Current status of hand-foot-and-mouth disease.

Hand-foot-and-mouth disease (HFMD) is a viral illness commonly seen in young children under 5 years of age, characterized by typical manifestations such as oral herpes and rashes on the hands and feet. These symptoms typically resolve spontaneously within a few days without complications. Over the past two decades, our understanding of HFMD has greatly improved and it has received significant attention. A variety of research studies, including epidemiological, animal, and in vitro studies, suggest that the disease may be associated with potentially fatal neurological complications. These findings reveal clinical, epidemiological, pathological, and etiological characteristics that are quite different from initial understandings of the illness. It is important to note that HFMD has been linked to severe cardiopulmonary complications, as well as severe neurological sequelae that can be observed during follow-up. At present, there is no specific pharmaceutical intervention for HFMD. An inactivated Enterovirus A71 (EV-A71) vaccine that has been approved by the China Food and Drug Administration (CFDA) has been shown to provide a high level of protection against EV-A71-related HFMD. However, the simultaneous circulation of multiple pathogens and the evolution of the molecular epidemiology of infectious agents make interventions based solely on a single agent comparatively inadequate. Enteroviruses are highly contagious and have a predilection for the nervous system, particularly in child populations, which contributes to the ongoing outbreak. Given the substantial impact of HFMD around the world, this Review synthesizes the current knowledge of the virology, epidemiology, pathogenesis, therapy, sequelae, and vaccine development of HFMD to improve clinical practices and public health efforts.

The first molecular detection of Clostridium perfringens from pneumonic cases associated with foot and mouth disease in cattle and buffalo in Egypt.

Panting syndrome and respiratory infection have been recorded in complicated cases of foot and mouth disease (FMD) in cattle. However, investigations on the causative agents of respiratory disease in such cases are scarce. In this study, 30 animals (13 buffalo and 17 cattle) suffering from respiratory distress associated with signs of FMD were examined. Serum samples were collected and FMD infection was confirmed. Bacteriological examination of lungs from eight necropitized cases revealed the presence of C. perfringens. Multiplex polymerase chain reaction (mPCR) was performed on the positive samples followed by sequencing analysis. The alpha toxin gene (plc) of C. perfringens was identified in six cases. The present investigation highlights the role of clostridial infection as a complication of FMD in cattle and buffalo. This is the first report identifying the C. perfringens toxins from lung of animals with respiratory distress associated with FMD infection.

A Case-control Study of Haemorrhagic Septicaemia in Buffaloes and Cattle in Karachi, Pakistan, in 2012.

A retrospective epidemiological case-control study was performed in Karachi, Pakistan, from January to April 2013. The owners of 217 dairy cattle and buffalo farms from six different locations in Karachi were interviewed. The aim of the study was to identify risk factors associated with the presence of haemorrhagic septicaemia (HS). Farms with a history of at least one instance of sudden death in a dairy animal during 2012 and a positive clinical HS diagnosis (made by local veterinarians) were defined as cases. Farms having no history of sudden deaths in 2012 were defined as controls. Univariable analyses were initially conducted, and factors with P ≤ 0.25 were offered to a multivariable logistic regression model to identify putative risk factors. The final multivariable logistic model contained five factors. Vaccination was found to be a protective factor (OR = 0.22) along with the length of time cattle were kept on farm (months). For every extra month cattle were kept, the odds of HS disease were reduced by a factor of 0.9. In contrast, for every extra animal in a herd, the risk of infection increased by a factor of 1.01. Supplying underground water and the presence of foot and mouth disease on the farm increased the risk by 2.90 and 2.37, respectively. To understand the epidemiology of HS in Karachi dairy herds, more in-depth research is required to study the risk and protective factors identified in this survey and to evaluate risk mitigation strategies, where possible.

Foot-and-Mouth Disease Virus-Associated Abortion and Vertical Transmission following Acute Infection in Cattle under Natural Conditions.

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.

Serotyping of foot and mouth disease virus and Pasteurella multocida from Indian gaurs (Bos gaurus), concurrently infected with foot and mouth disease and haemorrhagic septicaemia.

We report the serotyping of foot-and-mouth disease virus (FMDV) and Pasteurella multocida from Indian gaurs which were concurrently infected with foot-and-mouth disease (FMD) and haemorrhagic septicaemia. Bannerghatta biological park (BBP), a national park located in the outskirts of Bengaluru city, Karnataka, India, is bordered by several villages. These villages witnessed massive outbreaks of FMD which spread rapidly to the herbivores at BBP. Post-mortem was conducted on carcasses of two Indian gaurs that died with symptoms of FMD. The salient gross findings included extensive vesicular lesions on the tongue, gums, cheeks, upper palate and hooves. Haemorrhagic tracheitis and ecchymotic haemorrhages on the heart were characteristic. The vesicular lesions of oral cavity were positive for 'O' type of FMD virus by sandwich enzyme-linked immuno sorbent assay (ELISA). The heart blood and spleen samples yielded growth of pure cultures of P. multocida. The isolates were typed as P. multocida type B using KTSP61 and KTT72 primers yielding specific amplicons of 620 bp. The phylogenetic analysis of the isolates was carried by sequencing of 1.4-Kbp nucleotides on the 16S ribosomal RNA (rRNA) gene of the isolates.

Onychomadesis after hand-foot-and-mouth disease outbreak in northern Greece: case series and brief review of the literature.

BACKGROUND: Nail abnormalities in childhood are generally uncommon. Recently, onychomadesis was described as a late complication of hand-foot-and-mouth disease (HFMD). Onychomadesis outbreaks following HFMD have been reported in many countries worldwide. AIM: To present a case series of onychomadesis in children, following HFMD outbreak in Northern Greece, and review literature data. METHODS: Children with evident onychomadesis attending the outpatient clinic between November 2012 and January 2013 were included in the study. A questionnaire including demographic personal and family history information of the children was completed by the parents. Patients were clinically examined, and their pediatric and dermatological records were studied to confirm precedent HFMD. Direct microscopic examination and cultures for fungi were performed. Exposure of participants to coxsackievirus, based on serology testing during infection, was also recorded. RESULTS: Sixty-eight children with onychomadesis were included. The mean number of affected nails was 8.82. Fingernails were more often involved. Previous clinical diagnosis of HFMD was confirmed in 67/68 cases. The mean time from HFMD diagnosis to onychomadesis development was 39.6 days (range: 28-56 days, STD: 7.33). Direct microscopic examination, as well as cultures for fungal species, was negative for the whole sample size. All the nail changes were transient with spontaneous regrowth after 1-4 months. CONCLUSION: Our data indicate that onychomadesis outbreak in the region of Thessaloniki during fall-winter 2012-13 was highly related to the outbreak of HFMD. Our study reinforces existing evidence for the association between onychomadesis and HFMD.

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

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 mononuclear inflammatory reaction, interstitial edema and cardiomyocyte degeneration in the myocardium of two pigs that died during acute infection with either of two different strains of FMDV. Despite similar clinical progression, there was a marked variation in morphological characteristics of myocarditis with a significant difference in intensity of myocardial inflammation between the two cases. Phenotypic characterization of leukocyte populations revealed that in both cases, the inflammatory infiltrate consisted mainly of combinations of CD172a+, CD163+ and CD44+ cells, with a distinct subset of CD8+ cells, but with consistent lack of detection of CD3+ and CD21+ cells. This suggests that the FMDV-associated acute myocardial inflammation in the two observed cases consisted mainly of leukocytes of monocyte lineage, with a distinct population of CD8+ cells which, based on lack of CD3 detection in serial sections, are likely to represent NK cells.

Observations on the incidence and seasonality of uterine torsion and left displaced abomasum following the 2001 outbreak of foot-and-mouth disease in the UK.

Time-series impact analysis was used to compare differences in the rate of reporting of left displaced abomasum (LDA) and uterine torsion by veterinarians in the UK before and after an outbreak of foot-and-mouth disease (FMD) in 2001. There were 150% and 35% increases in the reported incidences of LDA and uterine torsion, respectively, following the outbreak. Changes to feeding practices are likely to have been a major contributor to the increased incidence of LDA, but this factor is unlikely to have influenced the changed incidence in uterine torsion. Given that abdominal size and shape of dairy cows are recognised risk factors for both disease processes, the findings of this study suggest changes in these parameters may have a role in the altered incidences. Additional research is required to further elucidate the risk factors contributing to the increased incidence of LDA and uterine torsion in dairy cows under UK conditions.

Increased plasma cardiac troponin I concentration in lambs with myocarditis.

BACKGROUND: Cardiac troponin I (cTnI) is a blood biomarker of myocardial injury. A human cTnI assay may be useful for measuring cTnI concentrations in lambs with naturally occurring myocarditis. OBJECTIVE: The aims of this study were to evaluate the utility of a commercially available human chemiluminescent microparticle cTnI immunoassay for measuring plasma cTnI concentrations in lambs with naturally occurring myocarditis from infection with foot and mouth disease virus (FMDV), and to determine cTnI expression in cardiac muscle of affected lambs. METHODS: Ten lambs with myocarditis and 10 clinically healthy lambs (control group) were included. Clinical signs, gross and histologic necropsy findings, and immunoreactivity for cTnI in cardiac tissue were evaluated. Plasma cTnI concentration was determined using the commercial human immunoassay system. RESULTS: All lambs with myocarditis died within 1 day of clinical signs. Infection with FMDV was confirmed by PCR analysis. Gross cardiac lesions were evident and histologic examination revealed myocarditis. Immunoreactivity for cTnI was absent in cardiac myocytes that were degenerative or necrotic, but was strong in cardiac myocytes from unaffected areas of the myocardium and in all cardiac myocytes of healthy lambs. The geometric mean plasma concentrations of cTnI for lambs in the myocarditis and control groups were 146.78 µg/L (95% confidence interval [CI], 61.90-348.06) and 0.013 µg/L (95% CI, 0.010-0.017), respectively (t-value 19.27; P < .0001). CONCLUSIONS: A commercial human cTnI assay may be used to detect plasma cTnI concentrations in sheep, and cTnI may be used as a blood-based biomarker of myocarditis in this species.

Absence of heat intolerance (panting) syndrome in foot-and-mouth disease-affected Indian cattle (Bos indicus) is associated with intact thyroid gland function.

Foot-and-mouth disease (FMD) is a highly contagious and economically important viral disease with high morbidity and reduced productivity of affected animals. We studied the heat intolerance (HI) (panting) syndrome and the effect of FMD virus (FMDV) infection on thyroid gland function in Indian cattle (Bos indicus). Experimental infection with FMDV Asia 1 resulted in a mild form of disease with superficial lesions. Heat intolerance syndrome and its signs were not observed among the recovered animals. Subtle changes in the serum level of thyroid hormones, triiodothyronine (T3) and thyroxine (T4) were observed. However, there were no distinct histological changes in the thyroid gland, and FMDV antigens were not detected in the thyroid tissues. Our results thus suggest that the absence of panting syndrome in FMD-affected Bos indicus cattle may be associated with intact thyroid gland function.

The expressions of HSP70 and αB-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs.

This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (α-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. α-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and α-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins.

The expressions of HSP70 and alphaB-crystallin in myocarditis associated with foot-and-mouth disease virus in lambs

This study describes the expression of heat shock protein70 (HSP70) and alpha-basic-crystallin (alpha-BC) and their association with apoptosis and some related adaptor proteins in the pathogenesis of foot-and-mouth disease virus (FMDV)-induced myocarditis in lambs. HSP70 was generally overexpressed in the myocardial tissues and inflammatory cells of FMDV-induced myocarditis with differential accumulation and localization in same hearts when compared to non-foot-and-mouth disease control hearts. alpha-BC immunolabeling showed coarse aggregations in the Z line of the cardiomyocytes in FMDV-infected hearts in contrast to control hearts. Overall, the results of this study show that the anti-apoptotic proteins, HSP70 and alpha-BC, were overexpressed with increased apoptosis in FMDV-infected heart tissues. Both proteins failed to protect the cardiomyocytes from apoptosis as defense mechanisms to the FMDV during the infection, suggesting that the virus is able to increase apoptosis via both downregulation and/or upregulation of these anti-apoptotic proteins.

Myocarditis associated with foot-and-mouth disease virus type O in lambs.

The present study describes the pathogenetic mechanisms of myocarditis in 9 lambs that died in a foot-and-mouth disease outbreak in Samsun, Turkey. In all the heart samples tested, ELISA and sequencing for phylogenetic analyses showed that the virus, namely O/TUR/Samsun/05, was associated with the PanAsia pandemic strain of foot-and-mouth disease virus (FMDV) type O. The lambs had myocardial lesions but no typical vesicular lesions. In situ reverse transcription showed that many cardiomyocytes and some interstitial cells were positive for FMDV type O. Inflammatory infiltration, hyaline degeneration, and necrosis of sheets of myocytes were observed. The cellular infiltrates were mononuclear cells, including many lymphocytes, macrophages, a few plasma cells, and neutrophils. Major histocompatibility complex Class II+ dendritic and mononuclear cells, gammadelta T cells, CD172A+ and CD14+ macrophages and monocytes, and IgM+ B cells were detected mainly in the infected hearts. Inducible nitric oxide synthetase (iNOS) was seen mostly in areas of inflammation infiltrated by large numbers of cells. Of the 2 alpha-subunits of integrin known to be used as receptors by FMDV in epithelial tissues, CD49e (integrin alpha5) was detected in the membranes of cardiac myocytes with intercalated discs, but CD51 (integrin alphaV) was not detected in cardiac myocytes from infected or normal lambs. Interstitial and inflammatory cells were positive for both integrin subunits. The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)-positive signal was detected in the nuclei of both cardiac myocytes and interstitial cells from infected lambs. These findings suggest that the iNOS expressed by inflammatory cells in lesions may have a deleterious effect on cardiac myocytes in these lesions.

Dioxins and polychlorinated biphenyls (PCDD/Fs and PCBs) in food from farms close to foot and mouth disease animal pyres.

To control the outbreak of foot and mouth disease, which occurred in the UK in early 2001, a large number of farm animals were slaughtered. Where it was not possible to render or landfill the carcasses, they were destroyed by burning on open pyres, with wood, coal and other materials. Uncontrolled combustion such as this is known to produce small quantities of dioxins and an investigation was made into whether, as a result of the burning, there was an elevation in the concentrations of these compounds in food produced in the areas close to the pyres. With few exceptions, concentrations of PCDD/Fs and PCBs were within the expected ranges as predicted by reference data. No accumulation over time was evident from a repeat milk sampling exercise. Where elevated concentrations of PCDD/Fs and PCBs were found in chickens and eggs, they were in samples not destined for the food chain. Elevated levels in some samples of milk from Dumfries and Galloway were not found in earlier or later samples and may have been found as a result of a temporary feeding regime. Elevated concentrations in lamb from Carmarthenshire were from very young animals which would not have entered the food chain. There was no evidence of any significant increase in dietary exposure to PCDD/Fs and PCBs as a result of the FMD pyres.

Surgical treatment of a sloughed hoof by skin grafting in a young bull.

A sloughed hoof in a young bull as a sequela of foot and mouth disease was treated by skin grafting. Skin blocks obtained from the craniolateral thoracic area of the same animal were placed in slit-like pockets created on the coronary band. New hoof formation was completed within 20 weeks.

Human repercussions of foot and mouth disease and other similar viral diseases.

Foot and mouth disease is a frequent viral zoonosis in livestock that may occasionally also affect humans. Transmission to man usually occurs as a result of the consumption of unprocessed milk. The clinical manifestations include fever, headache, weakness, muscle pain, and the development of vesicles and ulcers throughout the oral mucosa. Vesicular stomatitis is another zoonosis similar to foot and mouth disease that can likewise affect humans with similar clinical manifestations, in which the presence of aphthae is highly suggestive. In turn, hand, foot and mouth disease and herpangina are two exclusively human diseases caused by different enteroviruses, with a special predilection for children under five years of age, and characterized by the presence of vesicles and ulcerations in the oral cavity. The present study provides a brief review of the salient characteristics of foot and mouth disease and of other similar viral diseases with which the differential diagnosis should be established.

Viral infections and bovine mastitis: a review.

This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or parainfluenza 3 virus-induced clinical mastitis, while an intramammary inoculation of foot-and-mouth disease virus resulted in necrosis of the mammary gland. Subclinical mastitis has been induced after a simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4. Bovine leukaemia virus has been detected in mammary tissue of cows with subclinical mastitis, but whether this virus was able to induce bovine mastitis has not been reported. Bovine herpesvirus 2, vaccinia, cowpox, pseudocowpox, vesicular stomatitis, foot-and-mouth disease viruses, and bovine papillomaviruses can play an indirect role in the aetiology of bovine mastitis. These viruses can induce teat lesions, for instance in the ductus papillaris, which result in a reduction of the natural defence mechanisms of the udder and indirectly in bovine mastitis due to bacterial pathogens. Bovine herpesvirus 1, bovine viral diarrhoea virus, bovine immunodeficiency virus, and bovine leukaemia virus infections may play an indirect role in bovine mastitis, due to their immunosuppressive properties. But, more research is warranted to underline their indirect role in bovine mastitis. We conclude that viral infections can play a direct or indirect role in the aetiology of bovine mastitis; therefore, their importance in the aetiology of bovine mastitis and their economical impact needs further attention.