Daniel Tsung-Ning Huang

Novel Swine-origin Influenza Virus A (H1N1): The First Pandemic of the 21st Century

An influenza epidemic was detected in April 2009 at the border between the United States and Mexico. The virus was identified soon after to be a swine-origin influenza virus A (S-OIV A) (H1N1). This virus has an HA gene that is derived from the 1918 swine influenza virus and other genes from human, avian, and Eurasian swine influenza viruses. Clinically, it behaves similarly to seasonal influenza. The only differentiating characteristics are vomiting and diarrhea in a quarter of infected patients, which are rare in seasonal influenza. On June 11, 2009, the World Health Organization declared the first pandemic of the 21st century, caused by S-OIV A (H1N1). Vaccination is the only way to dampen this pandemic. Many questions await answers, including the clinical impact of the pandemic, optimal doses of vaccine, and the future destiny of the virus. A breakthrough in vaccinology against influenza is needed to address the recurring influenza pandemic.

T-antigen activation for prediction of pneumococcus-induced hemolytic uremic syndrome and hemolytic anemia.

Background: Among the most severe complications of invasive pneumococcal infection are hemolytic uremic syndrome (P-HUS) and hemolytic anemia (P-HA), which occur when the Thomsen-Freidenreich antigen (TA) is exposed on erythrocytes, platelets and glomeruli. Methods: To determine the positive predictive value, sensitivity, and specificity of early TA activation testing for P-HUS or P-HA and to compare the microbiologic features of pneumococcus isolates associated or not associated with TA activation. The case records for 36 patients with invasive pneumococcal infection who had been tested for TA activation were retrospectively reviewed. Clinical and laboratory data were compared between patients with and without TA activation. Results: Positive TA activation was 86% sensitive and 57% specific for P-HUS or P-HA. The positive predictive value was 76%. There were no between-group differences in antibiotic susceptibility of the pneumococcal isolates. Pneumococcal serotype 14 was the most frequent (5/10 isolates tested) serotype causing P-HUS. Of the 36 patients, 13 required packed red blood cell transfusion, 3 died, and 2 required extracorporeal membrane oxygenation. No patient had long-term renal sequelae. Conclusions: TA activation is a reasonable predictor of P-HUS or P-HA and could be useful if tested soon after invasive pneumococcal disease is first diagnosed.

Prevalence and molecular characterization of staphylococcus aureus colonization among neonatal intensive care units in Taiwan

Background:Staphylococcus aureus, particularly methicillin-resistant (MRSA), is an important pathogen in neonatal intensive care units (NICUs). Carriage of S. aureus is a significant risk factor for subsequent infection. Objectives: To determine the current status of MRSA prevalence among NICU-hospitalized infants in Taiwan, we conducted this pilot island-wide survey. Methods: On two designated dates in 2011, each patient who stayed in the NICUs of 7 participating hospitals was included. Nasal and umbilical swabs were obtained and sent for detection of S. aureus. The prevalence and risk factors for MRSA carriage were analyzed. MRSA strains were tested for antimicrobial susceptibility and underwent molecular characterization. Results: A total of 251 subjects were included. The overall prevalence of S. aureus and MRSA carriage was 13 and 4.4%, respectively. Previous skin and soft tissue infection was the only predictor in multivariate analysis (OR 40.36; 95% CI 2.32-702.64; p = 0.011). Among 11 MRSA isolates, 3 pulsotypes were identified, with one major type (73%). Nine isolates carried a type IV staphylococcal chromosomal cassette, and 2 carried the type VT. All but one MRSA isolate belonged to linage sequence type 59, the community clone in Taiwan. Conclusions: On a designated date, 4.4% of the infants staying in NICUs in Taiwan carried almost genetically identical community strains of MRSA. MRSA colonization in these infants was significantly associated with previous skin and soft tissue infection.

Management of Bacillus Calmette-Guérin osteomyelitis/osteitis in immunocompetent children-A systematic review.

BACKGROUND Bacillus Calmette-Guérin (BCG) osteomyelitis/osteitis in immunocompetent children is a rare but serious complication of BCG immunization. Rationale for its treatment is unclear. METHODS Due to the rarity of this complication, no randomized control trials has ever been conducted to evaluate methods of intervention. As such, we searched the literature for any reported BCG vaccination-related osteomyelitis/osteitis among immunecompetent children published before April 15, 2014. We summarized the data from different affected regions of the body by recording the number of reported cases, while noting outcomes and their medical and/or surgical interventions. RESULTS From 34 eligible studies gleaned from a screening of 804 articles, a total of 331 cases were enrolled. Involvement of the lower limbs was present in 55.6%, followed by the axial skeleton (26.0%), the upper limbs (15.4%), and multiple bones (3.0%). Of the 64 patients having records of detailed chemotherapy regimens, 45 patients (70%) received two or fewer drugs. Among the 80 patients with detailed surgical records, 50 (62.5%) received surgical procedures for diagnostic purposes. While there were uneventful outcomes for those receiving diagnostic procedures, 7 of the 30 (23.3%) patients receiving surgical interventions had major complications (p=0.002, Fishers exact test). The overall prognosis was good with a 97.6% cure rate. Nevertheless, eight patients (2.4%) suffered major complications. CONCLUSIONS The rationale for treatment of BCG osteomyelitis/osteitis in immunocompetent children is highly subjective. However, patients receiving diagnostic procedures instead of surgical interventions may avoid major complications. Because only a few of the publications had detailed treatment information, further studies are needed to identify proper treatments, while infant BCG vaccination is still in use.

Serologic Status for Pandemic (H1N1) 2009 Virus, Taiwan

We studied preexisting immunity to pandemic (H1N1) 2009 virus in persons in Taiwan. A total of 18 (36%) of 50 elderly adults in Taiwan born before 1935 had protective antibodies against currently circulating pandemic (H1N1) 2009 virus. Seasonal influenza vaccines induced antibodies that did not protect against pandemic (H1N1) 2009 virus.

Juvenile Idiopathic Arthritis Presenting with Prolonged Fever

BACKGROUND/PURPOSE Systemic-onset juvenile idiopathic arthritis (s-JIA) is a systemic disease often accompanied by a fever. We examined 16 patients with s-JIA and reported the clinical manifestations, laboratory data, treatments and outcomes. METHODS From 1984 to 2007, 16 children (aged 1-16 years), who were diagnosed as having s-JIA, were admitted to the Mackay Memorial Hospital in Taiwan. We retrospectively reviewed their medical charts. RESULTS There were nine boys and seven girls, with mean age of onset of 7.4±5.5 years. Fever (100%), typical rash (63%), and arthritis (75%) were the three most common symptoms. Lymphadenopathy (50%), hepatosplenomegaly (63%), pleural pulmonary manifestations (13%) and myalgia (25%) were also noted. One patient had Epstein-Barr virus-associated hemophagocytic syndrome complications. Neutrophilic leukocytosis was a common feature. Other laboratory data showed elevated C-reactive protein levels (25.1±50.3 mg/dL), and erythrocyte sedimentation rates (69±28 mm/hr) and abnormal liver enzymes. Marked hyperferritinemia (> 2,000 ng/mL) was noted in 57% (4/7) of the patients. The mean time from onset of symptoms to diagnosis was 9.2 weeks. Non-steroidal anti-inflammatory drugs, steroids, disease-modifying anti-rheumatic drugs and anti-tumor necrosis factor agents were used for treatment. Due to prolonged fever, 2.0±1.6 (maximum=5) different kinds of antibiotics were used before a diagnosis was made. Most cases had satisfactory therapeutic outcomes except one boy, who had permanent joint contracture. CONCLUSION The clinical manifestations of s-JIA in Taiwan were often accompanied by a prolonged fever. This results in clinicians often suspecting bacterial infections and prescribing several kinds of antibiotics. In the case of prolonged fever, s-JIA should always be placed on the list of differential diagnoses.

Low Seroprotection against Preseasonal Influenza Local Strains in Children Might Predict the Upcoming Epidemic Influenza Strains

BACKGROUND. Our objective was to determine the serological signals that indicated the possible dominant circulating influenza virus subtypes for the coming influenza seasons. METHODS. Healthy children 6 months through 5 years of age, adults 18-60 years of age, and elderly adults >60 years of age were recruited to receive seasonal trivalent inactivated influenza vaccinations from October through December during the 2006-2007 and 2008-2009 seasons. Paired serum samples were collected at baseline and at 3 weeks after vaccination. Using a hemagglutination inhibition (HAI) assay, we measured antibody responses to local influenza strains circulating early in October, before each winter influenza season. RESULTS. A total of 301 subjects were tested for antibody to local strains (80, 120, and 101 subjects in the 2006-2007, 2007-2008, and 2008-2009 seasons, respectively). The dominant winter influenza strains in Taiwan were B/Malaysia/2506/2004-like in the 2006-2007 season, A/Brisbane/59/2007-like virus (H1N1) in the 2007-2008 season, and A/Brisbane/59/2007-like virus (H1N1) in the 2008-2009 season. The group with the lowest number of subjects with an HAI titer of 40 at baseline was children with antibody against the B/Taiwan/0050/2006 in the 2006-2007 season, A/Taiwan/785/2006 (H1N1) in 2007-2008 season, and A/Taiwan/951/2007 (H1N1) in 2008-2009 season. The emergence of these viruses correlated well with the circulating influenza subtype in the following winter peak seasons. CONCLUSIONS. Low seroprotection rate among children against a specific locally circulating influenza strain might predict the dominantly circulating subtype of influenza virus in the coming winter season. A year-end preseasonal serological survey of children could provide valuable information about the possible circulating strain and tailor the disease-control strategy accordingly.

Bacterial etiology of acute otitis media in the era prior to universal pneumococcal vaccination in Taiwanese children

BACKGROUND Acute otitis media (AOM) is one of the most frequent bacterial infections in children. Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) are the two major bacterial pathogens. Pneumococcal conjugate vaccine was introduced into Taiwan in 2005 and only some children were vaccinated. This retrospective study assessed the bacterial etiology of AOM and its antimicrobial susceptibility in the era prior to universal pneumococcal vaccination in Taiwan. METHODS From December 2009 to November 2011, children presenting with AOM and having a middle ear effusion sample collected by tympanocentesis were enrolled. The study period was divided into two parts. Demographic data of patients and antibiotic susceptibility of the pathogens were collected and analyzed. Serotypes of S. pneumoniae were identified. RESULTS Among the 151 episodes, 46% of samples found bacterial pathogens. S. pneumoniae and NTHi were the leading causes of AOM, detected in 55.7% and 22.9% of bacterial AOM episodes, respectively. The prevalent serotypes of S. pneumoniae were 19 A and 19 F. Significantly more pneumococcal and serotype 19 A AOM were found in the later study period (18.4% vs. 33.3%, p = 0.0036; 10.5% vs. 24.0%, p = 0.028). Among the 39 S. pneumoniae isolates, 11 strains (28.2%) were penicillin-susceptible. Of the 16 NTHi, 10 (62.5%) were susceptible to amoxicillin/clavulanate and all were susceptible to cefotaxime. CONCLUSION S. pneumoniae and NTHi were the leading causes of AOM in Taiwanese children in the study period. An increase in patient numbers and proportion of pneumococcal and serotype 19 A AOM occurred. Antimicrobial nonsusceptibility was common in the predominant pathogens.

The diagnostic value of serological studies in pediatric patients with acute Mycoplasma pneumoniae infection

BACKGROUND Mycoplasma pneumoniae is a common pathogen of respiratory tract infections in pediatric patients. Serological studies are traditional methods for the diagnosis. However, early diagnosis of M. pneumoniae infections remains problematic. We investigate the value of early serum immunoglobulin A (IgA), in addition to immunoglobulin G (IgG), and immunoglobulin M (IgM) levels, in children infected with M. pneumoniae. METHODS From August 2016 to February 2017, we enrolled pediatric patients based on both clinical symptoms and chest x-ray, and confirmed by positive throat culture for M. pneumoniae. Serum titers of M. pneumoniae IgM, IgG, and IgA during the acute phase were checked. All respiratory samples were further analyzed by polymerase chain reaction (PCR). Diagnostic values of different tests were evaluated. RESULTS Fifty-six patients fulfilled the diagnostic criteria, with a median age of 4.84 years. Most of them (89.3%) were enrolled within 7 days of disease onset. PCR was positive in 71.4% of the study population. Early IgG samples were of limited value in diagnosing M. pneumoniae infection, of which 89.3% showed a negative result. Positive rates of early serum IgA and IgM were 48.2% and 46.4%, respectively. In combination with IgA and/or IgM, the sensitivity increased to 71.4% during their early clinical course. CONCLUSIONS In the pediatric population, combined serological tests of M. pneumoniae IgA and IgM, offer an accurate method of early diagnosis comparable to that of PCR, and can be an alternative choice for prompt detection of mycoplasma infections when PCR and culture are not available.

Respiratory tract infections in children with tracheostomy

BACKGROUND Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear. METHODS We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups. RESULTS Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children. CONCLUSION In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use.