Reproductive potential does not cause loss of heat shock response performance in honey bees.

In other species characterized to date, aging, as a function of reproductive potential, results in the breakdown of proteaostasis and a decreased capacity to mount responses by the heat shock response (HSR) and other proteostatic network pathways. Our understanding of the maintenance of stress pathways, such as the HSR, in honey bees, and in the reproductive queen in particular, is incomplete. Based on the findings in other species showing an inverse relationship between reproductive potential and HSR function, one might predict that that HSR function would be lost in the reproductive queens. However, as queens possess an atypical uncoupling of the reproduction-maintenance trade-off typically found in solitary organisms, HSR maintenance might also be expected. Here we demonstrate that reproductive potential does not cause loss of HSR performance in honey bees as queens induce target gene expression to levels comparable to those induced in attendant worker bees. Maintenance of HSR function with advent of reproductive potential is unique among invertebrates studied to date and provides a potential model for examining the molecular mechanisms regulating the uncoupling of the reproduction-maintenance trade-off in queen bees, with important consequences for understanding how stresses impact different types of individuals in honey bee colonies.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Association between thyroid dysfunction and dysglycaemia: a prospective cohort study.

AIMS: To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid-stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia. METHODS: In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted. RESULTS: During a median 2.6 year follow-up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid-stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid-stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04-1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64-1.44). By contrast, participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia. CONCLUSIONS: People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify.

Pretreatment with a heat-killed probiotic modulates monocyte chemoattractant protein-1 and reduces the pathogenicity of influenza and enterovirus 71 infections.

It has been proposed that inactivated probiotics may modulate the host immune system and contribute to mitigation of viral infections. This study demonstrated that administration of heat-killed Enterococcus faecalis, a widely used probiotic, can protect host animals against viral infections. The influenza-mediated morbidity and lung inflammation in E. faecalis-treated mice decreased significantly compared with those of the control mice. Furthermore, we found that the protection is associated with production of monocyte chemoattractant protein-1 (MCP-1). The intratracheal injection of a recombinant mouse MCP-1 protein abrogated the antiviral effects elicited by pretreatment with E. faecalis. CC chemokine receptor 2 (CCR2) is a receptor for MCP-1, and the intraperitoneal administration of a CCR2 antagonist effectively inhibited viral pathogenicity. The reduced pathogenicity was also observed in CCR2-deficient mice. Finally, E. faecalis significantly attenuated neuropathogenicity induced by another RNA virus, enterovirus 71. This study demonstrates that killed probiotics can reduce viral disease severity and identify that the MCP-1 pathway might act as a key mediator in the improved antiviral immune response. Our findings suggest that MCP-1 and its related signaling pathway can serve as critical therapeutic targets for development of new antiviral strategies.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

BACKGROUND: An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. RESULTS: The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance.

Efficacy of alcohols and alcohol-based hand disinfectants against human enterovirus 71.

BACKGROUND: Human enterovirus 71 (HEV71) infections are a significant public health threat in the Asia-Pacific region and occasionally cause severe neurological complications and even death in children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against HEV71 are still lacking. AIM: To investigate the virucidal activity of alcohols and alcohol-based hand disinfectants against HEV71. METHODS: A common alcohol-based hand disinfectant (0.5% chlorhexidine gluconate + 70% isopropanol) as well as different concentrations of isopropanol and ethanol were tested for virucidal activity against HEV71 using the suspension and the fingerpad tests. FINDINGS: In suspension tests, 85% and 95% ethanol achieved a mean log10 reduction factor in HEV71 titre of >3 and nearly 6, respectively, within 10 min. By contrast, 70% and 75% ethanol and any concentration of isopropanol (70-95%) produced a factor of <1 in this test after the same exposure time. In fingerpad tests, only 95% ethanol showed a mean log10 reduction factor of >4, while both 75% ethanol and a chlorhexidine gluconate-containing formula were ineffective against HEV71 with a mean log10 reduction factor of <1 after a 30 s exposure time. CONCLUSIONS: Widely used alcohol-based hand disinfectants based on 70% ethanol or isopropanol have poor effectiveness against HEV71. Ninety-five percent ethanol is the most effective concentration, but still cannot fully inactivate HEV71 and may be impractical for use in many instances. Hand hygiene with alcohol-based hand disinfectants alone is not recommended for preventing HEV71 transmission.

The relationship between thyrotropin receptor antibody levels and intrathyroid vascularity in patients with Graves' disease.

OBJECTIVE: Thyroid stimulating hormone receptor antibodies (TSHRAbs) are specific autoantibodies of Graves' disease (GD). They activate adenylate cyclase, induce thyroid growth, and cause an increased rate of thyroid hormone production and secretion. TSHRAbs levels are decreased by treatment and may predict recurrence when they persist. Theoretically, TSHRAbs levels should be related to intrathyroid vascularity (ITV) due to the autoimmunity and inflammation. We aimed to analyze the relationship between TSHRAbs represented by thyrotropin-binding inhibitory immunoglobulin (TBII) levels and ITV measured by thyroid duplex sonography (TDS). PATIENTS: 56 GD patients were prospectively recruited. MEASUREMENTS: ITV, measured using TDS, was defined as follows: (average color-flow area in the right and left sides of the thyroid/total thyroid area in transverse view)×100. RESULTS: The average TBII level was 47.1% and average ITV was 27.24. ITV positively and significantly correlated with TBII (p<0.001). CONCLUSIONS: TSHRAbs show significant correlation with ITV. This may help doctors to estimate thyroid autoimmune activity when they performing sonography at clinics.

Performance of homeostasis model assessment and serum high-sensitivity C-reactive protein for prediction of isolated post-load hyperglycaemia.

AIMS: To evaluate whether homeostasis model assessment and high-sensitivity C-reactive protein improve the prediction of isolated post-load hyperglycaemia. METHODS: The subjects were 1458 adults without self-reported diabetes recruited between 2006 and 2010. Isolated post-load hyperglycaemia was defined as fasting plasma glucose < 7 mmol/l and 2-h post-load plasma glucose ≥ 11.1 mmol/l. Risk scores of isolated post-load hyperglycaemia were constructed by multivariate logistic regression. An independent group (n = 154) was enrolled from 2010 to 2011 to validate the models' performance. RESULTS: One hundred and twenty-three subjects (8.28%) were newly diagnosed as having diabetes mellitus. Among those with undiagnosed diabetes, 64 subjects (52%) had isolated post-load hyperglycaemia. Subjects with isolated post-load hyperglycaemia were older, more centrally obese and had higher blood pressure, HbA(1c), fasting plasma glucose, triglycerides, LDL cholesterol, high-sensitivity C-reactive protein and homeostasis model assessment of insulin resistance and lower homeostasis model assessment of ß-cell function than those without diabetes. The risk scores included age, gender, BMI, homeostasis model assessment, high-sensitivity C-reactive protein and HbA(1c). The full model had high sensitivity (84%) and specificity (87%) and area under the receiver operating characteristic curve (0.91), with a cut-off point of 23.81; validation in an independent data set showed 88% sensitivity, 77% specificity and an area under curve of 0.89. CONCLUSIONS: Over half of those with undiagnosed diabetes had isolated post-load hyperglycaemia. Homeostasis model assessment and high-sensitivity C-reactive protein are useful to identify subjects with isolated post-load hyperglycaemia, with improved performance over fasting plasma glucose or HbA(1c) alone.

In vitro anti-influenza virus activity of synthetic humate analogues derived from protocatechuic acid.

Two humic-like substances, the oxidative polymer of protocatechuic acid (OP-PCA) and humic acid inhibit the in vitro replication of influenza virus A/WSN/33 (H1N1) in Madin-Darby canine kidney (MDCK) cells at concentrations of no cytotoxicity. The 50% inhibitory concentration (IC50) for OP-PCA was 6.59 +/- 1.02 microg/ml when the compound was added at the stage of viral adsorption. When OP-PCA was added after virus adsorption, the IC50 was 53.27 +/- 8.12 microg/ml. The IC50 for humic acid was 48.61 +/- 7.32 microg/ml and 55.27 +/- 5.46 microg/ml respectively when the compound was added at the stage of viral adsorption or post-adsorption. In spite of structural resemblance of these two compounds, they exhibit different actions of anti-flu. The OP-PCA inhibits virus-induced hemagglutination and low pH-induced cell-cell fusion. Humic acid inhibits the endonuclease activity of viral RNA polymerase. The monomer of PCA shows no inhibition on influenza virus replication.

Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus.

Enterovirus 71 (EV71), the newest member of Enteroviridae, is notable for its etiological role in epidemics of severe neurological diseases in children. Developing effective vaccines is considered a top choice among all control measures. We compared the inactivated virus vaccine (10 microg protein/mouse) with subunit vaccines--VP1 DNA vaccine (100 microg/mouse) or recombinant VP1 protein (10 microg/mouse)--in its ability to elicit maternal antibody and to provide protection against lethal infection of EV71 in suckling mice. Prior to gestation, all three groups of vaccinated dams possessed similar levels of neutralizing antibody. With a challenge dose of 2300 LD(50) virus/mouse, suckling mice born to dams immunized with inactivated virus showed 80% survival. The subunit vaccines provided protection only at a lower challenge dosage of 230 LD(50) per mouse, with 40% survival for DNA vaccine and 80% survival for VP1 protein. The cytokine profile produced by splenocytes showed a high level of IL-4 in the inactivated virus group, high levels of IFN-gamma and IL-12 in the DNA vaccine group, and high levels of IL-10 and IFN-gamma in the VP1 protein group. Overall, the inactivated virus elicited a much greater magnitude of immune response than the subunit vaccines, including total IgG, all four IgG subtypes, and T-helper-cell responses; these antibodies were shown to be protective against lethal infection when passively transferred to susceptible newborn mice. Our data indicated that inactivated virus is the choice of vaccine preparation capable of fulfilling the demand for effective control, and that VP1 subunit vaccines remain promising vaccine strategies that require further refinement.

Amantadine-resistant influenza A virus in Taiwan.

BACKGROUND AND PURPOSE: Amantadine and rimantadine have been used for treatment and prophylaxis of influenza A virus infection. We examined the amantadine susceptibility of field isolates of influenza A virus in Taiwan from 1996 to 1998 to monitor the presence of resistant strains. METHODS: Eighty-four field isolates of influenza A virus were examined for resistance to amantadine by plaque inhibition assay. Virus isolates with amantadine 50% inhibitory concentrations (IC50) greater than 0.9 microgram were chosen for sequence analysis of the M gene that is the molecular target for amantadine/rimantadine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify the viral RNA. RT-PCR products were examined and purified by agarose gel electrophoresis for further sequence analysis. The Genetics Computer Group Sequence Analysis Package and the neighbor-joining method listed in the Molecular Evolutionary Genetic Analysis package were used for phylogenetic analysis. RESULTS: One field strain was amantadine resistant (IC50 > 10 micrograms/mL), with a mutation (position 31, serine to asparagine) in the M2 protein. The resistant virus was isolated from a non-immunocompromised child without a history of amantadine/rimantadine treatment. None of the family members reported previous exposure to amantadine/rimantadine. CONCLUSIONS: In this series, amantadine-resistant influenza A (H1N1) virus was isolated from a non-immunocompromised Taiwanese child without a known history of exposure to this drug. Resistant field isolates were rare. Due to the increasing use of amantadine/rimantadine in Taiwan, continued surveillance for amantadine/rimantadine-resistant influenza A viruses is warranted.

Association of pityriasis rosea with human herpesvirus-6 and human herpesvirus-7 in Taipei.

BACKGROUND AND PURPOSE: Pityriasis rosea (PR) is a common papulosquamous skin disease with unknown etiology. The possible relationship of PR with human herpesvirus infection (HHV) has been extensively studied. This study used the polymerase chain reaction (PCR) to investigate the presence of human herpesvirus 6 and 7 (HHV-6 and HHV-7) in 41 PR patients from two hospitals in Northern Taiwan. The epidemiologic features of PR in patients were also studied. METHODS: A total of 41 PR patients (11 males, 30 females) were enrolled in this study from April 1999 to March 2000. PCR of skin biopsy specimens from 24 PR patients was used to identify the existence of HHV-6 and HHV-7. Viral culture from PR biopsy specimens was also performed. Blood from these patients was sampled for Venereal Disease Research Laboratory tests. Skin biopsies from 20 age- and sex-matched controls with other skin diseases were also subjected to PCR study. RESULTS: The ages of the 41 PR patients ranged from 8 to 62 years. An increased incidence (17/41) of PR episodes was observed during the spring. Both HHV-6 and HHV-7 DNA was below the limit of detection in all biopsy specimens from patients and healthy controls. Viral culture for HHV was negative in all patients. CONCLUSION: The epidemiologic features of PR in this series are comparable to other studies except for an exaggerated female predominance (male:female ratio 1:2.7). Our data indicate a lack of association between HHV-6 and HHV-7 infection and PR.

Molecular epidemiology of enterovirus 71 in Taiwan.

Taiwan suffered a severe and widespread outbreak of enterovirus infection in 1998. More than 400 children were hospitalized, with seventy-eight fatalities due to central nerve system (CNS) involvement and cardiopulmonary collapse. Enterovirus 71 (EV71) was incriminated as the causative agent for the fatal cases. To understand the viral molecular epidemiology in this outbreak, fragments of 207-bp length of the VP4 region in 23 Taiwanese EV 71 isolates were sequenced. Pair-wise comparison revealed a 17.5-24.4% difference between the isolates and the prototype BrCr. However, all the changes in the VP4 region of the isolated strains were synonymous substitutions. Phylogenetic analysis was performed on these 23 isolates and 21 others deposited in GenBank. In this study, forty-four EV71 isolates from the world were separated into three distinct genotypes: A, B and C. The EV71 prototype strain, BrCr/70, is the only strain of genotype A. Group B included strains from the United States, Japan and Taiwan. Most strains in genotype B were isolated prior to 1990. Group C consisted of strains from Japan and Taiwan. Most strains of genotype C were isolated after 1990, they were further divided into 3 clusters: i.e. C-1, C-2 and C-3. In Taiwan, two genotypes, B and C-3, were co-circulating during the outbreak in 1998, although a minor group of genotype B may have appeared in Taiwan before 1986. The majority of the isolates clustered in genotype C-3. Genotype C showed a higher evolutionary rate than genotype B (3.9 x 10(-3) vs. 1.4 x 10(-3)) in the VP4 region. There seems to be a worldwide trend with strains of genotype B appearing earlier than strains of genotype C which took over later in the dominance.

Ultraprofound cerebral hypothermia and blood substitution with an acellular synthetic solution maintains neuronal viability in rat hippocampus.

The acute effects of ultraprofound hypothermia and blood substitution (UHBS) on neuronal cell viability were examined in adult rat hippocampus, a brain region particularly vulnerable to ischemic cell death. UHBS was performed using either artificial cerebrospinal fluid (ACSF) or Hypothermosol, an "intracellular-type" hypothermic preservation solution. After the procedure, the hippocampus was sliced and tested for cellular viability using a combination of cellular fluorochromes that are markers for live cells (acridine orange) and dead cells (propidium iodide). UHBS with ACSF resulted in a variable degree of neuronal death within the hippocampal subfields CA1/CA3, and dentate granular layer and hilus (CA4). In contrast, UHBS with Hypothermosol consistently resulted in hippocampal slices with only mild neuronal death. Our results of preserved hippocampal neuronal viability with use of UHBS and Hypothermosol support the demonstrated central nervous system (CNS) protective effects of UHBS and Hypothermosol when used during prolonged cardiac arrest. The results of this study also suggest that UHBS and Hypothermosol may be useful in the preparation and maintenance of viable hippocampal tissue for physiological studies, especially those involving aged animals, which are particularly vulnerable to hypoxic-ischemic cellular injury

Acute encephalomyelitis during an outbreak of enterovirus type 71 infection in Taiwan: report of an autopsy case with pathologic, immunofluorescence, and molecular studies.

We report a fatal case of enterovirus type 71 (EV 71) infection in an 8-year-old girl during a summer outbreak of hand, foot, and mouth disease in 1998 in Taiwan. The clinical course was rapidly progressive, with manifestations of hand, foot, and mouth disease, aseptic meningitis, encephalomyelitis, and pulmonary edema. The patient died 24 hours after admission. Postmortem study revealed extensive inflammation in the meninges and central nervous system and marked pulmonary edema with focal hemorrhage. Brain stem and spinal cord were most severely involved. The inflammatory infiltrates consisted largely of neutrophils involving primarily the gray matter with perivascular lymphocytic cuffing, and neuronophagia. The lungs and heart showed no evidence of inflammation. EV 71 was isolated from the fresh brain tissues and identified by immunofluorescence method with type-specific EV 71 monoclonal antibody. It was also confirmed by neutralization test and reverse-transcriptase polymerase chain reaction with sequence analysis. The present case was the first example in which EV 71 was demonstrated to be the causative agent of fatal encephalomyelitis during its epidemic in Taiwan.

Genetic analysis of enterovirus 71 isolated from fatal and non-fatal cases of hand, foot and mouth disease during an epidemic in Taiwan, 1998.

A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5'-non-coding region (5'-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5'-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97-100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3'-NCR where the nucleotide homology was 90-91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.

Expression of capsid [correction of caspid] protein VP1 for use as antigen for the diagnosis of enterovirus 71 infection.

To produce enterovirus 71 antigen for diagnostic purposes, the gene encoding the entire capsid protein VP1 was amplified by reverse transcription-polymerase chain reaction (RT-PCR), cloned and expressed in Escherichia coli as a poly-histidine fusion protein. Western blotting experiments with sera from patients with enterovirus 71 infection indicated that immunoglobulin G (IgG) and IgM antibodies bound to a single polypeptide VP1. According to these results, IgM anti-VP1 appeared in sera of patients with a symptomatic enterovirus 71 acute infection, whereas IgG anti-VP1 was present in sera of past infection. This finding suggests that detecting IgG and IgM immune responses against linear epitopes of recombinant VP1 is an effective means of determining the different phases of enterovirus 71 infection. In addition, sera containing coxsackie virus 16 (CA16) antibodies did not cross-react with the recombinant VP1 of enterovirus 71, despite the homology between VP1 proteins of both viruses. Comparison with reference PCR and neutralization assays showed these antibody tests to be appropriate for the serodiagnosis of enterovirus 71 infection.

Comparison of enterovirus 71 and coxsackie-virus A16 clinical illnesses during the Taiwan enterovirus epidemic, 1998.

OBJECTIVES: To compare enterovirus 71 (EV 71) with coxsackievirus A16 (Cox A16) clinical illness in patients at Chang Gung Children's Hospital during Taiwan's enterovirus epidemic of 1998. METHODS: With the use of the immunofluorescence assay and neutralization test, 177 cases of EV 71 and 64 cases of Cox A16 illness were confirmed from April to September, 1998. The clinical signs and symptoms, complications and case fatality rates were compared. RESULTS: Three-fourths of the cases were younger than 3 years of age, and the ratio of males to females was 1.3 in the EV 71 group and 1.2 in the Cox A16 group. In the EV 71 group 120 (68%) cases were uncomplicated, including 94 cases of hand, foot and mouth disease and 15 cases of herpangina, and 57 (32%) cases had complications, including 13 (7.3%) cases of aseptic meningitis, 18 (10%) cases of encephalitis, 4 (2.3%) cases of polio-like syndrome, 8 (4.5%) cases of encephalomyelitis and 12 (6.8%) cases of fatal pulmonary edema. Fourteen (7.9%) patients died, including 12 cases of pulmonary edema and 2 cases of encephalitis; seven (4%) patients had sequelae. By contrast, 60 (94%) of the 64 cases of Cox A16 infection were uncomplicated and only 4 (6.3%) cases were complicated by aseptic meningitis; no fatalities or sequelae were observed. By multivariate analysis vomiting (P = 0.01) and fever higher than 39 degrees C plus lasting longer than 3 days (P = 0.02) were significantly more frequent in the EV 71 group. CONCLUSION: EV 71 illness is more severe with significantly greater frequency of serious complications and fatality than is illness caused by Cox A16.

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.

BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Intussusception in a child infected with enterovirus: case report.

Most intussusceptions in childhood are idiopathic. The association of viral infection has been suspected for decades. We report a case of ileocolonic intussusception in a child during a course of enterovirus infection. A 20-month-old girl with vomiting and irritable crying of 4 days' duration was found to have intussusception by sonography. She had suffered from herpangina one week earlier. Due to her peritoneal signs, she underwent surgical manual reduction. A cluster of enlarged lymph nodes in the intussuscipiens was noted preoperatively by high resolution ultrasound. Two swollen lymph nodes were removed for pathologic evaluation and examined for a viral genome by polymerase chain reaction (PCR) amplification. Panenterovirus base pairs were confirmed on the electrophoresis print. During postoperative sonographic follow-up, significant shrinkage of previous mesenteric lymphoid hyperplasia was observed. In this article, we present the first case of childhood intussusception in associated with enterovirus infection, in which the panenterovirus genome was identified in the patient's mesenteric lymph nodes. This was also the first evaluation of the role of mesenteric lymph nodes in intussusception by high resolution sonography.