Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.
Matched MeSH terms: Hand, Foot and Mouth Disease/immunology
This article reviews the actual world FMD situation. In 2000, fifty nine countries officially reported outbreaks of FMD. The disease occurred in Europe (Greece), Asia (Russia, Mongolia, Bangladesh, Cambodia, China, Japan, Laos, Nepal, Pakistan, Philippines, Republic of Korea, Taiwan, Thailand, Vietnam, Iran, Iraq, Turkey, in Caucasian region--Georgia, Azerbaijan and Armenia as well as in Kazakhstan, Kyrgyzstan, Turkmenistan and Tajikistan), Africa (Egypt, Kenya, Mauritania, South Africa, Tanzania, Uganda, Malawi, Namibia, Zambia and Zimbabwe) and in South America (Brazil, Colombia, Uruguay, Bolivia, Peru, Ecuador and Venezuela). In 2001, FMD was still spreading throughout the endemic regions and appeared in some of the west European countries--Great Britain, The Netherlands, France and Ireland. In South America, FMD occurred in Argentina, Uruguay, Brazil and Colombia. In Asia the FMD spread in Turkey, Iran, Afghanistan, Georgia, Azerbaijan, Mongolia, Kuwait, Bahrain, Yemen, Qatar, United Arab Emirates, Oman, Iran, Bhutan, Nepal, Malaysia, Philippines, Thailand and Taiwan. The FMD situation in Africa was unclear, but probably most countries in West, East and South Africa were affected. The most recent data of the OIE from May 2002 confirmed FMD outbreaks in population of pigs in Republic of Korea.
Peripheral neuropathy is highly associated with foot complications among diabetics. This
study aimed to identify risk factors associated with the development of peripheral neuropathy in diabetic patients and their association with degree of severity of peripheral neuropathy. A cross-sectional study was conducted in follow-up clinics at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Malaysia involving 72 diabetic patients and 19 controls. Exclusion criteria were those with amputated limbs, gross foot deformity and existing peripheral neuropathy. Controls were non diabetics who walked normally, had no history of foot problem and attended the clinic as subjects’ companion. Quantitative assessment of neuropathy was done using Semmes-Weinstein monofilament. Neuropathy Disability Score (NDS) were used to quantify severity of diabetic neuropathy. Spearman’s Rank test and Mann-Whitney test were used to determine correlation between variables and their differences. Logistic regression analysis was used to determine risk factors associated with peripheral neuropathy. The mean HbA1c among diabetics was 8.6% + 4.1, and mean NDS was 7.0 + 6.0. A total of 79.1% demonstrated various level of neuropathy with presence of callus was associated with higher NDS scores. Older age (P=0.02), body weight (P=0.03), HbA1c (P=0.005) and duration of diabetes (P <0.005) showed positive correlation with NDS. Proper foot care program for diabetics should include recognition of the callus, with special emphasis given to those with heavier weight and increasing age.
Key words: diabetes mellitus, peripheral neuropathy, Neuropathy Disability Score
(NDS), Semmes Weinstein monofilament (SWMF), callus
Study site: follow-up clinics at the Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM)
A case-control study was conducted between November 2005 and May 2007 in the University of Malaya Medical Centre (UMMC), University of Malaya, Kuala Lumpur, Malaysia. The objective of this study was to identify specific socio-demographic and lifestyle factors which were associated with foot ulcer in Type 1 and Type 2 diabetes patients. There were 125 cases and 250 controls by using universal sampling. Diabetic foot ulcer was defined as "the full thickness skin break at least to Grade 1 Wagner Stage, occurring distal to malleoli". The case was defined as the diabetic patient who was newly diagnosed or who has a known case of diabetic foot ulcer and the control was defined as the diabetic patient without active foot ulcer. Data was collected via face-to-face interview using a structured questionnaire. Results showed that diabetic patients at younger age group, 44 years old and less (OR 5.90 95% CI 2.31, 15.10), Indian (OR 3.24 95% CI 1.66, 6.30), and smoker (OR 3.85 95% CI 1.77, 8.35) were the independent risk factor for diabetic foot ulcer.
Diabetes mellitus is a silent disease and is now recognized as one of the fastest growing threats to public death in almost all countries of the world. One of the important complications of diabetes mellitus is the foot related complications. Diabetic foot is the most common cause of hospitalization in diabetic patient. Increase the knowledge and awareness of Diabetic foot complication in diabetic patient could be one of the preventable measures. The aim of this study is to assess the level of knowledge and practice regarding foot care among patients with diabetic foot complications. A cross-sectional study performed on patients who attended the diabetic foot clinic and for those admitted for diabetic foot complications from the 1st September 2015 to 25th September 2015. The patients were interviewed with a questionnaire of 15 ‘yes’ or ‘no’ questions, on foot care knowledge and practice. Score of 1 was given for each ‘yes’ answer and 0 for a ‘no’ answer. The level of knowledge and practice were categorized into good, satisfactory or poor. The result was tested using chi-square in SPSS version 21. A total of 150 patients were included in this study. There were 75 male (50.0%) and 75 female (50.0%) with the majority of patients were over 55 years old (113 patients, 75.3%). Majority of the patients (64.0%) had poor foot care knowledge while 75 patients (50.0%) had poor foot care practice. In conclusion, based on our cross-sectional study that was done, most diabetic patients still have poor knowledge and practice regarding their diabetic foot care. Educational strategies regarding foot care should be emphasized and empowered within the diabetic population.
BACKGROUND: Hand, foot and mouth disease (HFMD) is caused by enteroviruses such as Coxsackie virus A16 (CVA16) and Enterovirus 71 (EV71). The diagnostic hallmarks are oral ulcers and maculo-papular or vesicular rash on the hands and feet. Severe form of this disease can lead to death due to neurological and cardiopulmonary complications. This case report aims to describe a fatal case of HFMD with minimal oral and skin manifestations.
CASE REPORT: A four-year-old girl was brought to a hospital after suddenly becoming unresponsive at home. She had a history of fever and lethargy for three days prior to her demise. The patient, and f ive other children in her neighbourhood had been diagnosed to have HFMD at a local health clinic; the other children had recovered without complications.
RESULTS: Autopsy revealed a few punctate, sub-epidermal vesicles measuring 1 to 2 mm on the palm of her right hand and sole of the right foot, visible only with a magnifying glass. Internal examination revealed prominent nodularity at the oro- and hypopharynxes. The lungs were markedly congested and oedematous. Histopathology of the lung showed marked oedema and haemorrhage with mild pneumonic changes. Oedema with increase in macroglia and astrocytic proliferation were seen in the cerebral tissue, but no lymphocytic infiltration was evident. Enterovirus EV71 was detected by polymerase chain reaction in samples from the lung, cerebrospinal fluid and serum. The cause of death was given as HFMD complicated by pneumonia.
CONCLUSION: Fatal HFMD may have minimal signs. A complete history, careful physical examination and relevant investigations lead to a diagnosis at post mortem examination. Awareness of the subtle signs and rapid deterioration associated with a fatal case of HFMD is a challenge to clinicians who encounter these cases.
Matched MeSH terms: Hand, Foot and Mouth Disease/pathology*
This simulation study aimed to explore the effects of mass and mass distribution of powered ankle-foot orthoses, on net joint moments and individual muscle forces throughout the lower limb. Using OpenSim inverse kinematics, dynamics, and static optimization tools, the gait cycles of ten subjects were analyzed. The biomechanical models of these subjects were appended with ideal powered ankle-foot orthoses of different masses and actuator positions, as to determine the effect that these design factors had on the subject's kinetics during normal walking. It was found that when the mass of the device was distributed more distally and posteriorly on the leg, both the net joint moments and overall lower limb muscle forces were more negatively impacted. However, individual muscle forces were found to have varying results which were attributed to the flow-on effect of the orthosis, the antagonistic pairing of muscles, and how the activity of individual muscles affect each other. It was found that mass and mass distribution of powered ankle-foot orthoses could be optimized as to more accurately mimic natural kinetics, reducing net joint moments and overall muscle forces of the lower limb, and must consider individual muscles as to reduce potentially detrimental muscle fatigue or muscular disuse. OpenSim modelling method to explore the effect of mass and mass distribution on muscle forces and joint moments, showing potential mass positioning and the effects of these positions, mass, and actuation on the muscle force integral.
Foot-and-mouth disease (FMD) is one of the most important animal diseases hindering livestock production in Thailand. In this study, a temporal and spatial analysis at the subdistrict level was performed on FMD outbreak reports in Thailand from 2011 to 2018. Risk factors associated with FMD outbreaks were furthermore investigated using generalized estimating equations. The results showed that the incidence of FMD outbreaks was the highest in 2016 and was affected by season, with a peak in FMD outbreaks occurring in the rainy-winter season, during October to December. FMD outbreaks were mostly distributed in small clusters within a few subdistricts. Some high-risk areas with repeated outbreaks were detected in the central regions. Risk factors, including the increase of subdistrict's size of the dairy population, beef population or pig population, the low percentage of forest area, subdistricts in the provinces adjacent to Malaysia, the presence of a livestock market and the occurrence of an FMD outbreak in a neighbouring subdistrict in the previous month significantly increased the odds of having an FMD outbreak. The increase in proximity to the nearest subdistrict with an FMD outbreak in the previous month decreased the odds of having FMD outbreaks. This study helped to identify high-risk areas and periods of FMD outbreaks in Thailand. Together with the identified risk factors, its results can be used to optimize the FMD control programme in Thailand and in other countries having a similar livestock industry and FMD situation.
Hand foot and mouth disease (HFMD) is a notifiable viral disease in Malaysia, and is transmitted primarily among young children. Although vaccines for enteroviruses 71 (EV-71) were approved in China against HFMD, the availability and the acceptance of the vaccine in the Malaysia are unknown. This study investigated and ascertained the determinants of willingness-to-pay (WTP) for HFMD vaccination in Selangor Malaysia. This study adopted a cross-sectional, contingent valuation method involving 390 parents of young children aged six and below. The double bounded dichotomous choice (DBDC) approach was employed to assess the WTP for HFMD vaccine among respondents. A bivariate probit model was used to assess the key determinants of WTP for HFMD vaccine, while the mean WTP was measured using the Krinsky and Robb procedure. We found that 279 (71.5%) of parents were willing to pay for the HFMD vaccination. The estimated single bounded mean WTP was MYR460.23 (equivalent to US$ 102.17) for two doses of HFMD vaccination. The double bounded analysis revealed that the vaccine's price, poor education background and lower income were the key factors that significantly affected the WTP, with the estimated mean WTP being MYR394.00 (US$ 87.47). In conclusion, most Malaysian parents are willing to pay for the HFMD vaccination. The estimated WTP identifies the optimal price point for HFMD vaccination in Malaysia. Furthermore, the government should focus on an awareness programme for the HFMD vaccination among parents who have lower income or education level.
Robotic technologies are being employed increasingly in the treatment of lower limb disabilities. Individuals suffering from stroke and other neurological disorders often experience inadequate dorsiflexion during swing phase of the gait cycle due to dorsiflexor muscle weakness. This type of pathological gait, mostly known as drop-foot gait, has two major complications, foot-slap during loading response and toe-drag during swing. Ankle foot orthotic (AFO) devices are mostly prescribed to resolve these complications. Existing AFOs are designed with or without articulated joint with various motion control elements like springs, dampers, four-bar mechanism, series elastic actuator, and so forth. This paper examines various AFO designs for drop-foot, discusses the mechanism, and identifies limitations and remaining design challenges. Along with two commercially available AFOs some designs possess promising prospective to be used as daily-wear device. However, the design and mechanism of AFO must ensure compactness, light weight, low noise, and high efficiency. These entailments present significant engineering challenges to develop a new design with wide consumer adoption.
The hand, food, and mouth disease (HFMD) is primarily caused by Enterovirus A71 (EV-A71). EV-A71 outbreaks in the Asia Pacific have been associated with severe neurological disease and high fatalities. Currently, there are no FDA-approved antivirals for the treatment of EV-A71 infections. In this study, the SP81 peptide, derived from the VP1 capsid protein of EV-A71 was shown to be a promising antiviral candidate for the treatment of EV-A71 infections. SP81 peptide was non-toxic to RD cells up to 45 μM, with a half-maximal cytotoxic concentration (CC50) of 90.32 μM. SP81 peptide exerted antiviral effects during the pre- and post-infection stages with 50% inhibitory concentrations (IC50) of 4.529 μM and 1.192 μM, respectively. Direct virus inactivation of EV-A71 by the SP81 peptide was also observed with an IC50 of 8.076 μM. Additionally, the SP81 peptide exhibited direct virus inactivation of EV-A71 at 95% upon the addition of the SP81 peptide within 5 min. This study showed that the SP81 peptide exhibited significant inhibition of EV-A71 and could serve as a promising antiviral agent for further clinical development against EV-A71 infections.
The genetic and phylogenetic characteristics of human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) sampled from children with hand, foot, and mouth disease in Shenzhen, People's Republic of China, over a 6-year period (1999 to 2004) were examined with reverse transcription-PCR and DNA sequencing. Out of 147 stool specimens, 60 showed positive signals when screened with EV71- and CA16-specific primers. EV71 was identified in 19 specimens, and CA16 was identified in 41 specimens; coinfection by EV71 and CA16 was not observed. Phylogenetic analysis of all EV71 strains isolated from the mainland Chinese samples established C4 as the predominant genotype. Only one other known strain (3254-TAI-98; AF286531), isolated in Taiwan in 1998, was identified as belonging to genotype C4. Phylogenetic analysis of CA16 strains allowed us to identify three new genetic lineages (A, B, and C), with lineage C recently predominating in Asian countries, such as the People's Republic of China, Malaysia, and Japan. These new observations indicate that CA16 circulating in the People's Republic of China is genetically diverse, and additional surveillance is warranted.
Matched MeSH terms: Hand, Foot and Mouth Disease/virology*
Enterovirus 71 (EV71) is a member of Picornaviridae that causes mild and self-limiting hand, foot, and mouth disease (HFMD). However, EV71 infections can progress to polio-like paralysis, neurogenic pulmonary edema, and fatal encephalitis in infants and young children. Large EV71 outbreaks have been reported in Taiwan, China, Japan, Malaysia, Singapore, and Australia. This virus is considered a critical emerging public health threat. EV71 is an important crucial neurotropic enterovirus for which there is currently no effective antiviral drug or vaccine. The mechanism by which EV71 causes severe central nervous system complications remains unclear. The interaction between the virus and the host is vital for viral replication, virulence, and pathogenicity. SCARB2 or PSGL-1 receptor binding is the first step in the development of viral infections, and viral factors (e.g., 5' UTR, VP1, 3C, 3D, 3' UTR), host factors and environments (e.g., ITAFs, type I IFN) are also involved in viral infections. The tissue tropism and pathogenesis of viruses are determined by a combination of several factors. This review article provides a summary of host and virus factors affecting cell and tissue tropism and the pathogenesis of enteroviruses.
Matched MeSH terms: Hand, Foot and Mouth Disease/genetics; Hand, Foot and Mouth Disease/epidemiology*; Hand, Foot and Mouth Disease/virology
Giant cell tumour in the metatarsal of a skeletally immature person is uncommon. Adequate surgical resection in this region can be difficult to achieve as there is little space between the rays of the foot. Furthermore, there is the challenge of restoring the metatarsophalangeal articulation after resection of the tumor. We describe a technique using non-vascularised fibular graft for reconstructing the 2nd metatarsal after en-bloc resection for giant cell tumour in a 14 year old adolescent female.
Mycetoma, also commonly referred to as Madura foot, is statistically rare in the United States. However, it is endemic to other parts of the world. It is a pseudotumor characterized by a triad of tumefaction, draining sinuses, and grains. Two types exist, with each caused by different groups of organisms that require different treatment approaches. Therefore, the exact diagnosis and culture of the organism is vital to successful treatment outcomes. Synovial sarcoma, in contrast, is a malignancy much more commonly seen in the United States. It is characterized by a well-circumscribed, often palpable, mass that is usually well delineated on magnetic resonance imaging. It has characteristic histologic and genetic features that help distinguish it from other soft tissue masses. We present a case of a soft tissue mass diagnosed in the United States. The patient had several clinical and radiographic features of synovial sarcoma but the histologic outcome was mycetoma. The case is followed by a review of the published data.
All known field isolates of enterovirus 71 (EV71) can be divided into three distinct genogroups (A, B, C) and 10 subgenogroups (A, B1-5, C1-4) based on VP1 gene sequences. We examined VP1 gene sequences of 10, 12 and 11 EV71 strains isolated in peninsular Malaysia during the outbreaks of hand, foot and mouth disease in 1997, 2000 and 2005 respectively. Four EV71 strains isolated in the hand, foot and mouth disease outbreak of 2006 in Sarawak (Malaysian Borneo) were included to describe their genetic relationship. Four subgenogroups (C1, C2, B3 and B4) of EV71 co-circulated and caused the outbreak of hand, foot and mouth disease in peninsular Malaysia in 1997. Two subgenogroups (C1 and B4) were noted to cause the outbreak in 2000. In the 2005 outbreak, besides EV71 strains of subgenogroup C1, EV71 strains belonged to subgenogroup B5 were isolated but formed a cluster which was distinct from EV71 strains of the subgenogroup B5 isolated in 2003. The four EV71 strains isolated from clinical specimens of patients with hand, foot and mouth disease in the Sarawak outbreak in early 2006 also belonged to subgenogroup B5. Phylogenetic analysis of the VP1 gene sequences showed that the four Sarawak EV71 isolates belonged to the same cluster as the EV71 strains that were isolated in peninsular Malaysia as early as May 2005. The data suggested that the EV71 strains causing the outbreak in Sarawak could have originated from peninsular Malaysia.
Matched MeSH terms: Hand, Foot and Mouth Disease/genetics*; Hand, Foot and Mouth Disease/epidemiology; Hand, Foot and Mouth Disease/virology*
Enterovirus 71 (EV71) is a major aetiological agent of hand, foot and mouth disease (HFMD). In recent years, several outbreaks in East Asia were associated with neurological complications and numerous deaths. An outbreak in Singapore in October 2000 afflicted thousands of children, resulting in four fatal cases from three of whom EV71 was isolated. The genomes of two representative EV71 strains isolated from a fatal case and a surviving patient were completely sequenced, and their nucleotide and amino acid sequences compared with known EV71 strains. The two outbreak strains were classified under genogroup B, together with those previously isolated in Singapore, Malaysia and Japan. Comparative sequence analysis of the two Singapore strains revealed 99% nucleotide similarity, while their deduced amino acid sequences were almost identical except for residue 1506 in the 3A non-structural region. Given that the outbreak involved closely related genetic variants of EV71, the broad spectrum of disease severity may be attributed to critical factors such as varying viral inoculation doses or differing host immune responses following infection, but is less likely to be due to the emergence of EV71 strains with heightened virulence.
Matched MeSH terms: Hand, Foot and Mouth Disease/mortality; Hand, Foot and Mouth Disease/epidemiology*; Hand, Foot and Mouth Disease/virology
Driving posture is important to determine the comfortability of the driver. The purpose of this study is to investigate the muscle response in car pedal operation. To evaluate this response, 11 volunteers involved in simulated driving experiment using an electrical impedance myography to detect the muscle contraction of the lower leg, particularly at Gastrocnemius medial (GM). The driver requires to perform different pedal actions. The results depict that GM muscle shows different reaction according to pedal actions. According to these results, different degree of ankle angle lead to different muscle response. These findings help us to understand the effect of physical attribute related to muscle response and joint angle on driver during monotonous driving task.
Since ancient Egypt, orthosis was generally made from wood and then later replaced with metal and leather which are either heavy, bulky, or thick decreasing comfort among the wearers. After the age of revolution, the manufacturing of products using plastics and carbon composites started to spread due to its low cost and form-fitting feature whereas carbon composite were due to its high strength/stiffness to weight ratio. Both plastic and carbon composite has been widely applied into medical devices such as the orthosis and prosthesis. However, carbon composite is also quite expensive, making it the less likely material to be used as an Ankle-Foot Orthosis (AFO) material whereas plastics has low strength. Kenaf composite has a high potential in replacing all the current materials due to its flexibility in controlling the strength to weight ratio properties, cost-effectiveness, abundance of raw materials, and biocompatibility. The aim of this review paper is to discuss on the possibility of using kenaf composite as an alternative material to fabricate orthotics and prosthetics. The discussion will be on the development of orthosis since ancient Egypt until current era, the existing AFO materials, the problems caused by these materials, and the possibility of using a Kenaf fiber composite as a replacement of the current materials. The results show that Kenaf composite has the potential to be used for fabricating an AFO due to its tensile strength which is almost similar to polypropylene's (PP) tensile strength, and the cheap raw material compared to other type of materials.
Thirteen enterovirus 71 (EV71) isolates were obtained from both fatal and non-fatal infections of patients seen in Peninsula Malaysia and in Sarawak during an outbreak of hand, foot and mouth disease (HFMD) in Malaysia in 1997, with incidences of fatal brainstem encephalomyelitis. The isolates were identified using immunofluorescence staining, neutralization assays, and partial sequencing of the 5' untranslated regions (UTR). Assessment of the potential genetic relationships of the isolates using the partial 5'UTR sequences suggested clustering of the isolates into at least two main clusters. Isolates from Peninsula Malaysia were found in both clusters whereas Sarawak-derived isolates clustered only in cluster II. Isolates derived from fatal infections, however, occurred in both clusters and no distinctive nucleotide sequences could be attributed to the fatal isolates. Examination of the nucleotide sequences revealed at least 13 nucleotide positions in all the isolates which differ completely from the previously reported EV71 5'UTR sequences. In addition, at least 11 nucleotide position differences within the 5'UTR were noted which differentiated cluster I from cluster II. Predicted secondary RNA structures drawn using the nucleotide sequences also suggested differences between isolates from the two clusters. These findings suggest the presence of at least two potentially virulent EV71 co-circulating in Malaysia during the 1997 HFMD outbreak.
Matched MeSH terms: Hand, Foot and Mouth Disease/mortality; Hand, Foot and Mouth Disease/epidemiology; Hand, Foot and Mouth Disease/virology*