Yhu Chering Huang

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.

Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus

A small number of clonal lineages dominates the global population structure of methicillin-resistant Staphylococcus aureus (MRSA), resulting in the concept that MRSA has emerged on a few occasions after penicillinase-stable β-lactam antibiotics were introduced to clinical practice, followed by intercontinental spread of individual clones. We investigated the evolutionary history of an MRSA clone (ST5) by mutation discovery at 108 loci (46 kb) within a global collection of 135 isolates. The SNPs that were ascertained define a radial phylogenetic structure within ST5 consisting of at least 5 chains of mutational steps that define geographically associated clades. These clades are not concordant with previously described groupings based on staphylococcal protein A gene (spa) typing. By mapping the number of independent imports of the staphylococcal cassette chromosome methicillin-resistance island, we also show that import has occurred on at least 23 occasions within this single sequence type and that the progeny of such recombinant strains usually are distributed locally rather than globally. These results provide strong evidence that geographical spread of MRSA over long distances and across cultural borders is a rare event compared with the frequency with which the staphylococcal cassette chromosome island has been imported.

Proinflammatory cytokine reactions in enterovirus 71 infections of the central nervous system

Enterovirus 71 (EV71) infection can lead to devastating clinical outcomes. An appreciation of the scientific relationship between cytokine response and patient mortality may help limit the risks posed by this deadly illness. We present the results of a study that compared the cerebrospinal fluid (CSF) and serum levels of interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) in 24 patients with EV71 infection. Cases in this study involved diverse manifestations or complications, including encephalitis, poliomyelitis-like syndrome, meningitis, and pulmonary edema. CSF levels of IL-6 in study patients were found to be consistently higher during the first 2 days of central nervous system (CNS) involvement than afterward. Compared with patients who did not have pulmonary edema, patients who experienced pulmonary edema had dramatically varied blood values, including IL-6, white blood cell counts, and glucose levels. Our findings suggest that the combination of CNS and systemic inflammatory response may trigger EV71-related cardiopulmonary collapse.

Comparison of enterovirus 71 and coxsackievirus 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 Childrens Hospital during Taiwans 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.

Fulminant neurogenic pulmonary oedema with hand, foot, and mouth disease

An 8-year-old girl was admitted with fever, oral ulcers, constipation, headache, and vomiting for 2 days. She had a rash on the soles of both feet, and had not urinated for a day. She was alert and not cyanosed, with a heart rate of 114/min, body temperature 37·2°C, and blood pressure 114/64 mm Hg. Her neck was stiff; breath sounds were clear; her heart beat was regular without gallop; her bladder was distended; and several small pink vesicles were found on both soles. There were no focal neurological signs. White blood cell count was 14·310 9 /L, blood sugar was 7·4 mmol/L, and creatine kinase MB fraction was 2 U/L. In cerebrospinal fluid, white cell count was 15310 6 /L with 70% neutrophils; glucose 4·2 mmol/L, and protein 43 mg/dL. The first chest radiograph was normal (figure A). Abdominal radiograph showed dilated loops of bowel and a distended bladder. Brain computed tomography was normal. Intravenous penicillin was given. 2 h after lumbar puncture, she complained of itching followed by pain in her right arm and then in her right forearm. Her muscle power was unimpaired. 1 h later, she had a severe headache and vomited bile. She became sweaty, with cold hands and feet, tachypnoeic (48/min), and had a heart rate up to 170/min. A second chest radiograph showed bilateral alveolar congestion. She coughed up pink frothy sputum and became cyanosed. She was intubated. Pink frothy fluid, followed by fresh blood, came from the endotracheal tube. She had increased leucocytosis (31·810 9

The 1998 Enterovirus 71 Outbreak in Taiwan: Pathogenesis and Management

The most recently discovered enterovirus, enterovirus 71 (EV71), is neurotropic and may cause severe disease and sudden death in children. In 1998, a large outbreak of enterovirus infection occurred in Taiwan that resulted in 405 severe cases in children and 78 deaths. Of the 78 children who died, 71 (91%) were <5 years old. EV71 was the primary agent in fatal cases of infection. Most of these patients died within 1-2 days of admission to the hospital. We hypothesize that EV71 directly attacks the central nervous system and causes neurogenic pulmonary edema and cardiac decompensation through the mechanism of sympathetic hyperactivity and inflammatory responses. Early recognition of risk factors and intensive care are crucial to successful treatment of this fulminant infection. After poliovirus is eradicated, EV71 will become the most important enterovirus that affects children, and development of a vaccine may be the only effective measure against it.

Methicillin-Resistant Staphylococcus aureus Colonization and Its Association With Infection Among Infants Hospitalized in Neonatal Intensive Care Units

OBJECTIVES. We conducted this study to assess the rate of methicillin-resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in methicillin-resistant S aureus–endemic NICUs. METHODS. Between March 2003 and February 2004, surveillance culture specimens from the nares, postauricular areas, axillae, and umbilicus of infants admitted to the NICUs at a children’s hospital in Taiwan were obtained weekly for the detection of methicillin-resistant S aureus. All colonized and clinical isolates from each study infant with methicillin-resistant S aureus infection were genotyped with pulsed-field gel electrophoresis, with Sma1 digestion, and compared. RESULTS. A total of 783 infants were included in this study. Methicillin-resistant S aureus colonization was detected for 323 infants during their NICU stays, with detection with the first 2 samples for 89%. Nares and umbilicus were the 2 most common sites of initial colonization. Methicillin-resistant S aureus colonization was associated significantly with premature birth (≤28 weeks) and low birth weight (≤1500 g), and infants with colonization had a significantly higher rate of methicillin-resistant S aureus infection, compared with those without colonization (26% vs 2%). Methicillin-resistant S aureus colonization was noted for 84 of 92 infants with methicillin-resistant S aureus infections. Of the 68 episodes with previous colonization and isolates available for genotyping analysis, colonized and clinical isolates were indistinguishable in 63 episodes, highly related in 2 episodes, and distinct in 3 episodes. CONCLUSIONS. More than 40% of the hospitalized infants were colonized with methicillin-resistant S aureus during their stay in methicillin-resistant S aureus–endemic NICUs; this was associated significantly with methicillin-resistant S aureus infection. Most infants with methicillin-resistant S aureus infections had previous colonization with an indistinguishable strain.

Association of fungal colonization and invasive disease in very low birth weight infants

BACKGROUND Fungi are common pathogens of nosocomial infections in the very low birth weight (VLBW) infants. The purpose of this study was to investigate the fungal colonization rate in VLBW infants and the association between fungal colonization and systemic fungal diseases. MATERIALS Between January 1, 1996, and December 31, 1996, 116 infants with birth weight < 1500 g admitted to the neonatal intensive care unit of Chang Gung Childrens Hospital in the first day of life were included in this prospective study. METHODS Cultures from oropharynx, rectum, skin (groin and axilla), bag urine and endotracheal aspirates were obtained in the first 24 h after birth and weekly thereafter throughout their neonatal intensive care unit stay. Medical records were reviewed weekly. RESULTS Fungal colonization was detected in 25 infants, among whom 17 infants developed colonization by 2 weeks of life. Candida albicans (61%) and Candida parapsilosis (29%) were the 2 most common organisms. The rectum (76%) was the most frequent site of colonization. Factors significantly associated with colonization were prolonged administration of antibiotic therapy, parenteral nutrition and intralipid emulsion. Three of 116 infants developed fungemia. The association between colonization and subsequent fungemia was demonstrated in 1 infant, representing 4% of colonized infants. CONCLUSION Fungal colonization was detected in one-fifth of VLBW infants and represents a risk factor for fungemia. Because disease occurred in the absence of apparent colonization, factors other than colonization may contribute to invasive candidiasis.

National survey of invasive pneumococcal diseases in Taiwan under partial PCV7 vaccination in 2007: emergence of serotype 19A with high invasive potential.

We conducted an active, population-based laboratory surveillance study to evaluate the epidemiologic features of invasive pneumococcal disease (IPD) in Taiwan. Concurrently, nasopharyngeal colonization of Streptococcus pneumoniae was evaluated among 1128 healthy children aged <or=5 years. The overall incidence was highest among children aged 2-4 years (15.6/100,000). Serotype 19A, which had never been reported in Taiwan previously, caused a substantial fraction of the invasive diseases (OR, 9.6; 95% CI, 3.1-29.4) among children aged 2-4 years. Comparing serotype distributions of the isolates from nasopharyngeal colonization among children aged <or=5 years, serotypes 14 (OR, 17.3; 95% CI, 5.2-57.9) and 19A (OR, 14.9; 95% CI, 1.9-117) had the highest invasive potential. The study found that serotype 19A expanded in Taiwan, a country with a low 7-valent conjugate pneumococcal vaccine coverage. The 7-valent conjugate pneumococcal vaccines covered 73% of cases in children aged between 2 and 4 years, and 64.7% of cases in children aged <2 years. Among patients aged >or=65 years, the 23-valent pneumococcal polysaccharide vaccine covered 70.4% of cases. In the future, a broader pneumococcal vaccine is needed.

Antibiotic Resistance Patterns of Community-Acquired Urinary Tract Infections in Children With Vesicoureteral Reflux Receiving Prophylactic Antibiotic Therapy

OBJECTIVE. The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. METHODS. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. RESULTS. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum β-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. CONCLUSIONS. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum β-lactamase-producing bacteria or multidrug-resistant uropathogens other than E coli for breakthrough urinary tract infections; therefore, these antibiotics are not appropriate for prophylactic use in patients with vesicoureteral reflux. Co-trimoxazole remains the preferred prophylactic agent for vesicoureteral reflux.