it is the most serious challenge for livestock's health. Official Veterinary Services from free countries invest considerable amount of money to prevent its introduction, whereas those from endemic countries invest most of their resources in the control of the disease. A very important volume of scientific production is developed every year in different aspects of FMD, and for that reason, the current knowledge makes the diagnosis of the disease easier to a great extent. However, FMD is still endemic in about two-thirds of the countries, and periodically re-emergent in several countries. This paper is a review of recent publications, focusing mainly on control measures and current world epidemiological situation, emphasizing primarily pigs. © 2012 Blackwell Verlag GmbH.

  15. A colorimetric bioassay for high-througput and cost-effectively assessing anti-foot-and-mouth disease virus activity

    USDA-ARS?s Scientific Manuscript database

    Foot-and-Mouth Disease virus (FMDV) is one of the most contagious animal viruses and has a devastating effect on livestock industries if an outbreaks occurs, especially in FMD-free countries. The virus is very sensitive to inhibition by type I interferons. Currently, a reported assay to measure FM...

  16. First Finding of Southeast Asia Topotype of Foot-and-Mouth Disease Virus in Kinmen, Taiwan, in the 2012 Outbreak

    PubMed Central

    LIN, Yeou-Liang; CHANG, Chia-Yi; PAN, Chu-Hsiang; DENG, Ming-Chung; TSAI, Hsiang-Jung; LEE, Fan

    2014-01-01

    ABSTRACT Foot-and-mouth disease virus, a member of genus Aphthovirus within the family Picornaviridae, affects cloven-hoofed animals, causing foot-and-mouth disease characterized by vesicle development. The Southeast Asia topotype, one of the topotypes within serotype O of the virus, is prevalent in some Asian countries, but had not previously been found in Taiwan. The topotype was first found in pigs in Kinmen Island, Taiwan, in 2012 and identified by nucleotide sequence comparison and phylogenetic analysis. Outbreaks were reported at 4 farms, resulting in the culling of 628 pigs and 1 cattle. Pigs were the only species infected during the outbreak. The incursion of Southeast Asia topotype into Taiwan implies the expansion of the topotype in East Asia. PMID:25056674

  17. Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses

    PubMed Central

    Lee, Seo-Yong; Lee, Yeo-Joo; Kim, Rae-Hyung; Park, Jeong-Nam; Park, Min-Eun; Ko, Mi-Kyeong; Choi, Joo-Hyung; Chu, Jia-Qi; Lee, Kwang-Nyeong; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jung-Won; Kim, Byounghan; Lee, Myoung-Heon

    2017-01-01

    ABSTRACT There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV. IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD

  18. Rapid Engineering of Foot-and-Mouth Disease Vaccine and Challenge Viruses.

    PubMed

    Lee, Seo-Yong; Lee, Yeo-Joo; Kim, Rae-Hyung; Park, Jeong-Nam; Park, Min-Eun; Ko, Mi-Kyeong; Choi, Joo-Hyung; Chu, Jia-Qi; Lee, Kwang-Nyeong; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jung-Won; Kim, Byounghan; Lee, Myoung-Heon; Lee, Jong-Soo; Park, Jong-Hyeon

    2017-08-15

    There are seven antigenically distinct serotypes of foot-and-mouth disease virus (FMDV), each of which has intratypic variants. In the present study, we have developed methods to efficiently generate promising vaccines against seven serotypes or subtypes. The capsid-encoding gene (P1) of the vaccine strain O1/Manisa/Turkey/69 was replaced with the amplified or synthetic genes from the O, A, Asia1, C, SAT1, SAT2, and SAT3 serotypes. Viruses of the seven serotype were rescued successfully. Each chimeric FMDV with a replacement of P1 showed serotype-specific antigenicity and varied in terms of pathogenesis in pigs and mice. Vaccination of pigs with an experimental trivalent vaccine containing the inactivated recombinants based on the main serotypes O, A, and Asia1 effectively protected them from virus challenge. This technology could be a potential strategy for a customized vaccine with challenge tools to protect against epizootic disease caused by specific serotypes or subtypes of FMDV. IMPORTANCE Foot-and-mouth disease (FMD) virus (FMDV) causes significant economic losses. For vaccine preparation, the selection of vaccine strains was complicated by high antigenic variation. In the present study, we suggested an effective strategy to rapidly prepare and evaluate mass-produced customized vaccines against epidemic strains. The P1 gene encoding the structural proteins of the well-known vaccine virus was replaced by the synthetic or amplified genes of viruses of seven representative serotypes. These chimeric viruses generally replicated readily in cell culture and had a particle size similar to that of the original vaccine strain. Their antigenicity mirrored that of the original serotype from which their P1 gene was derived. Animal infection experiments revealed that the recombinants varied in terms of pathogenicity. This strategy will be a useful tool for rapidly generating customized FMD vaccines or challenge viruses for all serotypes, especially for FMD-free countries

  19. Pathogenesis of primary foot-and-mouth disease virus infection in the nasopharynx of vaccinated and non-vaccinated cattle

    USDA-ARS?s Scientific Manuscript database

    A time-course pathogenesis study was performed to compare and contrast primary foot-and-mouth disease virus (FMDV) infection in vaccinated and non-vaccinated cattle following simulated-natural virus exposure. FMDV genome and infectious virus were detected during the initial phase of infection from b...

  20. Effect of foot-and-mouth disease virus infection on the frequency, phenotype and function of circulating dendritic cells in cattle

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms in FMDV-infected animals appear within 2 to 3 days of exposure. Dendritic cells (DC) play an essential role in protective immune responses agai...

  1. Foot-and-mouth disease eradication efforts in the Republic of Korea

    PubMed Central

    Joo, Yi-Suk; An, Soo-hwan; Kim, Ok-Kyung; Lubroth, Juan; Sur, Jung-Hyang

    2002-01-01

    On March 20, 2000, a suspected vesicular disease in cattle was reported to the National Veterinary Research and Quarantine Service (NVRQS) of the Republic of Korea. This represented the index case of a foot-and-mouth disease (FMD) outbreak, which spread through several provinces. The Republic of Korea had been free of FMD for 66 years prior to the reintroduction of the virus and had recently suspended imports of pork and pork products from neighboring Japan owing to a reported FMD outbreak in that country. The Korean outbreak was ultimately controlled through the combination of preemptive slaughter, animal movement restrictions, and a strategy of ring vaccination. The purpose of this paper is to review the current FMD situation in Korea in the aftermath of its 2000 epizootic and how it may affect future efforts to eradicate or reduce risk of reintroduction of the disease into Korea. PMID:11989734

  2. Pandemic Strain of Foot-and-Mouth Disease Virus Serotype O

    PubMed Central

    Samuel, Alan R.; Davies, Paul R.; Midgley, Rebecca J.; Valarcher, Jean-François

    2005-01-01

    A particular genetic lineage of foot-and-mouth disease virus (FMDV) serotype O, which we have named the PanAsia strain, was responsible for an explosive pandemic in Asia and extended to parts of Africa and Europe from 1998 to 2001. In 2000 and 2001, this virus strain caused outbreaks in the Republic of Korea, Japan, Russia, Mongolia, South Africa, the United Kingdom, Republic of Ireland, France, and the Netherlands, countries which last experienced FMD outbreaks decades before (ranging from 1934 for Korea to 1984 for the Netherlands). Although the virus has been controlled in all of these normally FMD-free or sporadically infected countries, it appears to be established throughout much of southern Asia, with geographically separated lineages evolving independently. A pandemic such as this is a rare phenomenon but demonstrates the ability of newly emerging FMDV strains to spread rapidly throughout a wide region and invade countries previously free from the disease. PMID:16485475

  3. Sero-prevalence of foot-and-mouth disease (FMD) in large ruminants at peri urban dairy farms near Islamabad, Pakistan

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is an important, endemic, trans-boundary viral disease affecting livestock in Pakistan and associated with high economic losses. This survey was conducted to estimate sero-prevalence of FMD in large ruminants from peri-urban dairy farms near Islamabad. Serum samples were...

  4. Identification of a novel cell culture adaptation site on the capsid of foot-and-mouth disease virus

    PubMed Central

    Chamberlain, Kyle; Fowler, Veronica L.; Barnett, Paul V.; Gold, Sarah; Wadsworth, Jemma; Knowles, Nick J.

    2015-01-01

    Vaccination remains the most effective tool for control of foot-and-mouth disease both in endemic countries and as an emergency preparedness for new outbreaks. Foot-and-mouth disease vaccines are chemically inactivated virus preparations and the production of new vaccines is critically dependent upon cell culture adaptation of field viruses, which can prove problematic. A major driver of cell culture adaptation is receptor availability. Field isolates of foot-and-mouth disease virus (FMDV) use RGD-dependent integrins as receptors, whereas cell culture adaptation often selects for variants with altered receptor preferences. Previously, two independent sites on the capsid have been identified where mutations are associated with improved cell culture growth. One is a shallow depression formed by the three major structural proteins (VP1–VP3) where mutations create a heparan sulphate (HS)-binding site (the canonical HS-binding site). The other involves residues of VP1 and is located at the fivefold symmetry axis. For some viruses, changes at this site result in HS binding; for others, the receptors are unknown. Here, we report the identification of a novel site on VP2 where mutations resulted in an expanded cell tropism of a vaccine variant of A/IRN/87 (called A − ). Furthermore, we show that introducing the same mutations into a different type A field virus (A/TUR/2/2006) resulted in the same expanded cell culture tropism as the A/IRN/87 A −  vaccine variant. These observations add to the evidence for multiple cell attachment mechanisms for FMDV and may be useful for vaccine manufacture when cell culture adaptation proves difficult. PMID:26296881

  5. Identification of a novel cell culture adaptation site on the capsid of foot-and-mouth disease virus.

    PubMed

    Chamberlain, Kyle; Fowler, Veronica L; Barnett, Paul V; Gold, Sarah; Wadsworth, Jemma; Knowles, Nick J; Jackson, Terry

    2015-09-01

    Vaccination remains the most effective tool for control of foot-and-mouth disease both in endemic countries and as an emergency preparedness for new outbreaks. Foot-and-mouth disease vaccines are chemically inactivated virus preparations and the production of new vaccines is critically dependent upon cell culture adaptation of field viruses, which can prove problematic. A major driver of cell culture adaptation is receptor availability. Field isolates of foot-and-mouth disease virus (FMDV) use RGD-dependent integrins as receptors, whereas cell culture adaptation often selects for variants with altered receptor preferences. Previously, two independent sites on the capsid have been identified where mutations are associated with improved cell culture growth. One is a shallow depression formed by the three major structural proteins (VP1-VP3) where mutations create a heparan sulphate (HS)-binding site (the canonical HS-binding site). The other involves residues of VP1 and is located at the fivefold symmetry axis. For some viruses, changes at this site result in HS binding; for others, the receptors are unknown. Here, we report the identification of a novel site on VP2 where mutations resulted in an expanded cell tropism of a vaccine variant of A/IRN/87 (called A - ). Furthermore, we show that introducing the same mutations into a different type A field virus (A/TUR/2/2006) resulted in the same expanded cell culture tropism as the A/IRN/87 A -  vaccine variant. These observations add to the evidence for multiple cell attachment mechanisms for FMDV and may be useful for vaccine manufacture when cell culture adaptation proves difficult.

  6. Short-term impacts of floods on enteric infectious disease in Qingdao, China, 2005-2011.

    PubMed

    Zhang, F; Liu, Z; Gao, L; Zhang, C; Jiang, B

    2016-11-01

    The current study aimed to examine the relationship between floods and the three enteric infectious diseases, namely bacillary dysentery (BD), hand-foot-mouth disease (HFMD) and other infectious diarrhoea (OID) in Qingdao, China. Relative risks (RRs) and 95% confidence intervals (CIs) of floods on BD, HFMD and OID were calculated using a quasi-Poisson generalized linear model, adjusting for daily average temperature, daily average relative humidity, and seasonal and long-term temporal trends. Two separate models within two different periods were designed. Model 1 for the summer period showed that floods were positively associated with BD for 4- to 12-day lags, with the greatest effects for 7-day (RR 1·41, 95% CI 1·22-1·62) and 11-day (RR 1·42, 95% CI 1·22-1·64) lags. Similar findings were found in model 2 for the whole study period for 5- to 12-day lags. However, HFMD and OID were not significantly associated with floods in both models. Results from this study will provide insight into the health risks associated with floods and may help inform public health precautionary measures for such disasters.

  7. Persistent foot-and-mouth disease virus infection in the nasopharynx of cattle: tissue-specific distribution and local cytokine expression

    USDA-ARS?s Scientific Manuscript database

    Tissues obtained post-mortem from cattle persistently infected with foot-and-mouth disease virus (FMDV) were analyzed to characterize the tissue-specific localization of FMDV and partial transcriptome profiles for selected immunoregulatory cytokines. Analysis of 28 distinct anatomic sites from 21 st...

  8. Genome sequence of foot-and-mouth disease virus serotype O lineage ind-2001d collected in Vietnam in 2015

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is endemic in several countries in Asia and Africa and is considered one of the most important livestock diseases worldwide. Three serotypes of FMD virus (A, O and Asia1) contribute to endemicity in mainland Southeast Asia. In 2015, FMDV lineage Ind-2001 was detected for...

  9. Complete Genome Sequence of the Circulatory Foot-and-Mouth Disease Virus Serotype Asia1 in Bangladesh

    PubMed Central

    Ali, M. Rahmat; Alam, A. S. M. Rubayet Ul; Amin, M. Al; Ullah, Huzzat; Siddique, Mohammad Anwar; Momtaz, Samina; Sultana, Munawar

    2017-01-01

    ABSTRACT The complete genome sequence of foot-and-mouth disease virus (FMDV) serotype Asia1 isolated from Bangladesh is reported here. Genome analysis revealed amino acid substitutions in the VP1 antigenic region and deletions in both the 5′ and 3′ untranslated regions (UTRs) compared to the genome of the existing vaccine strain (GenBank accession no. AY304994). PMID:29074654

  10. Disinfection of foot-and-mouth disease and African swine fever viruses with citric acid and sodium hypochlorite on birch wood carriers

    USDA-ARS?s Scientific Manuscript database

    Transboundary animal disease viruses such as foot-and-mouth disease virus (FMDV) and African swine fever virus (ASFV) are highly contagious and cause severe morbidity and mortality in livestock. Proper disinfection during an outbreak can help prevent virus spread and will shorten the time for contam...

  11. Evidence of subclinical foot-and-mouth disease virus infection in young calves born from clinically recovered cow under natural condition

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease (FMD) is a highly contagious and economically important, transboundary viral disease of cloven-hoofed animals. It is known that a chronic, asymptomatic FMD syndrome may occur subsequent to acute FMD in adult ruminants. However, neither asymptomatic nor persistent infection has...

  12. Molecular differentiation and phylogenetic analysis of the Egyptian foot-and-mouth disease virus SAT2.

    PubMed

    El-Shehawy, Laila I; Abu-Elnaga, Hany I; Rizk, Sonia A; Abd El-Kreem, Ahmed S; Mohamed, A A; Fawzy, Hossam G

    2014-03-01

    In February 2012, a massive new foot-and-mouth disease (FMD) outbreak struck Egypt. In this work, one-step RT-PCR assays were used for in-house detection and differentiation of foot-and-mouth disease virus (FMDV) in Egypt in this year using pan-serotypic and serotype-targeting sequence primers. FMDV SAT2 was the dominant virus in the examined isolates from the epidemic. The complete VP1 coding regions of two isolates were sequenced. The two isolates had 99.2 % sequence identity to most contemporary Egyptian SAT2 reference viruses, whereas they had 89.7-90.1 % identity to the SAT2/EGY/2/2012 isolate, which was collected from Alexandria, Egypt, and previously sequenced by WRLFMD. Phylogenetic analysis showed that Egypt had one topotype and two lineage of FMDV SAT2 in 2012. The Egyptian and the Palestinian 2012 strains were associated mainly with topotype VII, lineage SAT2/VII/Ghb-12, while the virus isolated from Alexandria Governorate belonged to the SAT2/VII/Alx-12 lineage. Topotype VII also comprised lineages that included strains isolated from Libya in 2012 and 2003. Furthermore, within the same topotype, the Egyptian SAT2/2012 isolates were related to strains from Saudi Arabia, Sudan, Eritrea, Cameroon and Nigeria. Nevertheless, more epidemiological work with neighboring countries is needed to prevent cross-border spread of disease and to reach a precise conclusion about the origin of the 2012 FMDV SAT2 emergency in the Middle East.

  13. Expression of porcine fusion protein IRF7/3(5D) efficiently controls foot-and-mouth disease virus replication

    USDA-ARS?s Scientific Manuscript database

    Several studies have demonstrated that administration of type I, II, or III interferons (IFN) delivered using a replication defective human adenovirus 5 (Ad5) vector is effective to control Foot-and-Mouth Disease (FMD) in cattle and swine during experimental infections. However, high doses are requi...

  14. Studies on Sam68 a cell factor involved in the life cycle of foot-and-mouth disease virus

    USDA-ARS?s Scientific Manuscript database

    As with other RNA viruses, Foot-and-Mouth Disease Virus (FMDV) recruits various host cell factors to assist in translation and replication of the virus genome. While FMDV translation has been thoroughly investigated, much remains unknown regarding replication of the positive-sense RNA genome. In th...

  15. Accuracy of Herdsmen Reporting versus Serologic Testing for Estimating Foot-and-Mouth Disease Prevalence

    PubMed Central

    Handel, Ian G.; Tanya, Vincent N.; Hamman, Saidou M.; Nfon, Charles; Bergman, Ingrid E.; Malirat, Viviana; Sorensen, Karl J.; Bronsvoort, Barend M. de C.

    2014-01-01

    Herdsman-reported disease prevalence is widely used in veterinary epidemiologic studies, especially for diseases with visible external lesions; however, the accuracy of such reports is rarely validated. Thus, we used latent class analysis in a Bayesian framework to compare sensitivity and specificity of herdsman reporting with virus neutralization testing and use of 3 nonstructural protein ELISAs for estimates of foot-and-mouth disease (FMD) prevalence on the Adamawa plateau of Cameroon in 2000. Herdsman-reported estimates in this FMD-endemic area were comparable to those obtained from serologic testing. To harness to this cost-effective resource of monitoring emerging infectious diseases, we suggest that estimates of the sensitivity and specificity of herdsmen reporting should be done in parallel with serologic surveys of other animal diseases. PMID:25417556

  16. Enhanced sensitivity in detection of antiviral antibody responses using biotinylation of foot-and-mouth disease virus (FMDV) capsids

    USDA-ARS?s Scientific Manuscript database

    Analysis of the immune response to infection of livestock by foot-and-mouth disease virus (FMDV) is most often reported as the serum antibody response to the virus. While measurement of neutralizing antibody has been sensitive and specific, measurements of the quality of the antibody response are le...

  17. Cell culture adaptation mutations in foot-and-mouth disease virus serotype A capsid proteins: implications for receptor interactions

    USDA-ARS?s Scientific Manuscript database

    In this study we describe the adaptive changes fixed on the capsid of several foot-and-mouth disease virus serotype A strains during propagation in cell monolayers. Viruses passaged extensively in three cell lines (BHK-21, LFBK and IB-RS-2), consistently gained several positively charged amino acids...

  18. An integrative analysis of foot-and-mouth disease virus carriers in Vietnam achieved through targeted surveillance and molecular epidemiology

    USDA-ARS?s Scientific Manuscript database

    A multidisciplinary, molecular and conventional epidemiological approach was applied to an investigation of endemic foot-and-mouth disease in Vietnam. Within the study space, it was found that 22.3 percent of sampled ruminants had previously been infected with FMD virus (FMDV) and that 2.4 percent w...

  19. Role of Jumonji c-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease virus (FMDV) can utilize as many as three distinct groups of receptor molecules to attach and enter a susceptible host cell. Four integrin heterodimers (alphavBeta1, alphavBeta3, alphavBeta6, and alphavBeta8) can function as the primary receptor for FMDV field strains. FMDV ...

  20. Novel chimeric foot-and-mouth disease virus-like particles harboring serotype O VP1 protect guinea pigs against challenge.

    PubMed

    Li, Haitao; Li, Zhiyong; Xie, Yinli; Qin, Xiaodong; Qi, Xingcai; Sun, Peng; Bai, Xingwen; Ma, Youji; Zhang, Zhidong

    2016-02-01

    Foot-and-mouth disease is a highly contagious, acute viral disease of cloven-hoofed animal species causing severe economic losses worldwide. Among the seven serotypes of foot-and-mouth disease virus (FMDV), serotype O is predominant, but its viral capsid is more acid sensitive than other serotypes, making it more difficult to produce empty serotype O VLPs in the low pH insect hemolymph. Therefore, a novel chimeric virus-like particle (VLP)-based candidate vaccine for serotype O FMDV was developed and characterized in the present study. The chimeric VLPs were composed of antigenic VP1 from serotype O and segments of viral capsid proteins from serotype Asia1. These VLPs elicited significantly higher FMDV-specific antibody levels in immunized mice than did the inactivated vaccine. Furthermore, the chimeric VLPs protected guinea pigs from FMDV challenge with an efficacy similar to that of the inactivated vaccine. These results suggest that chimeric VLPs have the potential for use in vaccines against serotype O FMDV infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Recovery of viral RNA and infectious foot-and-mouth disease virus from positive lateral-flow devices.

    PubMed

    Fowler, Veronica L; Bankowski, Bartlomiej M; Armson, Bryony; Di Nardo, Antonello; Valdazo-Gonzalez, Begoña; Reid, Scott M; Barnett, Paul V; Wadsworth, Jemma; Ferris, Nigel P; Mioulet, Valérie; King, Donald P

    2014-01-01

    Foot-and-mouth disease Virus (FMDV) is an economically important, highly contagious picornavirus that affects both wild and domesticated cloven hooved animals. In developing countries, the effective laboratory diagnosis of foot-and-mouth disease (FMD) is often hindered by inadequate sample preservation due to difficulties in the transportation and storage of clinical material. These factors can compromise the ability to detect and characterise FMD virus in countries where the disease is endemic. Furthermore, the high cost of sending infectious virus material and the biosecurity risk it presents emphasises the need for a thermo-stable, non-infectious mode of transporting diagnostic samples. This paper investigates the potential of using FMDV lateral-flow devices (LFDs) for dry transportation of clinical samples for subsequent nucleic acid amplification, sequencing and recovery of infectious virus by electroporation. FMDV positive samples (epithelial suspensions and cell culture isolates) representing four FMDV serotypes were applied to antigen LFDs: after which it was possible to recover viral RNA that could be detected using real-time RT-PCR. Using this nucleic acid, it was also possible to recover VP1 sequences and also successfully utilise protocols for amplification of complete FMD virus genomes. It was not possible to recover infectious FMDV directly from the LFDs, however following electroporation into BHK-21 cells and subsequent cell passage, infectious virus could be recovered. Therefore, these results support the use of the antigen LFD for the dry, non-hazardous transportation of samples from FMD endemic countries to international reference laboratories.

  2. Decision-making for foot-and-mouth disease control: Objectives matter

    USGS Publications Warehouse

    Probert, William J. M.; Shea, Katriona; Fonnesbeck, Christopher J.; Runge, Michael C.; Carpenter, Tim E.; Durr, Salome; Garner, M. Graeme; Harvey, Neil; Stevenson, Mark A.; Webb, Colleen T.; Werkman, Marleen; Tildesley, Michael J.; Ferrari, Matthew J.

    2016-01-01

    Formal decision-analytic methods can be used to frame disease control problems, the first step of which is to define a clear and specific objective. We demonstrate the imperative of framing clearly-defined management objectives in finding optimal control actions for control of disease outbreaks. We illustrate an analysis that can be applied rapidly at the start of an outbreak when there are multiple stakeholders involved with potentially multiple objectives, and when there are also multiple disease models upon which to compare control actions. The output of our analysis frames subsequent discourse between policy-makers, modellers and other stakeholders, by highlighting areas of discord among different management objectives and also among different models used in the analysis. We illustrate this approach in the context of a hypothetical foot-and-mouth disease (FMD) outbreak in Cumbria, UK using outputs from five rigorously-studied simulation models of FMD spread. We present both relative rankings and relative performance of controls within each model and across a range of objectives. Results illustrate how control actions change across both the base metric used to measure management success and across the statistic used to rank control actions according to said metric. This work represents a first step towards reconciling the extensive modelling work on disease control problems with frameworks for structured decision making.

  3. An improved, rapid cELISA using a novel conserved 3B epitope for the serological diagnosis of foot-and-mouth disease

    USDA-ARS?s Scientific Manuscript database

    The highly contagious foot-and-mouth disease virus (FMDV) afflicts cloven-hoofed livestock and wildlife resulting in heavy economic losses due to loss of trade and recovery from disease. We developed a rapid, sensitive, and specific competitive ELISA to detect serum antibodies to FMDV. This new cELI...

  4. Inactivation of Foot-and-Mouth Disease Virus by Citric Acid and Sodium Carbonate with Deicers

    PubMed Central

    Hong, Jang-Kwan; You, Su-Hwa; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Seo, Min-Goo; Park, Jong-Hyeon; Kim, Byounghan

    2015-01-01

    Three out of five outbreaks of foot-and-mouth disease (FMD) since 2010 in the Republic of Korea have occurred in the winter. At the freezing temperatures, it was impossible to spray disinfectant on the surfaces of vehicles, roads, and farm premises because the disinfectant would be frozen shortly after discharge and the surfaces of the roads or machines would become slippery in cold weather. In this study, we added chemical deicers (ethylene glycol, propylene glycol, sodium chloride, calcium chloride, ethyl alcohol, and commercial windshield washer fluid) to keep disinfectants (0.2% citric acid and 4% sodium carbonate) from freezing, and we tested their virucidal efficacies under simulated cold temperatures in a tube. The 0.2% citric acid could reduce the virus titer 4 logs at −20°C with all the deicers. On the other hand, 4% sodium carbonate showed little virucidal activity at −20°C within 30 min, although it resisted being frozen with the function of the deicers. In conclusion, for the winter season, we may recommend the use of citric acid (>0.2%) diluted in 30% ethyl alcohol or 25% sodium chloride solvent, depending on its purpose. PMID:26319879

  5. Host microRNA-203a is antagonistic to the progression of foot-and-mouth disease virus infection

    USDA-ARS?s Scientific Manuscript database

    Sam68 was previously shown to be a critical host factor for foot-and-mouth disease virus (FMDV) replication. MicroRNA (miR)-203a is a potent regulator of Sam68 expression both in vitro and in vivo. Here, we showed transfection of miR-203a-3p and miR-203a-5p mimics separately and in combination in a ...

  6. SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability.

    PubMed

    Scott, Katherine A; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E; Stuart, David I; Charleston, Bryan; Maree, Francois F

    2017-05-15

    Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for

  7. SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability

    PubMed Central

    Scott, Katherine A.; Kotecha, Abhay; Seago, Julian; Ren, Jingshan; Fry, Elizabeth E.; Stuart, David I.; Charleston, Bryan

    2017-01-01

    ABSTRACT Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important

  8. Adenovirus-vectored foot-and-mouth disease vaccine confers early and full protection against FMDV O1 Manisa in swine

    USDA-ARS?s Scientific Manuscript database

    A human adenovirus (Ad5) vectored foot-and-mouth disease virus (FMDV) sero-type O1-Manisa subunit vaccine (Ad5-O1Man) was engineered to deliver FMDV O1-Manisa empty capsids. Swine inoculated with Ad5-O1Man developed an FMDV-specific neutralizing antibody response as compared to animals inoculated wi...

  9. Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs.

    PubMed

    Stenfeldt, Carolina; Pacheco, Juan M; Brito, Barbara P; Moreno-Torres, Karla I; Branan, Matt A; Delgado, Amy H; Rodriguez, Luis L; Arzt, Jonathan

    2016-01-01

    Understanding the quantitative characteristics of a pathogen's capability to transmit during distinct phases of infection is important to enable accurate predictions of the spread and impact of a disease outbreak. In the current investigation, the potential for transmission of foot-and-mouth disease virus (FMDV) during the incubation (preclinical) period of infection was investigated in seven groups of pigs that were sequentially exposed to a group of donor pigs that were infected by simulated-natural inoculation. Contact-exposed pigs were comingled with infected donors through successive 8-h time slots spanning from 8 to 64 h post-inoculation (hpi) of the donor pigs. The transition from latent to infectious periods in the donor pigs was clearly defined by successful transmission of foot-and-mouth disease (FMD) to all contact pigs that were exposed to the donors from 24 hpi and later. This onset of infectiousness occurred concurrent with detection of viremia, but approximately 24 h prior to the first appearance of clinical signs of FMD in the donors. Thus, the latent period of infection ended approximately 24 h before the end of the incubation period. There were significant differences between contact-exposed groups in the time elapsed from virus exposure to the first detection of FMDV shedding, viremia, and clinical lesions. Specifically, the onset and progression of clinical FMD were more rapid in pigs that had been exposed to the donor pigs during more advanced phases of disease, suggesting that these animals had received a higher effective challenge dose. These results demonstrate transmission and dissemination of FMD within groups of pigs during the incubation period of infection. Furthermore, these findings suggest that under current conditions, shedding of FMDV in oropharyngeal fluids is a more precise proxy for FMDV infectiousness than clinical signs of infection. These findings may impact modeling of the propagation of FMD outbreaks that initiate

  10. Capsid coding sequences of foot-and-mouth disease viruses are determinants of pathogenicity in pigs.

    PubMed

    Lohse, Louise; Jackson, Terry; Bøtner, Anette; Belsham, Graham J

    2012-05-24

    The surface exposed capsid proteins, VP1, VP2 and VP3, of foot-and-mouth disease virus (FMDV) determine its antigenicity and the ability of the virus to interact with host-cell receptors. Hence, modification of these structural proteins may alter the properties of the virus.In the present study we compared the pathogenicity of different FMDVs in young pigs. In total 32 pigs, 7-weeks-old, were exposed to virus, either by direct inoculation or through contact with inoculated pigs, using cell culture adapted (O1K B64), chimeric (O1K/A-TUR and O1K/O-UKG) or field strain (O-UKG/34/2001) viruses. The O1K B64 virus and the two chimeric viruses are identical to each other except for the capsid coding region.Animals exposed to O1K B64 did not exhibit signs of disease, while pigs exposed to each of the other viruses showed typical clinical signs of foot-and-mouth disease (FMD). All pigs infected with the O1K/O-UKG chimera or the field strain (O-UKG/34/2001) developed fulminant disease. Furthermore, 3 of 4 in-contact pigs exposed to the O1K/O-UKG virus died in the acute phase of infection, likely from myocardial infection. However, in the group exposed to the O1K/A-TUR chimeric virus, only 1 pig showed symptoms of disease within the time frame of the experiment (10 days). All pigs that developed clinical disease showed a high level of viral RNA in serum and infected pigs that survived the acute phase of infection developed a serotype specific antibody response. It is concluded that the capsid coding sequences are determinants of FMDV pathogenicity in pigs.

  11. Construction of stabilized and tagged foot-and-mouth disease virus.

    PubMed

    Park, Jeong-Nam; Ko, Mi-Kyeong; Kim, Rae-Hyung; Park, Min-Eun; Lee, Seo-Yong; Yoon, Ji-Eun; Choi, Joo-Hyung; You, Su-Hwa; Park, Jung-Won; Lee, Kwang-Nyeong; Chun, Ji-Eun; Kim, Su-Mi; Tark, Dongseob; Lee, Hyang-Sim; Ko, Young-Joon; Kim, Byounghan; Lee, Myoung-Heon; Park, Jong-Hyeon

    2016-11-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease that affects cloven-hoofed animals worldwide. Construction and purification of stable antigen for vaccine are necessary but technically difficult and laborious. Here, we have tried to investigate an alternative method by inserting a hexa-histidine tag (6xHIS) in the VP1 C-terminal for easy purification and replacing two amino acids of VP1/VP2 to enhance the stability of the capsid of the FMD virus (FMDV) Asia1/MOG/05. In addition, infectious 6xHIS-tagged stable (S/T) FMDVs were maintained under acidic conditions (pH 6.0) and were readily purified from small-scale cultures using a commercial metal-affinity column. The groups vaccinated with the S/T FMDV antigen showed complete protection comparing to low survival rate in the group vaccinated with non-S/T FMDV against lethal challenge with Asia1 Shamir in mice. Therefore, the present findings indicate that the stabilized and tagged antigen offers an alternative to using the current methods for antigen purification and enhancement of stability and has potential for the development of a new FMD vaccine. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Spatial pattern of foot-and-mouth disease virus serotypes in North Central Nigeria

    PubMed Central

    Wungak, Yiltawe Simwal; Ishola, Olayinka O.; Olugasa, Babasola O.; Lazarus, David D.; Ehizibolo, David O.; Ularamu, Hussaini G.

    2017-01-01

    Aim: This study aimed to determine the foot-and-mouth disease virus (FMDV) serotypes circulating, the prevalence of FMDV serotypes, and the spatial distribution of FMDV among sedentary and pastoral cattle herds in the North-Central Nigeria. Materials and Methods: A cross-sectional study was undertaken, during which a total of 155 sera that tested positive for foot-and-mouth disease (FMD) 3ABC non-structural protein antibodies were selected and screened for FMD structural protein serotypes, A, O, SAT 1, and SAT 2 using a solid-phase competitive enzyme-linked immunosorbent assay (ELISA). Epithelial tissue specimens were collected during outbreak investigations which were tested for FMD using an antigen capture ELISA for serotype A, O, SAT 1, and SAT 2. Results: An overall serotype-specific prevalence of 79.35 (95% confidence interval [CI]: 72.4-85.18) was recorded for serotype O, 65.2% (95% CI: 57.41-72.3) for serotype A, 52.9% (95% CI: 45.03-60.67) for SAT 2, and 33.55% (95% CI: 26.45-41.26) for SAT 1. Evidence of exposure to multiple FMDV serotypes showed that 12.26% of the sera samples had antibodies against four serotypes circulating, 30.97% had antibodies against three serotypes circulating, 22.58% had antibodies against two serotypes, and 17% showed exposure to only one serotype. Clinical specimens (epithelial tissue) collected during outbreak investigations showed that serotype O has the highest proportion of 50% with serotype A - 25%; SAT 2 - 20.8%; and SAT 1 - 4.1%. Conclusion: The study detected diffuse and co-circulation of serotypes A, O, SAT 1, and SAT 2 within the study area, and hence the need for the appropriately matched multivalent vaccine is strongly advocated for FMD control in Nigeria. PMID:28507418

  13. Combination of Adt-O1MANISA AND Ad5-boIFN induces early protective immunity against foot-and-mouth diseases in cattle

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth-disease (FMD) remains one of the most important economic concerns for the agricultural industry worldwide. Although vaccination with a commercially available inactivated whole virus formulation, or a recently developed replication-defective human adenovirus 5 vector-based subunit vacc...

  14. Recombinant fusion protein and DNA vaccines against foot and mouth disease virus infection in guinea pig and swine.

    PubMed

    Huang, H; Yang, Z; Xu, Q; Sheng, Z; Xie, Y; Yan, W; You, Y; Sun, L; Zheng, Z

    1999-01-01

    In this study, we provide evidence that a recombinant fusion protein containing beta-galactosidase and a tandem repeat peptide of immunogenic dominant epitope of foot-and-mouth disease virus (FMDV) VP1 protein elicits high levels of neutralizing antibody and protects both guinea pigs and swine against infection. Vaccination with this fusion protein induced a FMDV-specific proliferative T-cell response and a neutralizing antibody response. The immunized guinea pigs and swine were protected against FMD type O virus infection. Two DNA plasmids expressing genes of foot-and-mouth disease were constructed. Both plasmids pBO1 and pCO1 contain a signal sequence of the swine immunoglobulin G (IgG) gene and fusion protein gene of pXZ84. The signal sequence and fusion protein gene were under the control of a metallothionein promoter in the case of the pBO1 plasmid and under the control of a cytomegalovirus immediate early promoter in the case of pCO1 plasmid. When pBO1 and pCO1 were inoculated intramuscularly into guinea pigs, both plasmids elicited a neutralizing antibody response and spleen cell proliferation increased following stimulation with FMDV antigen, but animals were not protected from viral challenge.

  15. Foot-and-Mouth Disease in the Middle East Caused by an A/ASIA/G-VII Virus Lineage, 2015-2016.

    PubMed

    Bachanek-Bankowska, Katarzyna; Di Nardo, Antonello; Wadsworth, Jemma; Henry, Elisabeth K M; Parlak, Ünal; Timina, Anna; Mischenko, Alexey; Qasim, Ibrahim Ahmad; Abdollahi, Darab; Sultana, Munawar; Hossain, M Anwar; King, Donald P; Knowles, Nick J

    2018-06-01

    Phylogenetic analyses of foot-and-mouth disease type A viruses in the Middle East during 2015-2016 identified viruses belonging to the A/ASIA/G-VII lineage, which originated in the Indian subcontinent. Changes in a critical antigenic site within capsid viral protein 1 suggest possible evolutionary pressure caused by an intensive vaccination program.

  16. The pathogenesis of foot-and-mouth disease II; viral pathways in swine, small ruminants, and wildlife, myotropism, chronic syndromes, and molecular virus-host interactions

    USDA-ARS?s Scientific Manuscript database

    Investigation of the pathogenesis of foot-and-mouth disease (FMD) has focused on study of the disease in cattle with less emphasis on pigs, small ruminants, and wildlife. “Atypical” FMD-associated syndromes such as myocarditis, reproductive losses, and chronic heat-intolerance have also received lit...

  17. Genetic diversity and comparison of diagnostic tests for characterization of foot-and-mouth disease virus strains from Pakistan 2008-2012

    USDA-ARS?s Scientific Manuscript database

    We report the laboratory analysis of 125 clinical samples from suspected cases of foot-and-mouth disease (FMD) in cattle and Asian buffalo collected in Pakistan between 2008 and 2012. Of these samples, 89 were found to contain viral RNA by rRT-PCR, of which 88 were also found to contain infectious F...

  18. Evolving perception on the benefits of vaccination as a foot and mouth disease control policy: contributions of South America.

    PubMed

    Bergmann, Ingrid E; Malirat, Viviana; Falczuk, Abraham J

    2005-12-01

    Within the past decade, changes in perceptions on the benefits of vaccination as an appropriate tool to achieve complete foot and mouth disease eradication have become evident. The former negative view was derived from misconceptions, resulting mainly from the belief that vaccines are not entirely effective and that vaccination masks asymptomatic viral circulation. The advent in the 1990s of vaccination policies implemented within a strategic eradication plan in South America, and during recurrence of the disease in disease-free regions contributed towards generating more reliable and visible outcomes of vaccination programs, paving the way towards a new perception. Particularly relevant was the development and application of novel serodiagnostic approaches to assess silent viral circulation, irrespective of vaccination. The use in South America of vaccination allied to serosurveys to accompany viral clarification during eradication campaigns and after emergencies clearly established the importance of this control tool to stop the spread of viral infection. This alliance gave input to break many myths associated with the use of vaccines, including the belief that immunized carrier animals pose an epidemiologic risk. This experience launched new concepts that supported the internationally recognized status of foot and mouth disease-free regions with vaccination and the 'vaccination to live' policy as an alternative to 'stamping out'.

  19. Custom-engineered chimeric foot-and-mouth disease vaccine elicits protective immune responses in pigs.

    PubMed

    Blignaut, Belinda; Visser, Nico; Theron, Jacques; Rieder, Elizabeth; Maree, Francois F

    2011-04-01

    Chimeric foot-and-mouth disease viruses (FMDV) of which the antigenic properties can be readily manipulated is a potentially powerful approach in the control of foot-and-mouth disease (FMD) in sub-Saharan Africa. FMD vaccine application is complicated by the extensive variability of the South African Territories (SAT) type viruses, which exist as distinct genetic and antigenic variants in different geographical regions. A cross-serotype chimeric virus, vKNP/SAT2, was engineered by replacing the external capsid-encoding region (1B-1D/2A) of an infectious cDNA clone of the SAT2 vaccine strain, ZIM/7/83, with that of SAT1 virus KNP/196/91. The vKNP/SAT2 virus exhibited comparable infection kinetics, virion stability and antigenic profiles to the KNP/196/91 parental virus, thus indicating that the functions provided by the capsid can be readily exchanged between serotypes. As these qualities are necessary for vaccine manufacturing, high titres of stable chimeric virus were obtained. Chemically inactivated vaccines, formulated as double-oil-in-water emulsions, were produced from intact 146S virion particles of both the chimeric and parental viruses. Inoculation of guinea pigs with the respective vaccines induced similar antibody responses. In order to show compliance with commercial vaccine requirements, the vaccines were evaluated in a full potency test. Pigs vaccinated with the chimeric vaccine produced neutralizing antibodies and showed protection against homologous FMDV challenge, albeit not to the same extent as for the vaccine prepared from the parental virus. These results provide support that chimeric vaccines containing the external capsid of field isolates can be successfully produced and that they induce protective immune responses in FMD host species.

  20. Multiple origins of foot-and-mouth disease virus serotype Asia 1 outbreaks, 2003-2007.

    PubMed

    Valarcher, Jean Francois; Knowles, Nick J; Zakharov, Valery; Scherbakov, Alexey; Zhang, Zhidong; Shang, You Jun; Liu, Zai Xin; Liu, Xiang Tao; Sanyal, Aniket; Hemadri, Divakar; Tosh, Chakradhar; Rasool, Thaha J; Pattnaik, Bramhadev; Schumann, Kate R; Beckham, Tammy R; Linchongsubongkoch, Wilai; Ferris, Nigel P; Roeder, Peter L; Paton, David J

    2009-07-01

    We investigated the molecular epidemiology of foot-and-mouth disease virus (FMDV) serotype Asia 1, which caused outbreaks of disease in Asia during 2003-2007. Since 2004, the region affected by outbreaks of this serotype has increased from disease-endemic countries in southern Asia (Afghanistan, India, Iran, Nepal, Pakistan) northward to encompass Kyrgyzstan, Tajikistan, Uzbekistan, several regions of the People's Republic of China, Mongolia, Eastern Russia, and North Korea. Phylogenetic analysis of complete virus capsid protein 1 (VP1) gene sequences demonstrated that the FMDV isolates responsible for these outbreaks belonged to 6 groups within the Asia 1 serotype. Some contemporary strains were genetically closely related to isolates collected historically from the region as far back as 25 years ago. Our analyses also indicated that some viruses have spread large distances between countries in Asia within a short time.

  1. Morphologic and phenotypic characteristics of myocarditis in two pigs infected by foot-and mouth disease virus strains of serotypes O or A

    USDA-ARS?s Scientific Manuscript database

    Myocarditis is often cited as the cause of fatalities associated with foot-and-mouth disease virus (FMDV) infection; however the pathogenesis of FMDV-associated myocarditis has not been described in detail. The current report describes substantial quantities of FMDV in association with a marked mono...

  2. Bayesian analysis of experimental epidemics of foot-and-mouth disease.

    PubMed Central

    Streftaris, George; Gibson, Gavin J.

    2004-01-01

    We investigate the transmission dynamics of a certain type of foot-and-mouth disease (FMD) virus under experimental conditions. Previous analyses of experimental data from FMD outbreaks in non-homogeneously mixing populations of sheep have suggested a decline in viraemic level through serial passage of the virus, but these do not take into account possible variation in the length of the chain of viral transmission for each animal, which is implicit in the non-observed transmission process. We consider a susceptible-exposed-infectious-removed non-Markovian compartmental model for partially observed epidemic processes, and we employ powerful methodology (Markov chain Monte Carlo) for statistical inference, to address epidemiological issues under a Bayesian framework that accounts for all available information and associated uncertainty in a coherent approach. The analysis allows us to investigate the posterior distribution of the hidden transmission history of the epidemic, and thus to determine the effect of the length of the infection chain on the recorded viraemic levels, based on the posterior distribution of a p-value. Parameter estimates of the epidemiological characteristics of the disease are also obtained. The results reveal a possible decline in viraemia in one of the two experimental outbreaks. Our model also suggests that individual infectivity is related to the level of viraemia. PMID:15306359

  3. The Foot-and-Mouth Disease Carrier State Divergence in Cattle

    PubMed Central

    Eschbaumer, Michael; Rekant, Steven I.; Pacheco, Juan M.; Smoliga, George R.; Hartwig, Ethan J.; Rodriguez, Luis L.

    2016-01-01

    ABSTRACT The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis

  4. Modeling the spread and control of foot-and-mouth disease in Pennsylvania following its discovery and options for control

    PubMed Central

    Tildesley, Michael J.; Smith, Gary; Keeling, Matt J.

    2013-01-01

    In this paper, we simulate outbreaks of foot-and-mouth disease in the Commonwealth of Pennsylvania, USA – after the introduction of a state-wide movement ban – as they might unfold in the presence of mitigation strategies. We have adapted a model previously used to investigate FMD control policies in the UK to examine the potential for disease spread given an infection seeded in each county in Pennsylvania. The results are highly dependent upon the county of introduction and the spatial scale of transmission. Should the transmission kernel be identical to that for the UK, the epidemic impact is limited to fewer than 20 premises, regardless of the county of introduction. However, for wider kernels where infection can spread further, outbreaks seeded in or near the county with highest density of premises and animals result in large epidemics (>150 premises). Ring culling and vaccination reduce epidemic size, with the optimal radius of the rings being dependent upon the county of introduction. Should the kernel width exceed a given county-dependent threshold, ring culling is unable to control the epidemic. We find that a vaccinate-to-live policy is generally preferred to ring culling (in terms of reducing the overall number of premises culled), indicating that well-targeted control can dramatically reduce the risk of large scale outbreaks of foot-and-mouth disease occurring in Pennsylvania. PMID:22169708

  5. Systemic foot-and-mouth disease vaccination in cattle promotes specific antibody secreting cells at the respiratory tract and triggers local anamnestic-compatible responses upon aerosol infection

    USDA-ARS?s Scientific Manuscript database

    Foot and mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated whole FMD virus (FMDV) particles, are regularly used worldwide in regions recognized as free from the disease. Here, we studied the generation of antibody ...

  6. The importance of quality assurance/quality control of diagnostics to increase the confidence in global foot-and-mouth disease control.

    PubMed

    De Clercq, K; Goris, N; Barnett, P V; MacKay, D K

    2008-01-01

    The last decade international trade in animals and animal products was liberated and confidence in this global trade can increase only if appropriate control measures are applied. As foot-and-mouth disease (FMD) diagnostics will play an essential role in this respect, the Food and Agriculture Organization European Commission for the Control of Foot-and-Mouth Disease (EUFMD) co-ordinates, in collaboration with the European Commission, several programmes to increase the quality of FMD diagnostics. A quality assurance (QA) system is deemed essential for laboratories involved in certifying absence of FMDV or antibodies against the virus. Therefore, laboratories are encouraged to validate their diagnostic tests fully and to install a continuous quality control (QC) monitoring system. Knowledge of performance characteristics of diagnostics is essential to interpret results correctly and to calculate sample rates in regional surveillance campaigns. Different aspects of QA/QC of classical and new FMD virological and serological diagnostics are discussed in respect to the EU FMD directive (2003/85/EC). We recommended accepting trade certificates only from laboratories participating in international proficiency testing on a regular basis.

  7. Transcriptomic analysis of persistent infection with foot-and-mouth disease virus in cattle suggests impairment of cell-mediated immunity in the nasopharynx

    USDA-ARS?s Scientific Manuscript database

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vac...

  8. Repeated exposure to 5D9, an inhibitor of 3D polymerase, effectively limits the replication of Foot-and-Mouth Disease Virus in host cells.

    USDA-ARS?s Scientific Manuscript database

    Foot-and-Mouth Disease (FMD) is a highly contagious disease of livestock caused by a highly variable RNA virus that has seven serotypes and more than sixty subtypes. Both prophylactic and post-infection means of controlling the disease outbreak, including universally applicable vaccines and emergenc...

  9. Phylogenetic Analysis of Enterovirus 71 Strains Isolated during Linked Epidemics in Malaysia, Singapore, and Western Australia

    PubMed Central

    McMinn, Peter; Lindsay, Katie; Perera, David; Chan, Hung Ming; Chan, Kwai Peng; Cardosa, Mary Jane

    2001-01-01

    Enterovirus 71 (EV71) is a frequent cause of hand, foot, and mouth disease (HFMD) epidemics associated with severe neurological sequelae in a small proportion of cases. There has been a significant increase in EV71 epidemic activity throughout the Asia-Pacific region since 1997. Recent HFMD epidemics in this region have been associated with a severe form of brainstem encephalitis associated with pulmonary edema and high case fatality rates. In this study, we show that four genetic lineages of EV71 have been prevalent in the Asia-Pacific region since 1997, including two previously undescribed genogroups (B3 and B4). Furthermore, we show that viruses belonging to genogroups B3 and B4 have circulated endemically in Southeast Asia during this period and have been the primary cause of several large HFMD or encephalitis epidemics in Malaysia, Singapore, and Western Australia. PMID:11462047

  10. An economic assessment of foot and mouth disease in Japan.

    PubMed

    Hayama, Y; Osada, Y; Oushiki, D; Tsutsui, T

    2017-04-01

    A large-scale foot and mouth disease (FMD) epidemic in Japan in 2010 caused severe economic losses for livestock and related industries. In this paper, the authors develop a clear and usable framework to estimate the economic impact of this FMD outbreak. An economic analysis is then conducted by combining this framework with an epidemiological model. The framework estimates the direct and indirect costs to livestock and related industries by applying an input-output model, as well as by addressing expenditure on disease control. The direct cost to the livestock industry was estimated at 51.2 billion Japanese yen (JPY), engendering an indirect cost to related industries of JPY 25.5 billion. The expenditure for disease control activities was estimated at JPY 8.2 billion. The total impact of the 2010 FMD epidemic was estimated at almost JPY 85 billion. Within the economic analysis, the authors evaluate several control measure scenarios: a baseline scenario, which assumes that the rapid disease spread observed in the early phase of the 2010 FMD epidemic would continue; prompt culling within 24 hours; early detection of the first case; and emergency vaccination within a radius of 10 km around the affected farms in either seven or 28 days. Prompt culling and early detection were superior from an economic point of view, reducing the total economic impact to 30% and 2% of that in the baseline scenario, respectively. Compared with these scenarios, vaccination was less cost effective. However, vaccination suppressed the speed of disease spread and shortened the duration of the epidemic, suggesting its potential effectiveness in curbing rapid disease spread in a densely populated area.

  11. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

    PubMed Central

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J.; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S.; Stockwell, Timothy B.; Rodriguez, Luis L.

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region. PMID:29390015

  12. Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts.

    PubMed

    Ramirez-Carvajal, Lisbeth; Pauszek, Steven J; Ahmed, Zaheer; Farooq, Umer; Naeem, Khalid; Shabman, Reed S; Stockwell, Timothy B; Rodriguez, Luis L

    2018-01-01

    Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

  13. Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development.

    PubMed

    Puckette, Michael; Clark, Benjamin A; Smith, Justin D; Turecek, Traci; Martel, Erica; Gabbert, Lindsay; Pisano, Melia; Hurtle, William; Pacheco, Juan M; Barrera, José; Neilan, John G; Rasmussen, Max

    2017-11-15

    The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production. Copyright © 2017 Puckette et al.

  14. Differential replication of Foot-and-mouth disease viruses in mice determine lethality.

    PubMed

    Cacciabue, Marco; García-Núñez, María Soledad; Delgado, Fernando; Currá, Anabella; Marrero, Rubén; Molinari, Paula; Rieder, Elizabeth; Carrillo, Elisa; Gismondi, María Inés

    2017-09-01

    Adult C57BL/6J mice have been used to study Foot-and-mouth disease virus (FMDV) biology. In this work, two variants of an FMDV A/Arg/01 strain exhibiting differential pathogenicity in adult mice were identified and characterized: a non-lethal virus (A01NL) caused mild signs of disease, whereas a lethal virus (A01L) caused death within 24-48h independently of the dose used. Both viruses caused a systemic infection with pathological changes in the exocrine pancreas. Virus A01L reached higher viral loads in plasma and organs of inoculated mice as well as increased replication in an ovine kidney cell line. Complete consensus sequences revealed 6 non-synonymous changes between A01L and A10NL genomes that might be linked to replication differences, as suggested by in silico prediction studies. Our results highlight the biological significance of discrete genomic variations and reinforce the usefulness of this animal model to study viral determinants of lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. A traditional evolutionary history of foot-and-mouth disease viruses in Southeast Asia challenged by analyses of non-structural protein coding sequences

    USDA-ARS?s Scientific Manuscript database

    Molecular epidemiology and evolution of foot-and-mouth disease virus (FMDV) are widely studied using genomic sequences encoding VP1, the capsid protein containing the most relevant antigenic domains. Although sequencing of the full viral genome is not used as a routine diagnostic or surveillance too...

  16. Promising MS2 mediated virus-like particle vaccine against foot-and-mouth disease.

    PubMed

    Dong, Yan-mei; Zhang, Guo-guang; Huang, Xiao-jun; Chen, Liang; Chen, Hao-tai

    2015-05-01

    Foot-and-mouth disease (FMD) has caused severe economic losses to millions of farmers worldwide. In this work, the coding genes of 141-160 epitope peptide (EP141-160) of VP1 were inserted into the coat protein (CP) genes of MS2 in prokaryotic expression vector, and the recombinant protein self-assembled into virus-like particles (VLP). Results showed that the CP-EP141-160 VLP had a strong immunoreaction with the FMD virus (FMDV) antigen in vitro, and also had an effective immune response in mice. Further virus challenge tests were carried out on guinea pigs and swine, high-titer neutralizing antibodies were produced and the CP-EP141-160 VLP vaccine could protect most of the animals against FMDV. Copyright © 2015. Published by Elsevier B.V.

  17. Experimental infection of giraffe (Giraffa camelopardalis) with SAT-1 and SAT-2 foot-and-mouth disease virus.

    PubMed

    Vosloo, W; Swanepoel, S P; Bauman, M; Botha, B; Esterhuysen, J J; Boshoff, C I; Keet, D F; Dekker, A

    2011-04-01

    The potential role of giraffe (Giraffa camelopardalis) in the epidemiology and spread of foot-and-mouth disease (FMD) SAT types was investigated by experimental infection and detection of virus in excretions using virus isolation on primary pig kidney cell cultures. In two experiments separated by a period of 24 months, groups of four animals were needle infected with a SAT-1 or SAT-2 virus, respectively and two in-contact controls were kept with each group. Viraemia was detected 3-9 days post-infection and virus isolated from mouth washes and faeces only occasionally up to day 13. The SAT-1 virus was transmitted to only one in-contact control animal, probably via saliva that contained virus from vesicles in the mouth of a needle-infected animal. None of the animals infected with the SAT-2 virus had any vesicles in the mouth, and there was no evidence of transmission to the in-contact controls. No virus was detected in probang samples for the duration of the experiments (60 days post-infection), indicating that persistent infection probably did not establish with either of these isolates. Giraffe most likely do not play an important role in FMD dissemination. Transmission of infection would possibly occur only during close contact with other animals when mouth vesicles are evident. © 2010 Blackwell Verlag GmbH.

  18. Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

    PubMed Central

    Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

    1978-01-01

    Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

  19. Transmission Pathways of Foot-and-Mouth Disease Virus in the United Kingdom in 2007

    PubMed Central

    Cottam, Eleanor M.; Wadsworth, Jemma; Shaw, Andrew E.; Rowlands, Rebecca J.; Goatley, Lynnette; Maan, Sushila; Maan, Narender S.; Mertens, Peter P. C.; Ebert, Katja; Li, Yanmin; Ryan, Eoin D.; Juleff, Nicholas; Ferris, Nigel P.; Wilesmith, John W.; Haydon, Daniel T.; King, Donald P.; Paton, David J.; Knowles, Nick J.

    2008-01-01

    Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O1 BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes. PMID:18421380

  20. Expression of a foot-and-mouth disease virus immunodominant epitope by a filamentous bacteriophage vector.

    PubMed

    Kim, Y J; Lebreton, F; Kaiser, C; Crucière, C; Rémond, M

    2004-02-01

    We described the construction of a recombinant filamentous phage displaying on its surface the immunodominant site of VP1 protein of foot-and-mouth disease virus (FMDV). The coding sequence was inserted at the amino-terminus of the major coat protein pVIII via a spacer. The hybrid phage proved to be antigenic as it was recognized by polyclonal and monoclonal anti FMDV sera. In two experiments involving immunisation of guinea-pigs with the recombinant phage, a low antibody response was generated. This suggests a possible role for phage displayed peptides in inducing anti FMDV immunity and the possibility of further development is discussed.

  1. U.K. Foot and Mouth Disease: A Systemic Risk Assessment of Existing Controls.

    PubMed

    Delgado, João; Pollard, Simon; Pearn, Kerry; Snary, Emma L; Black, Edgar; Prpich, George; Longhurst, Phil

    2017-09-01

    This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted 'features, events, and processes' (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

  2. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

    USDA-ARS?s Scientific Manuscript database

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

  3. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine

    USDA-ARS?s Scientific Manuscript database

    Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help preve...

  4. Development and evaluation of a rapid recombinase polymerase amplification assay for detection of coxsackievirus A6.

    PubMed

    Wang, Kaifeng; Wu, Yue; Yin, Dan; Tang, Shixing; Hu, Guifang; He, Yaqing

    2017-01-01

    Coxsackievirus A6 (CV-A6) is an important pathogen causing hand, foot and mouth disease (HFMD). The aim of this study was to develop and evaluate a rapid real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for detection of CV-A6. The sensitivity of this assay was 202 copies/reaction, with 100 % specificity. Furthermore, this assay yielded consistent results comparable with a commercial qRT-PCR diagnostic kit. This assay is therefore potentially useful for surveillance of CV-A6 infections and outbreak control.

  5. Detection of genome, antigen, and antibodies in oral fluids from pigs infected with foot-and-mouth disease virus.

    PubMed

    Senthilkumaran, Chandrika; Yang, Ming; Bittner, Hilary; Ambagala, Aruna; Lung, Oliver; Zimmerman, Jeffrey; Giménez-Lirola, Luis G; Nfon, Charles

    2017-04-01

    Virus nucleic acids and antibody response to pathogens can be measured using swine oral fluids (OFs). Detection of foot-and-mouth disease virus (FMDV) genome in swine OFs has previously been demonstrated. Virus isolation and viral antigen detection are additional confirmatory assays for diagnosing FMDV, but these methods have not been evaluated using swine OF. The objectives of this study were to further validate the molecular detection of FMDV in oral fluids, evaluate antigen detection and FMDV isolation from swine OFs, and develop an assay for isotypic anti-FMDV antibody detection in OFs. Ribonucleic acid (RNA) from FMDV was detected in OFs from experimentally infected pigs by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) from 1 day post-infection (dpi) to 21 dpi. Foot-and-mouth disease virus (FMDV) was isolated from OFs at 1 to 5 dpi. Additionally, FMDV antigens were detected in OFs from 1 to 6 dpi using a lateral flow immunochromatographic strip test (LFIST), which is a rapid pen-side test, and from 2 to 3 dpi using a double-antibody sandwich enzyme-linked immunosorbent assay (DAS ELISA). Furthermore, FMDV-specific immunoglobulin A (IgA) was detected in OFs using an isotype-specific indirect ELISA starting at dpi 14. These results further demonstrated the potential use of oral fluids for detecting FMDV genome, live virus, and viral antigens, as well as for quantifying mucosal IgA antibody response.

  6. Factors associated with combined hand and foot eczema.

    PubMed

    Agner, T; Aalto-Korte, K; Andersen, K E; Foti, C; Gimenéz-Arnau, A; Goncalo, M; Goossens, A; Le Coz, C; Diepgen, T L

    2017-05-01

    As for hand eczema, the aetiology of foot eczema is multifactorial and not very well understood. The aim of the present study was to identify factors associated with foot eczema in a cohort of hand eczema patients being classified into different subgroups. Associations between foot and hand eczema were studied in a cross-sectional design in a cohort of hand eczema patients. Consecutive patients were recruited from nine different European Centres during the period October 2011-September 2012. Data on demographic factors, presence of foot eczema, hand eczema duration and severity, and whether the hand eczema was work-related or not were available, as well as patch-test results. Of a total of 427 hand eczema patients identified, information on foot eczema was available in 419 patients who were included in the present study. A total of 125 patients (29.8%) had concomitant foot and hand eczema. It was found more often in association with hyperkeratotic hand eczema (P = 0.007) and was less often associated with irritant hand eczema (P < 0.001). However, foot eczema was nevertheless found in 18% of patient with irritant hand eczema and in 25% of patients with occupational hand eczema. Combined foot and hand eczema was associated with more severe and long-standing hand eczema (P < 0.001 and P = 0.004, respectively). Contact allergy was found in 51.8% with no difference between patients with combined foot and hand eczema and patients with hand eczema only. Occurrence of combined foot and hand eczema is a common finding and not restricted to endogenous hand eczema. © 2016 European Academy of Dermatology and Venereology.

  7. Modeling Estimated Personnel Needs for a Potential Foot and Mouth Disease Outbreak

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Simmons, K; Hullinger, P

    2008-01-29

    Foot and Mouth disease (FMD) is a highly infectious and contagious viral disease affecting cloven-hoofed livestock that was last detected in the United States (US) in 1929. The prevalence of FMD in other countries, as well as the current potential for this virus to be used as a form of agroterrorism, has made preparations for a potential FMD outbreak a national priority. To assist in the evaluation of national preparedness, all 50 states were surveyed via e-mail, telephone and web search to obtain emergency response plans for FMD or for foreign animal diseases in general. Information from 33 states wasmore » obtained and analyzed for estimates of personnel resources needed to respond to an outbreak. These estimates were consolidated and enhanced to create a tool that could be used by individual states to better understand the personnel that would be needed to complete various tasks over time during an outbreak response. The estimates were then coupled, post-processing, to the output from FMD outbreaks simulated in California using the Multiscale Epidemiological/Economic Simulation and Analysis (MESA) model at Lawrence Livermore National Laboratory to estimate the personnel resource demands, by task, over the course of an outbreak response.« less

  8. Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

    USDA-ARS?s Scientific Manuscript database

    Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

  9. Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging.

    PubMed

    Logan, Grace; Newman, Joseph; Wright, Caroline F; Lasecka-Dykes, Lidia; Haydon, Daniel T; Cottam, Eleanor M; Tuthill, Tobias J

    2017-10-18

    Non-enveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals and human. In the picornavirus family of non-enveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. Importance In order to transmit their genetic material to a new host, non-enveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA viruses the requirements for this critical part of the viral life cycle remain poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple and transferable to the

  10. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

    PubMed

    Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

    2017-08-01

    Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D pol ) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D pol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A 24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F HF ) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I LF ) and W237L LF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D pol mutations that affect polymerase

  11. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity

    PubMed Central

    Rai, Devendra K.; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A.; Kloc, Anna; de los Santos, Teresa; Peersen, Olve

    2017-01-01

    ABSTRACT Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3Dpol) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3Dpol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237ILF) and W237LLF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3Dpol mutations that affect polymerase fidelity

  12. Protection induced by a commercial bivalent vaccine against Foot-and-Mouth Disease 2010 field virus from Ecuador.

    PubMed

    Duque, Hernando; Naranjo, Jose; Carrillo, Consuelo; Burbano, Alexandra; Vargas, Javier; Pauszek, Lisa; Olesen, Ian; Sanchez-Vazquez, Manuel J; Cosivi, Ottorino; Allende, Rossana M

    2016-07-29

    Foot-and-Mouth Disease serotype O circulated endemically in Ecuador for many years, with an upsurge occurring in 2009. This manuscript describes retrospectively in vitro and in vivo laboratory studies to predict the field effectiveness of a commercial FMD vaccine to protect against the field strain, and explains the key actions and epidemiological strategies followed by the country to control the disease. The results established that the use of a good quality oil vaccine, manufactured with strains that were isolated long ago: O1 Campos Br/58 and A24 Cruzeiro Br/55; combined with the correct epidemiological strategies, are useful to control field strains when used in periodic biannual vaccination campaigns. Published by Elsevier Ltd.

  13. Psychosocial effects of the 2001 UK foot and mouth disease epidemic in a rural population: qualitative diary based study

    PubMed Central

    Mort, Maggie; Convery, Ian; Baxter, Josephine; Bailey, Cathy

    2005-01-01

    Objectives To understand the health and social consequences of the 2001 foot and mouth disease epidemic for a rural population. Design Longitudinal qualitative analysis. Setting North Cumbria, the worst affected area in Britain. Sample Purposive sample of 54 respondents divided in six demographically balanced rural occupational and population groups. Main outcome measures 3071 weekly diaries contributed over 18 months; 72 semistructured interviews (with the 54 diarists and 18 others); 12 group discussions with diarists Results The disease epidemic was a human tragedy, not just an animal one. Respondents' reports showed that life after the foot and mouth disease epidemic was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Distress was experienced across diverse groups well beyond the farming community. Many of these effects continued to feature in the diaries throughout the 18 month period. Conclusions The use of a rural citizens' panel allowed data capture from a wide spectrum of the rural population and showed that a greater number of workers and residents had traumatic experiences than has previously been reported. Recommendations for future disaster management include joint service reviews of what counts as a disaster, regular NHS and voluntary sector sharing of intelligence, debriefing and peer support for front line workers, increased community involvement in disposal site or disaster management, and wider, more flexible access to regeneration funding and rural health outreach work. PMID:16214809

  14. Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence

    PubMed Central

    Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Juleff, Nicholas

    2016-01-01

    ABSTRACT Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly

  15. Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence.

    PubMed

    Maree, Francois; de Klerk-Lorist, Lin-Mari; Gubbins, Simon; Zhang, Fuquan; Seago, Julian; Pérez-Martín, Eva; Reid, Liz; Scott, Katherine; van Schalkwyk, Louis; Bengis, Roy; Charleston, Bryan; Juleff, Nicholas

    2016-05-15

    Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more

  16. Role of the international organisation for animal health (Office International des Epizooties: OIE) in the control of foot and mouth disease.

    PubMed

    Vallat, B

    2002-10-01

    The author describes activities conducted by the International Organisation for Animal Health (OIE: Office International des Epizooties) to control foot and mouth disease (FMD) world-wide. These activities fall within the framework of the principal missions of the OIE. The first of these missions is the collection and dissemination of epidemiological information and of scientific knowledge on animal diseases, the socio-economic or disease implications of which can be particularly serious. The implementation of the measures required to control the disease and to protect countries threatened by FMD depends on the quality and rapidity of the transmission of this information. The co-ordination of studies, research and control programmes against FMD is equally important for the OIE. This work is based, in particular, on work conducted by the OlE foot and mouth disease and other epizootics Commission. OIE Member Countries not only have access to the most recent data on the diagnosis, surveillance and control of FMD but also have recourse to the official recognition procedure for disease-free status provided by this Commission. Finally, through the standardisation of health recommendations, diagnostic tests, manufacture protocols and the control of biological products, made available by the OIE International Animal Health Code Commission in regard to the former and by the OIE Standards Commission in regard to the latter, the OIE provides the reference for international trade in animals and animal products, and is recognised in this role by the World Trade Organization.

  17. Synonymous deoptimization of the foot-and-mouth disease virus P1 coding region causes attenuation in vivo while inducing a strong neutralizing antibody response

    USDA-ARS?s Scientific Manuscript database

    Codon bias deoptimization has been previously used to successfully attenuate human pathogens including polio, respiratory syncytial and influenza viruses. We have applied a similar technology to deoptimize the capsid coding region (P1 region) of the cDNA infectious clone of foot-and-mouth disease vi...

  18. Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus

    PubMed Central

    Li, Wenting; Wang, Kejun; Kang, Shimeng; Deng, Shoulong; Han, Hongbing; Lian, Ling; Lian, Zhengxing

    2015-01-01

    Foot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats’ cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene, and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV. PMID:26671568

  19. A 12-residue epitope displayed on phage T7 reacts strongly with antibodies against foot-and-mouth disease virus.

    PubMed

    Wong, Chuan Loo; Yong, Chean Yeah; Muhamad, Azira; Syahir, Amir; Omar, Abdul Rahman; Sieo, Chin Chin; Tan, Wen Siang

    2018-05-01

    Foot-and-mouth disease (FMD) is a major threat to the livestock industry worldwide. Despite constant surveillance and effective vaccination, the perpetual mutations of the foot-and-mouth disease virus (FMDV) pose a huge challenge to FMD diagnosis. The immunodominant region of the FMDV VP1 protein (residues 131-170) displayed on phage T7 has been used to detect anti-FMDV in bovine sera. In the present study, the functional epitope was further delineated using amino acid sequence alignment, homology modelling and phage display. Two highly conserved regions (VP1 145-152 and VP1 159-170 ) were identified among different FMDV serotypes. The coding regions of these two epitopes were fused separately to the T7 genome and displayed on the phage particles. Interestingly, chimeric phage displaying the VP1 159-170 epitope demonstrated a higher antigenicity than that displaying the VP1 131-170 epitope. By contrast, phage T7 displaying the VP1 145-152 epitope did not react significantly with the anti-FMDV antibodies in vaccinated bovine sera. This study has successfully identified a smaller functional epitope, VP1 159-170 , located at the C-terminal end of the structural VP1 protein. The phage T7 displaying this shorter epitope is a promising diagnostic reagent to detect anti-FMDV antibodies in vaccinated animals.

  20. Foot-and-mouth disease virus 5’-terminal S fragment is required for replication and modulation of the innate immune response in host cells

    USDA-ARS?s Scientific Manuscript database

    The foot-and-mouth disease virus (FMDV) contains a 5’ untranslated region (5’UTR) with multiple structural domains that regulate viral genome replication, translation, and virus-host interactions. At its 5’terminus, the S fragment of over 360 bp is predicted to form a stable stem-loop that is separ...

  1. Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle

    USDA-ARS?s Scientific Manuscript database

    Novel vaccination approaches against foot-and-mouth-disease (FMD) include the use of a replication-defective human adenovirus type 5 vector (Ad5) that contains the capsid encoding regions of FMD virus (FMDV). An Ad5.A24 has proven effective as a vaccine against FMD in swine and cattle. However, ther...

  2. Redistribution of demethylated RNA helicase A during foot-and-mouth disease virus infection: role of jumonji C-domain containing protein 6 in RHA demethylation

    USDA-ARS?s Scientific Manuscript database

    We previously reported that RNA Helicase A (RHA) re-localized from the nucleus to the cytoplasm in foot-and-mouth disease virus (FMDV) infected cells, coincident with a reduction in methylation of arginine residues in the RHA C-terminus. To further define the mechanism of RHA demethylation in FMDV-...

  3. Some Surface-Active Agents and Their Virucidal Effect on Foot-and-Mouth Disease Virus

    PubMed Central

    Fellowes, O. N.

    1965-01-01

    Selected cationic and anionic surface-active compounds were tested to determine their virucidal effect on the foot-and-mouth disease virus, type O, strain M11, propagated in primary calf kidney cells. The chemical inactivation of the virus was tested with 0.5, 1.0, 2.0, and 5.0% concentrations of the selected compounds. Virus controls with pH adjusted to cover the expected range of the mixtures of the chemicals and virus were also tested. The absence of virus from the mixtures of chemical and virus after reaction at 28 C for 2 hr was assayed by inoculating suckling mice with the mixtures. One cationic compound, alkyl methyl isoquinilinium chloride, showed considerable antiviral activity due largely to pH effect. The use of the surface-active agents investigated in this study, in the presence of organic material, would not be recommended as virucides. PMID:4286396

  4. Molecular characterization of foot-and-mouth disease virus: implications for disease control in Bangladesh.

    PubMed

    Loth, L; Osmani, M G; Kalam, M A; Chakraborty, R K; Wadsworth, J; Knowles, N J; Hammond, J M; Benigno, C

    2011-06-01

    Foot-and-mouth disease (FMD) is endemic in Bangladesh, and to implement an effective FMD control programme, it is essential to understand the complex epidemiology of the disease. Here, we report on the characterization of FMD virus (FMDV) recovered from FMD outbreaks in Bangladesh in late 2009. All isolated viruses belonged to the FMDV serotype O. The phylogenetic reconstruction showed that all isolates belonged to the Middle East-South Asia (ME-SA) topotype, but fell into two distinct sublineages, one named Ind-2001 (the other has not been named). Within both sublineages, the 2009 Bangladesh isolates were most closely related to viruses from Nepal collected during 2008 and 2009. Additionally, both sublineages contained older viruses from India collected in 2000 and 2001. In South Asia, there is extensive cross-border cattle movement from Nepal and India to Bangladesh. Both these findings have implications for the control of FMD in Bangladesh. Because of the porous borders, a regional FMD control strategy should be developed. Further, animal identification and monitoring animal movements are necessary to identify the cross-border movements and market chain interactions of ruminants, leading to improved border and movement controls. Additionally, a vaccination strategy should be developed with the initial objective of protecting small-scale dairy herds from disease. For any successful FMD control programme, long-term Government commitment and adequate resources are necessary. A sustainable programme will also need farmer education, commitment and financial contributions. © 2011 Blackwell Verlag GmbH.

  5. Study on the epidemiology of foot and mouth disease in Ethiopia.

    PubMed

    Ayelet, G; Gelaye, E; Negussie, H; Asmare, K

    2012-12-01

    This study was designed to describe the status of foot and mouth disease (FMD) in Ethiopia, through analysis of FMD outbreak reports and the detection of antibodies, to address the possibility of establishing a disease-free zone. Serum samples collected from cattle between 2003 and 2006 for the serosurveillance of rinderpest were used for this study. The records of the Ministry of Agriculture and Rural Development from 2002 to 2006 indicate that FMD outbreaks occurred each year in Ethiopia during this period, with the highest number in 2004, when 134 outbreaks took place. The highest rates were from the North Shoa zones of both the Oromia and Amhara regions. The serum samples were tested using the 3ABC enzyme-linked immunosorbent assay kit, to identify antibodies against FMD. From a total of 4,465 sera, 10.5% (n = 467) tested positive. The highest seroprevalence was detected in samples from the Eastern zone of Rgray with 41.5%; followed by the Guji zone of Oromia and Yeka district of the city of Addis Ababa, with 32.7% and 30%, respectively. Antibodies specific to FMD virus were not detected in Gambella or Benishangul. The effects of cattle, sheep and goat density, both separately and together, were analysed with a spatial regression model, but did not have a significant effect on seroprevalence. This indicates that other factors, such as farming systems and livestock movement, play a significant role in the occurrence of FMD. Based on these study findings, it might be appropriate to establish disease-free zones in Gambella and Benishangul.

  6. Hand, Foot and Mouth Disease

    MedlinePlus

    ... Emergency Preparedness & Response Environmental Health Healthy Living Injury, Violence & Safety Life Stages & Populations Travelers’ Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ...

  7. Foot and mouth disease vaccine strain selection: Current approaches and future perspectives.

    PubMed

    Mahapatra, Mana; Parida, Satya

    2018-06-27

    Lack of cross protection between foot and mouth disease (FMD) virus (FMDV) serotypes as well as incomplete protection between some subtypes of FMDV affect the application of vaccine in the field. Further, the emergence of new variant FMD viruses periodically makes the existing vaccine inefficient. Consequently, periodical vaccine strain selection either by in vivo methods or in vitro methods become an essential requirement to enable utilisation of appropriate and efficient vaccines. Areas covered: Here we describe the cross reactivity of the existing vaccines with the global pool of circulating viruses and the putative selected vaccine strains for targeting protection against the two major circulating serotype O and A FMD viruses for East Africa, the Middle East, South Asia and South East Asia. Expert Commentary: Although in vivo cross protection studies are more appropriate methods for vaccine matching and selection than in vitro neutralisation test or ELISA, in the face of an outbreak both in vivo and in vitro methods of vaccine matching are not easy, and time consuming. The FMDV capsid contains all the immunogenic epitopes, and therefore vaccine strain prediction models using both capsid sequence and serology data will likely replace existing tools in the future.

  8. Destructive tension: mathematics versus experience--the progress and control of the 2001 foot and mouth disease epidemic in Great Britain.

    PubMed

    Mansley, L M; Donaldson, A I; Thrusfield, M V; Honhold, N

    2011-08-01

    The 2001 foot and mouth disease epidemic in Great Britain was characterised by control using both traditional and novel methods, some resulting from conclusions of mathematical models. Seven days before the implementation of the novel controversial automatic pre-emptive culling of all susceptible livestock on premises adjacent to infected premises (the 'contiguous cull'), the spread of infection had already been controlled by a combination of the traditional stamping out policy with a national movement ban on livestock. A second controversial novel policy requiring the slaughter of sheep within 3 km of premises on which disease had been confirmed (the 3-km cull) also commenced after the peak of infection spread, was untargeted and took several weeks to complete; serosurveillance of culled sheep detected infection in only one flock, suggesting that cryptic infection of sheep was not propagating the epidemic. Extensive post-epidemic serological surveillance of sheep found only a small number of seropositive animals in a very few flocks, suggesting that foot and mouth disease may self-limit in extensive sheep populations. The epidemic was finally brought to an end following the introduction of enhanced agricultural movement restrictions and biosecurity measures. A welfare culling scheme of unaffected animals was required to support the prolonged national livestock movement ban. The models that supported the contiguous culling policy were severely flawed, being based on data from dissimilar epidemics; used inaccurate background population data, and contained highly improbable biological assumptions about the temporal and quantitative parameters of infection and virus emission in infected herds and flocks.

  9. Systemic immune response and virus persistence after foot-and-mouth disease virus infection of naïve cattle and cattle vaccinated with a homologous adenovirus-vectored vaccine

    USDA-ARS?s Scientific Manuscript database

    In order to investigate host factors associated with the establishment of persistent foot-and-mouth disease virus (FMDV) infection, the systemic immune response to vaccination and challenge was studied in 47 Holstein steers. Eighteen steers which had received one dose of recombinant FMDV A vaccine t...

  10. Determination of hand soil loading, soil transfer, and particle size variations after hand-pressing and hand-mouthing activities

    EPA Science Inventory

    Hand-pressing trials and hand-to-mouth soil transfer experiments were conducted to better understand soil loadings, soil transfer ratios for three mouthing activities, and variations in particle size distributions under various conditions. Results indicated that sand caused highe...

  11. Structure-based energetics of protein interfaces guide Foot-and-Mouth Disease virus vaccine design

    PubMed Central

    Scott, Katherine; Burman, Alison; Loureiro, Silvia; Ren, Jingshan; Porta, Claudine; Ginn, Helen M.; Jackson, Terry; Perez-Martin, Eva; Siebert, C. Alistair; Paul, Guntram; Huiskonen, Juha T.; Jones, Ian M.; Esnouf, Robert M.; Fry, Elizabeth E.; Maree, Francois F.; Charleston, Bryan; Stuart, David I.

    2018-01-01

    Summary Virus capsids are primed for disassembly yet capsid integrity is key to generating a protective immune response. Here we devise a computational method to assess relative stability of protein-protein interfaces and use it to design improved candidate vaccines for two of the least stable, but globally important, serotypes of Foot-and-Mouth Disease virus (FMDV), O and SAT2. FMDV capsids comprise identical pentameric protein subunits held together by tenuous non-covalent interactions, and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. We use a novel restrained molecular dynamics strategy, to rank mutations predicted to strengthen the pentamer interfaces to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralising antibody responses to stabilised particles over parental viruses and wild-type capsids. PMID:26389739

  12. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle

    USDA-ARS?s Scientific Manuscript database

    Non-structural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids in most FMDVs examined to date. The role of 3A in virus growth and virulence within the natural host is not well understood. Using a yeast two-hybrid approach, we identified cellular ...

  13. Impact of genetic changes, pathogenicity and antigenicity on Enterovirus- A71 vaccine development.

    PubMed

    Yee, Pinn Tsin Isabel; Laa Poh, Chit

    2017-06-01

    Enterovirus-A71 (EV-A71) is an etiological agent of the hand, foot and mouth disease (HFMD). EV-A71 infection produces high fever and ulcers in children. Some EV-A71 strains produce severe infections leading to pulmonary edema and death. Although the protective efficacy of the inactivated vaccine (IV) was ≥90% against mild HFMD, there was approximately 80% protection against severe HFMD. The monovalent EV-A71 IV elicits humoral immunity but lacks long-term immunogenicity. Spontaneous mutations of the EV-A71 genome could lead to antigenicity changes and the virus may not be neutralized by antibodies elicited by the IV. A better alternative would be the live attenuated vaccine (LAV) that elicits cellular and humoral immunity. The LAV induces excellent antigenicity and chances of reversion is reduced by presence of multiple mutations which could reduce pathogenicity. Besides CV-A16, outbreaks have been caused by CV-A6 and CV-A10, hence the development of bivalent and trivalent vaccines is required. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Phylogeography of Coxsackievirus A16 Reveals Global Transmission Pathways and Recent Emergence and Spread of a Recombinant Genogroup.

    PubMed

    Hassel, Chervin; Mirand, Audrey; Farkas, Agnes; Diedrich, Sabine; Huemer, Hartwig P; Peigue-Lafeuille, Hélène; Archimbaud, Christine; Henquell, Cécile; Bailly, Jean-Luc

    2017-09-15

    Coxsackievirus A16 (CV-A16; Picornaviridae ) is an enterovirus (EV) type associated with hand, foot, and mouth disease (HFMD) in children. To investigate the spatial spread of CV-A16, we used viral sequence data sampled during a prospective sentinel surveillance of HFMD in France (2010 to 2014) and phylogenetic reconstruction. A data set of 168 VP1 sequences was assembled with 416 publicly available sequences of various geographic origins. The CV-A16 sequences reported were assigned to two clades, genogroup B and a previously uncharacterized clade D. The time origins of clades B and D were assessed in 1978 (1973 to 1981) and 2004 (2001 to 2007), respectively. The shape of the global CV-A16 phylogeny indicated worldwide cocirculation of genetically distinct virus lineages over time and across geographic regions. Phylogenetic tree topologies and Bayes factor analysis indicated virus migration. Virus transportation events in clade B within Europe and Asia and between countries of the two geographic regions were assessed. The sustained transmission of clade D viruses over 4 years was analyzed at the township level in France and traced back to Peru in South America. Comparative genomics provided evidence of recombination between CV-A16 clades B and D and suggested an intertype recombinant origin for clade D. Time-resolved phylogenies and HFMD surveillance data indicated that CV-A16 persistence is sustained by continuing virus migration at different geographic scales, from community transmission to virus transportation between distant countries. The results showed a significant impact of virus movements on the epidemiological dynamics of HFMD that could have implications for disease prevention. IMPORTANCE Coxsackievirus A16 is one of the most prevalent enterovirus types in hand, foot, and mouth disease outbreaks reported in Southeast Asia. This study is based on epidemiological and viral data on HFMD caused by CV-A16 in a European country. The phylogeographic data

  15. Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

    PubMed

    Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

    2016-08-01

    The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within

  16. Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

    PubMed Central

    Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

    2016-01-01

    ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome

  17. Financial Impacts of Foot-and-Mouth Disease at Village and National Levels in Lao PDR.

    PubMed

    Nampanya, S; Khounsy, S; Abila, R; Young, J R; Bush, R D; Windsor, P A

    2016-10-01

    To assist policies on Foot-and-Mouth Disease (FMD) control in Laos and the Mekong region, the financial impact of recent outbreaks at village and national levels was examined. Village-level impacts were derived from recent research on financial losses due to FMD per smallholder household and number of households with FMD-affected livestock in the village. National-level impacts of FMD were determined from examination of 2011-2013 FMD reported to the Lao Department of Livestock and Fisheries (DLF), with the 2011 epidemic reported separately due to the large number and size of outbreaks of FMD in that year. Estimates of the national financial impact of FMD were based on (i) total FMD financial losses at the village level and (ii) the costs of FMD responses and other related costs at the DLF, provincial and district levels where FMD was reported, but excluding the costs of revenue forgone. A Monte Carlo simulation was utilized to account for likelihood of FMD over- and under-reporting. Foot-and-mouth disease was recorded in four provinces of Phonsaly, Bokeo, Xayyabouli and Champasak in three consecutive years from 2011 to 2013. However, the FMD epidemic in 2011 was more widely distributed and involved 414 villages in 14 provinces, with thousands of cases of morbidity in cattle and buffalo and some mortalities. The estimated financial losses due to FMD in 2011 were USD 30 881(±23 176) at the village level and USD 13 512 291 at the national level based on the number of villages with FMD outbreaks reported. However, when the likelihood of FMD under-reporting was accounted for, the estimated financial losses at the national level could potentially increase to USD 102 094 464 (±52 147 261), being almost 12% of the estimated farm gate value of the national large ruminant herd. These findings confirm that FMD causes substantial financial impacts in villages and to the national economy of Laos, providing justification for sustained investments in FMD control

  18. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    PubMed

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  19. A partial deletion within foot-and-mouth disease virus non-structural protein 3A causes clinical attenuation in cattle but does not prevent subclinical infection

    USDA-ARS?s Scientific Manuscript database

    Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are associated with decreased virulence in cattle; however, the mechanisms are unknown. We compared experimental infection of cattle with virulent FMDV O1Campos (O1Ca) and a mutant derivative (O1Ca-delta3A) lacking residues...

  20. Clinical and virological dynamics of a serotype O 2010 South East Asia lineage foot-and-mouth disease virus in sheep using natural and simulated natural inoculation and exposure systems

    USDA-ARS?s Scientific Manuscript database

    Infection dynamics of a recent field isolate of foot-and-mouth disease virus (FMDV), serotype O, topotype South East Asia, lineage Myamar ’98 were evaluated in sheep using four different systems for virus exposure. Two novel, simulated natural, inoculation systems consisting of intra-nasopharyngeal ...

  1. Effect of the nucleotides surrounding the start codon on the translation of foot-and-mouth disease virus RNA.

    PubMed

    Ma, X X; Feng, Y P; Gu, Y X; Zhou, J H; Ma, Z R

    2016-06-01

    As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA.

  2. Grasp with hand and mouth: a kinematic study on healthy subjects.

    PubMed

    Gentilucci, M; Benuzzi, F; Gangitano, M; Grimaldi, S

    2001-10-01

    Neurons involved in grasp preparation with hand and mouth were previously recorded in the premotor cortex of monkey. The aim of the present kinematic study was to determine whether a unique planning underlies the act of grasping with hand and mouth in humans as well. In a set of four experiments, healthy subjects reached and grasped with the hand an object of different size while opening the mouth (experiments 1 and 3), or extending the other forearm (experiment 4), or the fingers of the other hand (experiment 5). In a subsequent set of three experiments, subjects grasped an object of different size with the mouth, while opening the fingers of the right hand (experiments 6-8). The initial kinematics of mouth and finger opening, but not of forearm extension, was affected by the size of the grasped object congruently with the size effect on initial grasp kinematics. This effect was due neither to visual presentation of the object, without the successive grasp motor act (experiment 2) nor to synchronism between finger and mouth opening (experiments 3, 7, and 8). In experiment 9 subjects grasped with the right hand an object of different size while pronouncing a syllable printed on the target. Mouth opening and sound production were affected by the grasped object size. The results of the present study are discussed according to the notion that in an action each motor act is prepared before the beginning of the motor sequence. Double grasp preparation can be used for successive motor acts on the same object as, for example, grasping food with the hand and ingesting it after bringing it to the mouth. We speculate that the circuits involved in double grasp preparation might have been the neural substrate where hand motor patterns used as primitive communication signs were transferred to mouth articulation system. This is in accordance with the hypothesis that Broca's area derives phylogenetically from the monkey premotor area where hand movements are controlled.

  3. Validation of hand and foot anatomical feature measurements from smartphone images

    NASA Astrophysics Data System (ADS)

    Amini, Mohammad; Vasefi, Fartash; MacKinnon, Nicholas

    2018-02-01

    A smartphone mobile medical application, previously presented as a tool for individuals with hand arthritis to assess and monitor the progress of their disease, has been modified and expanded to include extraction of anatomical features from the hand (joint/finger width, and angulation) and foot (length, width, big toe angle, and arch height index) from smartphone camera images. Image processing algorithms and automated measurements were validated by performing tests on digital hand models, rigid plastic hand models, and real human hands and feet to determine accuracy and reproducibility compared to conventional measurement tools such as calipers, rulers, and goniometers. The mobile application was able to provide finger joint width measurements with accuracy better than 0.34 (+/-0.25) millimeters. Joint angulation measurement accuracy was better than 0.50 (+/-0.45) degrees. The automatically calculated foot length accuracy was 1.20 (+/-1.27) millimeters and the foot width accuracy was 1.93 (+/-1.92) millimeters. Hallux valgus angle (used in assessing bunions) accuracy was 1.30 (+/-1.29) degrees. Arch height index (AHI) measurements had an accuracy of 0.02 (+/-0.01). Combined with in-app documentation of symptoms, treatment, and lifestyle factors, the anatomical feature measurements can be used by both healthcare professionals and manufacturers. Applications include: diagnosing hand osteoarthritis; providing custom finger splint measurements; providing compression glove measurements for burn and lymphedema patients; determining foot dimensions for custom shoe sizing, insoles, orthotics, or foot splints; and assessing arch height index and bunion treatment effectiveness.

  4. Identification of a conformational neutralizing epitope on the VP1 protein of type A foot-and-mouth disease virus.

    PubMed

    Liu, Wenming; Yang, Baolin; Wang, Mingxia; Wang, Haiwei; Yang, Decheng; Ma, Wenge; Zhou, Guohui; Yu, Li

    2017-12-01

    Foot-and-mouth disease (FMD) caused by foot-and-mouth disease virus (FMDV), is a highly contagious infectious disease that affects domestic and wild cloven-hoofed animals worldwide. In recent years, outbreaks of serotype A FMD have occurred in many countries. High-affinity neutralizing antibodies against a conserved epitope could provide protective immunity against diverse subtypes of FMDV serotype A and protect against future pandemics. In this study, we generated a serotype A FMDV-specific potent neutralizing monoclonal antibody (MAb), 6C9, which recognizes a conformation-dependent epitope. MAb 6C9 potently neutralized FMDV A/XJBC/CHA/2010 with a 50% neutralization titer (NT 50 ) of 4096. Screening of a phage-displayed random 12-mer peptide library revealed that MAb 6C9 bound to phages displaying the consensus motif YxxPxGDLG, which is highly homologous to the 135 YxxPxxxxxGDLG 147 motif found in the serotype A FMDV virus-encoded structural protein VP1. To further verify the authentic epitope recognized by MAb 6C9, two FMDV A/XJBC/CHA/2010 mutant viruses, P138A and G144A, were generated using a reverse genetic system. Subsequent micro-neutralization assays and double-antibody sandwich (DAS) ELISA analyses revealed that the Pro 138 and Gly 144 residues of the conformational epitope that are recognized by 6C9 are important for MAb 6C9 binding. Importantly, the epitope 135 YxxPxxxxxGDLG 147 was highly conserved among different topotypes of serotype A FMDV strains in a sequence alignment analysis. Thus, the results of this study could have potential applications in the development of novel epitope-based vaccines and suitable a MAb-based diagnostic method for the detection of serotype A FMDV and the quantitation of antibodies against this serotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Efficacy of accelerated hydrogen peroxide® disinfectant on foot-and-mouth disease virus, swine vesicular disease virus and Senecavirus A.

    PubMed

    Hole, K; Ahmadpour, F; Krishnan, J; Stansfield, C; Copps, J; Nfon, C

    2017-03-01

    In a laboratory, disinfectants used to inactivate pathogens on contaminated surfaces and to prevent spread of diseases often have adverse side effects on personnel and the environment. It is, therefore, essential to find safer, fast-acting and yet effective disinfectants. The objective of this study was to evaluate an accelerated hydrogen peroxide ® (AHP ® )-based disinfectant against high consequence foreign animal disease pathogens such as foot-and-mouth disease virus (FMDV) and swine vesicular disease virus (SVDV), as well as Senecavirus A (SVA), which causes similar lesions as FMDV and SVDV. We tested varying dilutions and contact times of AHP against FMDV, SVDV and SVA by the standard US EPA and modified methods. AHP was effective against all three viruses, albeit at a higher concentration and double the manufacturer recommended contact time when testing wet films of SVDV. AHP is an effective disinfectant against FMDV, SVDV and SVA. AHP-based disinfectant can, therefore, be used in high containment laboratories working with FMDV, SVDV and related pathogens. © 2016 The Canadian Food Inspection Agency. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of The Society for Applied Microbiology.

  6. IRES-mediated translation of foot-and-mouth disease virus (FMDV) in cultured cells derived from FMDV-susceptible and -insusceptible animals.

    PubMed

    Kanda, Takehiro; Ozawa, Makoto; Tsukiyama-Kohara, Kyoko

    2016-03-31

    Foot-and-mouth disease virus (FMDV) possess a positive sense, single stranded RNA genome. Internal ribosomal entry site (IRES) element exists within its 5' untranslated region (5'UTR) of the viral RNA. Translation of the viral RNA is initiated by internal entry of the 40S ribosome within the IRES element. This process is facilitated by cellular factors known as IRES trans-acting factors (ITAFs). Foot-and-mouth disease (FMD) is host-restricted disease for cloven-hoofed animals such as cattle and pigs, but the factors determining the host range have not been identified yet. Although, ITAFs are known to promote IRES-mediated translation, these findings were confirmed only in cells derived from FMDV-insusceptible animals so far. We evaluated and compared the IRES-mediated translation activities among cell lines derived from four different animal species using bicistronic luciferase reporter plasmid, which possesses an FMDV-IRES element between Renilla and Firefly luciferase genes. Furthermore, we analyzed the effect of the cellular factors on IRES-mediated translation by silencing the cellular factors using siRNA in both FMDV-susceptible and -insusceptible animal cells. Our data indicated that IRES-mediated translational activity was not linked to FMDV host range. ITAF45 promoted IRES-mediated translation in all cell lines, and the effects of poly-pyrimidine tract binding protein (PTB) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) were observed only in FMDV-susceptible cells. Thus, PTB and 4E-BP1 may influence the host range of FMDV. IRES-mediated translation activity of FMDV was not predictive of its host range. ITAF45 promoted IRES-mediated translation in all cells, and the effects of PTB and 4E-BP1 were observed only in FMDV-susceptible cells.

  7. Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus.

    PubMed

    Xin, Xiu; Wang, Hailong; Han, Lingling; Wang, Mingzhen; Fang, Hui; Hao, Yao; Li, Jiadai; Zhang, Hu; Zheng, Congyi; Shen, Chao

    2018-05-01

    Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G 2 /M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell. IMPORTANCE It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells. Copyright © 2018 American Society for Microbiology.

  8. Atmospheric Spread of Foot-and-mouth Disease During The Early Phase of The Uk Epidemic 2001

    NASA Astrophysics Data System (ADS)

    Sørensen, J. H.; Mikkelsen, T.; Astrup, P.; Alexandersen, S.; Donaldson, A. I.

    Foot-and-mouth disease (FMD) is a highly contagious viral disease in cloven-hoofed domesticated and wild animals. The highly contagious nature of FMD is a reflection of the wide range of species which are susceptible, the enormous quantities of virus liberated by infected animals, the range of excretions and secretions which can be infectious, the stability of the virus in the environment, the multiplicity of routes of infection and the very small doses of virus that can initiate infection in susceptible hosts. One of the routes for the spread of the disease is the atmospheric dispersion of virus exhaled by infected animals. Such spread can be rapid and extensive, and it is known in certain circumstances to have occurred over a distance of several hundred kilometres. For the FMD epidemic in UK in 2001, atmospheric dispersion models were applied in real time in order to describe the atmospheric dispersion of virus for the larger outbreaks of the disease. The operational value of such modelling is first of all to identify risk zones, which is helpful to the emergency management. The paper addresses the modelling techniques and presents results related with the epidemic in UK in 2001.

  9. Foot-and-mouth disease virus (FMDV) with a stable FLAG epitope in the VP1 G-H loop as a new tool for studying FMDV pathogenesis

    USDA-ARS?s Scientific Manuscript database

    In this study, we generated a recombinant foot-and-mouth disease virus (FMDV) particle derived from A24 Cruzeiro with a FLAG tag (DYKDDDDK) substitution in the hypervariable antigenic site of the G-H loop of the VP1 capsid protein in an effort to expand the immunogenicity of the virus particle and t...

  10. Symbiotic symbolization by hand and mouth in sign language*

    PubMed Central

    Sandler, Wendy

    2010-01-01

    Current conceptions of human language include a gestural component in the communicative event. However, determining how the linguistic and gestural signals are distinguished, how each is structured, and how they interact still poses a challenge for the construction of a comprehensive model of language. This study attempts to advance our understanding of these issues with evidence from sign language. The study adopts McNeill’s criteria for distinguishing gestures from the linguistically organized signal, and provides a brief description of the linguistic organization of sign languages. Focusing on the subcategory of iconic gestures, the paper shows that signers create iconic gestures with the mouth, an articulator that acts symbiotically with the hands to complement the linguistic description of objects and events. A new distinction between the mimetic replica and the iconic symbol accounts for the nature and distribution of iconic mouth gestures and distinguishes them from mimetic uses of the mouth. Symbiotic symbolization by hand and mouth is a salient feature of human language, regardless of whether the primary linguistic modality is oral or manual. Speakers gesture with their hands, and signers gesture with their mouths. PMID:20445832

  11. Qualitative assessment of the commodity risk for spread of foot-and-mouth disease associated with international trade in deboned beef.

    PubMed

    Paton, D J; Sinclair, M; Rodríguez, R

    2010-06-01

    The risk of importing foot-and-mouth disease virus (FMDV) restricts trade in livestock and their products from parts of the world where the virus is present. This reduces trade opportunities and investment in the livestock sector of many developing countries and constrains global food supply. This review focuses on the risks associated with trade in deboned beef (DB) from foot-and-mouth disease (FMD)-infected cattle, countries or zones. A definition of DB is provided along with a description of the procedures for its preparation within beef slaughtering operations. Evidence is reviewed for circumstances under which DB can be contaminated with FMDV, and a commodity risk factor approach is used to consider the mitigating efficacy of slaughterhouse procedures. A combination of pre-slaughter and slaughterhouse measures has enabled DB to be safely imported into FMD-free countries from countries that were not nationally or zonally FMD-free. Nevertheless, current evidence does not provide absolute assurance that abattoir procedures for producing DB can result, by themselves, in a commodity with a negligible risk of transmitting FMDV without complementary measures to reduce the likelihood of slaughtering infected cattle. The main areas of uncertainty are the amounts of residual FMDV-harbouring tissues within DB, and our understanding of what constitutes a safe level of contamination. More detailed guidance should be developed to specify the mitigating measures needed in support of the export of DB from regions that are not officially FMD-free. This will help to avoid differences in interpretation of what is needed that give rise to obstacles to trade.

  12. Field-Deployable Reverse Transcription-Insulated Isothermal PCR (RT-iiPCR) Assay for Rapid and Sensitive Detection of Foot-and-Mouth Disease Virus.

    PubMed

    Ambagala, A; Fisher, M; Goolia, M; Nfon, C; Furukawa-Stoffer, T; Ortega Polo, R; Lung, O

    2017-10-01

    Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals, which can decimate the livestock industry and economy of countries previously free of this disease. Rapid detection of foot-and-mouth disease virus (FMDV) is critical to containing an FMD outbreak. Availability of a rapid, highly sensitive and specific, yet simple and field-deployable assay would support local decision-making during an FMDV outbreak. Here we report validation of a novel reverse transcription-insulated isothermal PCR (RT-iiPCR) assay that can be performed on a commercially available, compact and portable POCKIT ™ analyser that automatically analyses data and displays '+' or '-' results. The FMDV RT-iiPCR assay targets the 3D region of the FMDV genome and was capable of detecting 9 copies of in vitro-transcribed RNA standard with 95% confidence. It accurately identified 63 FMDV strains belonging to all seven serotypes and showed no cross-reactivity with viruses causing similar clinical diseases in cloven-hoofed animals. The assay was able to identify FMDV RNA in multiple sample types including oral, nasal and lesion swabs, epithelial tissue suspensions, vesicular and oral fluid samples, even before the appearance of clinical signs. Clinical sensitivity of the assay was comparable or slightly higher than the laboratory-based real-time RT-PCR assay in use. The assay was able to detect FMDV RNA in vesicular fluid samples without nucleic acid extraction. For RNA extraction from more complex sample types, a commercially available taco ™ mini transportable magnetic bead-based, automated extraction system was used. This assay provides a potentially useful field-deployable diagnostic tool for rapid detection of FMDV in an outbreak in FMD-free countries or for routine diagnostics in endemic countries with less structured laboratory systems. © 2016 Her Majesty the Queen in Right of Canada.

  13. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3 - Vaccines.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed research knowledge gaps in the field of FMDV (foot-and-mouth disease virus) vaccines. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD vaccine research. Vaccines play a vital role in FMD control, used both to limit the spread of the virus during epidemics in FMD-free countries and as the mainstay of disease management in endemic regions, particularly where sanitary controls are difficult to apply. Improvements in the performance or cost-effectiveness of FMD vaccines will allow more widespread and efficient disease control. FMD vaccines have changed little in recent decades, typically produced by inactivation of whole virus, the quantity and stability of the intact viral capsids in the final preparation being key for immunogenicity. However, these are exciting times and several promising novel FMD vaccine candidates have recently been developed. This includes the first FMD vaccine licensed for manufacture and use in the USA; this adenovirus-vectored FMD vaccine causes in vivo expression of viral capsids in vaccinated animals. Another promising vaccine candidate comprises stabilized empty FMDV capsids produced in vitro in a baculovirus expression system. Recombinant technologies are also being developed to improve otherwise conventionally produced inactivated vaccines, for example, by creating a chimeric vaccine virus to increase capsid stability and by inserting sequences into the vaccine virus for desired antigen expression. Other important areas of ongoing research include enhanced adjuvants, vaccine quality control procedures and predicting vaccine protection from immune correlates, thus reducing dependency on animal challenge studies. Globally, the degree of independent vaccine evaluation is highly variable, and this is essential for vaccine quality. Previously neglected, the

  14. Production of foot-and-mouth disease virus capsid proteins by the TEV protease.

    PubMed

    Puckette, Michael; Smith, Justin D; Gabbert, Lindsay; Schutta, Christopher; Barrera, José; Clark, Benjamin A; Neilan, John G; Rasmussen, Max

    2018-06-10

    Protective immunity to viral pathogens often includes production of neutralizing antibodies to virus capsid proteins. Many viruses produce capsid proteins by expressing a precursor polyprotein and related protease from a single open reading frame. The foot-and-mouth disease virus (FMDV) expresses a 3C protease (3Cpro) that cleaves a P1 polyprotein intermediate into individual capsid proteins, but the FMDV 3Cpro also degrades many host cell proteins and reduces the viability of host cells, including subunit vaccine production cells. To overcome the limitations of using the a wild-type 3Cpro in FMDV subunit vaccine expression systems, we altered the protease restriction sequences within a FMDV P1 polyprotein to enable production of FMDV capsid proteins by the Tobacco Etch Virus NIa protease (TEVpro). Separate TEVpro and modified FMDV P1 proteins were produced from a single open reading frame by an intervening FMDV 2A sequence. The modified FMDV P1 polyprotein was successfully processed by the TEVpro in both mammalian and bacterial cells. More broadly, this method of polyprotein production and processing may be adapted to other recombinant expression systems, especially plant-based expression. Published by Elsevier B.V.

  15. Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo.

    PubMed

    Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

    2015-01-01

    The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks.

  16. Construction and characterization of a full-length infectious cDNA clone of foot-and-mouth disease virus strain O/JPN/2010 isolated in Japan in 2010.

    PubMed

    Nishi, Tatsuya; Onozato, Hiroyuki; Ohashi, Seiichi; Fukai, Katsuhiko; Yamada, Manabu; Morioka, Kazuki; Kanno, Toru

    2016-06-01

    A full-length infectious cDNA clone of the genome of a foot-and-mouth disease virus isolated from the 2010 epidemic in Japan was constructed and designated pSVL-f02. Transfection of Cos-7 or IBRS-2 cells with this clone allowed the recovery of infectious virus. The recovered virus had the same in vitro characterization as the parental virus with regard to antigenicity in neutralization and indirect immunofluorescence tests, plaque size and one-step growth. Pigs were experimentally infected with the parental virus or the recombinant virus recovered from pSVL-f02 transfected cells. There were no significant differences in clinical signs or antibody responses between the two groups, and virus isolation and viral RNA detection from clinical samples were similar. Virus recovered from transfected cells therefore retained the in vitro characteristics and the in vivo pathogenicity of their parental strain. This cDNA clone should be a valuable tool to analyze determinants of pathogenicity and mechanisms of virus replication, and to develop genetically engineered vaccines against foot-and-mouth disease virus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    PubMed

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. The macro-economic impact of a foot-and-mouth disease incursion in New Zealand.

    PubMed

    Belton, D J

    2004-01-01

    The 2001 outbreak of Foot-and-Mouth Disease (FMD) in the United Kingdom heightened public concern in New Zealand about the economic consequences of an outbreak of FMD, and resulted in the Reserve Bank and Treasury conducting an assessment of the macro-economic impact of a small FMD outbreak in New Zealand. The study was based on a relatively small outbreak in which 50 properties were infected over a period of two months. Cumulative losses calculated over two years from the beginning of the hypothetical outbreak were estimated at around NZ dollars 10 billion, a figure twice as large as the initial Ministry of Agriculture and Forestry estimate. The main reason for this difference is that the Reserve Bank study included the additional macro-economic effects of a slump in domestic demand. The study also demonstrated that in New Zealand under the conditions of the current OIE Terrestrial Animal Health Code for FMD, the economic impact of any programme to control FMD by vaccination in which vaccinated animals are not slaughtered, is significantly worse than rapid eradication by stamping out.

  19. Immune Response and Viral Persistence in Indian Buffaloes (Bubalus bubalis) Infected with Foot-and-Mouth Disease Virus Serotype Asia 1 ▿

    PubMed Central

    Maddur, Mohan S.; Kishore, Subodh; Gopalakrishna, S.; Singh, Nem; Suryanarayana, V. V.; Gajendragad, Mukund R.

    2009-01-01

    Despite their potential role in the spread of foot-and-mouth disease (FMD), the immune response and viral persistence in FMD virus (FMDV)-infected Indian buffaloes (Bubalus bubalis) have been unexplored. We found similar kinetics of neutralizing antibody responses in the sera and secretory fluids of buffaloes following experimental FMDV Asia 1 infection, but the lymphocyte-proliferative response in infected buffaloes was of low magnitude. Despite inducing a significant systemic and secretory immune response, viral persistence seems to be a common outcome in buffaloes following FMDV Asia 1 infection, which is associated with a weak cellular immune response. PMID:19828770

  20. Sex determination from hand and foot dimensions in a North Indian population.

    PubMed

    Krishan, Kewal; Kanchan, Tanuj; Sharma, Abhilasha

    2011-03-01

    Hands and feet are often recovered from the site of natural as well as man-made disasters because of bomb blasts, train accidents, plane crashes, or mass homicides. This study is intended to establish standards for determination of sex from the dimensions of hands and feet in a North Indian population. The data for this study comprise 123 men and 123 women aged between 17 and 20 years from the "Rajput" population of Himachal Pradesh in North India. Four anthropometric measurements viz. hand length, hand breadth, foot length, and foot breadth have been taken on both sides of each subject following international anthropometric standards. The hand index (hand breadth/hand length × 100) and the foot index (foot breadth/foot length × 100) were calculated. Sectioning points and regression models are derived for the hand and foot dimensions and the derived indices. The hand and foot dimensions show a higher accuracy in sex determination by sectioning point analysis when compared to hand and foot index. Of the hand and the foot dimensions, hand breadth and foot breadth showed better accuracy in sex determination. Hand index and foot index remain poor sex discriminators in the study. © 2011 American Academy of Forensic Sciences.

  1. Overview of foot-and-mouth disease awareness among farmers and veterinarians in France.

    PubMed

    Raut, Noémie; Rivière, Julie; Hosteing, Soline; Collin, Eric; Philizot, Stéphanie; Debaere, Olivier; Zanella, Gina

    2018-06-15

    Foot-and-mouth disease (FMD) is of major concern in most countries including Europe, where no outbreaks have occurred since a decade. Indeed, the risk of FMD introduction from infected countries is not negligible and the awareness of field stakeholders (farmers, veterinarians) is essential to ensure an effective detection of the viral circulation. The French veterinary services launched in 2015 a survey to estimate the awareness of farmers and veterinarians and their knowledge about epidemiological and regulatory aspects of FMD. Official health visits were used to collect information from cattle farmers and veterinarians through two separate questionnaires. The results show that not all cattle farmers were aware of the risk of FMD reintroduction in France and of its routes of infection and speed of dissemination. As for the veterinarians, their promptness to report a suspicion was dependent on the occurrence of FMD cases in European countries. These results highlight key aspectsregarding FMD epidemiology which should be regularly reminded to the field stakeholders in FMD-free countries to increase their awareness and thus ensure an effective early detection in case of FMD introduction. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth and look-alike disease viruses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hindson, B J; Baker, B R; Bentley Tammero, L F

    2007-09-18

    A high-throughput multiplexed assay (Multiplex Version 1.0) was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspectmore » cases of foot-and-mouth disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRTPCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

  3. Changes in the EV-A71 Genome through Recombination and Spontaneous Mutations: Impact on Virulence.

    PubMed

    Mandary, Madiiha Bibi; Poh, Chit Laa

    2018-06-12

    Enterovirus 71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD) that mainly affects young children less than five years old. The onset of severe HFMD is due to neurological complications bringing about acute flaccid paralysis and pulmonary oedema. In this review, we address how genetic events such as recombination and spontaneous mutations could change the genomic organization of EV-A71, leading to an impact on viral virulence. An understanding of the recombination mechanism of the poliovirus and non-polio enteroviruses will provide further evidence of the emergence of novel strains responsible for fatal HFMD outbreaks. We aim to see if the virulence of EV-A71 is contributed solely by the presence of fatal strains or is due to the co-operation of quasispecies within a viral population. The phenomenon of quasispecies within the poliovirus is discussed to reflect viral fitness, virulence and its implications for EV-A71. Ultimately, this review gives an insight into the evolution patterns of EV-A71 by looking into its recombination history and how spontaneous mutations would affect its virulence.

  4. Evaluating the efficacy of hydrogen peroxide vapour against foot-and-mouth disease virus within a BSL4 biosafety facility.

    PubMed

    Petit, B M; Almeida, F C; Uchiyama, T R; Lopes, F O C; Tino, K H; Chewins, J

    2017-10-01

    An evaluation was made of the efficacy of 35% hydrogen peroxide vapour (HPV) against foot-and-mouth disease virus (FMDV) in a biosafety facility. Biological indicators (BIs) were produced using three serotypes of FMDV, all with a titre of ≥10 6 TCID 50 per ml. Fifteen BIs of each serotype were distributed across five locations, throughout a 30-m 3 airlock chamber, producing a total of 45 BIs. Thirty-five percent HPV was generated and applied using a Bioquell vaporization module located in the centre of the chamber. After a dwell period of 40 min, the HPV was removed via the enclosures air handling system and the BIs were collected. The surfaces of the BIs were recovered into Glasgow's modified Eagle's medium (GMEM), cultivated in BHK21 Cl13 cell culture and analysed for evidence of cytopathic effect (CPE). No CPE was detected in any BI sample. Positive controls showed CPE. The experimentation shows that FMDV is susceptible to HPV decontamination and presents a potential alternative to formaldehyde. Foot-and-mouth disease virus (FMDV) is an important pathogen in terms of biosafety due to its infectious nature and wide range of host animals, such as cattle, sheep, goats and pigs. Outbreaks of FMDV can have a severe impact on livestock production, causing morbidity, mortality, reduced yields and trade embargoes. Laboratories studying FMDV must possess BSL4 robust bio-decontamination methods to prevent inadvertent release. Formaldehyde has been the primary agent for environmental decontamination, but its designation as a human carcinogen has led to a search for alternatives. This study shows 35% hydrogen peroxide vapour has the potential to be a rapid, effective, residue-free alternative. © 2017 The Society for Applied Microbiology.

  5. [Construction and characterization of an epitope-mutated Asia 1 type foot-and-mouth disease virus].

    PubMed

    Zhang, Yan; Hu, Yonghao; Yang, Fan; Yang, Bo; Wang, Songhao; Zhu, Zixiang; Zheng, Haixue

    2015-01-01

    To generate an epitope-mutated foot-and-mouth disease virus (FMDV) as a marker vaccine, the infectious clone pAsia 1-FMDV containing the complete genomic cDNA of Asia 1 type FMDV was used as backbone, the residues at positions 27 and 31 in the 3D gene were mutated (H27Y and N31R). The resulting plasmid pAsia 1-FMDV-3DM encoding a mutated epitope was transfected into BHK-21 cells and the recombinant virus rAsia 1-3DM was rescued. The recombinant virus showed similar biological characteristics comparable with the parental virus. In serological neutralization test the antisera against recombine virus have a good reactivity with parental virus. The antisera against the mutant virus were shown to be reactive with the mutated epitope but not the wild-type one. The results indicated that the two virus strains could be distinguished by western blotting using synthetic peptides. This epitope-mutated FMDV strain will be evaluated as a potential marker vaccine against FMDV infections.

  6. Genetic characterization and molecular epidemiology of foot-and-mouth disease viruses isolated from Afghanistan in 2003-2005.

    PubMed

    Schumann, Kate R; Knowles, Nick J; Davies, Paul R; Midgley, Rebecca J; Valarcher, Jean-Francois; Raoufi, Abdul Quader; McKenna, Thomas S; Hurtle, William; Burans, James P; Martin, Barbara M; Rodriguez, Luis L; Beckham, Tammy R

    2008-04-01

    Foot-and-mouth disease virus (FMDV) isolates collected from various geographic locations in Afghanistan between 2003 and 2005 were genetically characterized, and their phylogeny was reconstructed utilizing nucleotide sequences of the complete VP1 coding region. Three serotypes of FMDV (types A, O, and Asia 1) were identified as causing clinical disease in Afghanistan during this period. Phylogenetic analysis revealed that the type A viruses were most closely related to isolates collected in Iran during 2002-2004. This is the first published report of serotype A in Afghanistan since 1975, therefore indicating the need for inclusion of serotype A in vaccine formulations that will be used to control disease outbreaks in this country. Serotype O virus isolates were closely related to PanAsia strains, including those that originated from Bhutan and Nepal during 2003-2004. The Asia 1 viruses, collected along the northern and eastern borders of Afghanistan, were most closely related to FMDV isolates collected in Pakistan during 2003 and 2004. Data obtained from this study provide valuable information on the FMDV serotypes circulating in Afghanistan and their genetic relationship with strains causing FMD in neighboring countries.

  7. Highly sensitive fetal goat tongue cell line for detection and isolation of foot-and-mouth disease virus.

    PubMed

    Brehm, K E; Ferris, N P; Lenk, M; Riebe, R; Haas, B

    2009-10-01

    A fetal goat cell line (ZZ-R 127) supplied by the Collection of Cell Lines in Veterinary Medicine of the Friedrich Loeffler Institute was examined for susceptibility to infection by foot-and-mouth disease (FMD) virus (FMDV) and by two other viruses causing clinically indistinguishable vesicular conditions, namely, the viruses of swine vesicular disease and vesicular stomatitis. Primary bovine thyroid (BTY) cells are generally the most sensitive cell culture system for FMDV detection but are problematic to produce, particularly for laboratories that infrequently perform FMD diagnostic tests and for those in countries where FMD is endemic that face problems in sourcing thyroid glands from FMD-negative calves. Strains representing all seven serotypes of FMDV could be isolated in ZZ-R 127 cells with a sensitivity that was considerably higher than that of established cell lines and within 0.5 log of that for BTY cells. The ZZ-R 127 cell line was found to be a sensitive, rapid, and convenient tool for the isolation of FMDV and a useful alternative to BTY cells for FMD diagnosis.

  8. Unilateral Cleft Hand with Cleft Foot

    PubMed Central

    Baba, Asif Nazir; Bhat, Yasmeen J.; Ahmed, Sheikh Mushtaq; Nazir, Abid

    2009-01-01

    Congenital anomalies of the hand form an important class of congenital malformations. They have a huge functional importance because of the part played by the hand in the daily activities of a person. The deformities also have significant cosmetic significance and may also be associated with other anomalies. Amongst the congenital anomalies, central deficiency or cleft hand is relatively rare. The association of cleft foot with cleft hand is an even more rare occurance. We present a case report of a 6 year old child, born of a non-consanginous marriage, having congenital central deficiency of ipsilateral hand and foot. PMID:21475543

  9. Degradation of foot-and-mouth disease virus during composting of infected pig carcasses

    PubMed Central

    Guan, J.; Chan, M.; Grenier, C.; Brooks, B.W.; Spencer, J.L.; Kranendonk, C.; Copps, J.; Clavijo, A.

    2010-01-01

    The objective of this study was to investigate the inactivation and degradation of foot-and-mouth disease (FMD) virus during composting of infected pig carcasses as measured by virus isolation in tissue culture and by real-time reverse transcriptase polymerase chain reaction (RRT-PCR). Three FMD-infected pig carcasses were composted in a mixture of chicken manure and wood shavings in a biocontainment level 3 facility. Compost temperatures had reached 50°C and 70°C by days 10 and 19, respectively. Under these conditions, FMD virus was inactivated in specimens in compost by day 10 and the viral RNA was degraded in skin and internal organ tissues by day 21. In comparison, at ambient temperatures close to 20°C, FMD virus survived to day 10 in the skin tissue specimen from the pig that had the highest initial level of viral RNA in its tissues and the viral RNA persisted to day 21. Similarly, beta-actin mRNA, tested as a PCR control, persisted to day 21 in specimens held at ambient temperatures, but it was degraded in the remnants of tissues recovered from compost on day 21. Results from this study provide evidence that composting could be used for safe disposal of pig carcasses infected with FMD virus. PMID:20357957

  10. Economic aspects of foot and mouth disease: perspectives of a free country, Australia.

    PubMed

    Garner, M G; Fisher, B S; Murray, J G

    2002-12-01

    Australia is a significant livestock producer and a major exporter of livestock, livestock products and livestock genetic material. An outbreak of foot and mouth disease (FMD) would have severe economic consequences on the economy. A recent study found that in an outbreak lasting six months, real gross domestic product in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by 0.8%, and a depreciation of 3% would be recorded in the exchange rate in the first year. Much of this impact would be due to the loss of export markets. Given the significant consequences of an outbreak of FMD, Australia invests considerable resources in prevention and planning. These measures can be viewed at three levels, namely: pre-border, border and post-border. Australia recently further enhanced quarantine at the border to minimise the risk of entry of FMD. However, no matter how much is invested, there is no guarantee that FMD will not enter the country. Accordingly, it is important to ensure that comprehensive contingency plans are also in place. Recent outbreaks in previously free countries have shown that a large outbreak of FMD poses major problems for the animal health services of a country and a combined government and industry response is required.

  11. Anti-foot-and-mouth disease virus effects of Chinese herbal kombucha in vivo

    PubMed Central

    Fu, Naifang; Wu, Juncai; Lv, Lv; He, Jijun; Jiang, Shengjun

    2015-01-01

    Abstract The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks. PMID:26691487

  12. Expanding specificity of class 1 restricted CD8+ T cells for viral epitopes following multiple inoculations of swine with a human adenivorus vectored foot-and-mouth disease virus (FMDV) vaccine

    USDA-ARS?s Scientific Manuscript database

    The immune response to the highly acute foot-and-mouth disease virus (FMDV) is routinely reported as a measure of serum antibody. However, a critical effector function of immune responses combating viral infection of mammals is the cytotoxic T lymphocyte (CTL) response, mediated by virus specific ...

  13. Index/Ring Finger Ratio, Hand and Foot Index: Gender Estimation Tools.

    PubMed

    Gupta, Sonia; Gupta, Vineeta; Tyagi, Nutan; Ettishree; Bhagat, Sinthia; Dadu, Mohit; Anthwal, Nishita; Ashraf, Tahira

    2017-06-01

    Gender estimation from dismembered human body parts and skeletal remains in cases of mass disasters, explosions, and assaults cases is an imperative element of any medico-legal investigations and has been a major challenge for forensic scientists. The aim of the present study was to estimate the gender by using index and ring finger length ratio, hand and foot index along with the correlation of both the hand and foot index to determine the vital role of all the indices in establishing gender identity. A descriptive cross-sectional study was done on 300 subjects (150 males and 150 females). Various anthropometric measurements like hand length, hand breadth and hand index, Index Finger Length (IFL), Ring Finger Length (RFL) and IFL/RFL ratio as well as foot length, foot breadth and foot index were estimated in millimeters (mm) with the help of sliding-anthropometric caliper. The data was analysed using independent t-test and Pearson correlation coefficient test. A probability value (p) of ≤ 0.05 was considered statistically significant. The index and ring finger ratio was found to be higher in females as compared to males. The hand and foot index was more in males than in females. The index and ring finger length ratio, hand and foot index between males and females was found to be statistically significant for both hands and feet. A statistically significant correlation was determined between hand indexes versus foot index. This study can be useful to establish the gender of a dismembered hand or foot when subjected for medicolegal examination.

  14. A novel inactivated enterovirus 71 vaccine can elicit cross-protective immunity against coxsackievirus A16 in mice.

    PubMed

    Yang, Lisheng; Liu, Yajing; Li, Shuxuan; Zhao, Huan; Lin, Qiaona; Yu, Hai; Huang, Xiumin; Zheng, Qingbing; Cheng, Tong; Xia, Ningshao

    2016-11-21

    Hand, foot, and mouth disease (HFMD) is a highly contagious disease that mainly affects infants and children. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the major pathogens of HFMD. Two EV71 vaccines were recently licensed in China and the administration of the EV71 vaccines is believed to significantly reduce the number of HFMD-related severe or fatal cases. However, a monovalent EV71 vaccine cannot cross-protect against CA16 infection, this may result in that it cannot effectively control the overall HFMD epidemic. In this study, a chimeric EV71, whose VP1/210-225 epitope was replaced by that of CA16, was constructed using a reverse genetics technique to produce a candidate EV71/CA16 bivalent vaccine strain. The chimeric EV71 was infectious and showed similar growth characteristics as its parental strain. The replacement of the VP1/210-225 epitope did not significantly affect the antigenicity and immunogenicity of EV71. More importantly, the chimeric EV71 could induce protective immunity against both EV71 and CA16, and protect neonatal mice against either EV71 or CA16 lethal infections, the chimeric EV71 constructed in this study was shown to be a feasible and promising candidate bivalent vaccine against both EV71 and CA16. The construction of a chimeric enterovirus also provides an alternative platform for broad-spectrum HFMD vaccines development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Review: Evaluation of Foot-and-Mouth Disease Control Using Fault Tree Analysis.

    PubMed

    Isoda, N; Kadohira, M; Sekiguchi, S; Schuppers, M; Stärk, K D C

    2015-06-01

    An outbreak of foot-and-mouth disease (FMD) causes huge economic losses and animal welfare problems. Although much can be learnt from past FMD outbreaks, several countries are not satisfied with their degree of contingency planning and aiming at more assurance that their control measures will be effective. The purpose of the present article was to develop a generic fault tree framework for the control of an FMD outbreak as a basis for systematic improvement and refinement of control activities and general preparedness. Fault trees are typically used in engineering to document pathways that can lead to an undesired event, that is, ineffective FMD control. The fault tree method allows risk managers to identify immature parts of the control system and to analyse the events or steps that will most probably delay rapid and effective disease control during a real outbreak. The present developed fault tree is generic and can be tailored to fit the specific needs of countries. For instance, the specific fault tree for the 2001 FMD outbreak in the UK was refined based on control weaknesses discussed in peer-reviewed articles. Furthermore, the specific fault tree based on the 2001 outbreak was applied to the subsequent FMD outbreak in 2007 to assess the refinement of control measures following the earlier, major outbreak. The FMD fault tree can assist risk managers to develop more refined and adequate control activities against FMD outbreaks and to find optimum strategies for rapid control. Further application using the current tree will be one of the basic measures for FMD control worldwide. © 2013 Blackwell Verlag GmbH.

  16. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway

    PubMed Central

    Li, Dan; Lei, Caoqi; Xu, Zhisheng; Yang, Fan; Liu, Huanan; Zhu, Zixiang; Li, Shu; Liu, Xiangtao; Shu, Hongbing; Zheng, Haixue

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-β signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG-I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N-terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-β induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID:26883855

  17. Beyond policy networks: policy framing and the politics of expertise in the 2001 Foot and Mouth Disease crisis.

    PubMed

    Wilkinson, Katy; Lowe, Philip; Donaldson, Andrew

    2010-01-01

    For the past decade, the policy community/issue network typology of pressure group interaction has been used to explain policy outcomes and the policy-making process. To re-examine the validity of this typology, the paper focuses on the UK government's response to the 2001 Foot and Mouth Disease (FMD) crisis, and in particular the decision to pursue contiguous culling rather than vaccination to overcome the epidemic. Rather than illustrating the emergence of an issue network in agricultural policy, the decision-making process of the FMD outbreak demonstrates continuity with prior crises. In addition, the politicization of scientific expertise is identified as an emerging trend in crisis management. Policy framing is used to explain the impetus behind the contiguous cull decision, concluding that the legacy of previous policy choices conditioned the crisis response to a far greater degree than contemporaneous pressure group action.

  18. Normal variation in thermal radiated temperature in cattle: implications for foot-and-mouth disease detection.

    PubMed

    Gloster, John; Ebert, Katja; Gubbins, Simon; Bashiruddin, John; Paton, David J

    2011-11-21

    Thermal imagers have been used in a number of disciplines to record animal surface temperatures and as a result detect temperature distributions and abnormalities requiring a particular course of action. Some work, with animals infected with foot-and-mouth disease virus, has suggested that the technique might be used to identify animals in the early stages of disease. In this study, images of 19 healthy cattle have been taken over an extended period to determine hoof and especially coronary band temperatures (a common site for the development of FMD lesions) and eye temperatures (as a surrogate for core body temperature) and to examine how these vary with time and ambient conditions. The results showed that under UK conditions an animal's hoof temperature varied from 10°C to 36°C and was primarily influenced by the ambient temperature and the animal's activity immediately prior to measurement. Eye temperatures were not affected by ambient temperature and are a useful indicator of core body temperature. Given the variation in temperature of the hooves of normal animals under various environmental conditions the use of a single threshold hoof temperature will be at best a modest predictive indicator of early FMD, even if ambient temperature is factored into the evaluation.

  19. Preserved immunogenicity of an inactivated vaccine based on foot-and-mouth disease virus particles with improved stability.

    PubMed

    Caridi, Flavia; Vázquez-Calvo, Ángela; Borrego, Belén; McCullough, Kenneth; Summerfield, Artur; Sobrino, Francisco; Martín-Acebes, Miguel A

    2017-05-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. Vaccines based on inactivated FMDV virions provide a useful tool for the control of this pathogen. However, long term storage at 4°C (the temperature for vaccine storage) or ruptures of the cold chain, provoke the dissociation of virions, reducing the immunogenicity of the vaccine. An FMDV mutant carrying amino acid replacements VP1 N17D and VP2 H145Y isolated previously rendered virions with increased resistance to dissociation at 4°C. We have evaluated the immunogenicity in swine (a natural FMDV host) of a chemically inactivated vaccine based on this mutant. The presence of these amino acid substitutions did not compromise the immunological potential, including its ability to elicit neutralizing antibodies. These results support the feasibility of this kind of mutants with increased capsid stability as suitable viruses for producing improved FMDV vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Foot-and-Mouth Disease Impact on Smallholders - What Do We Know, What Don't We Know and How Can We Find Out More?

    PubMed

    Knight-Jones, T J D; McLaws, M; Rushton, J

    2017-08-01

    Foot-and-mouth disease (FMD) endemic regions contain three-quarters of the world's FMD susceptible livestock and most of the world's poor livestock keepers. Yet FMD impact on smallholders in these regions is poorly understood. Diseases of low mortality can exert a large impact if incidence is high. Modelling and field studies commonly find high FMD incidence in endemic countries. Sero-surveys typically find a third of young cattle are sero-positive, however, the proportion of sero-positive animals that developed disease, and resulting impact, are unknown. The few smallholder FMD impact studies that have been performed assessed different aspects of impact, using different approaches. They find that FMD impact can be high (>10% of annual household income). However, impact is highly variable, being a function of FMD incidence and dependency on activities affected by FMD. FMD restricts investment in productive but less FMD-resilient farming methods, however, other barriers to efficient production may exist, reducing the benefits of FMD control. Applying control measures is costly and can have wide-reaching negative impacts; veterinary-cordon-fences may damage wildlife populations, and livestock movement restrictions and trade bans damage farmer profits and the wider economy. When control measures are ineffective, farmers, society and wildlife may experience the burden of control without reducing disease burden. Foot-and-mouth disease control has benefitted smallholders in South America and elsewhere. Success takes decades of regional cooperation with effective veterinary services and widespread farmer participation. However, both the likelihood of success and the full cost of control measures must be considered. Controlling FMD in smallholder systems is challenging, particularly when movement restrictions are hard to enforce. In parts of Africa this is compounded by endemically infected wildlife and limited vaccine performance. This paper reviews FMD impact on

  1. Foot-and-mouth Disease Transmission in Africa: Implications for Control, a Review.

    PubMed

    Tekleghiorghis, T; Moormann, R J M; Weerdmeester, K; Dekker, A

    2016-04-01

    In Africa, for the control of foot-and-mouth disease (FMD), more information is needed on the spread of the disease at local, regional and inter-regional level. The aim of this review is to identify the role that animal husbandry, trade and wildlife have on the transmission of FMD and to provide a scientific basis for different FMD control measures in Africa. Review of literature, published reports and databases shows that there is more long distance spread of FMD virus serotypes within North, West, Central and East Africa than in southern Africa. In North, West, Central and East Africa migratory animal husbandry systems often related with search for grazing and water as well as trade are practiced to a greater extent than in southern Africa. In southern Africa, the role of African buffalo (Syncerus caffer) is more extensively studied than in the other parts of Africa, but based on the densities of African buffalo in Central and East Africa, one would assume that buffalo should also play a role in the epidemiology of FMD in this part of Africa. More sampling of buffalo is necessary in West, Central and East Africa. The genetic analysis of virus strains has proven to be valuable to increase our understanding in the spread of FMD in Africa. This review shows that there is a difference in FMD occurrence between southern Africa and the rest of the continent; this distinction is most likely based on differences in animal husbandry and trade systems. Insufficient data on FMD in wildlife outside southern Africa is limiting our understanding on the role wildlife plays in the transmission of FMD in the other buffalo inhabited areas of Africa. © 2014 Blackwell Verlag GmbH.

  2. A comparison between two simulation models for spread of foot-and-mouth disease.

    PubMed

    Halasa, Tariq; Boklund, Anette; Stockmarr, Anders; Enøe, Claes; Christiansen, Lasse E

    2014-01-01

    Two widely used simulation models of foot-and-mouth disease (FMD) were used in order to compare the models' predictions in term of disease spread, consequence, and the ranking of the applied control strategies, and to discuss the effect of the way disease spread is modeled on the predicted outcomes of each model. The DTU-DADS (version 0.100), and ISP (version 2.001.11) were used to simulate a hypothetical spread of FMD in Denmark. Actual herd type, movements, and location data in the period 1st October 2006 and 30th September 2007 was used. The models simulated the spread of FMD using 3 different control scenarios: 1) A basic scenario representing EU and Danish control strategies, 2) pre-emptive depopulation of susceptible herds within a 500 meters radius around the detected herds, and 3) suppressive vaccination of susceptible herds within a 1,000 meters radius around the detected herds. Depopulation and vaccination started 14 days following the detection of the first infected herd. Five thousand index herds were selected randomly, of which there were 1,000 cattle herds located in high density cattle areas and 1,000 in low density cattle areas, 1,000 swine herds located in high density swine areas and 1,000 in low density swine areas, and 1,000 sheep herds. Generally, DTU-DADS predicted larger, longer duration and costlier epidemics than ISP, except when epidemics started in cattle herds located in high density cattle areas. ISP supported suppressive vaccination rather than pre-emptive depopulation, while DTU-DADS was indifferent to the alternative control strategies. Nonetheless, the absolute differences between control strategies were small making the choice of control strategy during an outbreak to be most likely based on practical reasons.

  3. A Comparison between Two Simulation Models for Spread of Foot-and-Mouth Disease

    PubMed Central

    Halasa, Tariq; Boklund, Anette; Stockmarr, Anders; Enøe, Claes; Christiansen, Lasse E.

    2014-01-01

    Two widely used simulation models of foot-and-mouth disease (FMD) were used in order to compare the models’ predictions in term of disease spread, consequence, and the ranking of the applied control strategies, and to discuss the effect of the way disease spread is modeled on the predicted outcomes of each model. The DTU-DADS (version 0.100), and ISP (version 2.001.11) were used to simulate a hypothetical spread of FMD in Denmark. Actual herd type, movements, and location data in the period 1st October 2006 and 30th September 2007 was used. The models simulated the spread of FMD using 3 different control scenarios: 1) A basic scenario representing EU and Danish control strategies, 2) pre-emptive depopulation of susceptible herds within a 500 meters radius around the detected herds, and 3) suppressive vaccination of susceptible herds within a 1,000 meters radius around the detected herds. Depopulation and vaccination started 14 days following the detection of the first infected herd. Five thousand index herds were selected randomly, of which there were 1,000 cattle herds located in high density cattle areas and 1,000 in low density cattle areas, 1,000 swine herds located in high density swine areas and 1,000 in low density swine areas, and 1,000 sheep herds. Generally, DTU-DADS predicted larger, longer duration and costlier epidemics than ISP, except when epidemics started in cattle herds located in high density cattle areas. ISP supported suppressive vaccination rather than pre-emptive depopulation, while DTU-DADS was indifferent to the alternative control strategies. Nonetheless, the absolute differences between control strategies were small making the choice of control strategy during an outbreak to be most likely based on practical reasons. PMID:24667525

  4. Comparison of self-processing of foot-and-mouth disease virus leader proteinase and porcine reproductive and respiratory syndrome virus leader proteinase nsp1α

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steinberger, Jutta; Kontaxis, Georg; Rancan, Chiara

    The foot-and-mouth disease virus leader proteinase (Lb{sup pro}) cleaves itself off the nascent viral polyprotein. NMR studies on the monomeric variant Lb{sup pro} L200F provide structural evidence for intramolecular self-processing. {sup 15}N-HSQC measurements of Lb{sup pro} L200F showed specifically shifted backbone signals in the active and substrate binding sites compared to the monomeric variant sLb{sup pro}, lacking six C-terminal residues. This indicates transient intramolecular interactions between the C-terminal extension (CTE) of one molecule and its own active site. Contrastingly, the porcine reproductive and respiratory syndrome virus (PRRSV) leader proteinase nsp1α, with a papain-like fold like Lb{sup pro}, stably binds itsmore » own CTE. Parts of the β-sheet domains but none of the α-helical domains of Lb{sup pro} and nsp1α superimpose; consequently, the α-helical domain of nsp1α is oriented differently relative to its β-sheet domain. This provides a large interaction surface for the CTE with the globular domain, stabilising the intramolecular complex. Consequently, self-processing inactivates nsp1α but not Lb{sup pro}. - Highlights: • We examine self-processing of the leader protease of foot-and-mouth disease virus. • NMR analysis strongly supports intramolecular self-processing. • Self-processing is a dynamic process with no stable complex. • Structural comparison with nsp1α of PRRSV which forms stable intramolecular complex. • Subdomain orientation explains differences in stability of intramolecular complexes.« less

  5. Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

    PubMed Central

    Zheng, Haixue; Guo, Jianhong; Jin, Ye; Yang, Fan; He, Jijun; Lv, Lv; Zhang, Kesan; Wu, Qiong; Liu, Xiangtao; Cai, Xuepeng

    2013-01-01

    Background No licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells. Methodology/Principal Findings A novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen. Conclusions/Significance Our data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD. PMID:23372840

  6. Identification of foot and mouth disease risk areas using a multi-criteria analysis approach

    PubMed Central

    Silva, Gustavo Sousa e; Weber, Eliseu José; Hasenack, Heinrich; Groff, Fernando Henrique Sautter; Todeschini, Bernardo; Borba, Mauro Riegert; Medeiros, Antonio Augusto Rosa; Leotti, Vanessa Bielefeldt; Canal, Cláudio Wageck; Corbellini, Luis Gustavo

    2017-01-01

    Foot and mouth disease (FMD) is a highly infectious disease that affects cloven-hoofed livestock and wildlife. FMD has been a problem for decades, which has led to various measures to control, eradicate and prevent FMD by National Veterinary Services worldwide. Currently, the identification of areas that are at risk of FMD virus incursion and spread is a priority for FMD target surveillance after FMD is eradicated from a given country or region. In our study, a knowledge-driven spatial model was built to identify risk areas for FMD occurrence and to evaluate FMD surveillance performance in Rio Grande do Sul state, Brazil. For this purpose, multi-criteria decision analysis was used as a tool to seek multiple and conflicting criteria to determine a preferred course of action. Thirteen South American experts analyzed 18 variables associated with FMD introduction and dissemination pathways in Rio Grande do Sul. As a result, FMD higher risk areas were identified at international borders and in the central region of the state. The final model was expressed as a raster surface. The predictive ability of the model assessed by comparing, for each cell of the raster surface, the computed model risk scores with a binary variable representing the presence or absence of an FMD outbreak in that cell during the period 1985 to 2015. Current FMD surveillance performance was assessed, and recommendations were made to improve surveillance activities in critical areas. PMID:28552973

  7. Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

    PubMed

    Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

    2016-03-02

    Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Outbreaks of Foot-and-Mouth Disease in Libya and Saudi Arabia During 2013 Due to an Exotic O/ME-SA/Ind-2001 Lineage Virus.

    PubMed

    Knowles, N J; Bachanek-Bankowska, K; Wadsworth, J; Mioulet, V; Valdazo-González, B; Eldaghayes, I M; Dayhum, A S; Kammon, A M; Sharif, M A; Waight, S; Shamia, A M; Tenzin, S; Wernery, U; Grazioli, S; Brocchi, E; Subramaniam, S; Pattnaik, B; King, D P

    2016-10-01

    Foot-and-mouth disease viruses are often restricted to specific geographical regions and spread to new areas may lead to significant epidemics. Phylogenetic analysis of sequences of the VP1 genome region of recent outbreak viruses from Libya and Saudi Arabia has revealed a lineage, O-Ind-2001, normally found in the Indian subcontinent. This paper describes the characterization of field viruses collected from these cases and provides information about a new real-time RT-PCR assay that can be used to detect viruses from this lineage and discriminate them from other endemic FMD viruses that are co-circulating in North Africa and western Eurasia. © 2014 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  9. Innate immune responses against foot-and-mouth disease virus: current understanding and future directions.

    PubMed

    Summerfield, Artur; Guzylack-Piriou, Laurence; Harwood, Lisa; McCullough, Kenneth C

    2009-03-15

    Foot-and-mouth disease (FMD) represents one of the most economically important diseases of farm animals. The basis for the threat caused by this virus is the high speed of replication, short incubation time, high contagiousness, and high mutation rate resulting in constant antigenic changes. Thus, although protective immune responses against FMD virus (FMDV) can be efficacious, the rapidity of virus replication and spread can outpace immune defence development and overrun the immune system. FMDV can also evade innate immune responses through its ability to shut down cellular protein synthesis, including IFN type I, in susceptible epithelial cells. This is important for virus evolution, as FMDV is quite sensitive to the action of IFN. Despite this, innate immune responses are probably induced in vivo, although detailed studies on this subject are lacking. Accordingly, this interaction of FMDV with cells of the innate immune system is of particular interest. Dendritic cells (DC) can be infected by FMDV and support viral RNA replication, and viral protein synthesis but the latter is inefficient or abortive, leading most often to incomplete replication and progeny virus release. As a result DC can be activated, and particularly in the case of plasmacytoid DC (pDC), this is manifest in terms of IFN-alpha release. Our current state of knowledge on innate immune responses induced by FMDV is still only at a relatively early stage of understanding. As we progress, the investigations in this area will help to improve the design of current vaccines and the development of novel control strategies against FMD.

  10. Favipiravir can evoke lethal mutagenesis and extinction of foot-and-mouth disease virus.

    PubMed

    de Avila, Ana Isabel; Moreno, Elena; Perales, Celia; Domingo, Esteban

    2017-04-02

    Antiviral agents are increasingly considered an option for veterinary medicine. An understanding of their mechanism of activity is important to plan their administration either as monotherapy or in combination with other agents. Previous studies have shown that the broad spectrum antiviral agent favipiravir (T-705) and its derivatives T-1105 and T-1106 are efficient inhibitors of foot-and-mouth disease virus (FMDV) replication in cell culture and in vivo. However, no mechanism for their activity against FMDV has been proposed. In the present study we show that favipiravir (T-705) can act as a lethal mutagen for FMDV in cell culture. Evidence includes virus extinction associated with increase in mutation frequency in the mutant spectrum of 860 residues of the 3D (polymerase)-coding region, and a decrease of specific infectivity while the consensus nucleotide sequence of the region analyzed remained invariant. The mutational spectrum evoked by favipiravir differs from that observed with other viruses in that no predominant transition type is observed, indicating that a movement towards A,U- or G,C-rich regions of sequence space is not a prerequisite for virus extinction. We discuss prospects for the use of favipiravir to assist in the control of FMDV, and its possible broader use in veterinary medicine as an extension of its current status as antiviral agent for human influenza virus. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle.

    PubMed

    Carr, B Veronica; Lefevre, Eric A; Windsor, Miriam A; Inghese, Cristina; Gubbins, Simon; Prentice, Helen; Juleff, Nicholas D; Charleston, Bryan

    2013-01-01

    We have performed a series of studies to investigate the role of CD4(+) T-cells in the immune response to foot-and-mouth disease virus (FMDV) post-vaccination. Virus neutralizing antibody titres (VNT) in cattle vaccinated with killed FMD commercial vaccine were significantly reduced and class switching delayed as a consequence of rigorous in vivo CD4(+) T-cell depletion. Further studies were performed to examine whether the magnitude of T-cell proliferative responses correlated with the antibody responses. FMD vaccination was found to induce T-cell proliferative responses, with CD4(+) T-cells responding specifically to the FMDV antigen. In addition, gamma interferon (IFN-γ) was detected in the supernatant of FMDV antigen-stimulated PBMC and purified CD4(+) T-cells from vaccinated cattle. Similarly, intracellular IFN-γ could be detected specifically in purified CD4(+) T-cells after restimulation. It was not possible to correlate in vitro proliferative responses or IFN-γ production of PBMC with VNT, probably as a consequence of the induction of T-independent and T-dependent antibody responses and antigen non-specific T-cell responses. However, our studies demonstrate the importance of stimulating CD4(+) T-cell responses for the induction of optimum antibody responses to FMD-killed vaccines.

  12. Multifunctional roles of leader protein of foot-and-mouth disease viruses in suppressing host antiviral responses.

    PubMed

    Liu, Yingqi; Zhu, Zixiang; Zhang, Miaotao; Zheng, Haixue

    2015-10-28

    Foot-and-mouth disease virus (FMDV) leader protein (L(pro)) is a papain-like proteinase, which plays an important role in FMDV pathogenesis. L(pro) exists as two forms, Lab and Lb, due to translation being initiated from two different start codons separated by 84 nucleotides. L(pro) self-cleaves from the nascent viral polyprotein precursor as the first mature viral protein. In addition to its role as a viral proteinase, L(pro) also has the ability to antagonize host antiviral effects. To promote FMDV replication, L(pro) can suppress host antiviral responses by three different mechanisms: (1) cleavage of eukaryotic translation initiation factor 4 γ (eIF4G) to shut off host protein synthesis; (2) inhibition of host innate immune responses through restriction of interferon-α/β production; and (3) L(pro) can also act as a deubiquitinase and catalyze deubiquitination of innate immune signaling molecules. In the light of recent functional and biochemical findings regarding L(pro), this review introduces the basic properties of L(pro) and the mechanisms by which it antagonizes host antiviral responses.

  13. Thermal Inactivation of Foot-and-Mouth Disease Viruses in Suspension▿

    PubMed Central

    Kamolsiripichaiporn, Somjai; Subharat, Supatsak; Udon, Romphruke; Thongtha, Panithan; Nuanualsuwan, Suphachai

    2007-01-01

    The heat resistance of foot-and-mouth disease virus (FMDV) strains isolated from outbreaks in Thailand was investigated in phosphate-buffered saline (PBS) at 50, 60, 70, 80, 90, and 100°C. The first-order kinetic model fitted most of the observed linear inactivation curves. The ranges of decimal-reduction time (D value) of FMDV strains at 50, 60, 70, 80, 90, and 100°C were 732 to 1,275 s, 16.37 to 42.00 s, 6.06 to 10.87 s, 2.84 to 5.99 s, 1.65 to 3.18 s, and 1.90 to 2.94 s, respectively. The heat resistances of FMDV strains at lower temperature (50°C) were not serotype specific. The effective inactivating temperature is approximately 60°C. Heat resistances of FMDV strains at 90 and 100°C were not statistically different (P > 0.05), while the FMDV serotype O (OPN) appeared to be the most heat resistant at 60 to 80°C. The other observed inactivation curves were linear with shoulder or tailing (biphasic curves). The shoulder effect was mostly observed at 90 and 100°C, while the tailing effect was mostly observed at 50 to 80°C. The adjusted D values in the case of shoulder and tailing effects did not affect the overall estimated heat resistance of these FMDV strains, so even unadjusted D values of deviant inactivation curves were legitimate. The z values of FMDV serotypes O, A, and Asia 1 were 21.78 to 23.26, 20.75 to 22.79, and 19.87°C, respectively. The z values of FMDV strains studied were not statistically significantly different (P > 0.05). The results of this study indicated that the heat resistance in PBS of FMDV strains from Thailand was much less than had been reported for foreign epidemic FMDV strains. PMID:17660312

  14. Construction and characterization of 3A-epitope-tagged foot-and-mouth disease virus.

    PubMed

    Ma, Xueqing; Li, Pinghua; Sun, Pu; Bai, Xingwen; Bao, Huifang; Lu, Zengjun; Fu, Yuanfang; Cao, Yimei; Li, Dong; Chen, Yingli; Qiao, Zilin; Liu, Zaixin

    2015-04-01

    Nonstructural protein 3A of foot-and-mouth disease virus (FMDV) is a partially conserved protein of 153 amino acids (aa) in most FMDVs examined to date. Specific deletion in the FMDV 3A protein has been associated with the inability of FMDV to grow in primary bovine cells and cause disease in cattle. However, the aa residues playing key roles in these processes are poorly understood. In this study, we constructed epitope-tagged FMDVs containing an 8 aa FLAG epitope, a 9 aa haemagglutinin (HA) epitope, and a 10 aa c-Myc epitope to substitute residues 94-101, 93-101, and 93-102 of 3A protein, respectively, using a recently developed O/SEA/Mya-98 FMDV infectious cDNA clone. Immunofluorescence assay (IFA), Western blot and sequence analysis showed that the epitope-tagged viruses stably maintained and expressed the foreign epitopes even after 10 serial passages in BHK-21 cells. The epitope-tagged viruses displayed growth properties and plaque phenotypes similar to those of the parental virus in BHK-21 cells. However, the epitope-tagged viruses exhibited lower growth rates and smaller plaque size phenotypes than those of the parental virus in primary fetal bovine kidney (FBK) cells, but similar growth properties and plaque phenotypes to those of the recombinant viruses harboring 93-102 deletion in 3A. These results demonstrate that the decreased ability of FMDV to replicate in primary bovine cells was not associated with the length of 3A, and the genetic determinant thought to play key role in decreased ability to replicate in primary bovine cells could be reduced from 93-102 residues to 8 aa residues at positions 94-101 in 3A protein. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Molecular Characterization of Foot-and-Mouth Disease Viruses Collected in Tanzania Between 1967 and 2009.

    PubMed

    Kasanga, C J; Wadsworth, J; Mpelumbe-Ngeleja, C A R; Sallu, R; Kivaria, F; Wambura, P N; Yongolo, M G S; Rweyemamu, M M; Knowles, N J; King, D P

    2015-10-01

    This paper describes the molecular characterization of foot-and-mouth disease viruses (FMDV) recovered from outbreaks in Tanzania that occurred between 1967 and 2009. A total of 44 FMDV isolates, containing representatives of serotypes O, A, SAT 1 and SAT 2 from 13 regions of Tanzania, were selected from the FAO World Reference Laboratory for FMD (WRLFMD) virus collection. VP1 nucleotide sequences were determined for RT-PCR amplicons, and phylogenetic reconstructions were determined by maximum likelihood and neighbour-joining methods. These analyses showed that Tanzanian type O viruses fell into the EAST AFRICA 2 (EA-2) topotype, type A viruses fell into the AFRICA topotype (genotype I), type SAT 1 viruses into topotype I and type SAT 2 viruses into topotype IV. Taken together, these findings reveal that serotypes O, A, SAT 1 and SAT 2 that caused FMD outbreaks in Tanzania were genetically related to lineages and topotypes occurring in the East African region. The close genetic relationship of viruses in Tanzania to those from other countries suggests that animal movements can contribute to virus dispersal in sub-Saharan Africa. This is the first molecular description of viruses circulating in Tanzania and highlights the need for further sampling of representative viruses from the region so as to elucidate the complex epidemiology of FMD in Tanzania and sub-Saharan Africa. © 2014 The Authors. Transboundary and Emerging Diseases Published by Blackwell Verlag GmbH.

  16. Estimation of stature using hand and foot dimensions in Slovak adults.

    PubMed

    Uhrová, Petra; Beňuš, Radoslav; Masnicová, Soňa; Obertová, Zuzana; Kramárová, Daniela; Kyselicová, Klaudia; Dörnhöferová, Michaela; Bodoriková, Silvia; Neščáková, Eva

    2015-03-01

    Hand and foot dimensions used for stature estimation help to formulate a biological profile in the process of personal identification. Morphological variability of hands and feet shows the importance of generating population-specific equations to estimate stature. The stature, hand length, hand breadth, foot length and foot breadth of 250 young Slovak males and females, aged 18-24 years, were measured according to standard anthropometric procedures. The data were statistically analyzed using independent t-test for sex and bilateral differences. Pearson correlation coefficient was used for assessing relationship between stature and hand/foot parameters, and subsequently linear regression analysis was used to estimate stature. The results revealed significant sex differences in hand and foot dimensions as well as in stature (p<0.05). There was a positive and statistically significant correlation between stature and all measurements in both sexes (p<0.01). The highest correlation coefficient was found for foot length in males (r=0.71) as well as in females (r=0.63). Regression equations were computed separately for each sex. The accuracy of stature prediction ranged from ±4.6 to ±6.1cm. The results of this study indicate that hand and foot dimension can be used to estimate stature for Slovak for the purpose of forensic field. The regression equations can be of use for stature estimation particularly in cases of dismembered bodies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle.

    PubMed

    Arzt, Jonathan; Pacheco, Juan M; Stenfeldt, Carolina; Rodriguez, Luis L

    2017-05-02

    Understanding the mechanisms of attenuation and virulence of foot-and-mouth disease virus (FMDV) in the natural host species is critical for development of next-generation countermeasures such as live-attenuated vaccines. Functional genomics analyses of FMDV have identified few virulence factors of which the leader proteinase (L pro ) is the most thoroughly investigated. Previous work from our laboratory has characterized host factors in cattle inoculated with virulent FMDV and attenuated mutant strains with transposon insertions within L pro . In the current study, the characteristics defining virulence of FMDV in cattle were further investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). The only difference between the two viruses was an insertion mutation in the inter-AUG region of the leader proteinase of FMDV-Mut. All cattle were infected by simulated-natural, aerosol inoculation. Both viruses were demonstrated to establish primary infection in the nasopharyngeal mucosa with subsequent dissemination to the lungs. Immunomicroscopic localization of FMDV antigens indicated that both viruses infected superficial epithelial cells of the nasopharynx and lungs. The critical differences between the two viruses were a more rapid establishment of infection by FMDV-WT and quantitatively greater virus loads in secretions and infected tissues compared to FMDV-Mut. The slower replicating FMDV-Mut established a subclinical infection that was limited to respiratory epithelial sites, whereas the faster replication of FMDV-WT facilitated establishment of viremia, systemic dissemination of infection, and clinical disease. The mutant FMDV was capable of achieving all the same early pathogenesis landmarks as FMDV-WT, but was unable to establish systemic infection. The precise mechanism of attenuation remains undetermined; but current data suggests that the impaired replication

  18. Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus.

    PubMed

    King, David J; Freimanis, Graham L; Orton, Richard J; Waters, Ryan A; Haydon, Daniel T; King, Donald P

    2016-10-01

    Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT-PCR method was developed to amplify a 7.6kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves

    PubMed Central

    Feng, Xia; Ma, Jun-Wu; Sun, Shi-Qi; Guo, Hui-Chen; Yang, Ya-Min; Jin, Ye; Zhou, Guang-Qing; He, Ji-Jun; Guo, Jian-Hong; Qi, Shu-yun; Lin, Mi; Cai, Hu; Liu, Xiang-Tao

    2016-01-01

    The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 μg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings. PMID:26930597

  20. Quantitative Detection of the Foot-And-Mouth Disease Virus Serotype O 146S Antigen for Vaccine Production Using a Double-Antibody Sandwich ELISA and Nonlinear Standard Curves.

    PubMed

    Feng, Xia; Ma, Jun-Wu; Sun, Shi-Qi; Guo, Hui-Chen; Yang, Ya-Min; Jin, Ye; Zhou, Guang-Qing; He, Ji-Jun; Guo, Jian-Hong; Qi, Shu-yun; Lin, Mi; Cai, Hu; Liu, Xiang-Tao

    2016-01-01

    The efficacy of an inactivated foot-and-mouth disease (FMD) vaccine is mainly dependent on the integrity of the foot-and-mouth disease virus (FMDV) particles. At present, the standard method to quantify the active component, the 146S antigen, of FMD vaccines is sucrose density gradient (SDG) analysis. However, this method is highly operator dependent and difficult to automate. In contrast, the enzyme-linked immunosorbent assay (ELISA) is a time-saving technique that provides greater simplicity and sensitivity. To establish a valid method to detect and quantify the 146S antigen of a serotype O FMD vaccine, a double-antibody sandwich (DAS) ELISA was compared with an SDG analysis. The DAS ELISA was highly correlated with the SDG method (R2 = 0.9215, P<0.01). In contrast to the SDG method, the DAS ELISA was rapid, robust, repeatable and highly sensitive, with a minimum quantification limit of 0.06 μg/mL. This method can be used to determine the effective antigen yields in inactivated vaccines and thus represents an alternative for assessing the potency of FMD vaccines in vitro. But it still needs to be prospectively validated by analyzing a new vaccine preparation and determining the proper protective dose followed by an in vivo vaccination-challenge study to confirm the ELISA findings.

  1. Foot-and-mouth disease control and eradication in the Bicol Surveillance Buffer Zone of the Philippines.

    PubMed

    Windsor, P A; Freeman, P G; Abila, R; Benigno, C; Verin, B; Nim, V; Cameron, A

    2011-10-01

    Following the onset of an epidemic of foot and mouth disease (FMD) commencing in 1994 and affecting mainly pigs in the Philippines, a National Plan for the Control and Eradication of the disease was initiated. A disease surveillance buffer zone in the southern Luzon region of Bicol was established to protect the Visayas and Mindanao from infection and enable eventual elimination of the disease in Luzon. With achievement of Office International Epizooties (OIE)-certified FMD freedom with vaccination in the Philippines now imminent, the four components of the disease control strategy are reviewed, including quarantine and animal movement controls, strategic vaccination, surveillance and disease investigation, and enhanced public awareness with school on the air radio programmes. Although numbers of outbreaks declined following widespread vaccination, evaluation of serological responses in vaccinates suggested low levels of immune protection. The cessation of outbreaks was considered more likely a result of animal movement controls, improved surveillance and emergency response capability, and reduction in FMD-risk behaviours by livestock owners, particularly through efforts to enhance public awareness of biosecurity measures by the training of traders, livestock industry personnel and both commercial and smallholder farmers. A two-stage random sampling serosurveillance strategy enabled identification of residual infection that was not detected through opportunistic sampling and negative incident reporting. Intensive investigations of FMD outbreaks, particularly in Albay province in 1999, enabled improved understanding of the risk factors involved in disease transmission and implementation of appropriate interventions. The findings from this review are offered to assist development of FMD control and eradication programmes in other countries in south-east Asia that are now being encouraged to support the OIE goal of FMD freedom with vaccination by 2020. © 2011

  2. Diagnostic evaluation of a multiplexed RT-PCR microsphere array assay for the detection of foot-and-mouth disease virus and look-alike disease viruses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hindson, B J; Reid, S M; Baker, B R

    2007-07-26

    A high-throughput multiplexed assay was developed for the differential laboratory diagnosis of foot-and-mouth disease virus (FMDV) from viruses which cause clinically similar diseases of livestock. This assay simultaneously screens for five RNA and two DNA viruses using multiplexed reverse transcription PCR (mRT-PCR) amplification coupled with a microsphere hybridization array and flow-cytometric detection. Two of the seventeen primer-probe sets included in this multiplex assay were adopted from previously characterized real-time RT-PCR (rRT-PCR) assays for FMDV. The diagnostic accuracy of the mRT-PCR was evaluated using 287 field samples, including 248 (true positive n= 213, true negative n=34) from suspect cases of foot-and-mouthmore » disease collected from 65 countries between 1965 and 2006 and 39 true negative samples collected from healthy animals. The mRT-PCR assay results were compared with two singleplex rRT-PCR assays, using virus isolation with antigen-ELISA as the reference method. The diagnostic sensitivity of the mRT-PCR assay for FMDV was 93.9% [95% C.I. 89.8-96.4%], compared to 98.1% [95% C.I. 95.3-99.3%] for the two singleplex rRT-PCR assays used in combination. In addition, the assay could reliably differentiate between FMDV and other vesicular viruses such as swine vesicular disease virus and vesicular exanthema of swine virus. Interestingly, the mRT-PCR detected parapoxvirus (n=2) and bovine viral diarrhea virus (n=2) in clinical samples, demonstrating the screening potential of this mRT-PCR assay to identify viruses in FMDV-negative material not previously recognized using focused single-target rRT-PCR assays.« less

  3. Estimation of stature from hand and foot dimensions in a Korean population.

    PubMed

    Kim, Wonjoon; Kim, Yong Min; Yun, Myung Hwan

    2018-04-01

    The estimation of stature using foot and hand dimensions is essential in the process of personal identification. The shapes of feet and hands vary depending on races and gender, and it is of great importance to design an adequate equation in consideration of variances to estimate stature. This study is based on a total of 5,195 South Korean males and females, aged from 20 to 59 years. Body dimensions of stature, hand length, hand breadth, foot length, and foot breadth were measured according to standard anthropometric procedures. The independent t-test was performed in order to verify significant gender-induced differences and the results showed that there was significant difference between males and females for all the foot-hand dimensions (p<0.01). All dimensions showed a positive and statistically significant relation with stature in both genders (p<0.01). For both genders, the foot length showed highest correlation, whereas the hand breadth showed least correlation. The stepwise regression analysis was conducted, and the results showed that males had the highest prediction accuracy in the regression equation consisting of foot length and hand length (R 2 =0.532), whereas females had the highest accuracy in the regression model consisting of foot length and hand breadth (R 2 =0.437) The findings of this study indicated that hand and foot dimensions can be used to predict the stature of South Korean in the forensic science field. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  4. Expression and Stability of Foreign Epitopes Introduced into 3A Nonstructural Protein of Foot-and-Mouth Disease Virus

    PubMed Central

    Li, Pinghua; Bai, Xingwen; Cao, Yimei; Han, Chenghao; Lu, Zengjun; Sun, Pu; Yin, Hong; Liu, Zaixin

    2012-01-01

    Foot-and-mouth disease virus (FMDV) is an aphthovirus that belongs to the Picornaviridae family and causes one of the most important animal diseases worldwide. The capacity of other picornaviruses to express foreign antigens has been extensively reported, however, little is known about FMDV. To explore the potential of FMDV as a viral vector, an 11-amino-acid (aa) HSV epitope and an 8 aa FLAG epitope were introduced into the C-terminal different regions of 3A protein of FMDV full-length infectious cDNA clone. Recombinant viruses expressing the HSV or FLAG epitope were successfully rescued after transfection of both modified constructs. Immunofluorescence assay, Western blot and sequence analysis showed that the recombinant viruses stably maintained the foreign epitopes even after 11 serial passages in BHK-21 cells. The 3A-tagged viruses shared similar plaque phenotypes and replication kinetics to those of the parental virus. In addition, mice experimentally infected with the epitope-tagged viruses could induce tag-specific antibodies. Our results demonstrate that FMDV can be used effectively as a viral vector for the delivery of foreign tags. PMID:22848509

  5. Response to foot-and-mouth disease vaccines in newborn calves. Influence of age, colostral antibodies and adjuvants.

    PubMed Central

    Sadir, A. M.; Schudel, A. A.; Laporte, O.; Braun, M.; Margni, R. A.

    1988-01-01

    Oil-emulsified (OE) and aqueous (Aq) vaccines were prepared with the same batch of inactivated A24 8345 foot and mouth disease virus (FMDV). Calves born to vaccinated dams did not respond to the Aq vaccine 30 or 90 days post partum. When the OE vaccine was used on a similar group of calves, no responses were elicited up to 21 days post partum. However, calves 30 or more days old responded like adult cattle to the OE vaccine. When the OE vaccine was used in colostral antibody-free calves 3-30 days old, all animals showed good antibody responses but, in calves vaccinated 3 or 7 days post partum, antibodies were detectable only after a considerable period of time. Our results show that both passively acquired colostral antibodies and age are important in the response of very young calves to FMDV oil vaccines. From a practical point of view, in endemic areas where adult cattle are periodically vaccinated, vaccination of calves between 30 and 60 days post partum with OE vaccines would lead to high levels of herd protection. PMID:2828089

  6. Economic effects of foot and mouth disease outbreaks along the cattle marketing chain in Uganda

    PubMed Central

    Baluka, Sylvia Angubua

    2016-01-01

    Aim: Disease outbreaks increase the cost of animal production; reduce milk and beef yield, cattle sales, farmers’ incomes, and enterprise profitability. The study assessed the economic effects of foot and mouth disease (FMD) outbreaks along the cattle marketing chain in selected study districts in Uganda. Materials and Methods: The study combined qualitative and quantitative study designs. Respondents were selected proportionally using simple random sampling from the sampling frame comprising of 224, 173, 291, and 185 farmers for Nakasongola, Nakaseke, Isingiro, and Rakai, respectively. Key informants were selected purposively. Data analysis combined descriptive, modeling, and regression analysis. Data on the socio-economic characteristics and how they influenced FMD outbreaks, cattle markets revenue losses, and the economic cost of the outbreaks were analyzed using descriptive measures including percentages, means, and frequencies. Results: Farmers with small and medium herds incurred higher control costs, whereas large herds experienced the highest milk losses. Total income earned by the actors per month at the processing level reduced by 23%. In Isingiro, bulls and cows were salvage sold at 83% and 88% less market value, i.e., a loss of $196.1 and $1,552.9 in small and medium herds, respectively. Conclusion: All actors along the cattle marketing chain incur losses during FMD outbreaks, but smallholder farmers are most affected. Control and prevention of FMD should remain the responsibility of the government if Uganda is to achieve a disease-free status that is a prerequisite for free movement and operation of cattle markets throughout the year which will boost cattle marketing. PMID:27397974

  7. Economic effects of foot and mouth disease outbreaks along the cattle marketing chain in Uganda.

    PubMed

    Baluka, Sylvia Angubua

    2016-06-01

    Disease outbreaks increase the cost of animal production; reduce milk and beef yield, cattle sales, farmers' incomes, and enterprise profitability. The study assessed the economic effects of foot and mouth disease (FMD) outbreaks along the cattle marketing chain in selected study districts in Uganda. The study combined qualitative and quantitative study designs. Respondents were selected proportionally using simple random sampling from the sampling frame comprising of 224, 173, 291, and 185 farmers for Nakasongola, Nakaseke, Isingiro, and Rakai, respectively. Key informants were selected purposively. Data analysis combined descriptive, modeling, and regression analysis. Data on the socio-economic characteristics and how they influenced FMD outbreaks, cattle markets revenue losses, and the economic cost of the outbreaks were analyzed using descriptive measures including percentages, means, and frequencies. Farmers with small and medium herds incurred higher control costs, whereas large herds experienced the highest milk losses. Total income earned by the actors per month at the processing level reduced by 23%. In Isingiro, bulls and cows were salvage sold at 83% and 88% less market value, i.e., a loss of $196.1 and $1,552.9 in small and medium herds, respectively. All actors along the cattle marketing chain incur losses during FMD outbreaks, but smallholder farmers are most affected. Control and prevention of FMD should remain the responsibility of the government if Uganda is to achieve a disease-free status that is a prerequisite for free movement and operation of cattle markets throughout the year which will boost cattle marketing.

  8. 'Outbreak Gold Standard' selection to provide optimized threshold for infectious diseases early-alert based on China Infectious Disease Automated-alert and Response System.

    PubMed

    Wang, Rui-Ping; Jiang, Yong-Gen; Zhao, Gen-Ming; Guo, Xiao-Qin; Michael, Engelgau

    2017-12-01

    The China Infectious Disease Automated-alert and Response System (CIDARS) was successfully implemented and became operational nationwide in 2008. The CIDARS plays an important role in and has been integrated into the routine outbreak monitoring efforts of the Center for Disease Control (CDC) at all levels in China. In the CIDARS, thresholds are determined using the "Mean+2SD‟ in the early stage which have limitations. This study compared the performance of optimized thresholds defined using the "Mean +2SD‟ method to the performance of 5 novel algorithms to select optimal "Outbreak Gold Standard (OGS)‟ and corresponding thresholds for outbreak detection. Data for infectious disease were organized by calendar week and year. The "Mean+2SD‟, C1, C2, moving average (MA), seasonal model (SM), and cumulative sum (CUSUM) algorithms were applied. Outbreak signals for the predicted value (Px) were calculated using a percentile-based moving window. When the outbreak signals generated by an algorithm were in line with a Px generated outbreak signal for each week, this Px was then defined as the optimized threshold for that algorithm. In this study, six infectious diseases were selected and classified into TYPE A (chickenpox and mumps), TYPE B (influenza and rubella) and TYPE C [hand foot and mouth disease (HFMD) and scarlet fever]. Optimized thresholds for chickenpox (P 55 ), mumps (P 50 ), influenza (P 40 , P 55 , and P 75 ), rubella (P 45 and P 75 ), HFMD (P 65 and P 70 ), and scarlet fever (P 75 and P 80 ) were identified. The C1, C2, CUSUM, SM, and MA algorithms were appropriate for TYPE A. All 6 algorithms were appropriate for TYPE B. C1 and CUSUM algorithms were appropriate for TYPE C. It is critical to incorporate more flexible algorithms as OGS into the CIDRAS and to identify the proper OGS and corresponding recommended optimized threshold by different infectious disease types.

  9. Foot-and-mouth disease in the Americas: epidemiology and ecologic changes affecting distribution.

    PubMed

    Saraiva, Victor

    2004-10-01

    Foot-and-mouth disease(FMD) was first recorded in South America (SA) circa 1870, in Buenos Aires, Argentina, in Uruguay, and in southern Brazil as a result of the introduction of cattle from Europe during the early days of colonization. Livestock production to trade with neighboring countries was established in the La Plata Region, and the trade of livestock and products with Chile, northeastern and central western states of Brazil, to Peru, Bolivia, and Paraguay spread FMD, which reached Venezuela and Colombia in the 1950s and finally Ecuador in 1961. The traditional forms of livestock husbandry influence the diffusion and maintenance of the FMD virus (FMDV) in different areas. Cattle production in SA depends mainly on a strong relation between cattle-calf operations and fattening operations in a complementary cycle, revealing the vulnerability and susceptibility of these areas to FMDV. Understanding the relationship between time-space behavior of the disease and the forms of production defines the FMD ecosystems, a key concept to elaborating the control/eradication strategies of national FMD eradication programs, which must be modified when trade opportunities between zones of differing sanitary status change. The role of other susceptible species besides bovines, including wildlife, in maintaining and spreading FMDV has been the subject of several studies, but in SA, bovines are so far considered to determine disease presentation. Buffalo (Bubalus bubalis) have been implicated in the spread of the disease between farms in at least one case in Brazil. Sheep are almost on a par with bovine in terms of number, especially in the Southern Cone, but their role in the maintenance of infection is not considered important, possibly owing to rearing practices. Camelid populations in the Andean region do not play an important role in the maintenance of FMD, because of short persistence of infection and low population densities in these species. The importance of wildlife

  10. Antiviral activity of Lactobacillus reuteri Protectis against Coxsackievirus A and Enterovirus 71 infection in human skeletal muscle and colon cell lines.

    PubMed

    Ang, Lei Yin Emily; Too, Horng Khit Issac; Tan, Eng Lee; Chow, Tak-Kwong Vincent; Shek, Lynette Pei-Chi; Tham, Elizabeth Huiwen; Alonso, Sylvie

    2016-06-24

    Recurrence of hand, foot and mouth disease (HFMD) pandemics continues to threaten public health. Despite increasing awareness and efforts, effective vaccine and drug treatment have yet to be available. Probiotics have gained recognition in the field of healthcare worldwide, and have been extensively prescribed to babies and young children to relieve gastrointestinal (GI) disturbances and diseases, associated or not with microbial infections. Since the faecal-oral axis represents the major route of HFMD transmission, transient persistence of probiotic bacteria in the GI tract may confer some protection against HFMD and limit transmission among children. In this work, the antiviral activity of two commercially available probiotics, namely Lactobacillus reuteri Protectis (L. reuteri Protectis) and Lactobacillus casei Shirota (L. casei Shirota), was assayed against Coxsackieviruses and Enterovirus 71 (EV71), the main agents responsible for HFMD. In vitro infection set-ups using human skeletal muscle and colon cell lines were designed to assess the antiviral effect of the probiotic bacteria during entry and post-entry steps of the infection cycle. Our findings indicate that L. reuteri Protectis displays a significant dose-dependent antiviral activity against Coxsackievirus type A (CA) strain 6 (CA6), CA16 and EV71, but not against Coxsackievirus type B strain 2. Our data support that the antiviral effect is likely achieved through direct physical interaction between bacteria and virus particles, which impairs virus entry into its mammalian host cell. In contrast, no significant antiviral effect was observed with L. casei Shirota. Should the antiviral activity of L. reuteri Protectis observed in vitro be translated in vivo, such probiotics-based therapeutic approach may have the potential to address the urgent need for a safe and effective means to protect against HFMD and limit its transmission among children.

  11. Decisions on control of foot-and-mouth disease informed using model predictions.

    PubMed

    Halasa, T; Willeberg, P; Christiansen, L E; Boklund, A; Alkhamis, M; Perez, A; Enøe, C

    2013-11-01

    The decision on whether or not to change the control strategy, such as introducing emergency vaccination, is perhaps one of the most difficult decisions faced by the veterinary authorities during a foot-and-mouth disease (FMD) epidemic. A simple tool that may predict the epidemic outcome and consequences would be useful to assist the veterinary authorities in the decision-making process. A previously proposed simple quantitative tool based on the first 14 days outbreaks (FFO) of FMD was used with results from an FMD simulation exercise. Epidemic outcomes included the number of affected herds, epidemic duration, geographical size and costs. The first 14 days spatial spread (FFS) was also included to further support the prediction. The epidemic data was obtained from a Danish version (DTU-DADS) of a pre-existing FMD simulation model (Davis Animal Disease Spread - DADS) adapted to model the spread of FMD in Denmark. The European Union (EU) and Danish regulations for FMD control were used in the simulation. The correlations between FFO and FFS and the additional number of affected herds after day 14 following detection of the first infected herd were 0.66 and 0.82, respectively. The variation explained by the FFO at day 14 following detection was high (P-value<0.001). This indicates that the FFO may take a part in the decision of whether or not to intensify FMD control, for instance by introducing emergency vaccination and/or pre-emptive depopulation, which might prevent a "catastrophic situation". A significant part of the variation was explained by supplementing the model with the FFS (P-value<0.001). Furthermore, the type of the index-herd was also a significant predictor of the epidemic outcomes (P-value<0.05). The results of the current study suggest that national veterinary authorities should consider to model their national situation and to use FFO and FFS to help planning and updating their contingency plans and FMD emergency control strategies. Copyright

  12. First detection of foot-and-mouth disease virus O/Ind-2001d in Vietnam.

    PubMed

    Vu, Le T; Long, Ngo T; Brito, Barbara; Stenfeldt, Carolina; Phuong, Nguyen T; Hoang, Bui H; Pauszek, Steven J; Hartwig, Ethan J; Smoliga, George R; Vu, Pham P; Quang, Le T V; Hung, Vo V; Tho, Nguyen D; Dong, Pham V; Minh, Phan Q; Bertram, Miranda; Fish, Ian H; Rodriguez, Luis L; Dung, Do H; Arzt, Jonathan

    2017-01-01

    In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Đắk Nông province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Đắk Nông province, pigs in Đắk Lắk province and Đắk Nông province, and cattle in Ninh Thuận province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia.

  13. A Portable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of Foot-and-Mouth Disease Virus

    PubMed Central

    Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A.; Hufert, Frank T.; Weidmann, Manfred

    2013-01-01

    Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4–10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection. PMID:23977101

  14. A portable reverse transcription recombinase polymerase amplification assay for rapid detection of foot-and-mouth disease virus.

    PubMed

    Abd El Wahed, Ahmed; El-Deeb, Ayman; El-Tholoth, Mohamed; Abd El Kader, Hanaa; Ahmed, Abeer; Hassan, Sayed; Hoffmann, Bernd; Haas, Bernd; Shalaby, Mohamed A; Hufert, Frank T; Weidmann, Manfred

    2013-01-01

    Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock, which causes huge economic losses and constitutes a serious infectious threat for livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact by adequate outbreak management. In this study, we describe the development of a real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the 3D gene of FMDV and a 260 nt molecular RNA standard was used for assay validation. The RT-RPA assay was fast (4-10 minutes) and the analytical sensitivity was determined at 1436 RNA molecules detected by probit regression analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV serotypes but did not detect classical swine fever virus or swine vesicular disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD outbreak in Egypt. In clinical samples, reverse transcription polymerase chain reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%, respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to perform diagnostics at quarantine stations or farms for rapid spot-of-infection detection.

  15. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 5 - Biotherapeutics and Disinfectants.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed knowledge gaps in foot-and-mouth disease (FMD) research. Findings are reported in a series of papers, and in this article, we consider biotherapeutics and disinfectants. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. While vaccines will remain the key immunological intervention used against FMD virus (FMDV) for the foreseeable future, it takes a few days for the immune system to respond to vaccination. In an outbreak situation, protection could potentially be provided during this period by the application of rapid, short-acting biotherapeutics, aiming either to stimulate a non-specific antiviral state in the animal or to specifically inhibit a part of the viral life cycle. Certain antiviral cytokines have been shown to promote rapid protection against FMD; however, the effects of different immune-modulators appear to vary across species in ways and for reasons that are not yet understood. Major barriers to the effective incorporation of biotherapeutics into control strategies are cost, limited understanding of their effect on subsequent immune responses to vaccines and uncertainty about their potential impact if used for disease containment. Recent research has highlighted the importance of environmental contamination in FMDV transmission. Effective disinfectants for FMDV have long been available, but research is being conducted to further develop methods for quantitatively evaluating their performance under field, or near-field, conditions. During outbreaks in South Korea in 2010 there was public concern about potential environmental contamination after the mass use of disinfectant and mass burial of culled stock; this should be considered during outbreak contingency planning. © 2016 Blackwell Verlag GmbH.

  16. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tully, Damien C.; Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification eventsmore » spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.« less

  17. Foot-and-mouth disease virus replicates only transiently in well-differentiated porcine nasal epithelial cells.

    PubMed

    Dash, Pradyot; Barnett, Paul V; Denyer, Michael S; Jackson, Terry; Stirling, Catrina M A; Hawes, Philippa C; Simpson, Jennifer L; Monaghan, Paul; Takamatsu, Haru-H

    2010-09-01

    Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seen in vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin alphav beta6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-beta) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-beta mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-alpha mRNA was constitutively expressed in nasal mucosal epithelial cells in vitro and in vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.

  18. The characteristics of autonomic nervous system disorders in burning mouth syndrome and Parkinson disease.

    PubMed

    Koszewicz, Magdalena; Mendak, Magdalena; Konopka, Tomasz; Koziorowska-Gawron, Ewa; Budrewicz, Sławomir

    2012-01-01

    To conduct a clinical electrophysiologic evaluation of autonomic nervous system functions in patients with burning mouth syndrome and Parkinson disease and estimate the type and intensity of the autonomic dysfunction. The study involved 83 subjects-33 with burning mouth syndrome, 20 with Parkinson disease, and 30 controls. The BMS group included 27 women and 6 men (median age, 60.0 years), and the Parkinson disease group included 15 women and 5 men (median age, 66.5 years). In the control group, there were 20 women and 10 men (median age, 59.0 years). All patients were subjected to autonomic nervous system testing. In addition to the Low autonomic disorder questionnaire, heart rate variability (HRV), deep breathing (exhalation/inspiration [E/I] ratio), and sympathetic skin response (SSR) tests were performed in all cases. Parametric and nonparametric tests (ANOVA, Kruskal-Wallis, and Scheffe tests) were used in the statistical analysis. The mean values for HRV and E/I ratios were significantly lower in the burning mouth syndrome and Parkinson disease groups. Significant prolongation of SSR latency in the foot was revealed in both burning mouth syndrome and Parkinson disease patients, and lowering of the SSR amplitude occurred in only the Parkinson disease group. The autonomic questionnaire score was significantly higher in burning mouth syndrome and Parkinson disease patients than in the control subjects, with the Parkinson disease group having the highest scores. In patients with burning mouth syndrome, a significant impairment of both the sympathetic and parasympathetic nervous systems was found but sympathetic/parasympathetic balance was preserved. The incidence and intensity of autonomic nervous system dysfunction was similar in patients with burning mouth syndrome and Parkinson disease, which may suggest some similarity in their pathogeneses.

  19. Symbrachydactyly involving both the hand and foot. A report of two cases.

    PubMed

    Uchida, T; Kojima, T; Hirakawa, M; Uchida, M

    1995-01-01

    Symbrachydactyly involving both the hand and foot is extremely rare. Two such cases are described. The first patient was a two-month-old female with symbrachydactyly of the left hand and foot. The second patient was a one-year-old female with symbrachydactyly of the right hand and foot. No other abnormalities were identified. The diagnosis of this congenital anomaly is discussed and the literature reviewed.

  20. Evolutionary Analysis of Structural Protein Gene VP1 of Foot-and-Mouth Disease Virus Serotype Asia 1

    PubMed Central

    Zhang, Qingxun; Liu, Xinsheng; Fang, Yuzhen; Pan, Li; Lv, Jianliang; Zhang, Zhongwang; Zhou, Peng; Ding, Yaozhong; Chen, Haotai; Shao, Junjun; Zhao, Furong; Lin, Tong; Chang, Huiyun; Zhang, Jie; Wang, Yonglu; Zhang, Yongguang

    2015-01-01

    Foot-and-mouth disease virus (FMDV) serotype Asia 1 was mostly endemic in Asia and then was responsible for economically important viral disease of cloven-hoofed animals, but the study on its selection and evolutionary process is comparatively rare. In this study, we characterized 377 isolates from Asia collected up until 2012, including four vaccine strains. Maximum likelihood analysis suggested that the strains circulating in Asia were classified into 8 different groups (groups I–VIII) or were unclassified (viruses collected before 2000). On the basis of divergence time analyses, we infer that the TMRCA of Asia 1 virus existed approximately 86.29 years ago. The result suggested that the virus had a high mutation rate (5.745 × 10−3 substitutions/site/year) in comparison to the other serotypes of FMDV VP1 gene. Furthermore, the structural protein VP1 was under lower selection pressure and the positive selection occurred at many sites, and four codons (positions 141, 146, 151, and 169) were located in known critical antigenic residues. The remaining sites were not located in known functional regions and were moderately conserved, and the reason for supporting all sites under positive selection remains to be elucidated because the power of these analyses was largely unknown. PMID:25793223

  1. Time Clustered Sampling Can Inflate the Inferred Substitution Rate in Foot-And-Mouth Disease Virus Analyses.

    PubMed

    Pedersen, Casper-Emil T; Frandsen, Peter; Wekesa, Sabenzia N; Heller, Rasmus; Sangula, Abraham K; Wadsworth, Jemma; Knowles, Nick J; Muwanika, Vincent B; Siegismund, Hans R

    2015-01-01

    With the emergence of analytical software for the inference of viral evolution, a number of studies have focused on estimating important parameters such as the substitution rate and the time to the most recent common ancestor (tMRCA) for rapidly evolving viruses. Coupled with an increasing abundance of sequence data sampled under widely different schemes, an effort to keep results consistent and comparable is needed. This study emphasizes commonly disregarded problems in the inference of evolutionary rates in viral sequence data when sampling is unevenly distributed on a temporal scale through a study of the foot-and-mouth (FMD) disease virus serotypes SAT 1 and SAT 2. Our study shows that clustered temporal sampling in phylogenetic analyses of FMD viruses will strongly bias the inferences of substitution rates and tMRCA because the inferred rates in such data sets reflect a rate closer to the mutation rate rather than the substitution rate. Estimating evolutionary parameters from viral sequences should be performed with due consideration of the differences in short-term and longer-term evolutionary processes occurring within sets of temporally sampled viruses, and studies should carefully consider how samples are combined.

  2. Willingness and influential factors of parents to vaccinate their children with novel inactivated enterovirus 71 vaccines in Guangzhou, China.

    PubMed

    Li, Tiegang; Wang, Hui; Lu, Yin; Li, Qin; Chen, Chun; Wang, Dahu; Li, Meixia; Li, Yilan; Lu, Jianyun; Chen, Zongqiu; Ma, Yu; Liu, Wenhui; Ma, Mengmeng; Wu, Di; Lu, Jiachun; Yang, Zhicong

    2018-05-15

    Hand, foot and mouth disease (HFMD) primarily affects children younger than 5 years of age. Recently, HFMD has ranked as the top notifiable infectious disease in China. In December 2015, China approved two novel inactivated enterovirus 71 vaccines (EV71 vaccines) for HFMD. Parents' acceptance is often essential for vaccination program success. The goal of this study was to identify willingness and influential factors to vaccinate among parents of kindergarteners in Guangzhou, China. A cross-sectional survey of face-to-face interviews was conducted from March to July 2016. Fifty-five kindergartens were randomly selected from 11 districts of Guangzhou. An anonymous self-designed questionnaire was used to investigate awareness, knowledge and attitude towards HFMD and EV71 vaccines. A total of 868 parents participated in the survey. Mean(±standard deviation) knowledge score of HFMD was 6.32(±1.70). Approximately 32.03% of parents had heard of the EV71 vaccines with 22.58% receiving information before this study. Nearly 44.24% of parents showed willingness to vaccinate their children. Previously receiving EV71 vaccine-related information [adjusted odds ratio (aOR) = 1.48, 95% confidence interval (CI): 1.04-2.11], no fear of adverse effects (aOR = 4.25, 95%CI: 2.77-6.53), perceived susceptibility of children to HFMD (aOR = 2.15, 95%CI: 1.42-3.25) and children not previously diagnosed with HFMD (aOR = 1.56, 95%CI: 1.07-2.27) were positively associated with EV71 vaccination acceptability. However, parental education background (aOR = 0.54, 95%CI: 0.37-0.80) was negatively correlated with vaccination acceptability. Our study provides baseline information for future vaccination campaigns to help improve the EV71 vaccine uptake rate. Special efforts are urgently needed to improve the awareness and knowledge of EV71 vaccines in China. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Challenges and Economic Implications in the Control of Foot and Mouth Disease in Sub-Saharan Africa: Lessons from the Zambian Experience

    PubMed Central

    Sinkala, Y.; Simuunza, M.; Pfeiffer, D. U.; Munang'andu, H. M.; Mulumba, M.; Kasanga, C. J.; Muma, J. B.; Mweene, A. S.

    2014-01-01

    Foot and mouth disease is one of the world's most important livestock diseases for trade. FMD infections are complex in nature and there are many epidemiological factors needing clarification. Key questions relate to the control challenges and economic impact of the disease for resource-poor FMD endemic countries like Zambia. A review of the control challenges and economic impact of FMD outbreaks in Zambia was made. Information was collected from peer-reviewed journals articles, conference proceedings, unpublished scientific reports, and personal communication with scientists and personal field experiences. The challenges of controlling FMD using mainly vaccination and movement control are discussed. Impacts include losses in income of over US$ 1.6 billion from exports of beef and sable antelopes and an annual cost of over US$ 2.7 million on preventive measures. Further impacts included unquantified losses in production and low investment in agriculture resulting in slow economic growth. FMD persistence may be a result of inadequate epidemiological understanding of the disease and ineffectiveness of the control measures that are being applied. The identified gaps may be considered in the annual appraisal of the FMD national control strategy in order to advance on the progressive control pathway. PMID:25276472

  4. Challenges and economic implications in the control of foot and mouth disease in sub-saharan Africa: lessons from the zambian experience.

    PubMed

    Sinkala, Y; Simuunza, M; Pfeiffer, D U; Munang'andu, H M; Mulumba, M; Kasanga, C J; Muma, J B; Mweene, A S

    2014-01-01

    Foot and mouth disease is one of the world's most important livestock diseases for trade. FMD infections are complex in nature and there are many epidemiological factors needing clarification. Key questions relate to the control challenges and economic impact of the disease for resource-poor FMD endemic countries like Zambia. A review of the control challenges and economic impact of FMD outbreaks in Zambia was made. Information was collected from peer-reviewed journals articles, conference proceedings, unpublished scientific reports, and personal communication with scientists and personal field experiences. The challenges of controlling FMD using mainly vaccination and movement control are discussed. Impacts include losses in income of over US$ 1.6 billion from exports of beef and sable antelopes and an annual cost of over US$ 2.7 million on preventive measures. Further impacts included unquantified losses in production and low investment in agriculture resulting in slow economic growth. FMD persistence may be a result of inadequate epidemiological understanding of the disease and ineffectiveness of the control measures that are being applied. The identified gaps may be considered in the annual appraisal of the FMD national control strategy in order to advance on the progressive control pathway.

  5. Expression and immunogenicity of novel subunit enterovirus 71 VP1 antigens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Juan; Department of Microbiology and Immunology, Nanjing Medical University; Wang, Shixia

    Highlights: Black-Right-Pointing-Pointer EV71 is a major emerging infectious disease in many Asian countries. Black-Right-Pointing-Pointer Inactivated EV71 vaccines are in clinical studies but their safety and efficacy are unknown. Black-Right-Pointing-Pointer Developing subunit based EV71 vaccines is significant and novel antigen design is needed. Black-Right-Pointing-Pointer DNA immunization is an efficient tool to test the immunogenicity of VP1 based EV71 vaccines. Black-Right-Pointing-Pointer Multiple VP1 antigens are developed showing immunogenic potential. -- Abstract: Hand, foot, and mouth disease (HFMD) is a common viral illness in young children. HFMD is caused by viruses belonging to the enterovirus genus of the picornavirus family. Recently, enterovirus 71more » (EV71) has emerged as a virulent agent for HFMD with severe clinical outcomes. In the current report, we conducted a pilot antigen engineering study to optimize the expression and immunogenicity of subunit VP1 antigen for the design of EV71 vaccines. DNA immunization was adopted as a simple technical approach to test different designs of VP1 antigens without the need to express VP1 protein in vitro first. Our studies indicated that the expression and immunogenicity of VP1 protein can be improved with alternated VP1 antigen designs. Data presented in the current report revealed novel pathways to optimize the design of VP1 antigen-based EV71 vaccines.« less

  6. Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study.

    PubMed

    Roche, S E; Garner, M G; Sanson, R L; Cook, C; Birch, C; Backer, J A; Dube, C; Patyk, K A; Stevenson, M A; Yu, Z D; Rawdon, T G; Gauntlett, F

    2015-04-01

    Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

  7. Hydrolytic properties and substrate specificity of the foot-and-mouth disease leader protease.

    PubMed

    Santos, Jorge A N; Gouvea, Iuri E; Júdice, Wagner A S; Izidoro, Mario A; Alves, Fabiana M; Melo, Robson L; Juliano, Maria A; Skern, Tim; Juliano, Luiz

    2009-08-25

    Foot-and-mouth disease virus, a global animal pathogen, possesses a single-stranded RNA genome that, on release into the infected cell, is immediately translated into a single polyprotein. This polyprotein product is cleaved during synthesis by proteinases contained within it into the mature viral proteins. The first cleavage is performed by the leader protease (Lb(pro)) between its own C-terminus and the N-terminus of VP4. Lb(pro) also specifically cleaves the two homologues of cellular eukaryotic initiation factor (eIF) 4G, preventing translation of capped mRNA. Viral protein synthesis is initiated internally and is thus unaffected. We used a panel of specifically designed FRET peptides to examine the effects of pH and ionic strength on Lb(pro) activity and investigate the size of the substrate binding site and substrate specificity. Compared to the class prototypes, papain and the cathepsins, Lb(pro) possesses several unusual characteristics, including a high sensitivity to salt and a very specific substrate binding site extending up to P(7). Indeed, almost all substitutions investigated were detrimental to Lb(pro) activity. Analysis of structural data showed that Lb(pro) binds residues P(1)-P(3) in an extended conformation, whereas residues P(4)-P(7) are bound in a short 3(10) helix. The specificity of Lb(pro) as revealed by the substituted peptides could be explained for all positions except P(5). Strikingly, Lb(pro) residues L178 and L143 contribute to the architecture of more than one substrate binding pocket. The diverse functions of these two Lb(pro) residues explain why Lb(pro) is one of the smallest, but simultaneously most specific, papain-like enzymes.

  8. Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle.

    PubMed

    Sreenivasa, B P; Mohapatra, J K; Pauszek, S J; Koster, M; Dhanya, V C; Tamil Selvan, R P; Hosamani, M; Saravanan, P; Basagoudanavar, Suresh H; de Los Santos, T; Venkataramanan, R; Rodriguez, L L; Grubman, M J

    2017-05-01

    Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O, A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutralizing antibody response in indigenous cattle (Bos indicus). Purified Ad5-FMD viruses were inoculated in cattle as monovalent (5×10 9 pfu/animal) or trivalent (5×10 9 pfu/animal per serotype) vaccines. Animals vaccinated with monovalent Ad5-FMD vaccines were boosted 63days later with the same dose. After primary immunization, virus neutralization tests (VNT) showed seroconversion in 83, 67 and 33% of animals vaccinated with Ad5-FMD O, A and Asia 1, respectively. Booster immunization elicited seroconversion in all of the animals (100%) in the monovalent groups. When used in a trivalent form, the Ad5-FMD vaccine induced neutralizing antibodies in only 33, 50 and 16% of animals against serotypes O, A and Asia 1, respectively on primo-vaccination, and titers were significantly lower than when the same vectors were used in monovalent form. Neutralizing antibody titers differed by serotype for both Ad5-FMD monovalent and trivalent vaccines, with Asia 1 serotype inducing the lowest titers. Antibody response to Ad5 vector in immunized cattle was also assessed by VNT. It appeared that the vector immunity did not impact the recall responses to expressed FMDV antigens on booster immunization. In summary, the study suggested that the recombinant Ad5-FMD vaccine has a potential use in monovalent form, while its application in multivalent form is not currently encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cost-benefit analysis of foot and mouth disease control in Ethiopia.

    PubMed

    Jemberu, Wudu T; Mourits, Monique; Rushton, Jonathan; Hogeveen, Henk

    2016-09-15

    Foot and mouth disease (FMD) occurs endemically in Ethiopia. Quantitative insights on its national economic impact and on the costs and benefits of control options are, however, lacking to support decision making in its control. The objectives of this study were, therefore, to estimate the annual costs of FMD in cattle production systems of Ethiopia, and to conduct an ex ante cost-benefit analysis of potential control alternatives. The annual costs of FMD were assessed based on production losses, export losses and control costs. The total annual costs of FMD under the current status quo of no official control program were estimated at 1354 (90% CR: 864-2042) million birr. The major cost (94%) was due to production losses. The costs and benefits of three potential control strategies: 1) ring vaccination (reactive vaccination around outbreak area supported by animal movement restrictions, 2) targeted vaccination (annual preventive vaccination in high risk areas plus ring vaccination in the rest of the country), and 3) preventive mass vaccination (annual preventive vaccination of the whole national cattle population) were compared with the baseline scenario of no official control program. Experts were elicited to estimate the influence of each of the control strategies on outbreak incidence and number of cases per outbreak. Based on these estimates, the incidence of the disease was simulated stochastically for 10 years. Preventive mass vaccination was epidemiologically the most efficient control strategy by reducing the national outbreak incidence below 5% with a median time interval of 3 years, followed by targeted vaccination strategy with a corresponding median time interval of 5 years. On average, all evaluated control strategies resulted in positive net present values. The ranges in the net present values were, however, very wide, including negative values. The targeted vaccination strategy was the most economic strategy with a median benefit cost ratio of 4

  10. Feasibility of depopulation of a large feedlot during a foot-and-mouth disease outbreak.

    PubMed

    McReynolds, Sara W; Sanderson, Michael W

    2014-02-01

    To examine the feasibility of depopulation of a large feedlot during a foot-and-mouth disease (FMD) outbreak in the United States. Delphi survey followed by facilitated discussion. 27 experts, including veterinary toxicologists and pharmacologists, animal welfare experts, feedlot managers, and consulting veterinarians. 4 veterinary pharmacologists, 5 veterinary toxicologists, 4 animal welfare experts, 26 consulting veterinarians, and 8 feedlot managers were invited to participate in a Delphi survey to identify methods for depopulation of a large feedlot during an FMD outbreak. A facilitated discussion that included 1 pharmacologist, 1 toxicologist, 1 animal welfare expert, 2 consulting veterinarians, and 2 feedlot managers was held to review the survey results. 27 of 47 invited experts participated in the Delphi survey. Survey consensus was that, although several toxic agents would effectively cause acute death in a large number of animals, all of them had substantial animal welfare concerns. Pentobarbital sodium administered IV was considered the most effective pharmacological agent for euthanasia, and xylazine was considered the most effective sedative. Animal welfare concerns following administration of a euthanasia solution IV or a penetrating captive bolt were minimal; however, both veterinarians and feedlot managers felt that use of a captive bolt would be inefficient for depopulation. Veterinarians were extremely concerned about public perception, human safety, and timely depopulation of a large feedlot during an FMD outbreak. Depopulation of a large feedlot during an FMD outbreak would be difficult to complete in a humane and timely fashion.

  11. Purification of foot-and-mouth disease virus by heparin as ligand for certain strains.

    PubMed

    Du, Ping; Sun, Shiqi; Dong, Jinjie; Zhi, Xiaoying; Chang, Yanyan; Teng, Zhidong; Guo, Huichen; Liu, Zaixin

    2017-04-01

    The goal of this project was to develop an easily operable and scalable process for the recovery and purification of foot-and-mouth disease virus (FMDV) from cell culture. Heparin resins HipTrap Heparin HP and AF-Heparin HC-650 were utilized to purify FMDV O/HN/CHA/93. Results showed that the purity of AF-Heparin HC-650 was ideal. Then, the O/HN/CHA/93, O/Tibet/CHA/99, Asia I/HN/06, and A/CHA/HB/2009 strains were purified by AF-Heparin HC-650. Their affinity/virus recoveries were approximately 51.2%/45.8%, 71.5%/70.9%, 96.4%/73.5, and 59.5%/42.1%, respectively. During a stepwise elution strategy, the viral particles were mainly eluted at 300mM ionic strength peaks. The heparin affinity chromatography process removed more than 94% of cellular and medium proteins. Anion exchange resin Capto Q captured four FMD virus particles; 40% of binding proteins and 80%-90% of viral particles were eluted at 450mM NaCl. Moreover, ionic strength varied from 30 to 450mM had no effect on the immunity to FMDV. The results revealed that heparin sulfate may be the main receptor for CHA/99 strain attachment-susceptible cells. Heparin affinity chromatography can reach perfect results, especially when used as a ligand of the virus. Anion exchange is useful only as previous step for further purification. Copyright © 2016. Published by Elsevier B.V.

  12. Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

    PubMed Central

    Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

    2015-01-01

    ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against

  13. The Clinical Correlation of Regulatory T Cells and Cyclic Adenosine Monophosphate in Enterovirus 71 Infection

    PubMed Central

    Wang, Shih-Min; Chen, I-Chun; Liao, Yu-Ting; Liu, Ching-Chuan

    2014-01-01

    Background Brainstem encephalitis (BE) and pulmonary edema (PE) are notable complications of enterovirus 71 (EV71) infection. Objective This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment. Study Design Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD) or BE group, and the autonomic nervous system (ANS) dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP) levels, and the regulatory T cell (Tregs) profiles of the patients were determined. Results Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4+CD25+Foxp3+ and CD4+Foxp3+ T cells compared with patients with HFMD or BE. The expression frequency of CD4−CD8− was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment. Conclusions These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels. PMID:25010330

  14. Genetic characterization of Enterovirus 71 strains circulating in Vietnam in 2012.

    PubMed

    Donato, Celeste; Hoi, Le Thi; Hoa, Nguyen Thi; Hoa, Tran Mai; Van Duyet, Le; Dieu Ngan, Ta Thi; Van Kinh, Nguyen; Vu Trung, Nguyen; Vijaykrishna, Dhanasekaran

    2016-08-01

    Enterovirus 71 subgenogroup C4 caused the largest outbreak of Hand, Foot and Mouth Disease (HFMD) in Vietnam during 2011-2012, resulting in over 200,000 hospitalisations and 207 fatalities. A total of 1917 samples with adequate volume for RT-PCR analysis were collected from patients hospitalised with HFMD throughout Vietnam and 637 were positive for EV71. VP1 gene (n=87) and complete genome (n=9) sequencing was performed. Maximum-likelihood phylogenetic analysis was performed to characterise the B5, C4 and C5 strains detected. Sequence analyses revealed that the dominant subgenogroup associated with the 2012 outbreak was C4, with B5 and C5 strains representing a small proportion of these cases. Numerous countries in the region including Malaysia, Taiwan and China have a large influence on strain diversity in Vietnam and understanding the transmission of EV71 throughout Southeast Asia is vital to inform preventative public health measures and vaccine development efforts. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Complete Sequence Analysis and Antiviral Screening of Medicinal Plants for Human Coxsackievirus A16 Isolated in Korea

    PubMed Central

    Song, Jae-Hyoung; Park, Kwisung; Shim, Aeri; Kwon, Bo-Eun; Ahn, Jae-Hee; Choi, Young Jin; Kim, Jae Kyung; Yeo, Sang-Gu; Yoon, Kyungah; Ko, Hyun-Jeong

    2015-01-01

    Objectives Coxsackievirus A group 16 strain (CVA16) is one of the predominant causative agents of hand, foot, and mouth disease (HFMD). Methods Using a specimen from a male patient with HFMD, we isolated and performed sequencing of the Korean CVA16 strain and compared it with a G10 reference strain. Also, we were investigated the effects of medicinal plant extract on the cytopathic effects (CPE) by CPE reduction assay against Korean CVA16. Results Phylogenetic analysis showed that the Korean CVA16 isolate belonged to cluster B-1 and was closely related to the strain PM-15765-00 isolated in Malaysia in 2000. The Korean CVA16 isolate showed 73.2% nucleotide identity to the G10 prototype strain and 98.7% nucleotide identity to PM-15765-00. Next, we assessed whether the Korean CVA16 isolate could be used for in vitro screening of antiviral agents to treat HFMD infection. Vero cells infected with the Korean CVA16 isolate showed a cytopathic effect 2 days after the infection, and the treatment of cells with Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. davidiana Hemsl extracts exhibited strong antiviral activity against CVA16. Conclusion Collectively, our work provides potential candidates for the development of vaccine and novel drugs to treat the CVA16 strain isolated from a Korean patient. PMID:25737832

  16. Complete sequence analysis and antiviral screening of medicinal plants for human coxsackievirus a16 isolated in Korea.

    PubMed

    Song, Jae-Hyoung; Park, Kwisung; Shim, Aeri; Kwon, Bo-Eun; Ahn, Jae-Hee; Choi, Young Jin; Kim, Jae Kyung; Yeo, Sang-Gu; Yoon, Kyungah; Ko, Hyun-Jeong

    2015-02-01

    Coxsackievirus A group 16 strain (CVA16) is one of the predominant causative agents of hand, foot, and mouth disease (HFMD). Using a specimen from a male patient with HFMD, we isolated and performed sequencing of the Korean CVA16 strain and compared it with a G10 reference strain. Also, we were investigated the effects of medicinal plant extract on the cytopathic effects (CPE) by CPE reduction assay against Korean CVA16. Phylogenetic analysis showed that the Korean CVA16 isolate belonged to cluster B-1 and was closely related to the strain PM-15765-00 isolated in Malaysia in 2000. The Korean CVA16 isolate showed 73.2% nucleotide identity to the G10 prototype strain and 98.7% nucleotide identity to PM-15765-00. Next, we assessed whether the Korean CVA16 isolate could be used for in vitro screening of antiviral agents to treat HFMD infection. Vero cells infected with the Korean CVA16 isolate showed a cytopathic effect 2 days after the infection, and the treatment of cells with Cornus officinalis, Acer triflorum, Pulsatilla koreana, and Clematis heracleifolia var. davidiana Hemsl extracts exhibited strong antiviral activity against CVA16. Collectively, our work provides potential candidates for the development of vaccine and novel drugs to treat the CVA16 strain isolated from a Korean patient.

  17. How to select a proper early warning threshold to detect infectious disease outbreaks based on the China infectious disease automated alert and response system (CIDARS).

    PubMed

    Wang, Ruiping; Jiang, Yonggen; Michael, Engelgau; Zhao, Genming

    2017-06-12

    China Centre for Diseases Control and Prevention (CDC) developed the China Infectious Disease Automated Alert and Response System (CIDARS) in 2005. The CIDARS was used to strengthen infectious disease surveillance and aid in the early warning of outbreak. The CIDARS has been integrated into the routine outbreak monitoring efforts of the CDC at all levels in China. Early warning threshold is crucial for outbreak detection in the CIDARS, but CDCs at all level are currently using thresholds recommended by the China CDC, and these recommended thresholds have recognized limitations. Our study therefore seeks to explore an operational method to select the proper early warning threshold according to the epidemic features of local infectious diseases. The data used in this study were extracted from the web-based Nationwide Notifiable Infectious Diseases Reporting Information System (NIDRIS), and data for infectious disease cases were organized by calendar week (1-52) and year (2009-2015) in Excel format; Px was calculated using a percentile-based moving window (moving window [5 week*5 year], x), where x represents one of 12 centiles (0.40, 0.45, 0.50….0.95). Outbreak signals for the 12 Px were calculated using the moving percentile method (MPM) based on data from the CIDARS. When the outbreak signals generated by the 'mean + 2SD' gold standard were in line with a Px generated outbreak signal for each week during the year of 2014, this Px was then defined as the proper threshold for the infectious disease. Finally, the performance of new selected thresholds for each infectious disease was evaluated by simulated outbreak signals based on 2015 data. Six infectious diseases were selected in this study (chickenpox, mumps, hand foot and mouth diseases (HFMD), scarlet fever, influenza and rubella). Proper thresholds for chickenpox (P75), mumps (P80), influenza (P75), rubella (P45), HFMD (P75), and scarlet fever (P80) were identified. The selected proper thresholds for these

  18. Phylodynamic reconstruction of O CATHAY topotype foot-and-mouth disease virus epidemics in the Philippines.

    PubMed

    Di Nardo, Antonello; Knowles, Nick J; Wadsworth, Jemma; Haydon, Daniel T; King, Donald P

    2014-08-24

    Reconstructing the evolutionary history, demographic signal and dispersal processes from viral genome sequences contributes to our understanding of the epidemiological dynamics underlying epizootic events. In this study, a Bayesian phylogenetic framework was used to explore the phylodynamics and spatio-temporal dispersion of the O CATHAY topotype of foot-and-mouth disease virus (FMDV) that caused epidemics in the Philippines between 1994 and 2005. Sequences of the FMDV genome encoding the VP1 showed that the O CATHAY FMD epizootic in the Philippines resulted from a single introduction and was characterised by three main transmission hubs in Rizal, Bulacan and Manila Provinces. From a wider regional perspective, phylogenetic reconstruction of all available O CATHAY VP1 nucleotide sequences identified three distinct sub-lineages associated with country-based clusters originating in Hong Kong Special Administrative Region (SAR), the Philippines and Taiwan. The root of this phylogenetic tree was located in Hong Kong SAR, representing the most likely source for the introduction of this lineage into the Philippines and Taiwan. The reconstructed O CATHAY phylodynamics revealed three chronologically distinct evolutionary phases, culminating in a reduction in viral diversity over the final 10 years. The analysis suggests that viruses from the O CATHAY topotype have been continually maintained within swine industries close to Hong Kong SAR, following the extinction of virus lineages from the Philippines and the reduced number of FMD cases in Taiwan.

  19. Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro.

    PubMed

    Zhao, Fu-Rong; Xie, Yin-Li; Liu, Ze-Zhong; Shao, Jun-Jun; Li, Shi-Fang; Zhang, Yong-Guang; Chang, Hui-Yun

    2017-11-01

    Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus. In this study, our findings were the first to demonstrate that LiCl inhibition of the FMDV replication. In this study, BHK-21 cell was dose-dependent with LiCl at various stages of FMDV. Virus titration assay was calculated by the 50% tissue culture infected dose (TCID 50 ) with the Reed and Muench method. The cytotoxicity assay of LiCl was performed by the CCK8 kit. The expression level of viral mRNA was measured by RT-qPCR. The results revealed LiCl can inhibit FMDV replication, but it cannot affect FMDV attachment stage and entry stage in the course of FMDV life cycle. Further studies confirmed that the LiCl affect the replication stage of FMDV, especially the early stages of FMDV replication. So LiCl has potential as an effective anti-FMDV drug. Therefore, LiCl may be an effective drug for the control of FMDV. Based on that, the mechanism of the antiviral effect of LiCl on FMDV infection is need to in-depth research in vivo. © 2017 Wiley Periodicals, Inc.

  20. Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001.

    PubMed

    Thompson, D; Muriel, P; Russell, D; Osborne, P; Bromley, A; Rowland, M; Creigh-Tyte, S; Brown, C

    2002-12-01

    The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.

  1. Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase

    PubMed Central

    Han, Shi-Chong; Guo, Hui-Chen; Sun, Shi-Qi; Jin, Ye; Wei, Yan-Quan; Feng, Xia; Yao, Xue-Ping; Cao, Sui-Zhong; Xiang Liu, Ding; Liu, Xiang-Tao

    2016-01-01

    Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na+/H+ exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses. PMID:26757826

  2. Farmers’ Intentions to Implement Foot and Mouth Disease Control Measures in Ethiopia

    PubMed Central

    Jemberu, Wudu T.; Mourits, M. C. M.; Hogeveen, H.

    2015-01-01

    The objectives of this study were to explore farmers’ intentions to implement foot and mouth disease (FMD) control in Ethiopia, and to identify perceptions about the disease and its control measures that influence these intentions using the Health Belief Model (HBM) framework. Data were collected using questionnaires from 293 farmers in three different production systems. The influence of perceptions on the intentions to implement control measures were analyzed using binary logistic regression. The effect of socio-demographic and husbandry variables on perceptions that were found to significantly influence the intentions were analyzed using ordinal logistic regression. Almost all farmers (99%) intended to implement FMD vaccination free of charge. The majority of farmers in the pastoral (94%) and market oriented (92%) systems also had the intention to implement vaccination with charge but only 42% of the crop-livestock mixed farmers had the intention to do so. Only 2% of pastoral and 18% of crop-livestock mixed farmers had the intention to implement herd isolation and animal movement restriction continuously. These proportions increased to 11% for pastoral and 50% for crop-livestock mixed farmers when the measure is applied only during an outbreak. The majority of farmers in the market oriented system (>80%) had the intention to implement herd isolation and animal movement restriction measure, both continuously and during an outbreak. Among the HBM perception constructs, perceived barrier was found to be the only significant predictor of the intention to implement vaccination. Perceived susceptibility, perceived benefit and perceived barrier were the significant predictors of the intention for herd isolation and animal movement restriction measure. In turn, the predicting perceived barrier on vaccination control varied significantly with the production system and the age of farmers. The significant HBM perception predictors on herd isolation and animal movement

  3. Farmers' Intentions to Implement Foot and Mouth Disease Control Measures in Ethiopia.

    PubMed

    Jemberu, Wudu T; Mourits, M C M; Hogeveen, H

    2015-01-01

    The objectives of this study were to explore farmers' intentions to implement foot and mouth disease (FMD) control in Ethiopia, and to identify perceptions about the disease and its control measures that influence these intentions using the Health Belief Model (HBM) framework. Data were collected using questionnaires from 293 farmers in three different production systems. The influence of perceptions on the intentions to implement control measures were analyzed using binary logistic regression. The effect of socio-demographic and husbandry variables on perceptions that were found to significantly influence the intentions were analyzed using ordinal logistic regression. Almost all farmers (99%) intended to implement FMD vaccination free of charge. The majority of farmers in the pastoral (94%) and market oriented (92%) systems also had the intention to implement vaccination with charge but only 42% of the crop-livestock mixed farmers had the intention to do so. Only 2% of pastoral and 18% of crop-livestock mixed farmers had the intention to implement herd isolation and animal movement restriction continuously. These proportions increased to 11% for pastoral and 50% for crop-livestock mixed farmers when the measure is applied only during an outbreak. The majority of farmers in the market oriented system (>80%) had the intention to implement herd isolation and animal movement restriction measure, both continuously and during an outbreak. Among the HBM perception constructs, perceived barrier was found to be the only significant predictor of the intention to implement vaccination. Perceived susceptibility, perceived benefit and perceived barrier were the significant predictors of the intention for herd isolation and animal movement restriction measure. In turn, the predicting perceived barrier on vaccination control varied significantly with the production system and the age of farmers. The significant HBM perception predictors on herd isolation and animal movement

  4. Transmission Parameters of the 2001 Foot and Mouth Epidemic in Great Britain

    PubMed Central

    Chis Ster, Irina; Ferguson, Neil M.

    2007-01-01

    Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models. PMID:17551582

  5. Development of a Blocking ELISA Using a Monoclonal Antibody to a Dominant Epitope in Non-Structural Protein 3A of Foot-and-Mouth Disease Virus, as a Matching Test for a Negative-Marker Vaccine.

    PubMed

    Fu, Yuanfang; Li, Pinghua; Cao, Yimei; Wang, Na; Sun, Pu; Shi, Qian; Ji, Xincheng; Bao, Huifang; Li, Dong; Chen, Yingli; Bai, Xingwen; Ma, Xueqing; Zhang, Jing; Lu, Zengjun; Liu, Zaixin

    2017-01-01

    Foot-and-mouth disease (FMD) is a devastating animal disease. Strategies for differentiation of infected from vaccinated animals (DIVA) remain very important for controlling disease. Development of an epitope-deleted marker vaccine and accompanying diagnostic method will improve the efficiency of DIVA. Here, a monoclonal antibody (Mab) was found to recognize a conserved "AEKNPLE" epitope spanning amino acids 109-115 of non-structural protein (NSP) 3A of foot-and-mouth disease virus (FMDV; O/Tibet/CHA/99 strain), which could be deleted by a reverse-genetic procedure. In addition, a blocking ELISA was developed based on this Mab against NSP 3A, which could serve as a matching test for a negative-marker vaccine. The criterion of this blocking ELISA was determined by detecting panels of sera from different origins. The serum samples with a percentage inhibition (PI) equal or greater than 50% were considered to be from infected animals, and those with <50% PI were considered to be from non-infected animals. This test showed similar performance when compared with other 2 blocking ELISAs based on an anti-NSP 3B Mab. This is the first report of the DIVA test for an NSP antibody based on an Mab against the conserved and predominant "AEKNPLE" epitope in NSP 3A of FMDV.

  6. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 2 - Epidemiology, Wildlife and Economics.

    PubMed

    Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed knowledge gaps in foot-and-mouth disease (FMD) research, and in this study, we consider (i) epidemiology, (ii) wildlife and (iii) economics. The study took the form of a literature review (2011-2015) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. During 2011-2015, modelling studies were dominant in the broad field of epidemiology; however, continued efforts are required to develop robust models for use during outbreaks in FMD-free countries, linking epidemiologic and economics models. More guidance is needed for both the evaluation and the setting of targets for vaccine coverage, population immunity and vaccine field efficacy. Similarly, methods for seroprevalence studies need to be improved to obtain more meaningful outputs that allow comparison across studies. To inform control programmes in endemic countries, field trials assessing the effectiveness of vaccination in extensive smallholder systems should be performed to determine whether FMD can be controlled with quality vaccines in settings where implementing effective biosecurity is challenging. Studies need to go beyond measuring only vaccine effects and should extend our knowledge of the impact of FMD and increase our understanding of how to maximize farmer participation in disease control. Where wildlife reservoirs of virus exist, particularly African Buffalo, we need to better understand when and under what circumstances transmission to domestic animals occurs in order to manage this risk appropriately, considering the impact of control measures on livelihoods and wildlife. For settings where FMD eradication is unfeasible, further ground testing of commodity-based trade is recommended. A thorough review of global FMD control programmes, covering successes and failures, would be extremely valuable and could be used to guide other control programmes. © 2016 Blackwell Verlag GmbH.

  7. Importation of beef from countries infected with foot and mouth disease: a review of risk mitigation measures.

    PubMed

    Sutmoller, P

    2001-12-01

    Risk mitigation measures to reduce the risks associated with importing beef from countries affected by foot and mouth disease (FMD) consist of controls at the farm of origin, inspection of slaughterhouses and maturation and deboning of carcasses. This assessment evaluates the effect of these measures on the mitigation of the risks presented by meat from cattle with FMD, for each of the different stages of the disease. The four disease stages considered are the incubation period, the period of clinical signs, convalescence and the carrier stage. Efficient animal health systems, disease surveillance, and ante-mortem and post-mortem inspection of all cattle effectively reduce the risk of FMD transmission from cattle slaughtered during the period of clinical signs or convalescence. These measures fail if the cattle are slaughtered during the incubation period, because of the absence of clinical signs. Cattle in this stage of the infection are likely to be viraemic, with FMD virus present in the skeletal muscles. Maturation of the carcasses of viraemic cattle reduces the risk of virus presence in the beef. In addition, deboning and removal of the principal lymph nodes and large blood vessels eliminate a source of FMD contamination of the beef. However, the slaughter of viraemic cattle creates an additional hazard of gross environmental viral contamination of the slaughterhouse facilities. Therefore, the maturation process may create a false sense of security, and the emphasis should instead be placed on disease surveillance within the infected zone and on the farms of origin, to prevent the slaughter of herds that are incubating FMD. Cattle slaughtered during the carrier stage do not pose a risk for the international beef trade.

  8. Aerosol transmission of foot-and-mouth disease virus Asia-1 under experimental conditions.

    PubMed

    Colenutt, C; Gonzales, J L; Paton, D J; Gloster, J; Nelson, N; Sanders, C

    2016-06-30

    Foot-and-mouth disease virus (FMDV) control measures rely on understanding of virus transmission mechanisms. Direct contact between naïve and infected animals or spread by contaminated fomites is prevented by quarantines and rigorous decontamination procedures during outbreaks. Transmission of FMDV by aerosol may not be prevented by these control measures and this route of transmission may allow infection of animals at distance from the infection source. Understanding the potential for aerosol spread of specific FMDV strains is important for informing control strategies in an outbreak. Here, the potential for transmission of an FMDV Asia 1 strain between pigs and cattle by indirect aerosol exposure was evaluated in an experimental setting. Four naïve calves were exposed to aerosols emitted from three infected pigs in an adjacent room for a 10h period. Direct contact between pigs and cattle and fomite transfer between rooms was prevented. Viral titres in aerosols emitted by the infected pigs were measured to estimate the dose that calves were exposed to. One of the calves developed clinical signs of FMD, whilst there was serological evidence for spread to cattle by aerosol transmission in the remaining three calves. This highlights the possibility that this FMDV Asia 1 strain could be spread by aerosol transmission given appropriate environmental conditions should an outbreak occur in pigs. Our estimates suggest the exposure dose required for aerosol transmission was higher than has been previously quantified for other serotypes, implying that aerosols are less likely to play a significant role in transmission and spread of this FMDV strain. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Market Impact of Foot-and-Mouth Disease Control Strategies: A UK Case Study

    PubMed Central

    Feng, Siyi; Patton, Myles; Davis, John

    2017-01-01

    Foot-and-mouth disease (FMD) poses a serious threat to the agricultural sector due to its highly contagious nature. Outbreaks of FMD can lead to substantial disruptions to livestock markets due to loss of production and access to international markets. In a previously FMD-free country, the use of vaccination to augment control of an FMD outbreak is increasingly being recognized as an alternative control strategy to direct slaughtering [stamping-out (SO)]. The choice of control strategy has implications on production, trade, and hence prices of the sector. Specific choice of eradication strategies depends on their costs and benefits. Economic impact assessments are often based on benefit–cost framework, which provide detailed information on the changes in profit for a farm or budget implications for a government (1). However, this framework cannot capture price effects caused by changes in production due to culling of animals; access to international markets; and consumers’ reaction. These three impacts combine to affect equilibrium within commodity markets (2). This paper provides assessment of sectoral level impacts of the eradication choices of FMD outbreaks, which are typically not available from benefit–cost framework, in the context of the UK. The FAPRI-UK model, a partial equilibrium model of the agricultural sector, is utilized to investigate market outcomes of different control strategies (namely SO and vaccinate-to-die) in the case of FMD outbreaks. The outputs from the simulations of the EXODIS epidemiological model (number of animals culled/vaccinated and duration of outbreak) are used as inputs within the economic model to capture the overall price impact of the animal destruction, export ban, and consumers’ response. PMID:28920059

  10. The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage

    PubMed Central

    Abeyratne, S. A. E.; Amarasekera, S. S. C.; Knowles, N. J.; Wadsworth, J.; Puvanendiran, S.; Kothalawala, H.; Jayathilake, B. K.; Wijithasiri, H. A.; Chandrasena, M. M. P. S. K.

    2018-01-01

    Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many times in the past. Despite its seriousness, limited attempts have been made to understand the disease to ameliorate its effects–current recommendation for vaccines being based solely on immunological assessments rather than on molecular identification. The general belief is that the cattle population in Sri Lanka acquired the FMD virus (FMDV) strains via introductions from India. However, there could be endemic FMDV lineages circulating in Sri Lanka. To infer the phylogenetic relationships of the FMDV strains in the island, we sequenced the VP1 genomic region of the virus isolates collected during the 2014 outbreak together with a few reported cases in 2012 and 1997 and compared them to VP1 sequences from South Asia. The FMDV strains collected in the 2014 outbreak belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected in 2012 and 1997 belonged to another lineage called 'unnamed' by the World Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively, suggesting that Srl-97 evolves slowly. PMID:29570746

  11. The phylogenetic analysis of VP1 genomic region in foot-and-mouth disease virus serotype O isolates in Sri Lanka reveals the existence of 'Srl-97', a newly named endemic lineage.

    PubMed

    Abeyratne, S A E; Amarasekera, S S C; Ranaweera, L T; Salpadoru, T B; Thilakarathne, S M N K; Knowles, N J; Wadsworth, J; Puvanendiran, S; Kothalawala, H; Jayathilake, B K; Wijithasiri, H A; Chandrasena, M M P S K; Sooriyapathirana, S D S S

    2018-01-01

    Foot and mouth disease (FMD) has devastated the cattle industry in Sri Lanka many times in the past. Despite its seriousness, limited attempts have been made to understand the disease to ameliorate its effects-current recommendation for vaccines being based solely on immunological assessments rather than on molecular identification. The general belief is that the cattle population in Sri Lanka acquired the FMD virus (FMDV) strains via introductions from India. However, there could be endemic FMDV lineages circulating in Sri Lanka. To infer the phylogenetic relationships of the FMDV strains in the island, we sequenced the VP1 genomic region of the virus isolates collected during the 2014 outbreak together with a few reported cases in 2012 and 1997 and compared them to VP1 sequences from South Asia. The FMDV strains collected in the 2014 outbreak belonged to the lineage, Ind-2001d, of the topotype, ME-SA. The strains collected in 2012 and 1997 belonged to another lineage called 'unnamed' by the World Reference Laboratory for Foot and Mouth Disease (WRLFMD). Based on the present analysis, we designate the lineage 'unnamed' as Srl-97 which we found endemic to Sri Lanka. The evolutionary rates of Srl-97 and Ind-2001d in Sri Lanka were estimated to be 0.0004 and 0.0046 substitutions/site/year, respectively, suggesting that Srl-97 evolves slowly.

  12. Genetic evolution of Human Enterovirus A71 subgenotype C4 in Shenzhen, China, 1998-2013.

    PubMed

    He, Yaqing; Zou, Linjie; Chong, Marc Ka Chun; Men, Ruoting; Xu, Wenbo; Yang, Hong; Yao, Xiangjie; Chen, Long; Xian, Huixia; Zhang, Hailong; Luo, Min; Cheng, Jinquan; Ma, Hanwu; Feng, Qianjin; Huang, Yun; Wang, Yujie; Yeoh, Eng-Kiong; Zee, Benny Chung-Ying; Zhou, Yuanping; He, Ming-Liang; Wang, Maggie Haitian

    2016-06-01

    Human Enterovirus A71 (EV-A71) is one of the severest enteroviruses that causes hand, foot, and mouth disease (HFMD) among children. This study identified the mutations of EV-A71 VP1 amino acid residues over a number of years and explored the possible association of identified mutations and HFMD epidemic outbreaks in Shenzhen, China. A total of 3760 stool specimens were collected from HFMD patients by Shenzhen Centers for Disease Control and Prevention (CDC) between 1998 and 2013. In total 289 VP1 strains were sequenced in this study, and amino acids mutation frequency was calculated. There were 2040 China nationwide sequences downloaded from Genebank as replication data. In our samples, 1036 subjects (27.6%) were EV-A71 infected. Three amino acid positions on VP1 protein were found to have high mutation prevalence. These are Q22H, S283T, and A289H. Site 22 showed a fast mutation fixation in the year 2008, at the time of the large scale epidemic outbreak in Shenzhen. Analysis of the nationwide data replicated the same trend of mutation prevalence of the three sites. The switching from Q to H on site 22 of the EV-A71 VP1 strain might be associated with the HFMD outbreak in Shenzhen in 2008. The identified amino acid sites 22, 283 and 289 provided information for developing anti-viral drugs against EV-A71 in the future. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. Evolutionary phylodynamics of foot-and-mouth disease virus serotypes O and A circulating in Vietnam.

    PubMed

    Le, Van Phan; Vu, Thi Thu Hang; Duong, Hong-Quan; Than, Van Thai; Song, Daesub

    2016-11-29

    Foot-and-mouth disease virus (FMDV) is one of the highest risk factors that affects the animal industry of the country. The virus causes production loss and high ratio mortality in young cloven-hoofed animals in Vietnam. The VP1 coding gene of 80 FMDV samples (66 samples of the serotype O and 14 samples of the serotype A) collected from endemic outbreaks during 2006-2014 were analyzed to investigate their phylogeny and genetic relationship with other available FMDVs globally. Phylogenetic analysis indicated that the serotype O strains were clustered into two distinct viral topotypes (the SEA and ME-SA), while the serotype A strains were all clustered into the genotype IX. Among the study strains, the amino acid sequence identities were shared at a level of 90.1-100, 92.9-100, and 92.8-100% for the topotypes SEA, ME-SA, and genotype IX, respectively. Substitutions leading to changes in the amino acid sequence, which are critical for the VP1 antigenic sites were also identified. Our results showed that the studied strains are most closely related to the recent FMDV isolates from Southeast Asian countries (Myanmar, Thailand, Cambodia, Malaysia, and Laos), but are distinct from the earlier FMDV isolates within the genotypes. This study provides important evidence of recent movement of FMDVs serotype O and A into Vietnam within the last decade and their genetic accumulation to be closely related to strains causing FMD in surrounding countries.

  14. Herd Immunity Against Foot-and-Mouth Disease Under Different Vaccination Practices in India.

    PubMed

    Sharma, G K; Mahajan, S; Matura, R; Biswal, J K; Ranjan, R; Subramaniam, S; Misri, J; Bambal, R G; Pattnaik, B

    2017-08-01

    A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot-and-mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi-annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group-D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log 10 1.93 (95% CI 1.92-1.93), 2.02 (2.02-2.02) and 2.02 (2.02-2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log 10 1.68 (95% CI 1.67-1.69), 1.77 (1.76-1.78) and 1.85 (1.84-1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme. © 2016 Blackwell Verlag GmbH.

  15. Molecular characterization of serotype Asia-1 foot-and-mouth disease viruses in Pakistan and Afghanistan; emergence of a new genetic Group and evidence for a novel recombinant virus.

    PubMed

    Jamal, Syed M; Ferrari, Giancarlo; Ahmed, Safia; Normann, Preben; Belsham, Graham J

    2011-12-01

    Foot-and-mouth disease (FMD) is endemic in Pakistan and Afghanistan. The FMD virus serotypes O, A and Asia-1 are responsible for the outbreaks in these countries. Diverse strains of FMDV, even within the same serotype, co-circulate. Characterization of the viruses in circulation can facilitate appropriate vaccine selection and tracing of outbreaks. The present study characterized foot-and-mouth disease serotype Asia-1 viruses circulating in Pakistan and Afghanistan during the period 1998-2009. Phylogenetic analysis of FMDV type Asia-1 revealed that three different genetic Groups of serotype Asia-1 have circulated in Pakistan during this time. These are Group-II, -VI and, recently, a novel Group (designated here as Group-VII). This new Group has not been detected in neighbouring Afghanistan during the study period but viruses from Groups I and -II are in circulation there. Using near complete genome sequences, from FMD viruses of serotypes Asia-1 and A that are currently circulating in Pakistan, we have identified an interserotypic recombinant virus, which has the VP2-VP3-VP1-2A coding sequences derived from a Group-VII Asia-1 virus and the remainder of the genome from a serotype A virus of the A-Iran05(AFG-07) sub-lineage. The Asia-1 FMDVs currently circulating in Pakistan and Afghanistan are not efficiently neutralized by antisera raised against the Asia-1/Shamir vaccine strain. Thus, new Asia-1 vaccine strains may be required to block the spread of the current Asia-1 viruses. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 4 - Diagnostics.

    PubMed

    Knight-Jones, T J D; Robinson, L; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed knowledge gaps in foot-and-mouth disease (FMD) research in the field of diagnostics. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from around the world. Findings were used to identify priority areas for future FMD research. Molecular and genetic technologies, including sequencing, are developing at an increasing rate both in terms of capability and affordability. These advances potentiate progress in many other fields of research, from vaccine development to epidemiology. The development of RT-LAMP represents an important breakthrough allowing greater use and access to molecular diagnostics. It is now possible to determine virus serotype using PCR, although only for certain virus pools, continued progress is needed to cover the global spectrum of FMD viruses. Progress has also been made in the development of pen-side rapid diagnostics, some with the ability to determine serotype. However, further advances in pen-side serotype or strain determination would benefit both FMD-free countries and endemic countries with limited access to well-resourced laboratories. Novel sampling methods that show promise include air sampling and baited ropes, the latter may aid sampling in wildlife and swine. Studies of infrared thermography for the early detection of FMD have not been encouraging, although investigations are ongoing. Multiplex tests have been developed that are able to simultaneously screen for multiple pathogens with similar clinical signs. Crucial for assessing FMDV freedom, tests exist to detect animals that have been infected with FMDV regardless of vaccination status; however, limitations exist, particularly when testing previously vaccinated animals. Novel vaccines are being developed with complementary DIVA tests for this purpose. Research is also needed to improve the current imprecise approaches to FMD vaccine matching. The development of simple, affordable

  17. Formulation and In Vitro Release Kinetics of Mucoadhesive Blend Gels Containing Matrine for Buccal Administration.

    PubMed

    Chen, Xiaojin; Yan, Jun; Yu, Shuying; Wang, Pingping

    2018-01-01

    Enterovirus 71 (EV71) is a pathogenic factor of severe hand, foot, and mouth disease (HFMD). No vaccine or specific treatment is currently available for EV71 infection. Hence, we developed a buccal mucoadhesive gel containing matrine to protect against HFMD. Mucoadhesive gels were prepared by Carbopol 974P and were combined with Carbopol 971P, sodium carboxymethyl cellulose (CMC-Na), or hydroxypropylmethy cellulose (HPMC K100M). The formulations were characterized in terms of tensile testing and continuous flow techniques for mucoadhesion. The rheological studies and in vitro drug release characteristics were also investigated. The results showed that combinations of two polymers significantly improved mucoadhesion, especially Carbopol 974P blended with HPMC. Carbopol 974P to HPMC blend ratios of 1:1 and 2:1 induced better mucoadhesion in the tensile test and continuous flow method, respectively. The most sustained release was obtained at a Carbopol 974P to HPMC ratio of 2.5:1. A predominantly non-Fickian diffusion release mechanism was obtained. The gel containing 2.5% Carbopol 974P combined with 1% HPMC showed good mucoadhesion properties and sustained drug release.

  18. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 7 - Pathogenesis and Molecular Biology.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    We assessed research knowledge gaps in the fields of FMDV (foot-and-mouth disease virus) pathogenesis and molecular biology by performing a literature review (2011-15) and collecting research updates (2014) from 33 institutes from across the world. Findings were used to identify priority areas for future research. There have been important advances in FMDV pathogenesis; FMDV remains in lymph nodes of many recovered animals that otherwise do not appear persistently infected, even in species previously not associated with the carrier state. Whether virus retention helps maintain host immunity and/or virus survival is not known. Studies of FMDV pathogenesis in wildlife have provided insights into disease epidemiology, in endemic and epidemic settings. Many aspects of FMDV infection and virus entry remain unknown; however, at the cellular level, we know that expression level and availability of integrins (that permit viral entry), rate of clearance of infected cells and strength of anti-viral type I IFN (interferon) response are key determinants of tissue tropism. Extending findings to improved understanding of transmission requires a standardized approach and adoption of natural routes of infection during experimental study. There has been recognition of the importance of autophagosomes for FMDV entry into the cytoplasm following cell surface receptor binding, and that distinct internal cellular membranes are exploited for viral replication and immune evasion. New roles for viral proteins in blocking type I IFN production and downstream signalling have been identified facilitating research in anti-viral therapeutics. We know more about how infection affects cell protein expression, and research into molecular determinants of capsid stability has aided the development of stable vaccines. We have an expanding knowledge of viral and host molecular determinates of virulence and infectiousness, and of how phylogenetics may be used to estimate vaccine match and strain

  19. Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge.

    PubMed

    Barrionuevo, Florencia; Di Giacomo, Sebastián; Bucafusco, Danilo; Ayude, Andrea; Schammas, Juan; Miraglia, M Cruz; Capozzo, Alejandra; Borca, Manuel V; Perez-Filgueira, Mariano

    2018-05-01

    The role of passively transferred sera in the protection against aerogenous foot-and-mouth disease (FMD) virus infection in cattle was evaluated using vaccine-induced immune serum preparations obtained at 7 and 26 days post-vaccination (dpv). We showed that circulating antibodies were sufficient to prevent disease generalization after oronasal infection in animals passively transferred with 26-dpv serum but not with the 7-dpv serum. Conversely, conventional FMD vaccination provided clinical protection at 7 dpv, promoting fast and robust antibody responses upon challenge and even though antibody titers were similar to those found in animals passively immunized with 7-dpv serum. These results demonstrate that presence of antigen-specific antibodies is critical to prevent the dissemination of the virus within the animal. Conventional FMD vaccination additionally promoted the deployment of rapid, high titer and isotype-switched antibody responses at systemic and mucosal levels after infection, thus conferring protection even in the presence of low pre-challenge antibody titers. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Epidemiological analysis, serological prevalence and genotypic analysis of foot-and-mouth disease in Nigeria 2008-2009.

    PubMed

    Ehizibolo, D O; Perez, A M; Carrillo, C; Pauszek, S; AlKhamis, M; Ajogi, I; Umoh, J U; Kazeem, H M; Ehizibolo, P O; Fabian, A; Berninger, M; Moran, K; Rodriguez, L L; Metwally, S A

    2014-12-01

    The epidemiological situation of foot-and-mouth disease virus (FMDV) is uncertain in Nigeria, where the disease is endemic, and the majority of outbreaks are unreported. Control measures for FMD in Nigeria are not being implemented due to the absence of locally produced vaccines and an official ban on vaccine importation. This study summarizes the findings of a 3-year study aimed at quantifying the seroprevalence of FMD, its distribution in susceptible species and the genetic diversity of FMDV isolated from the Plateau State of Nigeria. A 29% FMD prevalence was estimated using 3ABC enzyme-linked immunosorbent assay (3ABC ELISA). Farms with suspected FMD nearby, with contact with wildlife, that used drugs or FMD vaccines or with >100 animals, and animals of large ruminant species and in pastures other than nomadic grazing were significantly (P < 0.05) associated with FMD. Antibodies against five FMDV serotypes, (A, O, SAT1, SAT2 and SAT3) were detected by the virus neutralization test (VNT) at various titres (<100->800) from all tested sera from most parts of the region. This is probably the first report of the presence of FMDV SAT3 in Nigeria. Further studies to investigate the potential probable presence and prevalence of SAT 3 virus in Nigeria are required. Tissue samples collected from clinical animals were positive for FMDV. Virus isolates were sequenced and confirmed as serotype A. All of the isolates showed marked genetic homogeneity with >99% genetic identity in the VP1 region and were most closely related to a previously described virus collected from Cameroon in 2000. This study provides knowledge on the epidemiological situation of FMD in Plateau State, Nigeria, and will probably help to develop effective control and preventive strategies for the disease in Nigeria and other countries in the West African subregion. © 2013 Blackwell Verlag GmbH.

  1. Interleukin-10 production at the early stage of infection with foot-and-mouth disease virus related to the likelihood of persistent infection in cattle.

    PubMed

    Zhang, Zhidong; Doel, Claudia; Bashiruddin, John B

    2015-11-19

    The factors leading to persistent infection of foot-and-mouth disease (FMD) virus in ruminants are not well defined. This paper provides evidence of the presence of interleukin-10 (IL-10) early in the course of infection (1-4 days) as a factor in the development of persistence of FMD virus in cattle. Results showed that serum IL-10 in carrier cattle infected with FMD virus type O (n = 4) was detected and peaked at 1 or 2 days post infection and rapidly declined thereafter. In contract, serum IL-10 levels in non-carrier cattle (n = 21) were very low or undetectable during the same period.

  2. Simple, quick and cost-efficient: A universal RT-PCR and sequencing strategy for genomic characterisation of foot-and-mouth disease viruses.

    PubMed

    Dill, V; Beer, M; Hoffmann, B

    2017-08-01

    Foot-and-mouth disease (FMD) is a major contributor to poverty and food insecurity in Africa and Asia, and it is one of the biggest threats to agriculture in highly developed countries. As FMD is extremely contagious, strategies for its prevention, early detection, and the immediate characterisation of outbreak strains are of great importance. The generation of whole-genome sequences enables phylogenetic characterisation, the epidemiological tracing of virus transmission pathways and is supportive in disease control strategies. This study describes the development and validation of a rapid, universal and cost-efficient RT-PCR system to generate genome sequences of FMDV, reaching from the IRES to the end of the open reading frame. The method was evaluated using twelve different virus strains covering all seven serotypes of FMDV. Additionally, samples from experimentally infected animals were tested to mimic diagnostic field samples. All primer pairs showed a robust amplification with a high sensitivity for all serotypes. In summary, the described assay is suitable for the generation of FMDV sequences from all serotypes to allow immediate phylogenetic analysis, detailed genotyping and molecular epidemiology. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Protection against Foot-and-Mouth Disease Virus in Guinea Pigs via Oral Administration of Recombinant Lactobacillus plantarum Expressing VP1

    PubMed Central

    Wang, Miao; Pan, Li; Zhou, Peng; Lv, Jianliang; Zhang, Zhongwang; Wang, Yonglu; Zhang, Yongguang

    2015-01-01

    Mucosal vaccination is an effective strategy for generating antigen-specific immune responses against mucosal infections of foot-and-mouth disease virus (FMDV). In this study, Lactobacillus plantarum strains NC8 and WCFS1 were used as oral delivery vehicles containing a pSIP411-VP1 recombinant plasmid to initiate mucosal and systemic immune responses in guinea pigs. Guinea pigs were orally vaccinated (three doses) with NC8-pSIP411, NC8-pSIP411-VP1, WCFS1-pSIP411, WCFS1-pSIP411-VP1 or milk. Animals immunized with NC8-pSIP411-VP1 and WCFS1-pSIP411-VP1 developed high levels of antigen-specific serum IgG, IgA, IgM, mucosal secretory IgA (sIgA) and neutralizing antibodies, and revealed stronger cell-mediated immune responses and enhanced protection against FMDV challenge compared with control groups. The recombinant pSIP411-VP1 effectively improved immunoprotection against FMDV in guinea pigs. PMID:26629822

  4. Modifications to the Foot-and-Mouth Disease Virus 2A Peptide: Influence on Polyprotein Processing and Virus Replication.

    PubMed

    Kjær, Jonas; Belsham, Graham J

    2018-04-15

    Foot-and-mouth disease virus (FMDV) has a positive-sense single-stranded RNA (ssRNA) genome that includes a single, large open reading frame encoding a polyprotein. The cotranslational "cleavage" of this polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues in length) using a nonproteolytic mechanism termed "ribosome skipping" or "StopGo." Multiple variants of the 2A polypeptide with this property among the picornaviruses share a conserved C-terminal motif [D(V/I)E(S/T)NPG↓P]. The impact of 2A modifications within this motif on FMDV protein synthesis, polyprotein processing, and virus viability were investigated. Amino acid substitutions are tolerated at residues E 14 , S 15 , and N 16 within the 2A sequences of infectious FMDVs despite their reported "cleavage" efficiencies at the 2A/2B junction of only ca. 30 to 50% compared to that of the wild type (wt). In contrast, no viruses containing substitutions at residue P 17 , G 18 , or P 19 , which displayed little or no "cleavage" activity in vitro , were rescued, but wt revertants were obtained. The 2A substitutions impaired the replication of an FMDV replicon. Using transient-expression assays, it was shown that certain amino acid substitutions at residues E 14 , S 15 , N 16 , and P 19 resulted in partial "cleavage" of a protease-free polyprotein, indicating that these specific residues are not essential for cotranslational "cleavage." Immunofluorescence studies, using full-length FMDV RNA transcripts encoding mutant 2A peptides, indicated that the 2A peptide remained attached to adjacent proteins, presumably 2B. These results show that efficient "cleavage" at the 2A/2B junction is required for optimal virus replication. However, maximal StopGo activity does not appear to be essential for the viability of FMDV. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes one of the most economically important diseases of farm animals. Cotranslational "cleavage" of the FMDV polyprotein precursor at

  5. Transient gene expression in serum-free suspension-growing mammalian cells for the production of foot-and-mouth disease virus empty capsids.

    PubMed

    Mignaqui, Ana Clara; Ruiz, Vanesa; Perret, Sylvie; St-Laurent, Gilles; Singh Chahal, Parminder; Transfiguracion, Julia; Sammarruco, Ayelén; Gnazzo, Victoria; Durocher, Yves; Wigdorovitz, Andrés

    2013-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. It produces severe economic losses in the livestock industry. Currently available vaccines are based on inactivated FMD virus (FMDV). The use of empty capsids as a subunit vaccine has been reported to be a promising candidate because it avoids the use of virus in the vaccine production and conserves the conformational epitopes of the virus. In this report, we explored transient gene expression (TGE) in serum-free suspension-growing mammalian cells for the production of FMDV recombinant empty capsids as a subunit vaccine. The recombinant proteins produced, assembled into empty capsids and induced protective immune response against viral challenge in mice. Furthermore, they were recognized by anti-FMDV bovine sera. By using this technology, we were able to achieve expression levels that are compatible with the development of a vaccine. Thus, TGE of mammalian cells is an easy to perform, scalable and cost-effective technology for the production of a recombinant subunit vaccine against FMDV.

  6. Adenovirus-mediated RNA interference against foot-and-mouth disease virus infection both in vitro and in vivo.

    PubMed

    Chen, Weizao; Liu, Mingqiu; Jiao, Ye; Yan, Weiyao; Wei, Xuefeng; Chen, Jiulian; Fei, Liang; Liu, Yang; Zuo, Xiaoping; Yang, Fugui; Lu, Yonggan; Zheng, Zhaoxin

    2006-04-01

    Foot-and-mouth disease virus (FMDV) infection is responsible for the heavy economic losses in stockbreeding each year. Because of the limited effectiveness of existing vaccines and antiviral drugs, the development of new strategies is needed. RNA interference (RNAi) is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with recombinant, replication-defective human adenovirus type 5 (Ad5) expressing short-hairpin RNAs (shRNAs) directed against either structural protein 1D (Ad5-NT21) or polymerase 3D (Ad5-POL) of FMDV totally protects swine IBRS-2 cells from homologous FMDV infection, whereas only Ad5-POL inhibits heterologous FMDV replication. Moreover, delivery of these shRNAs significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. Three of five guinea pigs inoculated with 10(6) PFU of Ad5-POL and challenged 24 h later with 50 50% infectious doses (ID50) of homologous virus were protected from the major clinical manifestation of disease: the appearance of vesicles on the feet. Two of three swine inoculated with an Ad5-NT21-Ad5-POL mixture containing 2 x 10(9) PFU each and challenged 24 h later with 100 ID50 of homologous virus were protected from the major clinical disease, but treatment with a higher dose of adenovirus mixture cannot promote protection of animals. The inhibition was rapid and specific because treatment with a control adenovirus construct (Ad5-LacZ) expressing Escherichia coli galactosidase-specific shRNA showed no marked antiviral activity. Our data highlight the in vivo potential of RNAi technology in the case of FMD.

  7. Epidemiology of Foot and Mouth Disease in Ethiopia: a Retrospective Analysis of District Level Outbreaks, 2007-2012.

    PubMed

    Jemberu, W T; Mourits, M C M; Sahle, M; Siraw, B; Vernooij, J C M; Hogeveen, H

    2016-12-01

    This study aimed at determining the incidence, distribution, risk factors, and causal serotypes of foot and mouth disease (FMD) outbreaks in Ethiopia based on 5 years of retrospective outbreak data (September 2007 until August 2012). District level outbreak data were collected from 115 randomly selected districts using a questionnaire administered to district animal health officers. The national incidence of FMD outbreaks during the study period was 1.45 outbreaks per five district years. Outbreaks were geographically widespread affecting all major regional states in the country and were more frequent in the central, southern, and southeastern parts of the country. Neither long-term nor seasonal trends were observed in the incidence of outbreaks. A mixed effects logistic regression analysis revealed that the type of production system (market oriented system versus subsistence systems), presence of a major livestock market and/or route, and adjacency to a national parks or wildlife sanctuary were found to be associated with increased risk of outbreaks in the districts. FMD virus serotypes O, A, SAT 2, and SAT 1 were identified as the causal serotypes of the outbreaks during the study period. Whereas O was the dominant serotype, SAT 2 was the serotype that showed increase in relative frequency of occurrence. The estimated incidence of outbreaks is useful in assessing the economic impacts of the disease, and the identified risk factors provide important knowledge to target a progressive FMD control policy for Ethiopia. © 2015 Blackwell Verlag GmbH.

  8. Chemiluminescence Immunoassay for the Detection of Antibodies against the 2C and 3ABC Nonstructural Proteins Induced by Infecting Pigs with Foot-and-Mouth Disease Virus.

    PubMed

    Liu, Zezhong; Shao, Junjun; Zhao, Furong; Zhou, Guangqing; Gao, Shandian; Liu, Wei; Lv, Jianliang; Li, Xiumei; Li, Yangfan; Chang, Huiyun; Zhang, Yongguang

    2017-08-01

    The potential diagnostic value of chemiluminescence immunoassays (CLIAs) has been accepted in recent years, although their use for foot-and-mouth disease (FMD) diagnostics has not been reported. Full-length 3ABC and 2C proteins were expressed in bacteria and purified by affinity chromatography to develop a rapid and accurate approach to distinguish pigs infected with foot-and-mouth disease virus (FMDV) from vaccinated pigs. The recombinant proteins were then used as antigens to develop two CLIAs for the detection of antibodies against nonstructural viral proteins. The diagnostic performance of the two assays was compared by analyzing serum from pigs (naive pigs, n = 63; vaccinated, uninfected pigs, n = 532; naive, infected pigs, n = 117) with a known infection status. The 3ABC-2C CLIA had a higher accuracy rate, with a diagnostic sensitivity of 100% and a diagnostic specificity of 96.5%, than the 3ABC CLIA, which had a diagnostic sensitivity of 95.7% and a diagnostic specificity of 96.0%. The results of the 3ABC-2C CLIA also had a high rate of concordance with those of two commercial FMDV enzyme-linked immunosorbent assay (ELISA) kits used to assess serum collected from 962 pigs in the field (96.2% and 97.8%, respectively). The 3ABC-2C CLIA detected infection in serum samples from infected pigs earlier than the commercial ELISA kits. In addition, the 3ABC-2C CLIA produced results within 15 min. On the basis of these findings, the 3ABC-2C CLIA could serve as the foundation for the development of penside FMD diagnostics and offers an alternative method to detect FMDV infections. Copyright © 2017 American Society for Microbiology.

  9. Effect of Foot-and-Mouth Disease Virus Infection on the Frequency, Phenotype and Function of Circulating Dendritic Cells in Cattle

    PubMed Central

    Sei, Janet J.; Waters, Ryan A.; Kenney, Mary; Barlow, John W.; Golde, William T.

    2016-01-01

    Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms develop within 2 to 3 days of exposure and include fever and vesicular lesions on the tongue and hooves. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection would lead to a better understanding of host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of conventional (cDC) and plasmacytoid DC (pDC) in blood by using multi-color flow cytometry. We show that the frequency of cDC and pDC increased following FMDV infection and peaked 3 to 4 days post-infection. During peak viremia, the cattle became lymphopenic, the expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, the processing of exogenous antigen by cDC and pDC was impaired, and there was an increase in IL-10 production by DC and monocytes. Notably, after clearance of FMDV from the blood, MHC class II expression returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, potentially enhancing virus shedding during the acute phase of infection. PMID:27008425

  10. The economic impacts of foot and mouth disease - what are they, how big are they and where do they occur?

    PubMed

    Knight-Jones, T J D; Rushton, J

    2013-11-01

    Although a disease of low mortality, the global impact of foot and mouth disease (FMD) is colossal due to the huge numbers of animals affected. This impact can be separated into two components: (1) direct losses due to reduced production and changes in herd structure; and (2) indirect losses caused by costs of FMD control, poor access to markets and limited use of improved production technologies. This paper estimates that annual impact of FMD in terms of visible production losses and vaccination in endemic regions alone amount to between US$6.5 and 21 billion. In addition, outbreaks in FMD free countries and zones cause losses of >US$1.5 billion a year. FMD impacts are not the same throughout the world: FMD is highly contagious and the actions of one farmer affect the risk of FMD occurring on other holdings; thus sizeable externalities are generated. Control therefore requires coordination within and between countries. These externalities imply that FMD control produces a significant amount of public goods, justifying the need for national and international public investment. Equipping poor countries with the tools needed to control FMD will involve the long term development of state veterinary services that in turn will deliver wider benefits to a nation including the control of other livestock diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Differential gene expression in porcine SK6 cells infected with wild-type and SAP domain-mutant foot-and-mouth disease virus.

    PubMed

    Ni, Zixin; Yang, Fan; Cao, Weijun; Zhang, Xiangle; Jin, Ye; Mao, Ruoqing; Du, Xiaoli; Li, Weiwei; Guo, Jianhong; Liu, Xiangtao; Zhu, Zixiang; Zheng, Haixue

    2016-06-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease in livestock. The viral proteinase L(pro) of FMDV is involved in pathogenicity, and mutation of the L(pro) SAP domain reduces FMDV pathogenicity in pigs. To determine the gene expression profiles associated with decreased pathogenicity in porcine cells, we performed transcriptome analysis using next-generation sequencing technology and compared differentially expressed genes in SK6 cells infected with FMDV containing L(pro) with either a wild-type or mutated version of the SAP domain. This analysis yielded 1,853 genes that exhibited a ≥ 2-fold change in expression and was validated by real-time quantitative PCR detection of several differentially expressed genes. Many of the differentially expressed genes correlated with antiviral responses corresponded to genes associated with transcription factors, immune regulation, cytokine production, inflammatory response, and apoptosis. Alterations in gene expression profiles may be responsible for the variations in pathogenicity observed between the two FMDV variants. Our results provided genes of interest for the further study of antiviral pathways and pathogenic mechanisms related to FMDV L(pro).

  12. The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes.

    PubMed

    Grant, Clare F J; Carr, B Veronica; Kotecha, Abhay; van den Born, Erwin; Stuart, David I; Hammond, John A; Charleston, Bryan

    2017-05-01

    Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV. Copyright © 2017 American Society for Microbiology.

  13. Molecular epidemiological studies on foot-and-mouth disease type O Taiwan viruses from the 1997 epidemic.

    PubMed

    Tsai, C P; Pan, C H; Liu, M Y; Lin, Y L; Chen, C M; Huang, T S; Cheng, I C; Jong, M H; Yang, P C

    2000-06-01

    Sequence diversity was assessed of the complete VP1 gene directly amplified from 49 clinical specimens during an explosive foot-and-mouth disease (FMD) outbreak in Taiwan. Type O Taiwan FMD viruses are genetically highly homogenous, as seen by the minute divergence of 0.2-0.9% revealed in 20 variants. The O/HCP-0314/TW/97 and O/TCP-022/TW/97 viral variants dominated FMD outbreaks and were prevalent in most affected pig-raising areas. Comparison of deduced amino acid sequences around the main neutralizable antigenic sites on the VP1 polypeptide showed no significant antigenic variation. However, the O/CHP-158/TW/97 variant had an alternative critical residue at position 43 in antigenic site 3, which may be due to selective pressure in the field. Two vaccine production strains (O1/Manisa/Turkey/69 and O1/Campos/Brazil/71) probably provide partial heterologous protection of swine against O Taiwan viruses. The type O Taiwan variants clustered in sublineage A1 of four main lineages in the phylogenetic tree. The O/Hong Kong/9/94 and O/1685/Moscow/Russia/95 viruses in sublineage A2 are closely related to the O Taiwan variants. The causative agent for the 1997 epidemic presumably originated from a single common source of type O FMD viruses prevalent in neighboring areas.

  14. Relationship between limited joint mobility of the hand and diabetic foot risk in patients with type 2 diabetes.

    PubMed

    Mineoka, Yusuke; Ishii, Michiyo; Tsuji, Akiko; Komatsu, Yoriko; Katayama, Yuko; Yamauchi, Mitsuko; Yamashita, Aki; Hashimoto, Yoshitaka; Nakamura, Naoto; Katsumi, Yasukazu; Isono, Motohide; Fukui, Michiaki

    2017-06-01

    Foot ulceration is a serious problem for patients with type 2 diabetes (T2D), and the early detection of risks for this condition is important to prevent complications. The present cross-sectional study in T2D patients determined the relationship between limited joint mobility (LJM) of the hand and diabetic foot risk classified using the criteria of the International Working Group on the Diabetic Foot (IWGDF). Relationships between LJM of the hand and foot risk according to IWGDF category, HbA1c, age, body mass index, blood pressure, estimated glomerular filtration (eGFR), and diabetic complications (including diabetic peripheral neuropathy [DPN] and peripheral arterial disease [PAD]) were evaluated in 528 consecutive T2D patients. Poor glycemic control was defined as HbA1c ≥ 7%. Patients with LJM of the hand were older and had a longer duration of diabetes, a higher prevalence of diabetic complications, including DPN and PAD, and a higher IWDGF category (all P < 0.001). Multivariate logistic regression analysis revealed that the foot risk assessed with IWDGF category was correlated with age (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.01-1.06; P = 0.001), poor glycemic control (OR 1.66; 95% CI 1.00-2.77; P = 0.04), eGFR (OR 0.98; 95% CI 0.97-0.99; P = 0.02), and the presence of LJM of the hand (OR 3.86; 95% CI 2.21-6.86; P < 0.001). The results demonstrate a correlation between LJM of the hand and foot risk. Diagnosis of diabetic hand is simple and non-invasive, and is thus a useful method for assessing the risk of diabetic foot in T2D patients. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  15. Crystal structure of the 3C protease from Southern African Territories type 2 foot-and-mouth disease virus

    PubMed Central

    Yang, Jingjie; Leen, Eoin N.; Maree, Francois F.

    2016-01-01

    The replication of foot-and-mouth disease virus (FMDV) is dependent on the virus-encoded 3C protease (3Cpro). As in other picornaviruses, 3Cpro performs most of the proteolytic processing of the polyprotein expressed from the large open reading frame in the RNA genome of the virus. Previous work revealed that the 3Cpro from serotype A—one of the seven serotypes of FMDV—adopts a trypsin-like fold. On the basis of capsid sequence comparisons the FMDV serotypes are grouped into two phylogenetic clusters, with O, A, C, and Asia 1 in one, and the three Southern African Territories serotypes, (SAT-1, SAT-2 and SAT-3) in another, a grouping pattern that is broadly, but not rigidly, reflected in 3Cpro amino acid sequences. We report here the cloning, expression and purification of 3C proteases from four SAT serotype viruses (SAT2/GHA/8/91, SAT1/NIG/5/81, SAT1/UGA/1/97, and SAT2/ZIM/7/83) and the crystal structure at 3.2 Å resolution of 3Cpro from SAT2/GHA/8/91. PMID:27168976

  16. A recombinant fusion protein and DNA vaccines against foot-and-mouth disease virus type Asia 1 infection in guinea pigs.

    PubMed

    Zhang, Q; Zhu, M W; Yang, Y Q; Shao, M; Zhang, Z Y; Lan, H Y; Yan, W Y; Wu, J J; Zheng, Z X

    2003-01-01

    On the basis of amino acid (aa) sequence of the tandem repeat 133-158-20-34-133-158 which consisted of aa 133-158 of VP1 and aa 20-34 of VP4 of Foot-and-mouth disease virus (FMDV) type Asia 1 a recombinant prokaryotic expression vector pAS1-P encoding a fusion protein and eukaryotic expression vectors pAS1-E and pAS1-EdeltaCpG-ODN representing DNA vaccines were constructed. Guinea pigs immunized with these vaccines showed both neutralizing antibody and T cell proliferation responses. FMDV challenge tests for the first time showed that the recombinant fusion protein and pAS1-E and pAS1-EdeltaCpG-ODN vaccines protected 86%, 60% and 43% of guinea pigs from FMDV type Asia1 challenge, respectively. The results also indicated that the immune response of animals treated with the vector pAS1-E containing an oligodeoxynucleotide (ODN), which consisted of immunostimulatory cytosine-phosphate-guanosine (CpG) motifs, was augmented by CpG ODN.

  17. Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo.

    PubMed

    Xu, Jinfang; Qian, Ping; Wu, Qunfeng; Liu, Shasha; Fan, Wenchun; Zhang, Keshan; Wang, Rong; Zhang, Huawei; Chen, Huanchun; Li, Xiangmin

    2014-09-01

    The interferon-induced transmembrane protein 3 (IFITM3) is a widely expressed potent antiviral effector of the host innate immune system. It restricts a diverse group of pathogenic, enveloped viruses, by interfering with endosomal fusion. In this report, the swine IFITM3 (sIFITM3) gene was cloned. It shares the functionally conserved CD225 domain and multiple critical amino acid residues (Y19, F74, F77, R86 and Y98) with its human ortholog, which are essential for antiviral activity. Ectopic expression of sIFITM3 significantly inhibited non-enveloped foot-and-mouth disease virus (FMDV) infection in BHK-21 cells. Furthermore, sIFITM3 blocked FMDV infection at early steps in the virus life cycle by disrupting viral attachment to the host cell surface. Importantly, inoculation of 2-day-old suckling mice with a plasmid expressing sIFITM3 conferred protection against lethal challenge with FMDV. These results suggest that sIFITM3 is a promising antiviral agent and that can safeguard the host from infection with FMDV. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Emergence of an exotic strain of serotype O foot-and-mouth disease virus O/ME-SA/Ind-2001d in South-East Asia in 2015.

    PubMed

    Qiu, Y; Abila, R; Rodtian, P; King, D P; Knowles, N J; Ngo, L T; Le, V T; Khounsy, S; Bounma, P; Lwin, S; Verin, B C; Widders, P

    2018-02-01

    The O/Middle East-South Asia (ME-SA)/Ind-2001 lineage of foot-and-mouth disease virus (FMDV) is endemic in the Indian subcontinent and has been reported in the Middle East and North Africa, but it had not been detected in South-East Asia (SEA) before 2015. This study reports the recent incursions of this viral lineage into SEA, which caused outbreaks in Vientiane Capital of Lao People's Democratic Republic (PDR) in April 2015, in Dak Nong, Dak Lak and Ninh Thuan Provinces of Vietnam from May to October 2015, and in Rakhine State of Myanmar in October 2015. Disease investigations were conducted during the outbreaks and followed up after laboratory results confirmed the involvement of FMDV O/ME-SA/Ind-2001 sublineage d (O/ME-SA/Ind-2001d). Affected host species included cattle, buffalo and pig, and all the outbreaks resolved within 2 months. Animals with clinical signs were separated, and affected premises were disinfected. However, strict movement restrictions were not enforced, and emergency vaccinations were only implemented in Vientiane Capital of Lao PDR and Dak Nong and Ninh Thuan Provinces of Vietnam. Clinical samples were collected from each outbreak and examined by nucleotide sequencing of the FMDV viral protein 1 coding region. Sequence analysis revealed that the O/ME-SA/Ind-2001d isolates from Lao PDR and Vietnam were closely related to each other and similar to viruses previously circulating in India in 2013. Viruses collected from Myanmar were divergent from viruses of the same sublineage recovered from Lao PDR and Vietnam but were closely related to viruses present in Bangladesh in 2015. These findings imply that at least two independent introductions of O/ME-SA/Ind-2001d into SEA have occurred. Our study highlights the transboundary nature of foot-and-mouth disease (FMD) and reinforces the importance of improved FMD surveillance and promotion of safer cross-border trade in SEA to control the risk of introduction and spread of exotic FMDV strains.

  19. [The comparison of two different types of baseline data regarding the performance of aberration detection algorithm for infectious disease outbreaks].

    PubMed

    Lai, Sheng-jie; Li, Zhong-jie; Zhang, Hong-long; Lan, Ya-jia; Yang, Wei-zhong

    2011-06-01

    To compare the performance of aberration detection algorithm for infectious disease outbreaks, based on two different types of baseline data. Cases and outbreaks of hand-foot-and-mouth disease (HFMD) reported by six provinces of China in 2009 were used as the source of data. Two types of baseline data on algorithms of C1, C2 and C3 were tested, by distinguishing the baseline data of weekdays and weekends. Time to detection (TTD) and false alarm rate (FAR) were adopted as two evaluation indices to compare the performance of 3 algorithms based on these two types of baseline data. A total of 405 460 cases of HFMD were reported by 6 provinces in 2009. On average, each county reported 1.78 cases per day during the weekdays and 1.29 cases per day during weekends, with significant difference (P < 0.01) between them. When using the baseline data without distinguish weekdays and weekends, the optimal thresholds for C1, C2 and C3 was 0.2, 0.4 and 0.6 respectively while the TTD of C1, C2 and C3 was all 1 day and the FARs were 5.33%, 4.88% and 4.50% respectively. On the contrast, when using the baseline data to distinguish the weekdays and weekends, the optimal thresholds for C1, C2 and C3 became 0.4, 0.6 and 1.0 while the TTD of C1, C2 and C3 also appeared equally as 1 day. However, the FARs became 4.81%, 4.75% and 4.16% respectively, which were lower than the baseline data from the first type. The number of HFMD cases reported in weekdays and weekends were significantly different, suggesting that when using the baseline data to distinguish weekdays and weekends, the FAR of C1, C2 and C3 algorithm could effectively reduce so as to improve the accuracy of outbreak detection.

  20. The association between gout and radiographic hand, knee and foot osteoarthritis: a cross-sectional study.

    PubMed

    Bevis, Megan; Marshall, Michelle; Rathod, Trishna; Roddy, Edward

    2016-04-16

    Gout is the most common type of inflammatory arthritis and is largely managed in primary care. It classically affects the first metatarsophalangeal joint and distal peripheral joints, whereas the axial joints are typically spared. The reason for this particular distribution is not well understood, however, it has been suggested that osteoarthritis (OA) may be the key factor. One hypothesis is that there is an association between the disease states of gout and OA as the conditions share common risk factors. The objective of this study was to determine whether there is an association between gout and radiographic osteoarthritis (OA). A cross-sectional study was nested within three observational cohorts of people aged ≥ 50 years with hand, knee and foot pain. Participants with gout were identified through primary care medical records and each matched by age and gender to four individuals without gout. The presence and severity of radiographic OA were scored using validated atlases. Conditional logistic regression models were used to examine associations between gout and the presence, frequency and severity of radiographic OA at the hand, knee and foot and adjusted for BMI, diuretic use and site of joint pain. Fifty-three people with gout were compared to 211 matched subjects without gout. No statistically significant associations were observed between gout and radiographic hand, knee or foot OA. However, individuals with gout had increased odds of having nodal hand OA (aOR 1.46; 95% CI 0.61, 3.50), ≥8 hand joints with moderate to severe OA (aOR 3.57; 95%CI 0.62, 20.45), foot OA (aOR 2.16; 95% CI 0.66, 7.06), ≥3 foot joints affected (aOR 4.00; 95% CI 0.99, 16.10) and ≥1 foot joints with severe OA (aOR 1.46; 95% CI 0.54, 3.94) but decreased odds of tibiofemoral (aOR 0.44; 95% CI 0.15, 1.29) or patellofemoral (aOR 0.70; 95% CI 0.22, 2.22) OA in either knee. There was no association between gout and radiographic OA, however, people with gout appeared to be more

  1. Characteristics of leachate in Foot and Mouth Disease Carcass Disposal using Molecular Biology Method

    NASA Astrophysics Data System (ADS)

    Choi, E. J.; Kim, B. J.; Wi, D. W.; Choi, N. C.; Lee, S. J.; Min, J. E.; Park, C. Y.

    2012-04-01

    The Leachate from Foot and Mouth Disease(FMD) carcass disposal by is one of the types of high-concentration contaminated wastewater with the greatest environmental impact. This is due to its pollutants: nitrate nitrogen (NO3--N) and pathogenic microorganisms. Satisfactory treatment of leachate is not an easy task for its high concentrations of nitrate nitrogen and pathogenic microorganisms. Therefore suitable FMD leachate treatment processes should be adopted to improve treatment performance and to reduce overall running costs. The objective of this study was to determine the leachate characteristics through environmental analysis and molecular biology method (bacteria identification and Polymerase Chain Reaction) using FMD leachate samples for optimal FMD leachate treatment processes. The Sixteen FMD leachate samples was obtained from carcass disposal regions in Korea. Results of environmental analysis showed that pH and Eh was observed from 5.57 to 7.40, -134~358mV. This data was exhibited typical early carcass disposal (Neutral pH and Reducing Environment by abundant organic matter). TOC and nitrate nitrogen high concentrations in FMD leachate showed a large variability from 2.3 to 38,730 mg/L(mean - 6,821.93mg/L) and 0.335 ~231.998mg/L(mean - 37.46mg/L), respectively. The result of bacteria identification was observed Bacillus cereus, Pseudomonas putida, Acinetobacter ursingii, Aeromonas hydrophila, Serratia liquefaciens, Brevundimonas naejangsanensis, Serratia liquefaciens, Pseudomonas fluorescens, Pseudomonas aeruginosa, Acinetobacter ursingii. The results of Polymerase Chain Reaction(PCR) using EzTaxon server data revealed Pseudoclavibacter helvolus, Pseudochrobactrum saccharolyticum, Corynebacterium callunae, Paenibacillus lautus, Paenibacillus sp., Bacillus arvi, Brevundimonas bullata, Acinetobacter ursingii, Lysinibacillus sphaericus, Bacillus pumilus, Bacillus sphaericus, Bacillus psychrodurans, Pseudomonas sp.

  2. Reduction of Salmonella enterica serovar Choleraesuis carrying large virulence plasmids after the foot and mouth disease outbreak in swine in southern Taiwan, and their independent evolution in human and pig.

    PubMed

    Tzeng, Jann-Inn; Chu, Chi-Hong; Chen, Shu-Wun; Yeh, Chia-Ming; Chiu, Chern-Hsun; Chiou, Chien-Shun; Lin, Jiunn-Horng; Chu, Chishih

    2012-12-01

    Salmonella enterica serovar Choleraesuis (S. Choleraesuis) is a highly invasive zoonotic pathogen that causes bacteremia in humans and pigs. The prevalence of S. Choleraesuis in man has gradually decreased since the outbreak of foot and mouth disease in pigs in 1997 in southern Taiwan. The goal of this study was to investigate the change in prevalence of S. Choleraesuis carrying the virulence plasmid (pSCV) in human and swine isolates collected in 1995-2005 and characterize these. 380 isolates were collected from human and swine blood samples. Large pSCVs were determined by PCR and Southern blot analysis. Antimicrobial susceptibility and resistance genes, and the phylogenetic association of these large pSCV were analyzed. The number of isolates harboring the large pSCV was significantly reduced, and their prevalence differed between human and swine isolates. These large pSCVs were a recombinant of original 50-kb pSCV and R plasmid. In addition, some large pSCVs lacked two pSCV-specific deletion regions from pef to repC and from traT to samA. These large pSCVs carried the resistance genes bla(TEM,)aadA2, and sulI, as well as class I integrons of 0.65 and/or 1.9 kb in size, but were inconjugatible. Phylogenetic analysis demonstrated that the large pSCV evolves independently in human and swine isolates. S. Choleraesuis with large pSCV was significantly reduced after the foot and mouth disease outbreak and may evolve in human and swine specific isolates. Copyright © 2011. Published by Elsevier B.V.

  3. Benefit-Cost Analysis of Foot-and-Mouth Disease Vaccination at the Farm-Level in South Vietnam.

    PubMed

    Truong, Dinh Bao; Goutard, Flavie Luce; Bertagnoli, Stéphane; Delabouglise, Alexis; Grosbois, Vladimir; Peyre, Marisa

    2018-01-01

    This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit-cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42-16.45], 9.93 (95% CI 3.45-16.47), and 3.02 (95% CI 0.76-7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.

  4. Post-traumatic stress disorder in participants of foot-and-mouth disease epidemic control in Miyazaki, Japan, in 2010.

    PubMed

    Hibi, Juri; Kurosawa, Aiko; Watanabe, Takuto; Kadowaki, Hazumu; Watari, Michiko; Makita, Kohei

    2015-08-01

    Foot-and-mouth disease (FMD) occurred in Miyazaki, Japan, in 2010, and 290,000 animals were culled. This paper describes the mental distress of the volunteers who had been dispatched to Miyazaki for disease control two years after the epidemic. It also assesses risk factors for post-traumatic stress disorder (PTSD). A participatory appraisal and self-administered questionnaire survey were conducted in 2012 for those who were dispatched to Miyazaki in 2010. The Impact of Event Scale-Revised (IES-R) was used as an indicator of PTSD, and univariate and multivariable analyses were performed. Of the 875 respondents, 1.3% had higher IES-R scores than the cut-off point (25), which is suggestive of PTSD. Mental stresses during and soon after FMD control and after two years were described. Four risk factors associated with high IES-R scores were found: transporting culled animals (P<0.01), stress during FMD control (P<0.01) and at the time of the survey (P<0.01), and lack of someone to talk to about FMD-associated stress at the time of the survey (P<0.01). Veterinarians, livestock technicians and clerical officers involved in FMD control still suffer from mental stress two years later. Public services should provide an opportunity for them to consult with mental health specialists. These findings should be used to better prepare workers who deal with infectious diseases of animals, especially when they must be culled. The establishment of a collaborative framework between veterinary and mental health services is recommended.

  5. Management of deer for experimental studies with foor-and-mouth disease virus.

    PubMed

    Gibbs, E P; McDiarmid, A; Rowe, J J

    1975-06-07

    Red, sika, fallow, roe and muntjac deer adapted to captivity in experimental units designed for working with foot-and-mouth disease. The red, sika and fallow deer readily accepted rolled oats and hay as their staple diet. This diet was replaced for the roe and muntjac deer with flaked maize, calf starter pellets and green browse. Etorphine/acepromazine ans xylazine were found to be suitable sedatives for detailed examination of the tongue and oral cavity of the various species of deer and gave adequate analgesia for the inoculation and collection of virus samples.

  6. Global foot-and-mouth disease research update and gap analysis: 1 - overview of global status and research needs

    USDA-ARS?s Scientific Manuscript database

    Few, if any, animal diseases have a greater impact than footand-mouth disease (FMD). It is highly infectious, has enormous control costs and severe impacts on trade. FMD research is performed in numerous institutions around the world. The Global FMD Research alliance (GFRA) is an international conso...

  7. Collection of Oral Fluids Using Cotton Ropes as a Sampling Method to Detect Foot-and-Mouth Disease Virus Infection in Pigs.

    PubMed

    Vosloo, W; Morris, J; Davis, A; Giles, M; Wang, J; Nguyen, H T T; Kim, P V; Quach, N V; Le, P T T; Nguyen, P H N; Dang, H; Tran, H X; Vu, P P; Hung, V V; Le, Q T; Tran, T M; Mai, T M T; Le, Q T V; Singanallur, N B

    2015-10-01

    In high-density farming practices, it is important to constantly monitor for infectious diseases, especially diseases that have the potential to spread rapidly between holdings. Pigs are known to amplify foot-and-mouth disease (FMD) by excreting large amounts of virus, and it is therefore important to detect the virus quickly and accurately to minimize the spread of disease. Ropes were used to collect oral fluid samples from pigs, and each sample was compared to saliva samples collected from individual animals by detecting FMD virus RNA using real-time PCR. Two different experiments are described where groups of pigs were infected with different serotypes of FMD virus, either with or without vaccination, and unvaccinated pigs were kept in aerosol contact. The sensitivity of the rope sampling varied between 0.67 and 0.92, and the statistical agreement between this method and individual sampling ranged from substantial to moderate for the two different serotypes. The ease of collecting oral fluids using ropes together with the high sensitivity of subsequent FMD detection through PCR indicates that this could be a useful method to monitor pig populations for FMD virus infection. With further validation of the sensitivity of detection of FMD virus RNA, this can be a cost-effective, non-invasive diagnostic tool. © 2013 Blackwell Verlag GmbH.

  8. Analysis of Recent Serotype O Foot-and-Mouth Disease Viruses from Livestock in Kenya: Evidence of Four Independently Evolving Lineages.

    PubMed

    Wekesa, S N; Muwanika, V B; Siegismund, H R; Sangula, A K; Namatovu, A; Dhikusooka, M T; Tjørnehøj, K; Balinda, S N; Wadsworth, J; Knowles, N J; Belsham, G J

    2015-06-01

    Foot-and-mouth disease (FMD) is endemic in Kenya where four serotypes (O, A, SAT 1 and SAT 2) of the virus are currently in circulation. Within 2010 and 2011, the National Laboratory recorded an increase in the number of FMD outbreaks caused by serotype O virus. The characteristics of these viruses were determined to ascertain whether these were independent outbreaks or one single strain spreading throughout the country. The sequences of the complete VP1-coding region were analysed from viruses sampled within different areas of Kenya during 2010 and 2011. The results indicated that the 2010 to 2011 outbreaks in Kenya were caused by four independent strains. By comparison with earlier type O isolates from Eastern Africa, it was apparent that the outbreaks were caused by viruses from three different lineages of topotype EA-2 and a fourth virus strain belonging to topotype EA-4. The topotypes EA-1 and EA-3 were not detected from these outbreaks. Implications of these results for FMD control in Eastern Africa are discussed. © 2013 Blackwell Verlag GmbH.

  9. A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.

    PubMed

    Lefebvre, David J; De Vleeschauwer, Annebel R; Goris, Nesya; Van Borm, Steven; Chimirri, Alba; Monforte, Anna Maria; Valdazo-Gonzalez, Begona; King, Donald P; Neyts, Johan; De Clercq, Kris

    2014-12-12

    The stamping-out policy for the control of foot-and-mouth disease virus (FMDV) in countries that are free from FMD without vaccination has a dramatic socio-economic impact, huge animal welfare issues and may result in the loss of farm animal genetic resources. As an alternative to pre-emptive culling or emergency vaccination we further explore the possibility to use antiviral drugs in the event of an FMD outbreak. In the present study, we tested the in vitro cytotoxicity and anti-FMDV activity of 1,2,4,5-tetrahydro-[1,4]thiazepino[4,5-a]benzimidazole. The molecule was shown to inhibit the replication of reference strains of the Eurasian FMDV serotypes O, A, C and Asia but not the FMDV serotypes from the South African Territories (SAT) neither a related picornavirus, i.e. swine vesicular disease virus. The molecule can be added until 2h post inoculation in a 'single replication cycle experiment' without losing its antiviral activity. The genetic characterization of progressively selected resistant FMD viruses shows that the molecule presumably interacts with the non-structural 2C protein of FMDV. Further studies are required on the use of this molecule in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Economic Impacts of Potential Foot and Mouth Disease Agro-terrorism in the United States: A Computable General Equilibrium Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oladosu, Gbadebo A; Rose, Adam; Bumsoo, Lee

    2013-01-01

    The foot and mouth disease (FMD) virus has high agro-terrorism potential because it is contagious, can be easily transmitted via inanimate objects and can be spread by wind. An outbreak of FMD in developed countries results in massive slaughtering of animals (for disease control) and disruptions in meat supply chains and trade, with potentially large economic losses. Although the United States has been FMD-free since 1929, the potential of FMD as a deliberate terrorist weapon calls for estimates of the physical and economic damage that could result from an outbreak. This paper estimates the economic impacts of three alternative scenariosmore » of potential FMD attacks using a computable general equilibrium (CGE) model of the US economy. The three scenarios range from a small outbreak successfully contained within a state to a large multi-state attack resulting in slaughtering of 30 percent of the national livestock. Overall, the value of total output losses in our simulations range between $37 billion (0.15% of 2006 baseline economic output) and $228 billion (0.92%). Major impacts stem from the supply constraint on livestock due to massive animal slaughtering. As expected, the economic losses are heavily concentrated in agriculture and food manufacturing sectors, with losses ranging from $23 billion to $61 billion in the two industries.« less

  11. Virus-like particle-based vaccine against coxsackievirus A6 protects mice against lethal infections.

    PubMed

    Shen, Chaoyun; Ku, Zhiqiang; Zhou, Yu; Li, Dapeng; Wang, Lili; Lan, Ke; Liu, Qingwei; Huang, Zhong

    2016-07-25

    Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD. Mice immunized with these VLPs produced CA6-specific serum antibodies. Passive transfer of antisera from CA6 VLP-immunized mice protected recipient mice from lethal infections caused by homologous and heterologous CA6 strains. Moreover, active immunization of mice with CA6 VLPs efficiently conferred protection against both homologous and heterologous CA6 infections. These results suggested that CA6 VLP-based recombinant vaccine is a promising candidate vaccine for preventing CA6 infection and can be incorporated into a multivalent HFMD vaccine formulation to achieve broad-spectrum and effective prevention of this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Characterization of Foot-and-Mouth Disease Viruses Collected in Nigeria Between 2007 and 2014: Evidence for Epidemiological Links Between West and East Africa.

    PubMed

    Ularamu, H G; Ibu, J O; Wood, B A; Abenga, J N; Lazarus, D D; Wungak, Y S; Knowles, N J; Wadsworth, J; Mioulet, V; King, D P; Shamaki, D; Adah, M I

    2017-12-01

    This study describes the molecular characterization of 47 foot-and-mouth disease (FMD) viruses recovered from field outbreaks in Nigeria between 2007 and 2014. Antigen ELISA of viral isolates was used to identify FMD virus serotypes O, A and SAT 2. Phylogenetic analyses of VP1 nucleotide sequences provide evidence for the presence of multiple sublineages of serotype SAT 2, and O/EAST AFRICA 3 (EA-3) and O/WEST AFRICA topotypes in the country. In contrast, for serotype A, a single monophyletic cluster of viruses has persisted within Nigeria (2009-2013). These results demonstrate the close genetic relatedness of viruses in Nigeria to those from other African countries, including the first formal characterization of serotype O/EA-3 viruses in Nigeria. The introductions and persistence of certain viral lineages in Nigeria may reflect transmission patterns via nomadic pastoralism and animal trade. Continuous monitoring of field outbreaks is necessary to dissect the complexity of FMD epidemiology in sub-Saharan Africa. © 2016 Blackwell Verlag GmbH.

  13. Benefit-Cost Analysis of Foot and Mouth Disease Control in Large Ruminants in Cambodia.

    PubMed

    Young, J R; Suon, S; Rast, L; Nampanya, S; Windsor, P A; Bush, R D

    2016-10-01

    Foot and mouth disease (FMD) is endemic in Cambodia and throughout the Greater Mekong Subregion and causes significant losses to rural smallholders owning the majority of the national large ruminant population. However, due to underreporting, paucity of knowledge of FMD impacts, limited veterinary capacity and deficits of data available for analysis, the quantifiable benefits of a national FMD control programme are unknown. To address this deficit, existing literature and research data from the 'Best practice health and husbandry of cattle, Cambodia' project conducted between 2007 and 2012, were used to develop a three-phase analysis framework to: assess the impacts of the recent widespread FMD epizootic in Cambodia in 2010, conduct a value chain analysis of the large ruminant market and estimate the costs and benefits for a national large ruminant biannual FMD vaccination programme. A trader survey conducted in 2010-2011 provided cattle and buffalo value chain information and was matched to village herd structure data to calculate a total large ruminant farm-gate value of USD 1.271 billion in 2010. Monte Carlo simulation modelling that implemented a 5-year biannual vaccination programme at a cost of USD 6.3 an animal per year identified a benefit-cost ratio of 1.40 (95% CI 0.96-2.20) when accounting for recent prices of cattle and buffalo in Cambodia and based on an expected annual incidence of 0.2 (assuming one major epizootic in the 5-year vaccination programme). Given that the majority of the large ruminants are owned by rural smallholders, and mostly the poor are involved in agricultural employment, the successful implementation of an FMD control programme in Cambodia would be expected to avoid estimated losses of USD 135 million; equivalent to 10.6% of the 2010 farm-gate value and contributing to important reductions in rural poverty and food insecurity. © 2014 Blackwell Verlag GmbH.

  14. Xenoepitope substitution avoids deceptive imprinting and broadens the immune response to foot-and-mouth disease virus.

    PubMed

    Szczepanek, Steven M; Barrette, Roger W; Rood, Debra; Alejo, Diana; Silbart, Lawrence K

    2012-04-01

    Many RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as "decoy epitopes," which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined "B cell xenoepitope" from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines.

  15. Financial Impact of Foot-and-mouth disease outbreaks on pig farms in the Republic of Korea, 2014/2015.

    PubMed

    Yoon, Hachung; Jeong, Wooseog; Han, Jun-Hee; Choi, Jida; Kang, Yong-Myung; Kim, Yong-Sang; Park, Hong-Sig; Carpenter, Tim E

    2018-01-01

    The financial impact of foot-and-mouth disease (FMD) that occurred in 180 piggeries (100 farrow-to-finish and 80 fattening farms) confirmed infected during the 2014/2015 epidemic in the Republic of Korea was estimated at the farm level. The median loss due to slaughtering of pigs prior to their expected market weights was US$ 71.8 (uncovered compensation-compensation loss) plus US$ 57.3 (foregone net gain) per pig. Median loss per farm was US$ 27,487 (55.6% of total loss) for compensation and US$ 15,925 (44.4%) for foregone net gain. The total loss per farm (median, 25th-75th percentile) was US$ 43,822 (9,767-115,893), which represented 49.4% (11.5-112.8) of the annual net gain of pig farms. The total financial loss in 180 FMD outbreak pig farms was US$ 25.2 million, which was nearly one-half of the control cost (US$ 58.3 million) spent by the Korean government on this epidemic. The findings in this study should help planning to help reduce the impact at the farm level in the Republic of Korea in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. 2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study.

    PubMed

    Wei, Mingwei; Meng, Fanyue; Wang, Shiyuan; Li, Jingxin; Zhang, Yuntao; Mao, Qunying; Hu, Yuemei; Liu, Pei; Shi, Nianmin; Tao, Hong; Chu, Kai; Wang, Yuxiao; Liang, Zhenglun; Li, Xiuling; Zhu, Fengcai

    2017-01-01

     This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine.  In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years.  Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P < .0001), and the vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P < .0001). Geometric mean titers of neutralizing antibody in participants remained high during the 2-year follow-up period, and no vaccine-related serious adverse events were recorded.  Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children.  NCT01508247. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. The Kinase STK3 Interacts with the Viral Structural Protein VP1 and Inhibits Foot-and-Mouth Disease Virus Replication

    PubMed Central

    Xue, Qiao

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects domestic and wild cloven-hoofed animals. The structural protein VP1 plays an important role in FMDV pathogenesis. However, the interacting partners of VP1 in host cells and the effects of these interactions in FMDV replication remain incompletely elucidated. Here, we identified a porcine cell protein, serine/threonine kinase 3 (STK3), which interacts with FMDV VP1 using the yeast two-hybrid system. The VP1-STK3 interaction was further confirmed by coimmunoprecipitation experiments in human embryonic kidney 293T and porcine kidney 15 (PK-15) cells. The carboxyl-terminal region (amino acids 180–214) of VP1 was essential for its interaction with STK3. The effects of overexpression and underexpressing of STK3 in PK-15 cells were assessed, and the results indicated that STK3 significantly inhibited FMDV replication. Our data expand the role of STK3 during viral infection, provide new information regarding the host cell kinases that are involved in viral replication, and identify potential targets for future antiviral strategies. PMID:29226127

  18. Development of anti-bovine IgA single chain variable fragment and its application in diagnosis of foot-and-mouth disease

    PubMed Central

    Sridevi, N. V.; Shukra, A. M.; Neelakantam, B.; Anilkumar, J.; Madhanmohan, M.; Rajan, S.; Dev Chandran

    2014-01-01

    Recombinant antibody fragments like single chain variable fragments (scFvs) represent an attractive yet powerful alternative to immunoglobulins and hold great potential in the development of clinical diagnostic/therapeutic reagents. Structurally, scFvs are the smallest antibody fragments capable of retaining the antigen-binding capacity of whole antibodies and are composed of an immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a flexible polypeptide linker. In the present study, we constructed a scFv against bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody against bovine IgA using recombinant DNA technology. The scFv was expressed in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC). The binding activity and specificity of the scFv was established by its non-reactivity toward other classes of immunoglobulins as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement of the scFv indicated that the recombinant antibody fragment had an affinity in picomolar range toward purified IgA. Furthermore, the scFv was used to develop a sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier animals. PMID:24678404

  19. Using exceedance probabilities to detect anomalies in routinely recorded animal health data, with particular reference to foot-and-mouth disease in Viet Nam.

    PubMed

    Richards, K K; Hazelton, M L; Stevenson, M A; Lockhart, C Y; Pinto, J; Nguyen, L

    2014-10-01

    The widespread availability of computer hardware and software for recording and storing disease event information means that, in theory, we have the necessary information to carry out detailed analyses of factors influencing the spatial distribution of disease in animal populations. However, the reliability of such analyses depends on data quality, with anomalous records having the potential to introduce significant bias and lead to inappropriate decision making. In this paper we promote the use of exceedance probabilities as a tool for detecting anomalies when applying hierarchical spatio-temporal models to animal health data. We illustrate this methodology through a case study data on outbreaks of foot-and-mouth disease (FMD) in Viet Nam for the period 2006-2008. A flexible binomial logistic regression was employed to model the number of FMD infected communes within each province of the country. Standard analyses of the residuals from this model failed to identify problems, but exceedance probabilities identified provinces in which the number of reported FMD outbreaks was unexpectedly low. This finding is interesting given that these provinces are on major cattle movement pathways through Viet Nam. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Estimation of contamination sources of human enteroviruses in a wastewater treatment and reclamation system by PCR-DGGE.

    PubMed

    Ji, Zheng; Wang, Xiaochang C; Xu, Limei; Zhang, Chongmiao; Funamizu, Naoyuki; Okabe, Satoshi; Sano, Daisuke

    2014-06-01

    A polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) method was employed to estimate the contamination sources of human enteroviruses and understand how their dominant strains vary in a wastewater treatment and reclamation system consisting of sewage collection, wastewater treatment with membrane bioreactor and open lakes for reclaimed water storage and reuse. After PCR-DGGE using a selected primer set targeting enteroviruses, phylogenetic analysis of acquired enterovirus gene sequences was performed. Enteroviruses identified from the septic tank were much more diverse than those from grey water and kitchen wastewater. Several unique types of enterovirus different from those in wastewater samples were dominant in a biological wastewater treatment unit. Membrane filtration followed by chlorination was proved effective for physically eliminating enteroviruses; however, secondary contamination likely occurred as the reclaimed water was stored in artificial lakes. Enterovirus 71 (EV71), a hand-foot-and-mouth disease (HFMD) viral pathogen, was detected mainly from the artificial lakes, implying that wastewater effluent was not the contamination source of EV71 and that there were unidentified non-point sources of the contamination with the HFMD viral pathogen in the reclaimed water stored in the artificial lakes. The PCR-DGGE targeting enteroviruses provided robust evidence about viral contamination sources in the wastewater treatment and reclamation system.

  1. The destination defines the journey: an examination of the kinematics of hand-to-mouth movements

    PubMed Central

    Gonzalez, Claudia L. R.

    2016-01-01

    Long-train electrical stimulation of the motor and premotor cortices of nonhuman primates can produce either hand-to-mouth or grasp-to-inspect movements, depending on the precise location of stimulation. Furthermore, single-neuron recording studies identify discrete neuronal populations in the inferior parietal and ventral premotor cortices that respond uniquely to either grasp-to-eat or grasp-to-place movements, despite their identical mechanistic requirements. These studies demonstrate that the macaque motor cortex is organized around producing functional, goal-oriented movements, rather than simply fulfilling muscular prerequisites of action. In humans, right-handed hand-to-mouth movements have a unique kinematic signature; smaller maximum grip apertures are produced when grasping to eat than when grasping to place identical targets. This is evidence that the motor cortex in humans is also organized around producing functional movements. However, in both macaques and humans, grasp-to-eat/hand-to-mouth movements have always been elicited using edible targets and have (necessarily) been paired with mouth movement. It is therefore unknown whether the kinematic distinction is a natural result of grasping food and/or is simply attributable to concurrent opening of the mouth while grasping. In experiment 1, we used goal-differentiated grasping tasks, directed toward edible and inedible targets, to show that the unique kinematic signature is present even with inedible targets. In experiment 2, we used the same goal-differentiated grasping tasks, either coupled with or divorced from an open-mouth movement, to show that the signature is not attributable merely to a planned opening of the mouth during the grasp. These results are discussed in relation to the role of hand-to-mouth movements in human development, independently of grasp-to-eat behavior. PMID:27512020

  2. Genetic and antigenic analysis of foot-and-mouth disease virus serotype O responsible for outbreaks in India during 2013.

    PubMed

    Subramaniam, Saravanan; Mohapatra, Jajati K; Das, Biswajit; Sanyal, Aniket; Pattnaik, Bramhadev

    2015-03-01

    In recent times, majority of the foot-and-mouth disease (FMD) outbreaks in India are caused by serotype O Ind2001 lineage. The lineage has diverged into four sub-lineages (Ind2001a, b, c and d). We report here the genetic and antigenic analyses of nine Ind2001d isolates that caused outbreaks during April 2013-March 2014 in India. The length of the genomes of outbreak viruses varied between 8153 and 8181 nucleotides without any insertion or deletion in the coding region. Of the nine isolates analyzed antigenically against the currently used Indian vaccine strain INDR2/1975, eight showed good cross serological match (>0.3) indicating optimal antigenic coverage by the vaccine strain. An unprecedented deletion of 22 nucleotides between position 57 and 78 was observed in the 3' untranslated region of one of the isolates without compromising the virus viability, which imply that partial distortion in SL2 of 3'UTR may not have influence on virus viability at least under in-vitro conditions. Recently the Ind2001 lineage has been reported from several countries including Libya and spread of this lineage across a wide geographical area needs to be monitored carefully to avoid any future pandemic. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Adenovirus-vectored foot-and-mouth disease vaccine confers early and full protection against FMDV O1 Manisa in swine.

    PubMed

    Fernandez-Sainz, Ignacio; Medina, Gisselle N; Ramirez-Medina, Elizabeth; Koster, Marla J; Grubman, Marvin J; de Los Santos, Teresa

    2017-02-01

    A human adenovirus (Ad5) vectored foot-and-mouth disease virus (FMDV) O1-Manisa subunit vaccine (Ad5-O1Man) was engineered to deliver FMDV O1-Manisa capsid and capsid-processing proteins. Swine inoculated with Ad5-O1Man developed an FMDV-specific humoral response as compared to animals inoculated with an empty Ad5-vector. Vaccinated animals were completely protected against homologous challenge at 7 or 21 days post-vaccination. Potency studies exhibited a PD50 of about 10 7 pfu/animal while a dose of 4×10 7 pfu/animal fully protected swine against FMDV intradermal challenge. In-vitro cross-neutralization analysis distinctly predicted that swine vaccinated with Ad5-O1Man would be protected against challenge with homologous FMDV O1Man Middle East-South Asia (ME-SA) topotype and also against recent outbreak strains of Mya-98 South East Asia (SEA) lineage including O1-UK-2001 and O1-South Korea-2010. These results indicate that recombinant Ad5-O1Man is an effective, safe and cross-reacting vaccine that could potentially be used preventively and in outbreak situations, to control FMDV O Mya-98 lineage in swine. Published by Elsevier Inc.

  4. Validation of a short questionnaire to measure symptoms and functional limitations associated with hand-foot syndrome and mucositis in patients with metastatic renal cell carcinoma.

    PubMed

    Lai, Jin-Shei; Beaumont, Jennifer L; Diaz, Jose; Khan, Sadya; Cella, David

    2016-01-15

    Hand-foot syndrome and mucositis/stomatitis are frequent adverse events (AEs) of treatment with tyrosine kinase inhibitors in cancer therapy. Quality-of-life instruments that measure the functional consequences of these AEs are needed to assess the impact of therapeutic interventions and to guide patient care. The Hand-Foot and Mucositis Symptom and Impact Questionnaire (HAMSIQ [formerly the Supplementary Quality of Life Questionnaire]) was used in the COMPARZ trial (Pazopanib vs Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma [national clinical trial no. NCT00720941]) and the PISCES study (Patient Preference Study of Pazopanib vs Sunitinib in Advanced or Metastatic Kidney Cancer [clinicaltrials.gov NCT01064310]) to assess mouth/throat and hand/foot soreness symptoms and subsequent limitations in patients receiving pazopanib or sunitinib for metastatic renal cell carcinoma. The objective of the current analysis was to validate the HAMSIQ using data from the PISCES study. The HAMSIQ was administered in the PISCES study at baseline and every 2 weeks over two 10-week periods to patients who were receiving pazopanib or sunitinib. Data from the first 10-week period were used to assess the feasibility, validity, and responsiveness of the HAMSIQ. In total, ≥85% of 169 patients completed the HAMSIQ (excluding the item concerning days off work). Correlations among items within the same limitation subscale generally were high (Cronbach α ≥ .80). HAMSIQ limitation scores differentiated patients according to their baseline performance status and severity of soreness. Small-to-moderate correlations were observed for the symptoms/limitation scores and for changes from baseline scores between the HAMSIQ and the Functional Assessment of Chronic Illness Therapy fatigue survey. The HAMSIQ demonstrated responsiveness to changes in clinical status and the development of hand-foot syndrome AEs over time. The HAMSIQ is a feasible, valid

  5. Foot-and-Mouth Disease Virus Can Induce a Specific and Rapid CD4+ T-Cell-Independent Neutralizing and Isotype Class-Switched Antibody Response in Naïve Cattle▿ †

    PubMed Central

    Juleff, Nicholas; Windsor, Miriam; Lefevre, Eric A.; Gubbins, Simon; Hamblin, Pip; Reid, Elizabeth; McLaughlin, Kerry; Beverley, Peter C. L.; Morrison, Ivan W.; Charleston, Bryan

    2009-01-01

    The role of T-lymphocyte subsets in recovery from foot-and-mouth disease virus (FMDV) infection in calves was investigated by administering subset-specific monoclonal antibodies. The depletion of circulating CD4+ or WC1+ γδ T cells was achieved for a period extending from before challenge to after resolution of viremia and peak clinical signs, whereas CD8+ cell depletion was only partial. The depletion of CD4+ cells was also confirmed by analysis of lymph node biopsy specimens 5 days postchallenge. Depletion with anti-WC1 and anti-CD8 antibodies had no effect on the kinetics of infection, clinical signs, and immune responses following FMDV infection. Three of the four CD4+ T-cell-depleted calves failed to generate an antibody response to the nonstructural polyprotein 3ABC but generated a neutralizing antibody response similar to that in the controls, including rapid isotype switching to immunoglobulin G antibody. We conclude that antibody responses to sites on the surface of the virus capsid are T cell independent, whereas those directed against the nonstructural proteins are T cell dependent. CD4 depletion was found to substantially inhibit antibody responses to the G-H peptide loop VP1135-156 on the viral capsid, indicating that responses to this particular site, which has a more mobile structure than other neutralizing sites on the virus capsid, are T cell dependent. The depletion of CD4+ T cells had no adverse effect on the magnitude or duration of clinical signs or clearance of virus from the circulation. Overall, we conclude that CD4+ T-cell-independent antibody responses play a major role in the resolution of foot-and-mouth disease in cattle. PMID:19176618

  6. Initial experience with visualizing hand and foot tendons by dual-energy computed tomography.

    PubMed

    Deng, Kai; Sun, Cong; Liu, Cheng; Ma, Rui

    2009-01-01

    To assess the feasibility of visualizing hand and foot tendons by dual-energy computed tomography (CT). Twenty patients who suffered from hand or feet pains were scanned on dual-source CT (Definition, Forchheim, Germany) with dual-energy mode at tube voltages of 140 and 80 kV and a corresponding ratio of 1:4 between tube currents. The reconstructed images were postprocessed by volume rendering techniques (VRT) and multiplanar reconstruction (MPR). All of the suspected lesions were confirmed by surgery or follow-up studies. Twelve patients (total of 24 hands and feet, respectively) were found to be normal and the other eight patients (total of nine hands and feet, respectively) were found abnormal. Dual-energy techniques are very useful in visualizing tendons of the hands and feet, such as flexor pollicis longus tendon, flexor digitorum superficialis/profundus tendon, Achilles tendon, extensor hallucis longus tendon, and extensor digitorum longus tendon, etc. It can depict the whole shape of the tendons and their fixation points clearly. Peroneus longus tendon in the sole of the foot was not displayed very well. The distal ends of metacarpophalangeal joints with extensor digitoium tendon and extensor pollicis longus tendon were poorly shown. The lesions of tendons such as the circuitry, thickening, and adherence were also shown clearly. Dual-energy CT offers a new method to visualize tendons of the hand and foot. It could clearly display both anatomical structures and pathologic changes of hand and foot tendons.

  7. Evaluation of the solid phase competition ELISA for detecting antibodies against the six foot-and-mouth disease virus non-O serotypes.

    PubMed

    Li, Yanmin; Swabey, Kate G; Gibson, Debi; Keel, Phil J; Hamblin, Pip; Wilsden, Ginette; Corteyn, Mandy; Ferris, Nigel P

    2012-08-01

    The solid-phase competition ELISA (SPCE) has been evaluated in both screening and titration assay formats for detecting antibodies against foot-and-mouth disease virus (FMDV) for the six non-O serotypes A, C, SAT 1, SAT 2, SAT 3 and Asia 1. Cut-off values were determined as a percentage inhibition of 40 for the SAT serotypes and 50 for serotypes A, C and Asia 1, which gave rise to specificity values ranging from 99.41% to 99.9% for the different serotypes. The relative sensitivity between the SPCE and LPBE/virus neutralisation test was 100%/109%. Antiserum titres derived by the SPCE for samples of serotypes O, A(22) and Asia 1 were more than 11, 1 and 5 times of those determined by virus neutralisation test, respectively. This study indicated that the non-type O SPCEs have sufficient sensitivities and specificities for use as serological diagnostic tests for the qualitative and quantitative detection of antibodies against FMDV. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses.

    PubMed

    De Colibus, Luigi; Wang, Xiangxi; Tijsma, Aloys; Neyts, Johan; Spyrou, John A B; Ren, Jingshan; Grimes, Jonathan M; Puerstinger, Gerhard; Leyssen, Pieter; Fry, Elizabeth E; Rao, Zihe; Stuart, David I

    2015-10-01

    The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity.

  9. Multiple introductions of serotype O foot-and-mouth disease viruses into East Asia in 2010-2011.

    PubMed

    Valdazo-González, Begoña; Timina, Anna; Scherbakov, Alexey; Abdul-Hamid, Nor Faizah; Knowles, Nick J; King, Donald P

    2013-09-05

    Foot-and-mouth disease virus (FMDV) is a highly contagious and genetically variable virus. Sporadic introductions of this virus into FMD-free countries may cause outbreaks with devastating consequences. In 2010 and 2011, incursions of the FMDV O/SEA/Mya-98 strain, normally restricted to countries in mainland Southeast Asia, caused extensive outbreaks across East Asia. In this study, 12 full genome FMDV sequences for representative samples collected from the People's Republic of China (PR China) including the Hong Kong Special Administrative Region (SAR), the Republic of Korea, the Democratic People's Republic of Korea, Japan, Mongolia and The Russian Federation were generated and compared with additional contemporary sequences from viruses within this lineage. These complete genomes were 8119 to 8193 nucleotides in length and differed at 1181 sites, sharing a nucleotide identity ≥ 91.0% and an amino acid identity ≥ 96.6%. An unexpected deletion of 70 nucleotides within the 5'-untranslated region which resulted in a shorter predicted RNA stem-loop for the S-fragment was revealed in two sequences from PR China and Hong Kong SAR and five additional related samples from the region. Statistical parsimony and Bayesian phylogenetic analysis provide evidence that these outbreaks in East Asia were generated by two independent introductions of the O/SEA/Mya-98 lineage sometime between August 2008 and March 2010. The rapid emergence of these viruses from Southeast Asia highlights the importance of adopting approaches to closely monitor the spread of this lineage that now poses a threat to livestock industries in other regions.

  10. Application of the thermofluor PaSTRy technique for improving foot-and-mouth disease virus vaccine formulation.

    PubMed

    Kotecha, Abhay; Zhang, Fuquan; Juleff, Nicholas; Jackson, Terry; Perez, Eva; Stuart, Dave; Fry, Elizabeth; Charleston, Bryan; Seago, Julian

    2016-07-01

    Foot-and-mouth disease (FMD) has a major economic impact throughout the world and is a considerable threat to food security. Current FMD virus (FMDV) vaccines are made from chemically inactivated virus and need to contain intact viral capsids to maximize efficacy. FMDV exists as seven serotypes, each made up by a number of constantly evolving subtypes. A lack of immunological cross-reactivity between serotypes and between some strains within a serotype greatly complicates efforts to control FMD by vaccination. Thus, vaccines for one serotype do not afford protection against the others, and multiple-serotype-specific vaccines are required for effective control. The FMDV serotypes exhibit variation in their thermostability, and the capsids of inactivated preparations of the O, C and SAT serotypes are particularly susceptible to dissociation at elevated temperature. Methods to quantify capsid stability are currently limited, lack sensitivity and cannot accurately reflect differences in thermostability. Thus, new, more sensitive approaches to quantify capsid stability would be of great value for the production of more stable vaccines and to assess the effect of production conditions on vaccine preparations. Here we have investigated the application of a novel methodology (termed PaSTRy) that utilizes an RNA-binding fluorescent dye and a quantitative (q)PCR machine to monitor viral genome release and hence dissociation of the FMDV capsid during a slow incremental increase in temperature. PaSTRy was used to characterize capsid stability of all FMDV serotypes. Furthermore, we have used this approach to identify stabilizing factors for the most labile FMDV serotypes.

  11. Application of the thermofluor PaSTRy technique for improving foot-and-mouth disease virus vaccine formulation

    PubMed Central

    Kotecha, Abhay; Zhang, Fuquan; Juleff, Nicholas; Jackson, Terry; Perez, Eva; Stuart, Dave; Fry, Elizabeth; Charleston, Bryan

    2016-01-01

    Foot-and-mouth disease (FMD) has a major economic impact throughout the world and is a considerable threat to food security. Current FMD virus (FMDV) vaccines are made from chemically inactivated virus and need to contain intact viral capsids to maximize efficacy. FMDV exists as seven serotypes, each made up by a number of constantly evolving subtypes. A lack of immunological cross-reactivity between serotypes and between some strains within a serotype greatly complicates efforts to control FMD by vaccination. Thus, vaccines for one serotype do not afford protection against the others, and multiple-serotype-specific vaccines are required for effective control. The FMDV serotypes exhibit variation in their thermostability, and the capsids of inactivated preparations of the O, C and SAT serotypes are particularly susceptible to dissociation at elevated temperature. Methods to quantify capsid stability are currently limited, lack sensitivity and cannot accurately reflect differences in thermostability. Thus, new, more sensitive approaches to quantify capsid stability would be of great value for the production of more stable vaccines and to assess the effect of production conditions on vaccine preparations. Here we have investigated the application of a novel methodology (termed PaSTRy) that utilizes an RNA-binding fluorescent dye and a quantitative (q)PCR machine to monitor viral genome release and hence dissociation of the FMDV capsid during a slow incremental increase in temperature. PaSTRy was used to characterize capsid stability of all FMDV serotypes. Furthermore, we have used this approach to identify stabilizing factors for the most labile FMDV serotypes. PMID:27002540

  12. Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

    DOE PAGES

    Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan; ...

    2016-12-15

    Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genomemore » detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle.« less

  13. Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

    PubMed Central

    Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan; Singh, Karam Pal; Stenfeldt, Carolina; Rodriguez, Luis L.; Pattnaik, Bramhadev; Arzt, Jonathan

    2016-01-01

    Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genome detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle. PMID:27977708

  14. Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ranjan, Rajeev; Biswal, Jitendra K.; Subramaniam, Saravanan

    Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease of cloven-hoofed animals, including domestic and wild host species. During recent FMD outbreaks in India, spontaneous abortions were reported amongst FMD-affected and asymptomatic cows. The current study was an opportunistic investigation of these naturally occurring bovine abortions to assess causality of abortion and vertical transmission of FMDV from infected cows to fetuses. For this purpose, fetal tissue samples of eight abortuses (heart, liver, kidney, spleen, palatine tonsil, umbilical cord, soft palate, tongue, lungs, and submandibular lymph node) were collected and screened by various detection methods, including viral genomemore » detection, virus isolation, and immunomicroscopy. Amongst these cases, gross pathological changes were observed in 3 abortuses. Gross pathological findings included blood-tinged peritoneal and pleural effusions and myocarditis. Hearts of infected calves had mild to moderate degeneration and necrosis of the myocardium with moderate infiltration by mixed inflammatory cells. Localization of FMDV antigen was demonstrated in lungs and soft palate by immunomicroscopy. FMDV serotype O viral genome was recovered from 7 of 8 cases. Infectious FMDV serotype O was rescued by chemical transfection of the total RNA extracted from three soft palate samples and was sequenced to confirm 100% identity of the VP1 (capsid) coding region with isolates collected from infected cattle during the acute phase of infection. Based upon these findings, it may be concluded that FMDV-associated abortion occurred among the infected pregnant cows included within this study and FMDV was subsequently transmitted vertically to fetuses. This is the first documentation of FMDV-associated abortions in cattle.« less

  15. Comparison of immune responses to different foot-and-mouth disease genetically engineered vaccines in guinea pigs.

    PubMed

    Yao, Qingxia; Qian, Ping; Huang, Qinfeng; Cao, Yi; Chen, Huanchun

    2008-01-01

    The P12A3C gene from FMDV (serotype O) encoding the capsid precursor protein, and the highly immunogenic gene FHG, which encodes multiple epitopes of FMDV capsid proteins, were inserted into eukaryotic expression vectors to compare different candidate genetically engineered vaccines for foot-and-mouth disease (FMD). A modified live pseudorabies virus (MLPRV) was also used to deliver P12A3C. Guinea pigs were inoculated intramuscularly with the candidate vaccines to compare the ability to elicit immunity of the DNA vector and a live viral vector. An indirect enzyme-linked immunosorbent assay (iELISA), virus-neutralization test and lymphoproliferation assay were used to detect antibody and cellular responses. The group immunized with P12A3C delivered by MLPRV produced significantly greater antibody and cellular responses indicating that MLPRV has a greater ability to mediate exogenous gene delivery than the plasmid DNA vector. Comparison of the immune responses induced by P12A3C and FHG, which were both mediated by DNA plasmids, showed that FHG and P12A3C elicited similar cellular responses, while P12A3C induced higher antibody levels, suggesting that P12A3C is a more powerful immunogen than FHG. In challenge experiments, guinea pigs vaccinated with P12A3C delivered by MLPRV were protected fully from FMDV challenge, whereas guinea pigs vaccinated with P12A3C or FHG delivered by DNA plasmid were only protected partially. This study provides a basis for future construction of a genetically engineered vaccine for FMDV.

  16. Thermal inactivation of foot-and-mouth disease virus in milk using high-temperature, short-time pasteurization.

    PubMed

    Tomasula, P M; Kozempel, M F; Konstance, R P; Gregg, D; Boettcher, S; Baxt, B; Rodriguez, L L

    2007-07-01

    Previous studies of laboratory simulation of high temperature, short time pasteurization (HTST) to eliminate foot-and-mouth disease virus (FMDV) in milk have shown that the virus is not completely inactivated at the legal pasteurization minimum (71.7 degrees C/15 s) but is inactivated in a flow apparatus at 148 degrees C with holding times of 2 to 3 s. It was the intent of this study to determine whether HTST pasteurization conducted in a continuous-flow pasteurizer that simulates commercial operation would enhance FMDV inactivation in milk. Cows were inoculated in the mammary gland with the field strain of FMDV (01/UK). Infected raw whole milk and 2% milk were then pasteurized using an Arm-field pilot-scale, continuous-flow HTST pasteurizer equipped with a plate-and-frame heat exchanger and a holding tube. The milk samples, containing FMDV at levels of up to 10(4) plaque-forming units/mL, were pasteurized at temperatures ranging from 72 to 95 degrees C at holding times of either 18.6 or 36 s. Pasteurization decreased virus infectivity by 4 log10 to undetectable levels in tissue culture. However, residual infectivity was still detectable for selected pasteurized milk samples, as shown by intramuscular and intradermal inoculation of milk into naïve steers. Although HTST pasteurization did not completely inactivate viral infectivity in whole and 2% milk, possibly because a fraction of the virus was protected by the milk fat and the casein proteins, it greatly reduced the risk of natural transmission of FMDV by milk.

  17. The epidemiological characteristics of the 2007 foot-and-mouth disease epidemic in Sarpang and Zhemgang districts of Bhutan.

    PubMed

    Dukpa, K; Robertson, I D; Ellis, T M

    2011-02-01

    This study was undertaken to compare the epidemiological characteristics of the 2007 foot-and-mouth disease outbreak in two districts of Sarpang and Zhemgang in Bhutan. Zhemgang district recorded a significantly higher cumulative incidence in all species (26.9%) as well as for cattle (29.3%) compared to Sarpang (6.5% and 7.4%, respectively). The case fatality for cattle in Zhemgang (14.1%) was significantly higher than in Sarpang (3.3%). A total of 404 cattle and 73 pigs died of FMD in Zhemgang, whereas only 21 cattle died in Sarpang. Although all four species were affected in Sarpang, no sheep or goats were affected in Zhemgang. Spatiotemporal analyses showed the existence of four significant clusters, a primary one in Sarpang and three secondary clusters in Zhemgang. The virus belonged to the PanAsia strain of the Middle-East South-Asia topotype (O serotype), and the strain was closely related to the PanAsia strain that circulated in Bhutan during the 2003/2004 outbreaks. The severity of FMD infection in Zhemgang district could be attributed to low vaccination coverage (36.5% in 2006 when compared to 87.6% in Sarpang), inadequate biosecurity, poor nursing care of the sick animals and delayed reporting to the livestock centre. This study highlights the ability of the PanAsia strain of the O serotype to cause unprecedented morbidity and mortality, especially in a naïve population. The study also highlights the benefits of maintaining good herd immunity in the susceptible population, through adequate vaccination coverage, to minimize the severity of infection and limit the spread of disease from infected to non-infected herds. © 2010 Blackwell Verlag GmbH.

  18. Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics

    PubMed Central

    2012-01-01

    Background Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East–South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance. Results The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes. Conclusions Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus

  19. A Soft Casting Technique for Managing Pediatric Hand and Foot Burns.

    PubMed

    Choi, Young Mee; Nederveld, Cindy; Campbell, Kristen; Moulton, Steven

    2018-04-04

    Hand and foot burns in children are difficult to dress. The authors have developed a soft casting technique to manage burns to these areas. The aim of this study is to report the outcomes using weekly dressing changes with a soft casting technique to manage pediatric hand and foot burns in the outpatient setting. A retrospective chart review was performed on children with burns to the hands or feet, who underwent dressing changes with a soft casting technique at the Children's Hospital Colorado Burn Center. Soft casting was performed by placing antibiotic ointment-impregnated nonadherent gauze over the burn wound(s), wrapping the extremity using rolled gauze, applying soft cast pad, plaster, soft cast tape, and an elastic bandage. This was changed weekly. Two hundred ninety-eight children with hand burns had a mean age of 16.8 ± 2 months. Two hundred forty-eight children had partial thickness burn injuries (83%), 50 had full thickness burn injuries (17%), and the mean total body surface area (TBSA) was 1 ± 2.4%. The mean time to heal was 10.1 ± 1.7 days for all subjects. Sixty-six children with foot burns were identified with a mean age of 24 ± 2.6 months. Forty-six children had partial thickness injuries (70%), 20 had full thickness burn injuries (30%), and the mean TBSA was 2.3 ± 2.9%. The mean time to heal was 14.1 ± 2.2 days for all subjects. Weekly dressing changes using a soft casting technique are effective for the outpatient management of pediatric hand and foot burns. This method avoids costly inpatient hospital care, reduces the number of painful dressing changes, and allows children to heal in their own environment.

  20. The rescue and evaluation of FLAG and HIS epitope-tagged Asia 1 type foot-and-mouth disease viruses.

    PubMed

    Yang, Bo; Yang, Fan; Zhang, Yan; Liu, Huanan; Jin, Ye; Cao, Weijun; Zhu, Zixiang; Zheng, Haixue; Yin, Hong

    2016-02-02

    The VP1 G-H loop of the foot-and-mouth disease virus (FMDV) contains the primary antigenic site, as well as an Arg-Gly-Asp (RGD) binding motif for the αv-integrin family of cell surface receptors. We anticipated that introducing a foreign epitope tag sequence downstream of the RGD motif would be tolerated by the viral capsid and would not destroy the antigenic site of FMDV. In this study, we have designed, generated, and characterized two recombinant FMDVs with a FLAG tag or histidine (HIS) inserted in the VP1 G-H loop downstream of the RGD motif +9 position. The tagged viruses were genetically stable and exhibited similar growth properties with their parental virus. What is more, the recombinant viruses rFMDV-FLAG and rFMDV-HIS showed neutralization sensitivity to FMDV type Asia1-specific mAbs, as well as to polyclonal antibodies. Additionally, the r1 values of the recombinant viruses were similar to that of the parental virus, indicating that the insertion of FLAG or HIS tag sequences downstream of the RGD motif +9 position do not eradicate the antigenic site of FMDV and do not affect its antigenicity. These results indicated that the G-H loop of Asia1 FMDV is able to effectively display the foreign epitopes, making this a potential approach for novel FMDV vaccines development. Copyright © 2015 Elsevier B.V. All rights reserved.